high presentation in pregnancy

Fetal Presentation, Position, and Lie (Including Breech Presentation)

Variations in Fetal Position and Presentation |

During pregnancy, the fetus can be positioned in many different ways inside the mother's uterus. The fetus may be head up or down or facing the mother's back or front. At first, the fetus can move around easily or shift position as the mother moves. Toward the end of the pregnancy the fetus is larger, has less room to move, and stays in one position. How the fetus is positioned has an important effect on delivery and, for certain positions, a cesarean delivery is necessary. There are medical terms that describe precisely how the fetus is positioned, and identifying the fetal position helps doctors to anticipate potential difficulties during labor and delivery.

Presentation refers to the part of the fetus’s body that leads the way out through the birth canal (called the presenting part). Usually, the head leads the way, but sometimes the buttocks (breech presentation), shoulder, or face leads the way.

Position refers to whether the fetus is facing backward (occiput anterior) or forward (occiput posterior). The occiput is a bone at the back of the baby's head. Therefore, facing backward is called occiput anterior (facing the mother’s back and facing down when the mother lies on her back). Facing forward is called occiput posterior (facing toward the mother's pubic bone and facing up when the mother lies on her back).

Lie refers to the angle of the fetus in relation to the mother and the uterus. Up-and-down (with the baby's spine parallel to mother's spine, called longitudinal) is normal, but sometimes the lie is sideways (transverse) or at an angle (oblique).

For these aspects of fetal positioning, the combination that is the most common, safest, and easiest for the mother to deliver is the following:

Head first (called vertex or cephalic presentation)

Facing backward (occiput anterior position)

Spine parallel to mother's spine (longitudinal lie)

Neck bent forward with chin tucked

Arms folded across the chest

If the fetus is in a different position, lie, or presentation, labor may be more difficult, and a normal vaginal delivery may not be possible.

Variations in fetal presentation, position, or lie may occur when

The fetus is too large for the mother's pelvis (fetopelvic disproportion).

The uterus is abnormally shaped or contains growths such as fibroids .

The fetus has a birth defect .

There is more than one fetus (multiple gestation).

Position and Presentation of the Fetus

Toward the end of pregnancy, the fetus moves into position for delivery. Normally, the presentation is vertex (head first), and the position is occiput anterior (facing toward the pregnant person's spine) and with the face and body angled to one side and the neck flexed.

Variations in fetal presentations include face, brow, breech, and shoulder. Occiput posterior position (facing forward, toward the mother's pubic bone) is less common than occiput anterior position (facing backward, toward the mother's spine).

Variations in Fetal Position and Presentation

Some variations in position and presentation that make delivery difficult occur frequently.

Occiput posterior position

In occiput posterior position (sometimes called sunny-side up), the fetus is head first (vertex presentation) but is facing forward (toward the mother's pubic bone—that is, facing up when the mother lies on her back). This is a very common position that is not abnormal, but it makes delivery more difficult than when the fetus is in the occiput anterior position (facing toward the mother's spine—that is facing down when the mother lies on her back).

When a fetus faces up, the neck is often straightened rather than bent,which requires more room for the head to pass through the birth canal. Delivery assisted by a vacuum device or forceps or cesarean delivery may be necessary.

Breech presentation

In breech presentation, the baby's buttocks or sometimes the feet are positioned to deliver first (before the head).

When delivered vaginally, babies that present buttocks first are more at risk of injury or even death than those that present head first.

The reason for the risks to babies in breech presentation is that the baby's hips and buttocks are not as wide as the head. Therefore, when the hips and buttocks pass through the cervix first, the passageway may not be wide enough for the head to pass through. In addition, when the head follows the buttocks, the neck may be bent slightly backwards. The neck being bent backward increases the width required for delivery as compared to when the head is angled forward with the chin tucked, which is the position that is easiest for delivery. Thus, the baby’s body may be delivered and then the head may get caught and not be able to pass through the birth canal. When the baby’s head is caught, this puts pressure on the umbilical cord in the birth canal, so that very little oxygen can reach the baby. Brain damage due to lack of oxygen is more common among breech babies than among those presenting head first.

In a first delivery, these problems may occur more frequently because a woman’s tissues have not been stretched by previous deliveries. Because of risk of injury or even death to the baby, cesarean delivery is preferred when the fetus is in breech presentation, unless the doctor is very experienced with and skilled at delivering breech babies or there is not an adequate facility or equipment to safely perform a cesarean delivery.

Breech presentation is more likely to occur in the following circumstances:

Labor starts too soon (preterm labor).

The uterus is abnormally shaped or contains abnormal growths such as fibroids .

Fetal Presentation, Position, and Lie (Including Breech Presentation)

Key Points |

Abnormal fetal lie or presentation may occur due to fetal size, fetal anomalies, uterine structural abnormalities, multiple gestation, or other factors. Diagnosis is by examination or ultrasonography. Management is with physical maneuvers to reposition the fetus, operative vaginal delivery , or cesarean delivery .

Terms that describe the fetus in relation to the uterus, cervix, and maternal pelvis are

Fetal presentation: Fetal part that overlies the maternal pelvic inlet; vertex (cephalic), face, brow, breech, shoulder, funic (umbilical cord), or compound (more than one part, eg, shoulder and hand)

Fetal position: Relation of the presenting part to an anatomic axis; for vertex presentation, occiput anterior, occiput posterior, occiput transverse

Fetal lie: Relation of the fetus to the long axis of the uterus; longitudinal, oblique, or transverse

Normal fetal lie is longitudinal, normal presentation is vertex, and occiput anterior is the most common position.

Abnormal fetal lie, presentation, or position may occur with

Fetopelvic disproportion (fetus too large for the pelvic inlet)

Fetal congenital anomalies

Uterine structural abnormalities (eg, fibroids, synechiae)

Multiple gestation

Several common types of abnormal lie or presentation are discussed here.

Transverse lie

Fetal position is transverse, with the fetal long axis oblique or perpendicular rather than parallel to the maternal long axis. Transverse lie is often accompanied by shoulder presentation, which requires cesarean delivery.

Breech presentation

There are several types of breech presentation.

Frank breech: The fetal hips are flexed, and the knees extended (pike position).

Complete breech: The fetus seems to be sitting with hips and knees flexed.

Single or double footling presentation: One or both legs are completely extended and present before the buttocks.

Types of breech presentations

Breech presentation makes delivery difficult ,primarily because the presenting part is a poor dilating wedge. Having a poor dilating wedge can lead to incomplete cervical dilation, because the presenting part is narrower than the head that follows. The head, which is the part with the largest diameter, can then be trapped during delivery.

Additionally, the trapped fetal head can compress the umbilical cord if the fetal umbilicus is visible at the introitus, particularly in primiparas whose pelvic tissues have not been dilated by previous deliveries. Umbilical cord compression may cause fetal hypoxemia.

Predisposing factors for breech presentation include

Preterm labor

Uterine abnormalities

Fetal anomalies

If delivery is vaginal, breech presentation may increase risk of

Umbilical cord prolapse

Birth trauma

Perinatal death

Face or brow presentation

In face presentation, the head is hyperextended, and position is designated by the position of the chin (mentum). When the chin is posterior, the head is less likely to rotate and less likely to deliver vaginally, necessitating cesarean delivery.

Brow presentation usually converts spontaneously to vertex or face presentation.

Occiput posterior position

The most common abnormal position is occiput posterior.

The fetal neck is usually somewhat deflexed; thus, a larger diameter of the head must pass through the pelvis.

Progress may arrest in the second phase of labor. Operative vaginal delivery or cesarean delivery is often required.

Position and Presentation of the Fetus

Toward the end of pregnancy, the fetus moves into position for delivery. Normally, the presentation is vertex (head first), and the position is occiput anterior (facing toward the pregnant patient's spine) with the face and body angled to one side and the neck flexed.

Abnormal presentations include face, brow, breech, and shoulder. Occiput posterior position (facing toward the pregnant patient's pubic bone) is less common than occiput anterior position.

If a fetus is in the occiput posterior position, operative vaginal delivery or cesarean delivery is often required.

In breech presentation, the presenting part is a poor dilating wedge, which can cause the head to be trapped during delivery, often compressing the umbilical cord.

For breech presentation, usually do cesarean delivery at 39 weeks or during labor, but external cephalic version is sometimes successful before labor, usually at 37 or 38 weeks.

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Breech, posterior, transverse lie: What position is my baby in?

Fetal presentation, or how your baby is situated in your womb at birth, is determined by the body part that's positioned to come out first, and it can affect the way you deliver. At the time of delivery, 97 percent of babies are head-down (cephalic presentation). But there are several other possibilities, including feet or bottom first (breech) as well as sideways (transverse lie) and diagonal (oblique lie).

Fetal presentation and position

During the last trimester of your pregnancy, your provider will check your baby's presentation by feeling your belly to locate the head, bottom, and back. If it's unclear, your provider may do an ultrasound or an internal exam to feel what part of the baby is in your pelvis.

Fetal position refers to whether the baby is facing your spine (anterior position) or facing your belly (posterior position). Fetal position can change often: Your baby may be face up at the beginning of labor and face down at delivery.

Here are the many possibilities for fetal presentation and position in the womb.

Medical illustrations by Jonathan Dimes

Head down, facing down (anterior position)

A baby who is head down and facing your spine is in the anterior position. This is the most common fetal presentation and the easiest position for a vaginal delivery.

This position is also known as "occiput anterior" because the back of your baby's skull (occipital bone) is in the front (anterior) of your pelvis.

Head down, facing up (posterior position)

In the posterior position , your baby is head down and facing your belly. You may also hear it called "sunny-side up" because babies who stay in this position are born facing up. But many babies who are facing up during labor rotate to the easier face down (anterior) position before birth.

Posterior position is formally known as "occiput posterior" because the back of your baby's skull (occipital bone) is in the back (posterior) of your pelvis.

Frank breech

In the frank breech presentation, both the baby's legs are extended so that the feet are up near the face. This is the most common type of breech presentation. Breech babies are difficult to deliver vaginally, so most arrive by c-section .

Some providers will attempt to turn your baby manually to the head down position by applying pressure to your belly. This is called an external cephalic version , and it has a 58 percent success rate for turning breech babies. For more information, see our article on breech birth .

Complete breech

A complete breech is when your baby is bottom down with hips and knees bent in a tuck or cross-legged position. If your baby is in a complete breech, you may feel kicking in your lower abdomen.

Incomplete breech

In an incomplete breech, one of the baby's knees is bent so that the foot is tucked next to the bottom with the other leg extended, positioning that foot closer to the face.

Single footling breech

In the single footling breech presentation, one of the baby's feet is pointed toward your cervix.

Double footling breech

In the double footling breech presentation, both of the baby's feet are pointed toward your cervix.

Transverse lie

In a transverse lie, the baby is lying horizontally in your uterus and may be facing up toward your head or down toward your feet. Babies settle this way less than 1 percent of the time, but it happens more commonly if you're carrying multiples or deliver before your due date.

If your baby stays in a transverse lie until the end of your pregnancy, it can be dangerous for delivery. Your provider will likely schedule a c-section or attempt an external cephalic version , which is highly successful for turning babies in this position.

Oblique lie

In rare cases, your baby may lie diagonally in your uterus, with his rump facing the side of your body at an angle.

Like the transverse lie, this position is more common earlier in pregnancy, and it's likely your provider will intervene if your baby is still in the oblique lie at the end of your third trimester.

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BabyCenter's editorial team is committed to providing the most helpful and trustworthy pregnancy and parenting information in the world. When creating and updating content, we rely on credible sources: respected health organizations, professional groups of doctors and other experts, and published studies in peer-reviewed journals. We believe you should always know the source of the information you're seeing. Learn more about our editorial and medical review policies .

Ahmad A et al. 2014. Association of fetal position at onset of labor and mode of delivery: A prospective cohort study. Ultrasound in obstetrics & gynecology 43(2):176-182. https://www.ncbi.nlm.nih.gov/pubmed/23929533 Opens a new window [Accessed September 2021]

Gray CJ and Shanahan MM. 2019. Breech presentation. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK448063/ Opens a new window [Accessed September 2021]

Hankins GD. 1990. Transverse lie. American Journal of Perinatology 7(1):66-70. https://www.ncbi.nlm.nih.gov/pubmed/2131781 Opens a new window [Accessed September 2021]

Medline Plus. 2020. Your baby in the birth canal. U.S. National Library of Medicine. https://medlineplus.gov/ency/article/002060.htm Opens a new window [Accessed September 2021]

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What Causes Breech Presentation?

Learn more about the types, causes, and risks of breech presentation, along with how breech babies are typically delivered.

What Is Breech Presentation?

Types of breech presentation, what causes a breech baby, can you turn a breech baby, how are breech babies delivered.

FatCamera/Getty Images

Toward the end of pregnancy, your baby will start to get into position for delivery, with their head pointed down toward the vagina. This is otherwise known as vertex presentation. However, some babies turn inside the womb so that their feet or buttocks are poised to be delivered first, which is commonly referred to as breech presentation, or a breech baby.

As you near the end of your pregnancy journey, an OB-GYN or health care provider will check your baby's positioning. You might find yourself wondering: What causes breech presentation? Are there risks involved? And how are breech babies delivered? We turned to experts and research to answer some of the most common questions surrounding breech presentation, along with what causes this positioning in the first place.

During your pregnancy, your baby constantly moves around the uterus. Indeed, most babies do somersaults up until the 36th week of pregnancy , when they pick their final position in the womb, says Laura Riley , MD, an OB-GYN in New York City. Approximately 3-4% of babies end up “upside-down” in breech presentation, with their feet or buttocks near the cervix.

Breech presentation is typically diagnosed during a visit to an OB-GYN, midwife, or health care provider. Your physician can feel the position of your baby's head through your abdominal wall—or they can conduct a vaginal exam if your cervix is open. A suspected breech presentation should ultimately be confirmed via an ultrasound, after which you and your provider would have a discussion about delivery options, potential issues, and risks.

There are three types of breech babies: frank, footling, and complete. Learn about the differences between these breech presentations.

Frank Breech

With frank breech presentation, your baby’s bottom faces the cervix and their legs are straight up. This is the most common type of breech presentation.

Footling Breech

Like its name suggests, a footling breech is when one (single footling) or both (double footling) of the baby's feet are in the birth canal, where they’re positioned to be delivered first .

Complete Breech

In a complete breech presentation, baby’s bottom faces the cervix. Their legs are bent at the knees, and their feet are near their bottom. A complete breech is the least common type of breech presentation.

Preeclampsia

On this page, when to see a doctor, risk factors, complications.

Preeclampsia is a complication of pregnancy. With preeclampsia, you might have high blood pressure, high levels of protein in urine that indicate kidney damage (proteinuria), or other signs of organ damage. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had previously been in the standard range.

Left untreated, preeclampsia can lead to serious — even fatal — complications for both the mother and baby.

Early delivery of the baby is often recommended. The timing of delivery depends on how severe the preeclampsia is and how many weeks pregnant you are. Before delivery, preeclampsia treatment includes careful monitoring and medications to lower blood pressure and manage complications.

Preeclampsia may develop after delivery of a baby, a condition known as postpartum preeclampsia.

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The defining feature of preeclampsia is high blood pressure, proteinuria, or other signs of damage to the kidneys or other organs. You may have no noticeable symptoms. The first signs of preeclampsia are often detected during routine prenatal visits with a health care provider.

Along with high blood pressure, preeclampsia signs and symptoms may include:

Excess protein in urine (proteinuria) or other signs of kidney problems
Decreased levels of platelets in blood (thrombocytopenia)
Increased liver enzymes that indicate liver problems
Severe headaches
Changes in vision, including temporary loss of vision, blurred vision or light sensitivity
Shortness of breath, caused by fluid in the lungs
Pain in the upper belly, usually under the ribs on the right side
Nausea or vomiting

Weight gain and swelling (edema) are typical during healthy pregnancies. However, sudden weight gain or a sudden appearance of edema — particularly in your face and hands — may be a sign of preeclampsia.

Make sure you attend your prenatal visits so that your health care provider can monitor your blood pressure. Contact your provider immediately or go to an emergency room if you have severe headaches, blurred vision or other visual disturbances, severe belly pain, or severe shortness of breath.

Because headaches, nausea, and aches and pains are common pregnancy complaints, it's difficult to know when new symptoms are simply part of being pregnant and when they may indicate a serious problem — especially if it's your first pregnancy. If you're concerned about your symptoms, contact your doctor.

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The exact cause of preeclampsia likely involves several factors. Experts believe it begins in the placenta — the organ that nourishes the fetus throughout pregnancy. Early in a pregnancy, new blood vessels develop and evolve to supply oxygen and nutrients to the placenta.

In women with preeclampsia, these blood vessels don't seem to develop or work properly. Problems with how well blood circulates in the placenta may lead to the irregular regulation of blood pressure in the mother.

Other high blood pressure disorders during pregnancy

Preeclampsia is one high blood pressure (hypertension) disorder that can occur during pregnancy. Other disorders can happen, too:

Gestational hypertension is high blood pressure that begins after 20 weeks without problems in the kidneys or other organs. Some women with gestational hypertension may develop preeclampsia.
Chronic hypertension is high blood pressure that was present before pregnancy or that occurs before 20 weeks of pregnancy. High blood pressure that continues more than three months after a pregnancy also is called chronic hypertension.
Chronic hypertension with superimposed preeclampsia occurs in women diagnosed with chronic high blood pressure before pregnancy, who then develop worsening high blood pressure and protein in the urine or other health complications during pregnancy.

Conditions that are linked to a higher risk of preeclampsia include:

Preeclampsia in a previous pregnancy
Being pregnant with more than one baby
Chronic high blood pressure (hypertension)
Type 1 or type 2 diabetes before pregnancy
Kidney disease
Autoimmune disorders
Use of in vitro fertilization

Conditions that are associated with a moderate risk of developing preeclampsia include:

First pregnancy with current partner
Family history of preeclampsia
Maternal age of 35 or older
Complications in a previous pregnancy
More than 10 years since previous pregnancy

Other risk factors

Several studies have shown a greater risk of preeclampsia among Black women compared with other women. There's also some evidence of an increased risk among indigenous women in North America.

A growing body of evidence suggests that these differences in risk may not necessarily be based on biology. A greater risk may be related to inequities in access to prenatal care and health care in general, as well as social inequities and chronic stressors that affect health and well-being.

Lower income also is associated with a greater risk of preeclampsia likely because of access to health care and social factors affecting health.

For the purposes of making decisions about prevention strategies, a Black woman or a woman with a low income has a moderately increased risk of developing preeclampsia.

Complications of preeclampsia may include:

Fetal growth restriction. Preeclampsia affects the arteries carrying blood to the placenta. If the placenta doesn't get enough blood, the baby may receive inadequate blood and oxygen and fewer nutrients. This can lead to slow growth known as fetal growth restriction.
Preterm birth. Preeclampsia may lead to an unplanned preterm birth — delivery before 37 weeks. Also, planned preterm birth is a primary treatment for preeclampsia. A baby born prematurely has increased risk of breathing and feeding difficulties, vision or hearing problems, developmental delays, and cerebral palsy. Treatments before preterm delivery may decrease some risks.
Placental abruption. Preeclampsia increases your risk of placental abruption. With this condition, the placenta separates from the inner wall of the uterus before delivery. Severe abruption can cause heavy bleeding, which can be life-threatening for both the mother and baby.

hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome. HELLP stands for hemolysis (the destruction of red blood cells), elevated liver enzymes and low platelet count. This severe form of preeclampsia affects several organ systems. HELLP syndrome is life-threatening to the mother and baby, and it may cause lifelong health problems for the mother.

Signs and symptoms include nausea and vomiting, headache, upper right belly pain, and a general feeling of illness or being unwell. Sometimes, it develops suddenly, even before high blood pressure is detected. It also may develop without any symptoms.

Eclampsia. Eclampsia is the onset of seizures or coma with signs or symptoms of preeclampsia. It is very difficult to predict whether a patient with preeclampsia will develop eclampsia. Eclampsia can happen without any previously observed signs or symptoms of preeclampsia.

Signs and symptoms that may appear before seizures include severe headaches, vision problems, mental confusion or altered behaviors. But, there are often no symptoms or warning signs. Eclampsia may occur before, during or after delivery.

Other organ damage. Preeclampsia may result in damage to the kidneys, liver, lung, heart, or eyes, and may cause a stroke or other brain injury. The amount of injury to other organs depends on how severe the preeclampsia is.
Cardiovascular disease. Having preeclampsia may increase your risk of future heart and blood vessel (cardiovascular) disease. The risk is even greater if you've had preeclampsia more than once or you've had a preterm delivery.

The best clinical evidence for prevention of preeclampsia is the use of low-dose aspirin. Your primary care provider may recommend taking an 81-milligram aspirin tablet daily after 12 weeks of pregnancy if you have one high-risk factor for preeclampsia or more than one moderate-risk factor.

It's important that you talk with your provider before taking any medications, vitamins or supplements to make sure it's safe for you.

Lifestyle and healthy choices

Before you become pregnant, especially if you've had preeclampsia before, it's a good idea to be as healthy as you can be. Talk to your provider about managing any conditions that increase the risk of preeclampsia.

Apr 15, 2022

Ferri FF. Preeclampsia. In: Ferri's Clinical Advisor 2022. Elsevier; 2022. https://www.clinicalkey.com. Accessed Jan. 3, 2022.
Landon MB, et al., eds. Preeclampsia and hypertensive disorders. In: Gabbe's Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed Jan. 3, 2022.
Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstetrics & Gynecology. 2020; doi:10.1097/AOG.0000000000003891.
August P. Preeclampsia: Clinical features and diagnosis. https://www.uptodate.com/contents/search. Accessed Jan. 3, 2022.
Karumanchi SA, et al. Preeclampsia: Pathogenesis. https://www.uptodate.com/contents/search. Accessed Jan. 4, 2022.
U.S. Preventive Services Task Force, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force recommendation statement. JAMA. 2021; doi:10.1001/jama.2021.14781.
Johnson JD, et al. Does race or ethnicity play a role in the origin, pathophysiology, and outcomes of preeclampsia? An expert review of the literature. American Journal of Obstetrics and Gynecology. 2020; doi:10.1016/j.ajog.2020.07.038.
Preeclampsia and high blood pressure during pregnancy. American College of Obstetricians and Gynecologists. https://www.acog.org/womens-health/faqs/preeclampsia-and-high-blood-pressure-during-pregnancy. Accessed Jan. 3, 2022.
Preterm birth. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm. Accessed Jan. 5, 2022.
Special tests for monitoring fetal well-being. American College of Ostetricians and Gynecologists. https://www.acog.org/womens-health/faqs/special-tests-for-monitoring-fetal-well-being. Accessed Jan. 5, 2022.
Norwitz ER. Preeclampsia: Management and prognosis. https://www.uptodate.com/contents/search. Accessed Jan. 3, 2022.
Low-dose aspirin use for the prevention of preeclampsia and related morbidity and mortality: Practice advisory, Dec. 2021. American College of Obstetricians and Gynecologists. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/12/low-dose-aspirin-use-for-the-prevention-of-preeclampsia-and-related-morbidity-and-mortality. Accessed Jan. 3, 2022.
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High-Risk Pregnancy: What You Need to Know

Reviewed By:

Janice Lynn Henderson, M.D.

Whether it’s your first pregnancy or your third, hearing your obstetrician, nurse practitioner or midwife say that your pregnancy is high risk can feel concerning. High-risk pregnancy is a term that can denote a wide variety of common conditions. Many of them are related to pre-existing conditions you may have had before becoming pregnant or conditions you may have developed while pregnant or during delivery.

A high-risk pregnancy does not necessarily mean that your pregnancy will be more difficult or challenging than a low-risk pregnancy. However, it does sometimes mean that you will need to consult a maternal-fetal medicine specialist and undergo more monitoring than someone with a low-risk pregnancy.

Learn more about high-risk pregnancy from Janice Henderson, M.D. , a Johns Hopkins maternal-fetal medicine specialist.

Q: What’s the difference between a maternal-fetal medicine specialist and an obstetrician?

A: A maternal-fetal medicine specialist (perinatologist) receives a traditional obstetrics and gynecology education but with an additional three years of training to learn how to treat medical complications that are related to pregnancy. In addition, the maternal-fetal medicine specialist has extensive training in assessment and treatment of fetal problems. Most perinatal ultrasound is interpreted by maternal-fetal medicine specialists.

You may be referred to a maternal-fetal medicine specialist if you have a pre-existing medical condition prior to pregnancy, develop a medical condition during pregnancy or have problems during delivery. Additionally, you will see a maternal-fetal medicine specialist during pregnancy if your baby has an anomaly. In this case, the maternal-fetal medicine specialist will coordinate your care as well as your baby’s care during pregnancy and at delivery with the help of a pediatric care team.

Q: Should I see a maternal-fetal medicine specialist before pregnancy?

A: It can be beneficial to consult with a maternal-fetal medicine specialist before pregnancy if you have one (or more) of the following:

Pre-existing medical condition. There are many pre-existing medical conditions that may need to be monitored in relation to pregnancy, e.g., diabetes , lupus , renal disease and hypertension (high blood pressure). In some instances, a maternal-fetal medicine specialist may alter the type of medication you’re taking to maintain your health and prevent any adverse effects to your future pregnancies. If you have diabetes, a maternal-fetal medicine specialist can help you optimize your blood sugar control prior to conception to help reduce the risk of fetal anomalies. If you struggle with obesity , a maternal-fetal medicine specialist can review the benefits of weight loss before pregnancy. According to Henderson, “Losing weight in a healthy manner can reduce your risk of developing conditions such as hypertension and gestational diabetes during pregnancy.”
Genetic risks. Preconception genetic screening has become more common in recent years as technology has advanced and testing has become more accessible. If you have family members with a certain disease or if you belong to an ethnicity that has a greater risk of developing specific conditions (such as sickle cell disease or Tay-Sachs disease), genetic screening can be used to assess your and your partner’s risk of being a carrier. Also, common genetic conditions, such as cystic fibrosis or spinal muscular atrophy , can be screened for with a blood test.

Additionally, if you have a child affected by a genetic disorder or syndrome, a maternal-fetal medicine specialist can provide counseling and management to consider how the condition may impact your future pregnancies. Always speak with your health care provider to determine what’s best for you and your pregnancy.

Q: What conditions may lead to a high-risk pregnancy?

A: The following list represents the most common conditions that can lead to a high-risk pregnancy, but note that not all women with these conditions will have a high-risk pregnancy.

Diabetes. If you have diabetes before you become pregnant, you will likely be referred to a maternal-fetal medicine specialist to monitor your condition and determine the proper medications. Preconception counseling is ideal. Developing diabetes during pregnancy (gestational diabetes) is very common, and your obstetric provider will likely be able to care for you without a maternal-fetal medicine consult. If a maternal-fetal medicine specialist is consulted for gestational diabetes, he or she will follow your baby’s growth and well-being, and manage your health with nutrition counseling, glucose monitoring and, possibly, medications.
Pre-eclampsia . Pre-eclampsia is a condition unique to pregnancy where you have high blood pressure in conjunction with protein in your urine and edema (swelling of the skin). In some women with pre-eclampsia, liver or platelet abnormalities are present. You may be referred to a maternal-fetal medicine specialist depending on the severity of your disease or if you are preterm. “The only treatment for pre-eclampsia is delivering your baby,” explains Henderson, “so this is a condition that requires very close monitoring to balance maternal complications against the risks of delivering your baby early.”
Hypertension. If you have hypertension before pregnancy, a maternal-fetal medicine specialist will monitor your baby’s growth and may be consulted if problems arise. Some medications commonly used outside of pregnancy to treat hypertension are contraindicated in pregnancy.
Multiples. Pregnancies with twins or higher-order multiples have a greater risk of complications. Women with multiple pregnancies are more likely to develop pre-eclampsia or go into preterm labor. Twin pregnancies have a higher risk of fetal anomalies and growth problems, especially if they share a placenta. If you have a multiple pregnancy, a maternal-fetal medicine specialist will closely monitor the pregnancy by performing additional ultrasounds. The maternal-fetal medicine specialist will recommend how and when your babies should be delivered. “If you remain healthy and the growth of your babies is normal and without complications, you may continue to see your Ob/Gyn,” says Henderson, “or you may prefer to be seen in a specialty multiples clinic.”
Sexually transmitted diseases (STDs). In general, your obstetric provider can treat you for sexually transmitted diseases that may occur during pregnancy or if there is a pre-existing STD, such as herpes. In certain cases, consultation with a maternal-fetal medicine specialist will be required. For example, if you are being treated for syphilis and an ultrasound shows that your fetus may be affected, a maternal-fetal medicine specialist will provide further care and management. Women with HIV are also generally cared for by maternal-fetal medicine specialists because the medication regimens are complex.
Obesity. Women who are obese have a greater risk of developing diabetes, hypertension and pre-eclampsia during pregnancy. “Obesity is the one of the only health conditions affecting pregnant women that can be changed before pregnancy, which is why maternal-fetal medicine specialists encourage women to lose weight through healthy strategies,” explains Henderson.

Q: Will all my future pregnancies be high risk?

A: Having one high-risk pregnancy does not mean that all your future pregnancies will be deemed high risk as well. You may have a fetal complication occur in one pregnancy that wouldn’t in another, and certain health conditions may change over time.

However, if you have had a pregnancy that ended in preterm delivery, you are at greater risk of having preterm labor during your next pregnancy. If this occurs, your obstetric provider will manage your pregnancy using medication, and a maternal-fetal medicine specialist will monitor your cervical length with ultrasound surveillance.

Ultimately, the most important thing to remember about having a high-risk pregnancy is that your maternal-fetal medicine specialist and Ob/Gyn have the knowledge and experience required to keep you and your baby as healthy as possible.

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Presentation and position of baby through pregnancy and at birth

9-minute read

If you are concerned about your baby’s movements, contact your doctor or midwife for advice immediately.

If you baby is in a breech presentation, your doctor may recommend trying a technique called an external cephalic version to try and move your baby while they are still in the uterus for an easier birth.

What does presentation and position mean?

Presentation refers to the part of your baby’s body that is facing downwards in the direction of the birth canal.

Position refers to where your baby’s occiput (the bottom part of the back of their head) is in relation to your body.

If your baby is in a breech presentation , then position refers to where your baby’s sacrum (lower back) is in relation to your body.

People — including medical professionals — sometimes use these terms incorrectly. Sometimes when speaking about babies in breech presentation, the word ‘position’ will be used to refer to their presentation. For example, you may read information or hear people say ‘breech position’ instead of ‘breech presentation’.

What are the different types of presentation my baby could be in during pregnancy and birth?

Most babies present headfirst, also known as cephalic presentation. Most babies that are headfirst will be vertex presentation. This means that the crown of their head sits at the opening of your birth canal.

In rare cases, your baby can be headfirst but in face or brow presentation, which may not be suitable for vaginal birth.

If your baby is in a breech presentation, their feet or bottom will be closest to your birth canal. The 3 most common types of breech presentation are:

frank or extended breech — where your baby’s legs are straight up in front of their body, with their feet up near their face
complete or flexed breech — where your baby is in a sitting position with their legs crossed in front of their body and their feet near their bottom
footling breech — where one or both of your baby’s feet are hanging below their bottom, so the foot or feet are coming first

What are the different positions my baby could be in during pregnancy and birth?

If your baby is headfirst, the 3 main types of presentation are:

anterior – when the back of your baby’s head is at the front of your belly
lateral – when the back of your baby’s head is facing your side
posterior – when the back of your baby’s head is towards your back

Anterior, lateral and posterior fetal presentations

How will I know what presentation and position my baby is in?

Your doctor or midwife can usually work out your baby’s presentation by feeling your abdomen. They may also double check it with a portable ultrasound. Your baby’s presentation is usually checked around 36 weeks .

Your doctor or midwife will also confirm your baby’s head position in labour by examining your belly and using an ultrasound , and they may also do a vaginal examination . During the vaginal examination they are feeling for certain ridges on your baby’s head called sutures and fontanelles that help them work out which way your baby is positioned.

What is the ideal presentation and position for baby to be in for a vaginal birth?

For a vaginal birth, your baby will ideally be headfirst with the back of their head at the front of your belly, also known as being in the anterior position. This position is best for labour and birth since it means that the smallest part of your baby’s head goes down the birth canal first.

Vertex presentation, showing the narrow part of the baby’s head.

When does a baby usually get in the ideal presentation and position for birth?

Your baby will usually be in a headfirst position by 37 weeks of pregnancy. Around 3 in every 100 babies will be in breech presentation after 37 weeks.

Your baby’s position can change with your contractions during labour as they move down the birth canal, so their exact position can change during labour.

What are my options if baby isn't in the ideal presentation or position for a vaginal birth?

If your baby is in a breech presentation, your doctor may recommend a technique called an external cephalic version (ECV) to try and move your baby while they are still in the uterus . An ECV involves your doctor using their hands to apply pressure on your belly and help turn your baby to a headfirst position. It has a 1 in 2 chance of success and is a safe option in most pregnancies.

There is no evidence to show that alternative therapies, such as exercises, acupuncture or chiropractic treatments, help your baby change from a breech presentation to headfirst.

If your baby remains breech, your doctor may discuss having a breech vaginal birth. Not all doctors and hospitals offer this option. They may also suggest you birth your baby with a planned caesarean section .

If your baby’s presentation is headfirst but the position of your baby’s head is not ideal for labour, it can lead to a longer labour, and potential complications . The position of your baby’s head will often change as your labour progresses. If it doesn’t, sometimes you can still give birth without assistance, or you may need your doctor to help turn your baby’s head or help your birth with a vacuum or forceps .

Any procedure or decision for a type of birth will only go ahead with your consent . You will be able to discuss all the options with your doctor, and based on your preferences for yourself and your baby’s safety, make a decision together .

Resources and support

The Royal Australian and New Zealand College of Obstetrics and Gynaecology has a factsheet about the options available to you if your baby is in a breech presentation at the end of your pregnancy .

Mercy Perinatal has information on external cephalic version (ECV) safety and benefits if your baby is in a breech presentation at the end of your pregnancy.

The Women’s Hospital has information about the different presentations and positions your baby could be in, and how it can affect your birthing experience.

Speak to a maternal child health nurse

Call Pregnancy, Birth and Baby to speak to a maternal child health nurse on 1800 882 436 or video call . Available 7am to midnight (AET), 7 days a week.

Learn more here about the development and quality assurance of healthdirect content .

Last reviewed: October 2023

External cephalic version (ecv), malpresentation, breech pregnancy, search our site for.

Foetal Version
Breech Presentation

Need more information?

Breech presentation and turning the baby

In preparation for a safe birth, your health team will need to turn your baby if it is in a bottom first ‘breech’ position.

Breech Presentation at the End of your Pregnancy

Breech presentation occurs when your baby is lying bottom first or feet first in the uterus (womb) rather than the usual head first position. In early pregnancy, a breech position is very common.

Read more on RANZCOG - Royal Australian and New Zealand College of Obstetricians and Gynaecologists website

External Cephalic Version for Breech Presentation - Pregnancy and the first five years

This information brochure provides information about an External Cephalic Version (ECV) for breech presentation

Labour complications

Even if you’re healthy and well prepared for childbirth, there’s always a chance of unexpected problems. Learn more about labour complications.

ECV is a procedure to try to move your baby from a breech position to a head-down position. This is performed by a trained doctor.

Having a baby

The articles in this section relate to having a baby – what to consider before becoming pregnant, pregnancy and birth, and after your baby is born.

Anatomy of pregnancy and birth - pelvis

Your pelvis helps to carry your growing baby and is tailored for vaginal births. Learn more about the structure and function of the female pelvis.

Planned or elective caesarean

There are important things to consider if you are having a planned or elective caesarean such as what happens during and after the procedure.

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What is a high-risk pregnancy?

A high-risk pregnancy is one that threatens the health or life of the mother or her fetus. It often requires specialized care from specially trained providers.

Some pregnancies become high risk as they progress, while some women are at increased risk for complications even before they get pregnant for a variety of reasons.

Early and regular prenatal care helps many women have healthy pregnancies and deliveries without complications.

Risk factors for a high-risk pregnancy can include:

Existing health conditions , such as high blood pressure, diabetes, or being HIV-positive 1
Overweight and obesity. Obesity increases the risk for high blood pressure, preeclampsia, gestational diabetes, stillbirth, neural tube defects, and cesarean delivery. NICHD researchers have found that obesity can raise infants' risk of heart problems at birth by 15%. 3
Multiple births. The risk of complications is higher in women carrying more than one fetus (twins and higher-order multiples). Common complications include preeclampsia, premature labor, and preterm birth. More than one-half of all twins and as many as 93% of triplets are born at less than 37 weeks' gestation. 4
Young or old maternal age. Pregnancy in teens and women age 35 or older increases the risk for preeclampsia and gestational high blood pressure. 5 , 6

Women with high-risk pregnancies should receive care from a special team of health care providers to ensure the best possible outcomes.

For more information, visit the High-Risk Pregnancy topic.

American College of Obstetricians and Gynecologists. (2015). ACOG Practice Bulletin No. 156: Obesity in pregnancy. Obstetrics and Gynecology, 126 (6), e112–126. PMID: 26595582
NIH. (2010). Risk of newborn heart defects increases with maternal obesity [news release] . Retrieved July 30, 2012, from http://www.nih.gov/news/health/apr2010/nichd-07.htm
Hamilton, B. E., Martin, J. A., Osterman, M. J. K., Curtin, S. C., & Mathews, T. J. (2015). Births: Final data for 2014. National Vital Statistics Reports, 64 (12). Retrieved May 31, 2016, from http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64_12.pdf (PDF – 2.95 MB)
MedlinePlus. (2011). Medical Encyclopedia: Adolescent pregnancy. Retrieved May 31, 2016, from https://medlineplus.gov/ency/patientinstructions/000607.htm
MedlinePlus. (2014). Medical Encyclopedia: preeclampsia. Retrieved May 31, 2016, from https://medlineplus.gov/ency/article/000898.htm

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Breech presentation.

Caron J. Gray ; Meaghan M. Shanahan .

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Last Update: November 6, 2022 .

Continuing Education Activity

Breech presentation refers to the fetus in the longitudinal lie with the buttocks or lower extremity entering the pelvis first. The three types of breech presentation include frank breech, complete breech, and incomplete breech. In a frank breech, the fetus has flexion of both hips, and the legs are straight with the feet near the fetal face, in a pike position. This activity reviews the cause and pathophysiology of breech presentation and highlights the role of the interprofessional team in its management.

Describe the pathophysiology of breech presentation.
Review the physical exam of a patient with a breech presentation.
Summarize the treatment options for breech presentation.
Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by breech presentation.
Introduction

Breech presentation refers to the fetus in the longitudinal lie with the buttocks or lower extremity entering the pelvis first. The three types of breech presentation include frank breech, complete breech, and incomplete breech. In a frank breech, the fetus has flexion of both hips, and the legs are straight with the feet near the fetal face, in a pike position. The complete breech has the fetus sitting with flexion of both hips and both legs in a tuck position. Finally, the incomplete breech can have any combination of one or both hips extended, also known as footling (one leg extended) breech, or double footling breech (both legs extended). [1] [2] [3]

Clinical conditions associated with breech presentation include those that may increase or decrease fetal motility, or affect the vertical polarity of the uterine cavity. Prematurity, multiple gestations, aneuploidies, congenital anomalies, Mullerian anomalies, uterine leiomyoma, and placental polarity as in placenta previa are most commonly associated with a breech presentation. Also, a previous history of breech presentation at term increases the risk of repeat breech presentation at term in subsequent pregnancies. [4] [5] These are discussed in more detail in the pathophysiology section.

Epidemiology

Breech presentation occurs in 3% to 4% of all term pregnancies. A higher percentage of breech presentations occurs with less advanced gestational age. At 32 weeks, 7% of fetuses are breech, and 28 weeks or less, 25% are breech.

Specifically, following one breech delivery, the recurrence rate for the second pregnancy was nearly 10%, and for a subsequent third pregnancy, it was 27%. Prior cesarean delivery has also been described by some to increase the incidence of breech presentation two-fold.

Pathophysiology

As mentioned previously, the most common clinical conditions or disease processes that result in the breech presentation are those that affect fetal motility or the vertical polarity of the uterine cavity. [6] [7]

Conditions that change the vertical polarity or the uterine cavity, or affect the ease or ability of the fetus to turn into the vertex presentation in the third trimester include:

Mullerian anomalies: Septate uterus, bicornuate uterus, and didelphys uterus
Placentation: Placenta previa as the placenta is occupying the inferior portion of the uterine cavity. Therefore, the presenting part cannot engage
Uterine leiomyoma: Mainly larger myomas located in the lower uterine segment, often intramural or submucosal, that prevent engagement of the presenting part.
Prematurity
Aneuploidies and fetal neuromuscular disorders commonly cause hypotonia of the fetus, inability to move effectively
Congenital anomalies: Fetal sacrococcygeal teratoma, fetal thyroid goiter
Polyhydramnios: Fetus is often in unstable lie, unable to engage
Oligohydramnios: Fetus is unable to turn to vertex due to lack of fluid
Laxity of the maternal abdominal wall: Uterus falls forward, the fetus is unable to engage in the pelvis.

The risk of cord prolapse varies depending on the type of breech. Incomplete or footling breech carries the highest risk of cord prolapse at 15% to 18%, while complete breech is lower at 4% to 6%, and frank breech is uncommon at 0.5%.

History and Physical

During the physical exam, using the Leopold maneuvers, palpation of a hard, round, mobile structure at the fundus and the inability to palpate a presenting part in the lower abdomen superior to the pubic bone or the engaged breech in the same area, should raise suspicion of a breech presentation.

During a cervical exam, findings may include the lack of a palpable presenting part, palpation of a lower extremity, usually a foot, or for the engaged breech, palpation of the soft tissue of the fetal buttocks may be noted. If the patient has been laboring, caution is warranted as the soft tissue of the fetal buttocks may be interpreted as caput of the fetal vertex.

Any of these findings should raise suspicion and ultrasound should be performed.

Diagnosis of a breech presentation can be accomplished through abdominal exam using the Leopold maneuvers in combination with the cervical exam. Ultrasound should confirm the diagnosis.

On ultrasound, the fetal lie and presenting part should be visualized and documented. If breech presentation is diagnosed, specific information including the specific type of breech, the degree of flexion of the fetal head, estimated fetal weight, amniotic fluid volume, placental location, and fetal anatomy review (if not already done previously) should be documented.

Treatment / Management

Expertise in the delivery of the vaginal breech baby is becoming less common due to fewer vaginal breech deliveries being offered throughout the United States and in most industrialized countries. The Term Breech Trial (TBT), a well-designed, multicenter, international, randomized controlled trial published in 2000 compared planned vaginal delivery to planned cesarean delivery for the term breech infant. The investigators reported that delivery by planned cesarean resulted in significantly lower perinatal mortality, neonatal mortality, and serious neonatal morbidity. Also, there was no significant difference in maternal morbidity or mortality between the two groups. Since that time, the rate of term breech infants delivered by planned cesarean has increased dramatically. Follow-up studies to the TBT have been published looking at maternal morbidity and outcomes of the children at two years. Although these reports did not show any significant difference in the risk of death and neurodevelopmental, these studies were felt to be underpowered. [8] [9] [10] [11]

Since the TBT, many authors since have argued that there are still some specific situations that vaginal breech delivery is a potential, safe alternative to planned cesarean. Many smaller retrospective studies have reported no difference in neonatal morbidity or mortality using these specific criteria.

The initial criteria used in these reports were similar: gestational age greater than 37 weeks, frank or complete breech presentation, no fetal anomalies on ultrasound examination, adequate maternal pelvis, and estimated fetal weight between 2500 g and 4000 g. In addition, the protocol presented by one report required documentation of fetal head flexion and adequate amniotic fluid volume, defined as a 3-cm vertical pocket. Oxytocin induction or augmentation was not offered, and strict criteria were established for normal labor progress. CT pelvimetry did determine an adequate maternal pelvis.

Despite debate on both sides, the current recommendation for the breech presentation at term includes offering external cephalic version (ECV) to those patients that meet criteria, and for those whom are not candidates or decline external cephalic version, a planned cesarean section for delivery sometime after 39 weeks.

Regarding the premature breech, gestational age will determine the mode of delivery. Before 26 weeks, there is a lack of quality clinical evidence to guide mode of delivery. One large retrospective cohort study recently concluded that from 28 to 31 6/7 weeks, there is a significant decrease in perinatal morbidity and mortality in a planned cesarean delivery versus intended vaginal delivery, while there is no difference in perinatal morbidity and mortality in gestational age 32 to 36 weeks. Of note, due to lack of recruitment, no prospective clinical trials are examining this issue.

Differential Diagnosis
Face and brow presentation
Fetal anomalies
Fetal death
Grand multiparity
Multiple pregnancies
Oligohydramnios
Pelvis Anatomy
Preterm labor
Primigravida
Uterine anomalies
Pearls and Other Issues

In light of the decrease in planned vaginal breech deliveries, thus the decrease in expertise in managing this clinical scenario, it is prudent that policies requiring simulation and instruction in the delivery technique for vaginal breech birth are established to care for the emergency breech vaginal delivery.

Enhancing Healthcare Team Outcomes

A breech delivery is usually managed by an obstetrician, labor and delivery nurse, anesthesiologist and a neonatologist. The ultimate decison rests on the obstetrician. To prevent complications, today cesarean sections are performed and experienced with vaginal deliveries of breech presentation is limited. For healthcare workers including the midwife who has no experience with a breech delivery, it is vital to communicate with an obstetrician, otherwise one risks litigation if complications arise during delivery. [12] [13] [14]

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Disclosure: Caron Gray declares no relevant financial relationships with ineligible companies.

Disclosure: Meaghan Shanahan declares no relevant financial relationships with ineligible companies.

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I told my bosses I was pregnant and they fired me, N.J. teacher says in lawsuit

Updated: Aug. 10, 2024, 7:34 a.m.
| Published: Aug. 08, 2024, 11:51 a.m.
Anthony G. Attrino | NJ Advance Media for NJ.com

A teacher in Bergen County has filed a lawsuit against the Hackensack Board of Education claiming administrators terminated her employment after they discovered she was pregnant.

The 26-year-old woman says in court papers she was dismissed from her job at Hackensack High School on May 1, 2023, despite receiving consistently positive evaluations as “a highly effective teacher.”

“(The teacher) was not rehired because of her pregnancy. The outrageous and unjustified decision by the defendants to not rehire Paton was emotionally and psychologically devastating to her,” according to the lawsuit filed July 29 in Superior Court of Bergen County.

Hackensack school district administrators did not immediately respond Thursday to requests to comment on the lawsuit.

Court papers say the woman is a certified high school teacher with a master’s degree in education who began teaching in the district in January 2022.

In August 2022, the woman was assigned to teach special education classes despite not being certified for the role, according to the lawsuit.

The woman asked to remain a general education teacher, but her request was denied, and she received no support or a help in the classroom in her new position, the suit alleges.

She took a 30-day leave of absence, citing job pressures, from January to February 2023, the lawsuit says.

In February 2023, the teacher found out she was pregnant and notified her supervisors. In April 2023, she requested maternity leave, according to the suit.

The teacher was notified on May 1, 2023, she would not be rehired. The suit claims administrators told Paton she was terminated for “poor reviews.”

But the teacher’s lawsuit alleges the excuse was a “cover-up for the real reason, which was because she was a pregnant woman and would be due to give birth around November of the following school year.”

The lawsuit alleges the teacher was terminated due to her pregnancy, in violation of the New Jersey Law Against Discrimination. The lawsuit also alleges gender discrimination under state law because the teacher was allegedly “replaced by a non-pregnant person.”

The woman is seeking monetary damages for lost wages, emotional distress, damage to her reputation, and punitive damages for the districts’ alleged willful and malicious conduct.

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Here Are The Top Signs Of High Estrogen—And What Underlying Health Conditions Could Be At Play

Experts say it's not usually a cause for concern.

preview for Everything to Know About Your Menstrual Cycle

Whether at your annual physical or through one of the many direct-to-consumer companies offering lab tests these days, getting your blood work done can be an effective way to gain deeper insight into your health, especially if you have uncomfortable symptoms and can’t figure out the root cause. But if your panel comes back with something outside the normal range, like high estrogen, you understandably will have some questions!

Estrogen levels naturally fluctuate throughout your life, starting off low when you’re born, shooting up during puberty, and then eventually dropping after menopause .

Meet the experts: Irene Woo , MD, is a reproductive endocrinologist at HRC Fertility . Tamara Guichard , MD, is an ob-gyn at Modern Urology . Jillian LoPiano , MD, MPH, is an ob-gyn and chief health officer at Wisp .

Estrogen levels change throughout the menstrual cycle, too, peaking during ovulation. But, “generally, levels of estradiol (E2) between 30 to 400 pg/mL are considered normal during reproductive years,” says Irene Woo, MD, a reproductive endocrinologist at HRC Fertility. High estrogen is typically defined as “levels exceeding the normal range” for a specific age and menstrual phase, often accompanied by other symptoms (more on this soon), she says.

But “high estrogen” isn’t a diagnosis—rather, it’s usually related to a specific medical condition, such as polycystic ovary syndrome (PCOS), or even lifestyle factors like stress.

Ahead, doctors break down everything you need to know about high estrogen. But remember: It’s always best to consult your own doctor about any symptoms you're experiencing or medical concerns.

What causes high estrogen?

The short answer to this question is “it depends” since there’s no single universal cause of high estrogen. Genetics can play a slight role, but more often than not, high estrogen is associated with the following lifestyle factors or medical conditions, Dr. Woo says.

If you’re expecting, your estrogen levels naturally rise during pregnancy , says Dr. Woo. In particular, estriol increases during pregnancy to support fetal development and prepare the body for birth, she says. You may experience associated symptoms such as breast tenderness , fatigue, nausea, mood swings, fluid retention, headaches, and changes in sex drive , but having some or all of these symptoms does not necessarily mean there is a problem with estrogen levels during pregnancy, Dr. Woo says. In fact, it’s often normal and expected as the body adjusts, and your estrogen levels drop significantly and return to baseline (or slightly lower if you’re breastfeeding) after giving birth, she adds.

Polycystic Ovary Syndrome (PCOS)

PCOS is caused by an imbalance of reproductive hormones, often leading to high estrogen levels, says Dr. Guichard. In fact, estrogen and estrogen receptors are found to be particularly high in those with PCOS, according to a study published in the journal Cells . Estrogen levels may be chronically elevated in those with PCOS due to additional factors like insulin resistance and other hormone levels, but they can also fluctuate based on menstrual cycle irregularities or medications used to manage symptoms, says Dr. Woo.

Certain medications such as hormone replacement therapies and those used to treat breast cancer can affect your estrogen levels. Birth control pills can also impact estrogen levels, especially when you first start out, but doctors typically monitor your dosage to avoid potential spikes, adds Dr. Guichard.

Fat tissue can produce excess estrogen , so those with a higher body fat percentage may have high estrogen levels, says Dr. Guichard. There's an inverse relationship here, too: Higher estrogen levels can influence where fat is deposited in the body, often favoring storage in the hips and thighs in women, Dr. Woo says.

Environmental Factors

Exposure to estrogen-like chemicals (such as xenoestrogen) in pesticides, plastics/BPA, and certain cosmetics may contribute to higher estrogen levels since they disrupt the body’s natural hormonal balance, Dr. Guichard says. In particular, makeup, hair dye, and skincare products that contain parabens , phthalates , bisphenol A (BPA) , and triclosan can potentially disrupt hormonal balance, Dr. Woo says. To reduce exposure and minimize any risk, Dr. Woo says to look for products labeled as “paraben-free,” or “phthalate-free,” or opt for natural and organic alternatives.

Excessive alcohol intake can interfere with your liver function which is crucial for estrogen metabolism, so if you heavily drink, your estrogen levels can be high, says Dr. Woo.

Chronic stress may also disrupt hormone balance, says Dr. Woo. Why? When the hypothalamus (the part of the brain that helps with hormone regulation) perceives stress, the adrenal glands are stimulated to produce cortisol, the stress hormone. Cortisol can sometimes disrupt the main hormone of the HPA axis, which regulates reproductive hormones including estrogen. This disruption can result in menstrual irregularities or even anovulation (lack of ovulation), she says.

Signs And Symptoms Related To High Estrogen

Here are some of the common indicators of conditions that may be associated with high estrogen, according to Dr. Woo and Dr. Guichard.

Irregular menstrual periods
Breast tenderness
Mood swings
Weight gain (particularly in the hips and thighs)
Decreased sex drive
Difficulty concentrating

Should you get your estrogen levels tested?

Estrogen levels can vary significantly depending on your menstrual cycle phase and age, says Dr. Woo. That said, estrogen testing is not necessary in healthy women, says Jillian LoPiano, MD, MPH, a board-certified ob-gyn and chief health officer at Wisp. Doctors don’t typically “check levels” or draw estrogen labs to look for conditions, but if a patient comes in with specific complaints, a physician will form a diagnosis and draw appropriate labs (like estradiol) accordingly, she says.

However, many women do opt to get their hormones tested these days—even if they aren’t exhibiting symptoms. If you suspect your estrogen levels are high or simply want to get tested, a gynecologist, endocrinologist, or primary care physician can order a blood test to measure your levels, says Dr. Woo. From there, they’ll likely test your estradiol (E2) since it’s the main form of estrogen tested, though estrone (E1) and estriol (E3) may also be evaluated depending on your age, symptoms, and medical history, she says. These tests are usually covered by insurance if deemed “medically necessary” by your healthcare provider, but cost and coverage depend on your specific insurance plan, she adds.

If you discover you have high estrogen—meaning higher than “normal” considering your age, where you’re at in your cycle, whether or not you’re pregnant, and other factors— you may be referred to a reproductive endocrinologist who specializes in hormonal health and can provide expert interpretation of your lab results, Dr. Woo says. The doctor will then look for the root cause of the high estrogen and suggest appropriate treatment options.

Treating Conditions Related To High Estrogen

Lifestyle changes can go a long way in managing conditions related to high estrogen. Stress management techniques like yoga , mindfulness, and/or therapy can help reduce estrogen-related fluctuations, says Dr. Woo. Cutting back on alcohol can also help tone down your estrogen levels by improving liver function responsible for estrogen metabolism, Dr. Guichard adds.

A healthy diet and regular exercise may help lower your levels if they're due to excess estrogen production from fat tissue, Dr. Woo says.

In some cases, such as in those with PCOS or other chronic health conditions, medication such as aromatase inhibitors or hormone blockers may also be prescribed depending on your specific medical condition, says Dr. Woo. But if you suspect a prescription medication is the culprit of your high estrogen, talk to a doctor about adjusting your dose or prescribing an alternative drug, she adds.

Treating conditions related to high estrogen involves a multifaceted and tailored approach based on the individual, so it’s essential to consult with a doctor to pinpoint the underlying cause, says Dr. Woo. It’s also always a good idea to keep an open line of communication with your doctor so they can monitor your symptoms and determine how often you should test your estrogen levels, says Dr. Guichard. Regular testing isn’t usually necessary, and your “levels” are not followed by and large, but it may be helpful to monitor a specific condition, check-in on your hormones, and/or adjust treatment if needed, she says.

The bottom line: Estrogen greatly fluctuates throughout your life without a cause for concern, but if you’re worried or experience regular symptoms, talk with your doctor about testing options and lifestyle changes.

Andi Breitowich is a Chicago-based writer and graduate student at Northwestern Medill. She’s a mass consumer of social media and cares about women’s rights, holistic wellness, and non-stigmatizing reproductive care. As a former collegiate pole vaulter, she has a love for all things fitness and is currently obsessed with Peloton Tread workouts and hot yoga.

Dr. Jillian LoPiano is an ob-gyn and women’s health advocate with a Master’s Degree in Public Health from Yale University. She attended medical school at The George Washington University in Washington, DC, and has worked with reproductive health coalitions in underserved areas such as Texas and Florida. She is currently the Chief Health Officer at Wisp .

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Where Is the Real Information on Pregnancy and Childbirth?

Here's what you need to know for the transition to motherhood..

Posted July 26, 2024 | Reviewed by Davia Sills

What Is Pregnancy?
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Labor and delivery are naturally painful processes.
The idea that pain relief delays delivery is not correct if it is given at the appropriate time.
"Natural childbirth" has been idealized and misrepresented, especially to first-time mothers.

This is the sixth post in a series.

In the book Matrescence: Pregnancy , Childbirth, and Motherhood , Lucy Jones talks about the shocking lack of information available to women regarding what childbirth is really like, what the actual consequences are of using pain relief during labor, and what some of the potential risks are during delivery.

Jones takes up the subject of "natural childbirth." She says that women have been told for so long that "natural childbirth" is best that this has pretty much become the ideal. However, she lets us know that the concept of "natural childbirth" has a very particular origin.

She says that this goes back a long way in medicine to a British obstetrician named Grantly Dick-Read, who coined the phrase in the mid-1900s and who portrayed childbirth in a highly idealized way. Dick-Read promulgated the idea that childbirth is not necessarily painful and that fear is the main cause of pain during labor and delivery. He developed a form of hypnotherapy that he said would help women be less anxious about going through labor and delivery and, therefore, experience less pain. His work is still used and quoted today.

However, according to Jones, Dick-Read had scant evidence for this theory. And he also had little evidence that hypnosis and relaxation techniques could make the birth process far less painful.

This will come as shocking news to most women—as these ideas are still popular and routinely disseminated in childbirth classes to this day.

However, for most women who have actually labored and or given birth while conscious, it is not news that labor and delivery are extremely painful with or without relaxation and breathing techniques. Labor hurts. Delivery is very painful. And all the exercises you learned usually go out the window after a certain point. Anyone who does not remember it being this way either has a very high pain threshold, or they are good at repressing painful memories.

Jones goes on to talk about the misinformation given to women about the risks of using epidurals and pain medication during childbirth. Women are often told that having an epidural will slow the rate of labor and result in an increased likelihood of having a C-section. As it turns out, neither of these is true.

According to Zha et al. (2021), labor is not prolonged by the administration of an epidural if it is given after the woman is 6 cm dilated, and there is no difference in birth outcome for babies whose mothers have or have not had an epidural. And Ashagrie et al. (2023) reveal in their literature review that there is not a greater risk of C-section for women who choose to have an epidural (Ashagrie et al., 2023).

Jones also talks about the consequences of delivery. She talks about how common it is for there to be tearing of the vagina, the perineum, and the anus, and she says that women are usually not told about the risks of these occurring in advance of childbirth.

According to Okeahialam et al. (2023), 9 out of 10 women experience perineal tears during first-time deliveries, and 6 percent of first-time births include anal sphincter injury. A percentage of mothers also experience pelvic floor injuries during childbirth.

These things are important for pregnant women to know, not because they need one more thing to worry about, but in order to advocate for themselves prior to and following delivery. Especially for those women who choose home births, it is important to understand that prompt surgical repair of sphincter injuries is crucial to prevent fecal incontinence, something that will dramatically decrease a mother's quality of life following delivery. Mothers need to make sure their midwives are willing to check for such injuries and will tell them about them.

Moreover, it is helpful for first-time mothers to know that preventative measures can be taken. Doctors and midwives can manually protect the perineum during delivery if they know how. And prior to delivery, pregnant women can ask about whether their doctors or midwives are trained in such measures. Secondly, it can be helpful for pregnant women to know that perineal massage can be effective if done in the third trimester of pregnancy to increase the muscle elasticity of their perineum (Okeahialam et al., 2023). And lastly, it is important to know that women who have experienced pelvic floor injuries can seek out physical therapy following childbirth.

Lucy Jones says that not only are most women unaware of these issues, but many midwives, nurses, and OBs do not talk with their patients about these subjects.

It's time to talk about what childbirth is really like, and to be honest about it. And it is time for women to have the information they need prior to delivery in order to prepare for the realities of childbirth and life postpartum .

Thank you, Lucy Jones, for leading the way.

1 Caton, D., Who said childbirth is natural: the medical mission of Grantly Dick-Read. Aenesthesiology, 84, April 1996, p. 955 - 964.

Nicola Adanna Okeahialam, MBChB , Abdul H. Sultan, MD, FRCOG , Ranee Thakar, MD, The prevention of perineal trauma during Vaginal birth, American Journal of Obstetrics and Gynecology, https://www.ajog.org/article/S0002-9378(22)00464-1/fulltext#

Ashagire, D. et al (2021) A review article on epidural analgesia for labor pain management: A systematic review, International Journal of Surgery Open, Vol 24, 2020, p 100 - 104. Medicine (Baltimore). 2021 Mar 5; 100(9): e24923. Published online 2021 Mar 5. doi: 10.1097/MD.0000000000024923

Ying Zha , MM,a Xun Gong , MD,a Chengwu Yang , MD, MS, PhD,b Dongrui Deng , MD,a Ling Feng , MD,a Ailin Luo , MD,c Li Wan , MD,c Fuyuan Qiao , MD,a Wanjiang Zeng , MD,a Suhua Chen , MD,a Yuanyuan Wu , MD,a Dongji Han , MD,c and Haiyi Liu , MDa,∗Epidural analgesia during labor and its optimal initiation time-points A real-world study on 400 Chinese nulliparas

Corinne Masur, Psy.D., is a clinical psychologist and psychoanalyst in private practice in Chester Springs, Pennsylvania.

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UAH engineering program hosts drone presentation at Sparkman High School

HARVEST, Ala. ( WAFF ) - Some students in Madison County had the opportunity to see something cool on Thursday morning at Sparkman High School.

Sparkman High School, Monrovia Middle School, Sparkman Ninth Grade School, and Sparkman Middle School students gathered to see a professional fly-in drone presentation.

The presentation was put on by the University of Alabama in Huntsville’s Rotorcraft Systems Engineering and Simulation Center. Military-grade drones were demonstrated with all their capabilities in the sky of the football field at Sparkman High School.

Madison County School System officials said the demonstration aims to introduce students to the engineering program at UAH.

Sparkman High School science teacher Scott Coonfare said students interested in learning more about aerospace can see the impact firsthand at UAH.

“You look at UAH and may think, I don’t know, but once you get your hands on engineering projects and you’re doing it,” said Coonfare. “You see how much fun and easy it is, then they think ‘wow, I can do this, I love this’ — and it just opens the doors that they never thought were possible.”

The program is expected to make its way to other middle and elementary schools, inspiring the next generation in aerospace.

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Headaches and Pregnancy

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Frequently Asked Questions Expand All

More than 3 billion people around the world have frequent headaches that affect their ability to do daily tasks. Tension headaches are the most common, but migraines cause more problems for women younger than 50.

The most common headaches have the following symptoms:

Migraines —These headaches cause throbbing pain that’s usually on one side of the head. Some people have nausea, vomiting, and light sensitivity. It’s also common to have symptoms before a migraine starts, including blurred vision, eye pain, seeing flashes of light, and tunnel vision.

Tension headaches —These headaches cause muscle tightness and pain in the head, scalp, or neck. The pain can feel like a band that’s squeezing the head. They can be caused by stress, anxiety, depression, or injury.

Cluster headaches —These headaches cause pain on one side of the head and focus around an eye. Other symptoms may include eye tearing, a droopy eyelid, and a stuffy nose.

If you get headaches and you’re planning a pregnancy, the best time to tell your obstetrician–gynecologist (ob-gyn) is during a prepregnancy care checkup. If you didn’t have a prepregnancy care visit before you got pregnant, plan to talk about your headaches as soon as possible. You and your ob-gyn should discuss

your symptoms

how often you get headaches

any medication you take to prevent them

any medication you take to treat pain

Together you can discuss how you will manage headaches if you get them when you are pregnant or breastfeeding.

Sometimes the headaches people had before pregnancy continue when they are pregnant. These are called primary headaches.

For some people, headaches develop during pregnancy. These are called secondary headaches. They have several causes:

Early in pregnancy, hormone changes can lead to headaches.

Later in pregnancy, tension from carrying extra weight can cause headaches.

Throughout pregnancy, caffeine withdrawal, dehydration, lack of sleep, and low blood sugar can trigger headaches.

In the postpartum period, headache with neck and shoulder pain is common. This type of headache is related to the bodily stress of giving birth and lack of sleep when a new baby is in the house.

There’s another type of headache that’s caused by preeclampsia , a serious high blood pressure disorder that develops during pregnancy. Read the section “When is a headache a sign of a bigger problem?” for details.

If you got headaches before pregnancy, you and your ob-gyn should review the medication you took to prevent them and talk about whether it needs to change. Your ob-gyn may recommend continuing or changing your medication. They may also recommend decreasing or stopping the medication that prevents headaches. This may be true if you get migraines because this type of headache sometimes goes away during pregnancy.

Yes, there are two over-the-counter (OTC) medications that are safe to take during pregnancy.

Acetaminophen . This medication may be taken for all headaches. There are also acetaminophen tablets that have caffeine. This combination has been shown to help with migraine pain. If you take acetaminophen with caffeine during pregnancy, make sure your total caffeine from all sources (including coffee) does not go beyond 200 mg per day.

Nonsteroidal anti-inflammatory drugs (NSAIDs) . These OTC medications include ibuprofen and naproxen. They can be taken for migraines that don’t get better with acetaminophen, but only in the second trimester and only for 48 hours or less at a time. It’s not clear if NSAIDs are safe for a fetus during the first trimester. Taking NSAIDs during the third trimester may lead to birth defects .

Talk with your ob-gyn if you plan to take one of these medications. Also let them know if your pain continues or gets worse while taking OTC medication.

There’s a prescription medication called metoclopramide that can be used for headaches that are new in pregnancy, come every day, and cause constant pain. It may be taken as pills or given through an intravenous (IV) line . It may be combined with a medication called diphenhydramine. You and your ob-gyn may talk about whether this medication is right for you.

Acetaminophen, caffeine, and metoclopramide are all safe to take when you are breastfeeding. Most NSAIDs are also safe, but you should avoid aspirin.

Prescription migraine medications called triptans can also be used when you are breastfeeding. Small amounts of triptan medication pass to breast milk. Because of this, your ob-gyn may recommend you not breastfeed for several hours after taking a triptan. Together you can talk about whether this medication is right for you and whether you will need to avoid breastfeeding for a short time after taking it.

Sometimes a bad headache can be a sign of preeclampsia. This is a serious high blood pressure disorder that can affect all the organs in your body. It usually develops after 20 weeks of pregnancy, often in the third trimester. When it develops before 34 weeks of pregnancy, it is called early-onset preeclampsia. It can also develop in the weeks after childbirth.

In addition to a headache that will not go away, symptoms of preeclampsia can include

swelling of face or hands

seeing spots or changes in eyesight

pain in the upper abdomen or shoulder

nausea and vomiting (in the second half of pregnancy)

sudden weight gain

difficulty breathing

If you have a bad headache with any of these symptoms, especially if they develop in the second half of pregnancy or within 6 weeks of giving birth, call your ob-gyn right away.

A thunderclap headache comes on quickly with a lot of pain. It’s often a sign of something serious. There may be pain in the head and down the back of the neck. Some people with a thunderclap headache also have confusion, weakness, loss of vision, or changes in speaking or thinking. If you get a headache like this, go to an emergency room right away.

American Migraine Foundation americanmigrainefoundation.org/ A website with patient guides on living with migraines, getting emergency help, caring for a child with migraines, and more. Association of Migraine Disorders migrainedisorders.org/education/patient-resources/ A website with blogs, videos, and podcasts on the types of migraines. MotherToBaby mothertobaby.org/?s=headaches Fact sheets on different headache medications from the Organization of Teratology Information Specialists. National Headache Foundation headaches.org/resources/ A website featuring news and resources on all types of headaches. National Institute of Neurological Disorders and Stroke ninds.nih.gov/health-information/disorders/migraine A webpage with details on treatments for migraines.

Birth Defects : Physical problems that are present at birth.

Fetus : The stage of human development beyond 8 completed weeks after fertilization.

High Blood Pressure : Blood pressure above the normal level. Also called hypertension.

Hormone : A substance made in the body that controls the function of cells or organs.

Intravenous (IV) Line : A tube inserted into a vein and used to deliver medication or fluids.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) : Medications that relieve pain by reducing inflammation. Many types are available over the counter, including ibuprofen and naproxen.

Obstetrician–Gynecologist (Ob-Gyn) : A doctor with medical and surgical training and education in the female reproductive system.

Postpartum : Related to the weeks following the birth of a child.

Preeclampsia [pre-ee-KLAMP-see-uh]: A disorder during pregnancy or after childbirth that causes high blood pressure and other signs of organ injury. These signs include an abnormal amount of protein in the urine, a low number of platelets, abnormal kidney or liver function, pain over the upper abdomen, fluid in the lungs, a severe headache, or vision changes.

Prepregnancy Care : Medical care that is given before pregnancy to improve the chances of a healthy pregnancy. This care includes a physical exam; counseling about nutrition, exercise, and medications; and treatment of medical conditions that may affect the pregnancy.

Trimester : A time period of 3 months. There are three trimesters in pregnancy: the first trimester, second trimester, and third trimester.

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If you have further questions, contact your ob-gyn.

Don't have an ob-gyn? Learn how to find a doctor near you .

FAQ535 Published: July 2024 Last reviewed: July 2024

Copyright 2024 by the American College of Obstetricians and Gynecologists. All rights reserved. Read copyright and permissions information . This information is designed as an educational aid for the public. It offers current information and opinions related to women's health. It is not intended as a statement of the standard of care. It does not explain all of the proper treatments or methods of care. It is not a substitute for the advice of a physician. Read ACOG’s complete disclaimer .

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EL PASO, Texas (KVIA) -- Emergence Health Network (EHN) is hosting a substance use disorder community symposium. It will take place Friday, August 9th at the Starlight Event Center on 6650 Continental Dr. El Paso Texas from 9 a.m. to 11 a.m.

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Emergence Health Network says they will have a special presentation by the Drug Enforcement Agency regarding drug use trends in our community, specifically with the concern of fentanyl in El Paso. EHN said, “It’s a team effort, not just within EHN but throughout our community and local agencies. This type of collaboration is vital.” EHN states 300 people registered to attend the event.

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Vitamin D supplementation for women during pregnancy

Affiliations.

1 Department of Dietetics and Nutrition, Florida International University, Miami, Florida, USA.
2 Clinical Safety, Daiichi Sankyo, Basking Ridge, New Jersey, USA.
3 Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
PMID: 39077939
PMCID: PMC11287789 (available on 2025-07-30 )
DOI: 10.1002/14651858.CD008873.pub5

Background: Vitamin D supplementation during pregnancy may help improve maternal and neonatal health outcomes (such as fewer preterm birth and low birthweight babies) and reduce the risk of adverse pregnancy outcomes (such as severe postpartum haemorrhage).

Objectives: To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve certain maternal and neonatal outcomes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and relevant conference proceedings) (3 December 2022). We also searched the reference lists of retrieved studies.

Selection criteria: Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention.

Data collection and analysis: Two review authors independently i) assessed the eligibility of studies against the inclusion criteria, ii) assessed trustworthiness based on pre-defined criteria of scientific integrity, iii) extracted data from included studies, and iv) assessed the risk of bias of the included studies. We assessed the certainty of the evidence using the GRADE approach.

Main results: The previous version of this review included 30 studies; in this update, we have removed 20 of these studies to 'awaiting classification' following assessments of trustworthiness, one study has been excluded, and one new study included. This current review has a total of 10 included studies, 117 excluded studies, 34 studies in awaiting assessment, and seven ongoing studies. We used the GRADE approach to assess the certainty of the evidence. This removal of the studies resulted in evidence that was downgraded to low-certainty or very low-certainty due to study design limitations, inconsistency between studies, and imprecision. Supplementation with vitamin D compared to no intervention or a placebo A total of eight studies involving 2313 pregnant women were included in this comparison. We assessed four studies as having a low risk of bias for most domains and four studies as having high risk or unclear risk of bias for most domains. The evidence is very uncertain about the effect of supplementation with vitamin D during pregnancy compared to placebo or no intervention on pre-eclampsia (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.21 to 1.33; 1 study, 165 women), gestational diabetes (RR 0.53, 95% CI 0.03 to 8.28; 1 study, 165 women), preterm birth (< 37 weeks) (RR 0.76, 95% CI 0.25 to 2.33; 3 studies, 1368 women), nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 study, 135 women), or hypercalcaemia (1 study; no cases reported). Supplementation with vitamin D during pregnancy may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome (RR 0.68, 95% CI 0.51 to 0.91; 1 study, 1134 women; low-certainty evidence) and may reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out (RR 0.69, 95% CI 0.44 to 1.08; 3 studies, 371 infants; low-certainty evidence). Supplementation with vitamin D + calcium compared to no intervention or a placebo One study involving 84 pregnant women was included in this comparison. Overall, this study was at moderate to high risk of bias. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported. The evidence is very uncertain about the effect of supplementation with vitamin D and calcium on preterm birth (RR not estimable; very low-certainty evidence) or for low birthweight (RR 1.45, 95% CI 0.14 to 14.94; very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) One study involving 1298 pregnant women was included in this comparison. We assessed this study as having a low risk of bias in all domains. Pre-eclampsia was not reported. The evidence is very uncertain about the effect of supplementation with vitamin D, calcium, and other vitamins and minerals during pregnancy compared to no vitamin D on gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73; very low-certainty evidence), maternal adverse events (hypercalcaemia no events and hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; very low-certainty evidence), preterm birth (RR 1.04, 95% CI 0.68 to 1.59; low-certainty evidence), or low birthweight (RR 1.12, 95% CI 0.82 to 1.51; low-certainty evidence).

Authors' conclusions: This updated review using the trustworthy assessment tool removed 21 studies from the previous update and added one new study for a total of 10 included studies. In this setting, supplementation with vitamin D alone compared to no intervention or a placebo resulted in very uncertain evidence on pre-eclampsia, gestational diabetes, preterm birth, or nephritic syndrome. It may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome. It may also reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out. Supplementation with vitamin D and calcium versus placebo or no intervention resulted in very uncertain evidence on preterm birth and low birthweight. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported in the only study included in this comparison. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) resulted in very uncertain evidence on gestational diabetes and maternal adverse events (hypercalciuria) and uncertain evidence on preterm birth and low birthweight. Pre-eclampsia was not reported in the only study included in this comparison. All findings warrant further research. Additional rigorous, high-quality, and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.

Trial registration: ClinicalTrials.gov NCT01422122 NCT01732328 NCT01126528 NCT01924013 NCT01693510 NCT00938600 NCT00856947 NCT00610688 NCT02021864 NCT02506439 NCT01112891 NCT02215213 NCT01038453 NCT01417351 NCT00292591 NCT01932788 NCT00920621 .

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Conflict of interest statement

Cristina Palacios: none known.

Lia L Kostiuk: none known

Anna Cuthbert was previously employed by Cochrane Pregnancy and Childbirth as a research associate. She was then employed by the University of Liverpool for a project that included the work on this review. The project was funded by the Children’s Investment Foundation Fund (CIFF); however, the views expressed are those of the authors and not of CIFF. Anna Cuthbert has no known conflicts of interest to declare.

Jo Weeks was employed on a consultancy basis by the University of Liverpool for a project that included the work on this review. The project was funded by the Children’s Investment Foundation Fund (CIFF); however, the views expressed are those of the authors and not of CIFF. Jo Weeks has no known conflicts of interest to declare.

doi: 10.1002/14651858.CD008873.pub4

References to studies included in this review

Benson 2009 {published data only}.

Benson J. A randomised controlled trial on the effects of antenatal vitamin D supplementation to improve vitamin D levels in the maternal and cord blood at birth in vitamin D deficient pregnant women. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83375 (first received 4 February 2009).
Rodda CP, Benson JE, Vincent AJ, Whitehead CL, Polyakov A, Vollenhoven B. Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: a randomised controlled trial. Osteoporosis International 2011;Suppl 4:S521-59. - PubMed
Rodda CP, Benson JE, Vincent AJ, Whitehead CL, Polyakov A, Vollenhoven B. Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open label randomised controlled trial. Clinical Endocrinology 2015;83(3):363-8. - PubMed

Bhutta 2011 {published data only}

Bhutta ZA. Evaluation of the effectiveness of vitamin D supplementation to pregnant women and their infants in Pakistan. clinicaltrials.gov/ct2/show/NCT01229189 (first received 27 October 2010).
Bhutta ZA. Study of vitamin D supplementation on improvement of gums health. clinicaltrials.gov/ct2/show/NCT01422122 (first received 23 August 2011).
Khan F. A randomized controlled trial of oral vitamin D supplementation in pregnancy to improve maternal periodontal health and birth weight. Journal of International Oral Health 2016;8(6):657-65.
Khan FR, Iqbal NT, Ahmed K, Ahmad T, Hussain R, Bhutta ZA. Effect of vitamin d supplementation on the salivary cytokines of pregnant women: a randomized placebo-controlled trial. Journal of the International Academy of Periodontology 2017;19(4):118-25. 12269196 - PubMed

Diogenes 2013 {published data only}

Bezerra F. Calcium plus vitamin D supplementation during pregnancy of adolescent mothers: effects on maternal and infant bone mass, calcium and bone metabolism and breast milk composition. clinicaltrials.gov/ct2/show/NCT01732328 (first received 22 October 2012).
Diogenes ME, Bezerra FF, Rezende EP, Donangelo CM. Calcium plus vitamin D supplementation during third trimester of pregnancy in adolescents accustomed to low calcium diets did not affect infant bone mass at early lactation in a randomized controlled trial. Journal of Nutrition 2015;145:1515-23. - PubMed
Diogenes ME, Bezerra FF, Rezende EP, Taveira MF, Pinhal I, Donangelo CM. Effect of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers: a randomized, placebo-controlled trial. American Journal of Clinical Nutrition 2013;98(1):82-91. - PubMed
Normando P, Diogenes ME, Cabello PH, Cabello GM, Donangelo CM, Bezerra FF. Calcium plus vitamin D supplementation during pregnancy interacts with polymorphisms in the promoter region of the VDR gene to affect postpartum bone mass of Brazilian adolescent mothers: a randomized controlled trial. Nutrition 2016;32(10):1068-74. - PubMed

Grant 2013 {published data only}

Grant C, Milne T, Knight J, Sinclair J, Camargo C. Vitamin D supplementation during pregnancy and infancy reduces food allergen sensitisation and parental-reported food allergy: a randomised controlled trial. European Journal of Pediatrics 2016;175(11):1438. - PubMed
Grant C, Stewart A, Scragg R, Milne T, Rowden J, Ekeroma A, et al. What dose of vitamin D supplementation is required in pregnancy and infancy to increase infants' serum 25-hydroxyvitamin D concentration > 20ng/ml? In: Pediatric Academic Societies Annual Meeting; 2013 May 4-7; Washington DC, USA. 2013.
Grant C. Randomised placebo controlled study of vitamin D during pregnancy and infancy. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=320842 (first received 2 February 2010).
Grant CC, Crane J, Mitchell EA, Sinclair J, Stewart A, Milne T, et al. Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitisation: a randomised controlled trial. Allergy 2016;71(9):1325-34. - PubMed
Grant CC, Crane J, Mitchell EA, Sinclair J, Stewart A, Milne T, et al. Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: a randomized controlled trial. In: Pediatric Academic Societies Annual Meeting; 2016 April 30-May 3; Baltimore, USA. 2016:1650.8. - PubMed

Harvey 2012 {published data only}ISRCTN82927713

Barker M, D'Angelo S, Ntani G, Lawrence W, Baird J, Jarman M, et al. The relationship between maternal self-efficacy, compliance and outcome in a trial of vitamin D supplementation in pregnancy. Osteoporosis International 2017;28(1):77-84. - PMC - PubMed
Bishop NJ, Kennedy S, Papageorghiou AT, Fraser R, Gandhi SV, D'Angelo S, et al. Maternal gestational vitamin D supplementation and offspring bone mass: a multicentre randomised, double-blind, placebo-controlled trial (MAVIDOS). Journal of Bone and Mineral Research 2015;30(Suppl 1):1. [CENTRAL: CN-01463553] 8014570 [EMBASE: 620769697]
Braithwaite VS, Crozier SR, D'Angelo S, Prentice A, Cooper C, Harvey NC, et al. The effect of vitamin D supplementation on hepcidin, iron status, and inflammation in pregnant women in the United Kingdom. Nutrients 2019;11(1):E190. [CENTRAL: CN-01790984] 10406271 [EMBASE: 2001354559] [PMID: ] - PMC - PubMed
Cook E, Curtis EM, Krstic N, D'Angelo S, Crozier SR, Moon RJ, et al. Perinatal DNA methylation at the RXRA promoter is associated with gestational vitamin d supplementation: results from the MAVIDOS trial. Rheumatology 2017;56(Suppl 2):ii112. - PMC - PubMed
Cooper C, Harvey NC, Bishop NJ, Kennedy S, Papageorghiou AT, Schoenmakers I, et al. Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial. Lancet Diabetes and Endocrinology 2016;4(5):393-402. - PMC - PubMed

Roth 2010 {published data only}

Akhtar E, Mily A, Haq A, Al-Mahmud A, El-Arifeen S, Hel Baqui A, et al. Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses. Nutrition Journal 2016;15(1):75. - PMC - PubMed
Bailey D, Perumal N, Yazdanpanah M, Al Mahmud A, Baqui AH, Adeli K, et al. Maternal-fetal-infant dynamics of the C3-epimer of 25-hydroxyvitamin D. Clinical Biochemistry 2014;47(9):816-22. - PubMed
Dimitris MC, Perumal N, Craig-Barnes HA, Leadley M, Mahmud AA, Baqui AH, et al. Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women. Journal of Steroid Biochemistry and Molecular Biology 2016;158:76-81. - PubMed
Harrington J, Al Mahmud A, Raqib R, Baqui A, Roth D. The effect of antenatal vitamin d supplementation on early neonatal calcium homeostasis. Journal of Bone and Mineral Research 2012;27. [CENTRAL: CN-01025424] 1756030 [EMBASE: 71159206]
Harrington J, Perumal N, Al Mahmud A, Baqui A, Roth DE. Vitamin D and fetal-neonatal calcium homeostasis: findings from a randomized controlled trial of high-dose antenatal vitamin D supplementation. Pediatric Research 2014;76(3):302-9. - PubMed

Roth 2013 {published data only}

Bilic M, Qamar H, Onoyovwi A, Korsiak J, Papp E, Roth DE, et al. Prenatal vitamin D and cord blood insulin-like growth factors in Dhaka, Bangladesh. Endocrine Connections 2019;8(6):745-53. [CENTRAL: CN-01963204] 11930971 [EMBASE: 2002029463] - PMC - PubMed
Jukic AMZ, Zuchniak A, Qamar H, Ahmed T, Mahmud AA, Roth DE. Vitamin d treatment during pregnancy and maternal and neonatal cord blood metal concentrations at delivery: results of a randomized controlled trial in bangladesh. Environmental Health Perspectives 2020 Nov;128(11):117007-1. [CENTRAL: CN-02213463] 16146712 [EMBASE: 2005489122] [PMID: ] - PMC - PubMed
Morris SK, Pell LG, Rahman MZ, Dimitris MC, Mahmud A, Islam MM, et al. Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial. BMC Pregnancy and Childbirth 2016;16(1):309. - PMC - PubMed
NCT02388516. Maternal vitamin D for acute respiratory infections in infancy [Maternal vitamin D for acute respiratory infections in infancy (MDARI): a nested sub-study in a randomized controlled trial of vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh]. https://clinicaltrials.gov/show/NCT02388516 (first received 9 March 2015). [CENTRAL: CN-02035927] 12574397
O'Callaghan KM, Shanta SS, Fariha F, Harrington J, Mahmud AA, Emdin AL, et al. Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial. American Journal of Clinical Nutrition 2022;115(3):770-80. [CENTRAL: CN-02359370] 19741374 [EMBASE: 636833900] [PMID: ] - PMC - PubMed

Sablok 2015 {published data only}

Sablok A, Batra A, Thariani K, Batra A, Bharti R, Aggarwal AR, et al. Supplementation of vitamin D in pregnancy and its correlation with feto-maternal outcome. Clinical Endocrinology 2015;83(4):536-41. - PubMed

Vafaei 2019 {published data only}

Vafaei H, Asadi N, Kasraeian M, Shahraki HR, Bazrafshan K, Namazi N. Positive effect of low dose vitamin D supplementation on growth of fetal bones: a randomized prospective study. Bone 2019;122:136-42. [CENTRAL: CN-01917917] 10620631 [EMBASE: 2001631722] [PMID: ] - PubMed

Yu 2008 {published data only}

EUCTR2006-006080-23-GB. Vitamin D status in pregnancy and the effects of vitamin D supplementation in ethnic minority groups - vitamin D in pregnancy. http://www.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2006-006080-23-GB (first received 2006). [CENTRAL: CN-01817157] 10717085
Goldring S. Effects of prenatal vitamin D supplementation on respiratory and allergic phenotypes and bone density in the first three years of life. UKCRN ( http://public.ukcrn.org.uk ) (accessed 6 April 2011) 2010.
Goldring ST, Griffiths CJ, Martineau AR, Robinson S, Yu C, Poulton S, et al. Prenatal vitamin D supplementation and child respiratory health: a randomised controlled trial. PLOS One 2013;8(6):e66627. - PMC - PubMed
Griffiths M, Goldring S, Griffiths C, Shaheen SO, Martineau A, Cross L, et al. Effects of pre-natal vitamin D supplementation with partial correction of vitamin D deficiency on early life healthcare utilisation: a randomised controlled trial. PLOS One 2015;10(2):e0145303. - PMC - PubMed
Yu C, Newton L, Robinson S, Teoh TG, Sethi M. Vitamin D deficiency and supplementation in pregnant women of four ethnic groups. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93(Suppl 1):Fa68.

References to studies excluded from this review

Actrn12612001145897 (first received 2012) {published data only}.

ACTRN12612001145897. Does vitamin D supplementation in pregnancy improve maternal glucose metabolism or prevent gestational diabetes? [Effect of high-dose versus low-dose vitamin D supplementation in pregnancy on maternal glucose metabolism and the risk of gestational diabetes]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12612001145897 (first received 2012). [CENTRAL: CN-02439948] 21383518

Adegboye 2020 {published data only}

Adegboye AR, Santana DD, Cocate PG, Benaim C, Dos Santos PP, Heitmann BL, et al. Vitamin D and calcium milk fortification in pregnant women with periodontitis: a feasibility trial. International Journal of Environmental Research and Public Health 2020;17(21):1-17. [CENTRAL: CN-02201978] 15339412 [EMBASE: 2005364213] [PMID: ] - PMC - PubMed
Adegboye ARA, Santana DD, Dos Santos PPT, Cocate PG, Benaim C, Castro MBT, et al. Exploratory efficacy of calcium-vitamin D milk fortification and periodontal therapy on maternal oral health and metabolic and inflammatory profile. Nutrients 2021;13(3):1-15. [CENTRAL: CN-02264078] 17622059 [EMBASE: 2006113337] [PMID: ] - PMC - PubMed
Cocate PG, Kac G, Heitmann BL, Nadanovsky P, Da Veiga Soares Carvalho MC, Benaim C, et al. Calcium and vitamin D supplementation and/or periodontal therapy in the treatment of periodontitis among Brazilian pregnant women: protocol of a feasibility randomised controlled trial (the IMPROVE trial). Pilot and Feasibility Studies 2019;5(5):38. [CENTRAL: CN-02094137] 13483795 [EMBASE: 631422131] - PMC - PubMed
Cocate PG, Kac G, Hieitmann BL, Nadanovsky P, da Veiga Soares Carvalho MC, Benaim C, et al. Correction to: calcium and vitamin D supplementation and/or periodontal therapy in the treatment of periodontitis among Brazilian pregnant women: protocol of a feasibility randomised controlled trial (the IMPROVE trial) (Pilot and Feasibility Studies, (2019), 5, 1, (38), 10.1186/s40814-019-0417-6). Pilot and Feasibility Studies 2020;6(1):187. [CENTRAL: CN-02217852] 16130410 [EMBASE: 2007425197] [PMID: ] - PMC - PubMed

Ala‐Houhala 1986 {published data only}

Ala-Houhala M, Koskinen T, Terho A, Koivula T, Visakorpi J. Maternal compared with infant vitamin D supplementation. Archives of Disease in Childhood 1986;61:1159-63. - PMC - PubMed

Asemi 2013a {published data only}

Asemi Z, Hashemi T, Karamali M, Samimi M, Esmaillzadeh A. Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial. American Journal of Clinical Nutrition 2013a;98(6):1425-32. - PubMed
Asemi Z, Karamali M, Esmaillzadeh A. Favorable effects of vitamin d supplementation on pregnancy outcomes in gestational diabetes: a double blind randomized controlled clinical trial. Hormone and Metabolic Research 2015;47(8):565-70. - PubMed

Asemi 2013b {published data only}

Asemi Z, Samimi M, Siavashani MA, Mazloomi M, Tabassi Z, Karamali M, et al. Calcium-vitamin D co-supplementation affects metabolic profiles, but not pregnancy outcomes, in healthy pregnant women. International Journal of Preventive Medicine 2016;7:49. - PMC - PubMed
Asemi Z, Samimi M, Tabassi Z, Shakeri H, Esmaillzadeh A. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. Journal of Nutrition 2013;143(9):1432-8. - PubMed

Asemi 2014 {published data only}

Asemi Z, Karamali M, Esmaillzadeh A. Effects of calcium-vitamin D co-supplementation on glycaemic control, inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial. Diabetologia 2014;57(9):1798-806. - PubMed

Asemi 2015 {published data only}

Asemi Z, Esmaillzadeh A. The effect of multi mineral-vitamin D supplementation on pregnancy outcomes in pregnant women at risk for pre-eclampsia. International Journal of Preventive Medicine 2015;6:62. - PMC - PubMed

Atkinson 2010 {published data only}

Atkinson SA, Moore C. Bone Health in Pregnancy (B-Hip). clinicaltrials.gov/ct2/show/NCT01693510 (first received 26 September 2012).

Azami 2017 {published data only}

Azami M, Azadi T, Farhang S, Rahmati S, Pourtaghi K. The effects of multi mineral-vitamin D and vitamins (C+E) supplementation in the prevention of preeclampsia: an RCT. International Journal of Reproductive Biomedicine (Yazd, Iran) 2017;15(5):273-8. - PMC - PubMed
Azami M, IRCT2016062528617N1. The effects of multi minerals (Zn, Mg and Ca) and vitamins (C and E) supplementation in the prevention of preeclampsia. en.search.irct.ir/view/31125 (first received 24 September 2016).

Baidya 2022 {published data only}

Baidya A, Pathak Y, Sengupta N, Sahana PK, Goswami S, Tarenia S, et al. Effect of vitamin d replacement on glycemic status and pregnancy outcomes in vitamin d-deficient subjects with gestational diabetes mellitus. Diabetes 2022;71(71 (Suppl 1)):158-LB. [CENTRAL: CN-02467245] 21671369 [EMBASE: 638676768]

Baqui 2009 {published data only}

Baqui A. Antenatal vitamin D supplementation to improve neonatal health outcomes in Dhaka, Bangladesh: preliminary dose-finding and safety study. clinicaltrials.gov/ct2/show/NCT00938600 (first received 14 July 2009). [NCT00938600]
Roth DE, Al A, Raqib R, Akhtar E, Black RE, Baqui AH. Pharmacokinetics of high-dose weekly oral vitamin D3 supplementation during the third trimester of pregnancy in Dhaka, Bangladesh. Nutrients 2013;5(3):788-810. - PMC - PubMed
Roth DE, Al Mahmud A, Raqib R, Black RE, Baqui AH. Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women. Nutrition Journal 2012;11:114. [DOI: 10.1186/1475-2891-11-114] - DOI - PMC - PubMed
Roth DE, Al-Mahmud A, El S, Raqib R, Black RE, Baqui AH. Randomized open-label trial of two weekly oral vitamin D3 supplementation regimens during the third trimester of pregnancy in Bangladeshi women: effects on maternal vitamin D status and safety. FASEB Journal 2011;25(Suppl):236.6.

Bhatia 2010 {published data only}

Bhatia V. A study of the effect of vitamin D supplementation in pregnant women, on the growth and biochemical features of the newborn baby and infant. ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=1674&EncHid=&modid=&... (first received 19 May 2010). [CTRI/2010/091/000499]
Kalra P, Das V, Agarwal A, Kumar M, Ramesh V, Bhatia E, et al. Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant. British Journal of Nutrition 2012;108(6):1052-8. - PubMed
Sahu M, Das V, Aggarwal A, Rawat V, Saxena P, Bhatia V. Vitamin D replacement in pregnant women in rural north India: a pilot study. European Journal of Clinical Nutrition 2009;63(9):1157-9. - PubMed

Bhatia 2012 {published data only}

Bhatia V, Katam K, Agarwal A, Das V, Ramesh V. Vitamin D supplementation in pregnancy and its effect on cord blood 25 hydroxycholecalciferol and anthropometry of the newborn. Hormone Research in Paediatrics 2013;80(Suppl 1):220.
Bhatia V. Vitamin D supplementation in pregnancy: regimens and long term effects on offspring. Clinical Trials Registry - India CTRI/2012/02/002395 2012. [CTRI/2012/02/002395]
Sahoo SK, Katam KK, Das V, Agarwal A, Bhatia V. Maternal vitamin d supplementation in pregnancy and offspring outcomes: a double-blind randomized placebo-controlled trial. Journal of Bone and Mineral Metabolism 2017;35(4):464-71. - PubMed

Bhavya 2020 {published data only}

Bhavya Swetha RV, Samal R, George CE. The effect of vitamin D supplementation on improving glycaemic control in diabetic vitamin D-deficient pregnant women: a single-blinded randomized control trial. Journal of Obstetrics and Gynaecology of India 2020;70(2):119-25. [CENTRAL: CN-02051461] 12549794 [EMBASE: 2003843093] [PMID: ] - PMC - PubMed

Bimson 2017 {published data only}

Bimson B, Brustman L, Al Ibraheemi Z, Herrera K, Rosenn B. Can weekly vitamin D dosing adequately treat vitamin D deficiency in pregnancy? American Journal of Obstetrics and Gynecology 2017;216(1):S380-1.

Bisgaard 2009 {published data only}

Bisgaard H. Vitamin D supplementation during pregnancy for prevention of asthma in childhood (ABCvitaminD). clinicaltrials.gov/ct2/show/NCT00856947 (first received 6 March 2009).
Brustad N, Chawes BL, Thorsen J, Krakauer M, Lasky-Su J, Weiss ST, et al. High-dose vitamin D supplementation in pregnancy and 25(OH)D sufficiency in childhood reduce the risk of fractures and improve bone mineralization in childhood: follow-up of a randomized clinical trial. EClinicalMedicine 2022;43:101254. [CENTRAL: CN-02357879] 19627261 [EMBASE: 2016063112] - PMC - PubMed
Brustad N, Eliasen A, Stokholm J, Bonnelykke K, Bisgaard H, Chawes BL. High-dose vitamin D supplementation during pregnancy and asthma at age 6: a randomized controlled trial. Allergy: European Journal of Allergy and Clinical Immunology 2019;74(Suppl 106):60. [CENTRAL: CN-01995971] 12167698 [EMBASE: 629485006]
Brustad N, Eliasen AU, Stokholm J, Bonnelykke K, Bisgaard H, Chawes BL. High-dose vitamin D supplementation during pregnancy and asthma in offspring at the age of 6 years. JAMA 2019;321(10):1003-5. [CENTRAL: CN-01912906] 10548335 [EMBASE: 626728495] [PMID: ] - PMC - PubMed
Brustad N, Garland J, Thorsen J, Sevelsted A, Krakauer M, Vinding RK, et al. Effect of high-dose vs standard-dose vitamin D supplementation in pregnancy on bone mineralization in offspring until age 6 years a prespecified secondary analysis of a double-blinded, randomized clinical trial. JAMA Pediatrics 2020;174(5):419-27. [CENTRAL: CN-02096899] 12942864 [EMBASE: 631158074] [PMID: ] - PMC - PubMed

Camarena 2022 {published data only}

Camarena Pulido EE, Mora Gonzalez S, Corona Gutierrez AA, Robledo Aceves M, Basso Barba P, Salgado Leyva Y. Effect of supplementation with 5,000 IU of vitamin D on the glycemic profile of women with gestational diabetes mellitus. Journal of Perinatal Medicine 2022;50(9):1225-9. [CENTRAL: CN-02420815] 21178700 [EMBASE: 638396435] [PMID: ] - PubMed

Chandy 2016 {published data only}

Chandy DD, Kare J, Singh SN, Agarwal A, Das V, Singh U, et al. Effect of vitamin D supplementation, directly or via breast milk for term infants, on serum 25 hydroxyvitamin D and related biochemistry, and propensity to infection: a randomised placebo-controlled trial. British Journal of Nutrition 2016;116(1):52-8. - PubMed

ChiCTR1900027679 (first received 2019) {published data only}

ChiCTR1900027679. The role of prenatal vitamin D deficiency-metaflammation on maternal and child impaired glucose homeostasis and vitamin D supplementation trial based on a birth cohort study. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR1900027679 (first received 2019). [CENTRAL: CN-02445460] 21389028

ChiCTR‐TRC‐14005235 (first received 2014) {published data only}

ChiCTR-TRC-14005235. Glucose metabolism impact of a single injection of vitamin D3 on gestational diabetes with vitamin D deficiency [Glucose metabolism impact of a single injection of vitamin D3 on gestational diabetes with vitamin D]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-14005235 (first received 2014). [CENTRAL: CN-01877483] 10777235

Cockburn 1980 {published data only}

Cockburn F, Belton NR, Purvis RJ, Giles MM, Brown JK, Turner TL, et al. Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants. British Medical Journal 1980;281(6232):11-4. - PMC - PubMed

CTRI/2013/10/004056 (first received 2013) {published data only}

CTRI/2013/10/004056. To study the prevalence of vitamin D deficiency in pregnant women and the effect of supplementation in preventing adverse pregnancy outcome [Vitamin D deficiency in pregnancy: Its prevalence and role of supplementation in preventing adverse maternal and fetal outcome: a double blind randomized placebo-controlled trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2013/10/004056 (first received 2013). [CENTRAL: CN-01805697] 10705649

CTRI/2014/12/005343 (first received 2014) {published data only}

CTRI/2014/12/005343. Role of vitamin D & calcium supplementation in gestational diabetic mothers [Role of vitamin D- calcium supplementation on metabolic profile and oxidative stress in gestational diabetes mellitus: an open labeled, parallel arm randomised control trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2014/12/005343 (first received 2014). [CENTRAL: CN-01800493] 10700451

CTRI/2019/01/017185 (first received 2019) {published data only}

CTRI/2019/01/017185. Usefulness of vitamin D in pregnant diabetics [Effect of vitamin D supplementation among women with low vitamin D levels in gestational diabetes mellitus]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2019/01/017185 (first received 2019). [CENTRAL: CN-01971456] 12073568

CTRI/2022/01/039091 (first received 2022) {published data only}

CTRI/2022/01/039091. Vitamin D supplements during pregnancy [Oral vitamin D supplementation as a safe, affordable treatment for profound vitamin D deficiency in pregnancy]. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2022/01/039091 (first received 2022). [CENTRAL: CN-02449634] 21393174

Cullers 2019 {published data only}

Cullers A, King JC, Van Loan M, Gildengorin G, Fung EB. Effect of prenatal calcium supplementation on bone during pregnancy and 1 y postpartum. American Journal of Clinical Nutrition 2019;109(1):197-206. [CENTRAL: CN-01967619] 11933332 [EMBASE: 626589056] [PMID: ] - PMC - PubMed

Czech‐Kowalska 2013 {published data only}

Czech-Kowalska J, Latka-Grot J, Bulsiewicz D, Jaworski M, Pludowski P, Chazan B, et al. Influence of vitamin D supplementation on vitamin D status and bone mass during lactation - double blinded randomized control trial. Annals of Nutrition & Metabolism 2013;63(Suppl 1):796, Abstract no: PO1128.

Das 2009 {published data only}

Das V, Agarwal A, Bhatia V, Pandey A, Agarwal S, Saxena P, et al. Evaluation of vitamin d status and need for supplementation in pregnant women of a rural area of North India (abstract 0205). International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S151.

Das 2010 {published data only}

Das V. Vitamin D and calcium nutrition in pregnancy-evaluation of optimal supplementation dose of vitamin D during antenatal period. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=1553 (first received 2 June 2010). [CTRI/2010/091/000352]

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Dawodu A, Saadi HF, Bekdache G, Javed Y, Altaye M, Hollis BW. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. Journal of Clinical Endocrinology & Metabolism 2013;98(6):2337-46. - PubMed

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Menibus CH, Mallet E, Henocq A, Lemeur H. Should vitamin D supplements be given to pregnant women? Bulletin De L'academie Nationale De Medecine 1984;168(7-8):909-16. - PubMed

DRKS00005421 (first received 2013) {published data only}

DRKS00005421. Observational study of the daily intake of 1000 IU vitamin D3 during pregnancy on the 25-hydroxyvitamin D status. http://www.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00005421 (first received 2013). [CENTRAL: CN-01814338] 10714273

Enkhmaa 2018 Dec {published data only}

Enkhmaa D, Tanz L, Ganmaa D, Enkhtur S, Oyun-Erdene B, Stuart J, et al. Randomized trial of three doses of vitamin D to reduce deficiency in pregnant Mongolian women. EBioMedicine 2018;39:510-9. [CENTRAL: CN-01789782] 10405306 [EMBASE: 2001370065] [PMID: ] - PMC - PubMed

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Etemadifar M, Janghorbani M. Efficacy of high-dose vitamin D3 supplementation in vitamin D deficient pregnant women with multiple sclerosis: preliminary findings of a randomized-controlled trial. Iranian Journal of Neurology 2015;14(2):67-73. - PMC - PubMed

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Fang CEH, Hamill M, Ahern T, Hoashi S, Collins C, Gannon M. Measuring 25-hydroxyvitamin D levels early during pregnancy: a randomised clinical trial. Irish Journal of Medical Science 2019;188:S209. [CENTRAL: CN-02138317] 14211336 [EMBASE: 632078923]

Gerais 2015 {published data only}

Gerais AS, Hussein S. Vitamin D deficiency in pregnancy and pregnancy outcome. International Journal of Gynecology and Obstetrics 2015;131(Suppl 5):E352.

Gunasegaran 2020 {published data only}

Gunasegaran P, Tahmina S, Daniel M, Nanda SK. Role of vitamin D-calcium supplementation on metabolic profile and oxidative stress in gestational diabetes mellitus: a randomized controlled trial. Journal of Obstetrics and Gynaecology Research 2020;47(3):1016-22. [CENTRAL: CN-02288957] 16145179 [PMID: ] - PubMed

Gupta 2018 {published data only}

Gupta T, Sharma H, Bajpai J, Kachhawa G, Kulshreshtha V, Khadgawat R, et al. A randomized double blind controlled trial to investigate the effects of vitamin D supplementation on maternal and new-born baby's vitamin D status in Asian-Indian subjects. Indian Journal of Endocrinology and Metabolism 2018;22(7):S89. [CENTRAL: CN-01914880] 10843234 [EMBASE: 626683869]
Gupta T, Sharma H, Bajpai J, Kachhawa G, Kulshreshtha V, Khadgawat R, et al. A randomized double blind controlled trial to investigate the effects of vitamin D supplementation on maternal and new-born baby's vitamin D status in Asian-Indian subjects. Osteoporosis and Sarcopenia 2017;3(3 Suppl):S38-9. 14128844

Gurkan 2022 {published data only}

Gurkan N. Vitamin D supplementation during pregnancy inhibits the activation of fetal membrane NF-κB pathway. European Review for Medical and Pharmacological Sciences 2022;26(16):5926-31. [CENTRAL: CN-02461125] 21593047 [PMID: ] - PubMed

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Hajhashemi M, Khorsandi A, Haghollahi F. Comparison of sun exposure versus vitamin D supplementation for pregnant women with vitamin D deficiency. Journal of Maternal-fetal & Neonatal Medicine 2017;32(8):1-6. [CENTRAL: CN-01787857] 7743503 [EMBASE: 619456883] - PubMed
IRCT2016101227998N2. Comparison of sun exposure versus vitamin D supplementation for pregnant women with vitamin D deficiency. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2016101227998N2 (first received 2016). [CENTRAL: CN-01818009] 10717937 - PubMed

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Hanieh S, Ha TT, Simpson JA, Thuy TT, Khuong NC, Thoang DD, et al. Maternal vitamin D status and infant outcomes in rural Vietnam: a prospective cohort study. PLOS One 2014;9(6):e99005. [CENTRAL: CN-01105815] 1836324 [EMBASE: 24967813] [PMID: ] - PMC - PubMed

Hashemipour 2014 {published data only}

Abotorabi S, Hashemi poor S, Esmailzadehha N, Ziaee A, Khoeiniha MH. Effect of treatment with vitamin D on maternal and neonatal indices in pregnant women with hypocalcemia: a randomized controlled trial. International Journal of Pediatrics 2017;5(9):5733-9.
Hashemipour S, Ziaee A, Javadi A, Movahed F, Elmizadeh K, Javadi EH, et al. Effect of treatment of vitamin D deficiency and insufficiency during pregnancy on fetal growth indices and maternal weight gain: a randomized clinical trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 2014;172:15-9. - PubMed
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Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Erratum: Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness (Journal of Bone and Mineral Research (2011) 26 (2341-2357) DOI: 10 DOI: 10.1002/jbmr.463). Journal of Bone and Mineral Research 2011;26(12):3001. [CENTRAL: CN-01017003] 1747609 [EMBASE: 362976584] - PMC - PubMed
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Wagner CL, Brady SK, Newton D, Baatz JE, Shary JR, Hollis BW. The effects of vitamin D binding protein (VDBP) genotypes on circulating 25(OH)D and VDBP levels during pregnancy. FASEB Journal 2017;31(1):0. [CENTRAL: CN-01709144] 10342345 [EMBASE: 616960020]
Wagner CL, Wei W, Shary JR, Ebeling MD, Garrett-Mayer E, Taylor SN, et al. Preventing health disparities during pregnancy through vitamin D (VitD) supplementation: preliminary results: of a randomized controlled trial. FASEB Journal 2017;31(1):lb356. [CENTRAL: CN-01714693] 10346632 [EMBASE: 616959990]

Hossain 2012 {published data only}

Hossain N, Kanani F, Khanani R, Ayaz S, Pal L. Effect of maternal supplementation with vitamin D during pregnancy on neonatal serum vitamin D levels and anthropometric measurements. International Journal of Gynecology and Obstetrics 2012;119(Suppl 3):S372.
Hossain N, Kanani FH, Ramzan S, Kausar R, Ayaz S, Khanani R, et al. Obstetric and neonatal outcomes of maternal vitamin D supplementation: results of an open-label, randomised controlled trial of antenatal vitamin D supplementation in Pakistani women. Journal of Clinical Endocrinology and Metabolism 2013;99(7):2448-55. - PubMed
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Hosseinzadeh 2020 {published data only}

Hosseinzadeh M, Razmpoosh E, Elham shareghfarid, Hosseinzadeh E, Hadinedoushan H, Salami M-A, et al. The effect of a single mega dose injection of vitamin D on serum adiponectin concentration at first gestational diabetes mellitus: a randomized controlled clinical trial. Clinical Nutrition Experimental (first received 2020);33:39-48. [CENTRAL: CN-02175508] 14780234 [EMBASE: 2007677195]

Huang 2021 {published data only}

Huang S, Fu J, Zhao R, Wang B, Zhang M, Li L, et al. The effect of combined supplementation with vitamin D and omega-3 fatty acids on blood glucose and blood lipid levels in patients with gestational diabetes. Annals of Palliative Medicine 2021;10(5):5652-8. [CENTRAL: CN-02276974] 17897674 [PMID: ] - PubMed

IRCT20100102002954N11 (first received 2018) {published data only}

IRCT20100102002954N11. Calcium-D supplementation effects in sugar control in gestational diabetes [Evaluation of calcium-D supplementation effects in sugar control in patients with gestational diabetes]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20100102002954N11 (first received 2018). [CENTRAL: CN-01909573] 10809256

IRCT20120718010324N59 (first received 2020) {published data only}

IRCT20120718010324N59. The effect of vitamin D on fasting plasma glucose and insulin levels [The effect of vitamin D on insulin resistance biomarker and fasting blood glucose in pregnant women: a randomized controlled trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20120718010324N59 (first received 2020). [CENTRAL: CN-02187178] 15373359

IRCT20120718010324N61 (first received 2021) {published data only}

IRCT20120718010324N61. The effect of vitamin D on sleep quality and pregnancy symptoms [The effect of vitamin D on sleep quality and pregnancy symptoms in pregnant women: a randomized controlled clinical trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20120718010324N61 (first received 2021). [CENTRAL: CN-02239288] 16906137

IRCT2012101611144N1 (first received 2012) {published data only}

IRCT2012101611144N1. Gestational diabetes and vitamin D [The impact of vitamin D supplementation in gestational diabetes cases on post-partum glucose tolerance and insulin resistance: a randomized controlled trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2012101611144N1 (first received 2012). [CENTRAL: CN-01883554] 10783294

IRCT20130616013678N29 (first received 2019) {published data only}

IRCT20130616013678N29. Effect of vitamin D supplementation on control of gestational diabetes [Study of the effect of vitamin D oral supplementation on glycemic control, serum levels of growth hormone, insulin-like growth factor-1 and lipid profile in gestational diabetes mellitus patients]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20130616013678N29 (first received 2019). [CENTRAL: CN-01970840] 12072954

IRCT201306253140N11 (first received 2013) {published data only}

IRCT201306253140N11. Effect of vitamin D supplementation in the treatment of patients with gestational diabetes [Effect of vitamin D supplementation on serum vitamin D levels and markers of metabolic and inflammatory in women with gestational diabetes]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201306253140N11 (first received 2013). [CENTRAL: CN-01816063] 10715993

IRCT2015022714275N2 (first received 2015) {published data only}

IRCT2015022714275N2. Effect of vitamin D on gestational diabetes [Comparison of vitamin D supplements effect on gestational diabetes in pregnant women with and without vitamin D deficiency]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2015022714275N2 (first received 2015). [CENTRAL: CN-01818951] 10718879

IRCT20150607022585N3 (first received 2018) {published data only}

IRCT20150607022585N3. Effect of vitamin D supplementation on fasting plasma glucose and insulin resistance indices in gestational diabetes mellitus [Comparison of the effect of vitamin D supplementation on fasting plasma glucose and insulin resistance indices in pregnant women with gestational diabetes mellitus with a group of gestational diabetic pregnant women who do not receive vitamin D supplement]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20150607022585N3 (first received 2018). [CENTRAL: CN-01910057] 10809739

IRCT2015122725725N1 (first received 2016) {published data only}

IRCT2015122725725N1. Effect of vitamin D supplementation on controlling blood sugar in patients with gestational diabetes [A clinical trial to investigate the effect of vitamin D supplementation on glucose status in mothers with gestational diabetes]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2015122725725N1 (first received 2016). [CENTRAL: CN-01877760] 10777512

Ito 1994 {published data only}

Ito M, Koyama H, Ohshige A, Maeda T, Yoshimura T, Okamura H. Prevention of preeclampsia with calcium supplementation and vitamin D3 in an antenatal protocol. International Journal of Gynecology & Obstetrics 1994;47(2):115-20. - PubMed

Jamilian 2016 {published data only}

Jamilian M, Karamali M, Taghizadeh M, Sharifi N, Jafari Z, Memarzadeh MR, et al. Vitamin D and evening primrose oil administration improve glycemia and lipid profiles in women with gestational diabetes. Lipids 2016;51(3):349-56. - PubMed

Jamilian 2017a {published data only}

Jamilian M, Samimi M, Ebrahimi FA, Hashemi T, Taghizadeh M, Razavi M, et al. The effects of vitamin D and omega-3 fatty acid co-supplementation on glycemic control and lipid concentrations in patients with gestational diabetes. Journal of Clinical Lipidology 2017;11(2):459-68. - PubMed

Jamilian 2017b {published data only}

Jamilian M, Afshar R. Effects of combined evening primrose oil and vitamin D intake on HS-CRP, oxidative stress and pregnancy outcomes in women with gestational diabetes. Journal of Arak University Medical Science 2017;19(12):43-51. [CENTRAL: CN-02111924] 13657441

Jamilian 2019 {published data only}

Jamilian M, Mirhosseini N, Eslahi M, Bahmani F, Shokrpour M, Chamani M, et al. The effects of magnesium-zinc-calcium-vitamin D co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes. BMC Pregnancy and Childbirth 2019;19(1):107. [CENTRAL: CN-01939221] 11482502 [EMBASE: 626988998] [PMID: ] - PMC - PubMed

Jefferson 2019 {published data only}

Jefferson KK, Parikh HI, Garcia EM, Edwards DJ, Serrano MG, Hewison M, et al. Relationship between vitamin D status and the vaginal microbiome during pregnancy. Journal of Perinatology 2019;39(6):824-36. [CENTRAL: CN-02102943] 13575922 [EMBASE: 626750133] [PMID: ] - PMC - PubMed

Judkins 2010 {published data only}

Judkins A. A randomised double blinded interventional trial to determine the effect of 50,000 IU vitamin D supplementation monthly or twice monthly from 20 weeks gestation. anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12610001044011 (first received 23 November 2010).

Kachhawa 2014 {published data only}

Gupta T, Kachhawa G, Sharma H, Bajpai J, Kulshreshtha V, Khadgawat R, et al. A randomized double blind controlled trial to investigate the effects of vitamin D supplementation on maternal and new-born baby's vitamin D status in Asian-Indian subjects. Indian Journal of Endocrinology and Metabolism 2017;21(8 Suppl 2):S44-5.
Kachhawa G. A randomized controlled trial to investigate the effects of vitamin D supplementation on maternal and new-born baby's vitamin D status in Asian-Indian subjects - VIDIMAN. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=8544&EncHid=&... (first received 13 June 2014).

Karamali 2014 {published data only}

Karamali M, Asemi Z, Ahmadi-Dastjerdi M, Esmaillzadeh A. Calcium plus vitamin D supplementation affects pregnancy outcomes in gestational diabetes: randomized, double-blind, placebo-controlled trial. Public Health Nutrition 2016;19(1):156-63. - PMC - PubMed
Karamali M, IRCT201407115623N23. Effect of vitamin D plus calcium co-supplementation on pregnancy outcomes in gestational diabetes. en.search.irct.ir/view/19118 (first received 21 July 2014).

Karamali 2015 {published data only}

Karamali M, Beihaghi E, Mohammadi AA, Asemi Z. Effects of high-dose vitamin D supplementation on metabolic status and pregnancy outcomes in pregnant women at risk for pre-eclampsia. Hormone and Metabolic Research 2015;47(12):867-82. - PubMed

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Kermack AJ, Calder PC, Macklon NS, Fisk HL, Houghton FD, Lowen PK, et al. Prepare trial: a randomised double blinded controlled trial of a preconception omega 3 and vitamin D rich dietary supplement in couples undergoing assisted reproduction treatment. Human Reproduction 2017;32:i290.

Khatiwada 2020 {published data only}

Khatiwada A, Wolf BJ, Mulligan JK, Shary JR, Hewison M, Baatz JE, et al. Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy. Pediatric Research 2020;89(3):554-62. [CENTRAL: CN-02131724] 13575712 [EMBASE: 2005037282] [PMID: ] - PMC - PubMed

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Kiely M. Randomized controlled trial to determine the nutritional requirement for vitamin D for prevention of deficiency during pregnancy and in the early neonatal period (D-MAT). clinicaltrials.gov/ct2/show/NCT02506439 (first received 23 July 2015). [NCT02506439]
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O'Callaghan K, Hennessy A, Kiely M, Kenny LC. Habitual calcium and vitamin D intakes in pregnant Irish women; preliminary data from the DMAT randomised controlled trial. Proceedings of the Nutrition Society 2016;75(OCE3):E191.
O'Callaghan KM, Hennessy A, Hull GL, Healy K, Ritz C, Kenny LC, et al. Estimation of the maternal vitamin D intake that maintains circulating 25-hydroxyvitamin D in late gestation at a concentration sufficient to keep umbilical cord sera >/=25-30 nmol/L: a dose-response, double-blind, randomized placebo-controlled trial in pregnant women at northern latitude. American Journal of Clinical Nutrition 2018;108(1):77-91. - PMC - PubMed

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Lalooha F. The effect of vitamin D supplementation during pregnancy on newborn's anthropometric index. en.irct.ir/trial/10079IRCT (first received 16 August 2012).

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Li Q, Xing B. Vitamin D3-supplemented yogurt drink improves insulin resistance and lipid profiles in women with gestational diabetes mellitus: a randomized double blinded clinical trial. Annals of Nutrition & Metabolism 2016;68(4):285-90. - PubMed

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EUCTR2010-019483-37-SE. Vitamin D supplementation for prevention of placenta mediated pregnancy complications. Prevention of pregnancy complications with vitamin D. http://www.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2010-019483-37-SE (first received 2010). [CENTRAL: CN-01813254] 10713192
Lindqvist P. Vitamin D supplementation for prevention of placenta mediated pregnancy complications. Prevention of pregnancy complications with vitamin D. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_nu... (first received 4 June 2010).

MacDonald 1986 {published data only}

MacDonald HN. Fetal and maternal benefits from calcium and vitamin D supplementation of pregnant Asians. Personal communication 1986.

March 2010 {published data only}

Anon. Erratum for March et al. Maternal vitamin D3 supplementation at 50 μg/d protects against low serum 25-hydroxyvitamin D in infants at 8 wk of age: a randomised controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation. Am J Clin Nutr 2015;102:402–10. American Journal of Clinical Nutrition 2016;104(5):1491. - PubMed
Chen NN, March K, Innis SM, Shand A, Dadelszen P, Lyon P, et al. The effect of vitamin D supplementation during pregnancy and lactation on maternal and infant 25-hydroxyvitamin D (25OHD) concentration. FASEB Journal 2013;27(Suppl 1).
March K. Vitamin D dose-response study throughout pregnancy and lactation. clinicaltrials.gov/ct2/show/NCT01112891 (first received 29 April 2010).
March KM, Chen NN, Karakochuk CD, Shand AW, Innis SM, Dadelszen P, et al. Maternal vitamin D3 supplementation at 50 ug/d protects against low serum 25-hydroxyvitamin D in infants at 8 wk of age: a randomized controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation. American Journal of Clinical Nutrition 2015;102(2):402-10. - PubMed

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Marya RK, Rathee S, Lata V, Mudgil S. Effects of vitamin D supplementation in pregnancy. Gynecologic and Obstetric Investigation 1981;12:155-61. - PubMed

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McLean M. Effect of high-dose versus low-dose vitamin D supplementation in pregnancy on maternal glucose metabolism and the risk of gestational diabetes. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=308236 (first received 30 October 2012).

Mirzaei‐Azandaryani 2022 {published data only}

Mirzaei-Azandaryani Z, Mohammad-Alizadeh-Charandabi S, Shaseb E, Abbasalizadeh S, Mirghafourvand M. Effects of vitamin D on insulin resistance and fasting blood glucose in pregnant women with insufficient or deficient vitamin D: a randomized, placebo-controlled trial. BMC Endocrine Disorders 2022;22(1):254. [CENTRAL: CN-02486763] 21970654 [PMID: ] - PMC - PubMed

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Moghaddam MJ. The effect of 50000 IU Vitamin D supplement administered two weekly on gestational diabetes melitus [The effect of 50000 IU Vitamin D supplement administered two weekly on neonatal and pregnant women outcome]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201107237097N1 (first received 2012). [CENTRAL: CN-01881754] 10781501

Mojibian 2015 {published data only}

Mojibian M, Soheilykhah S, Fallah Zadeh MA, Jannati Moghadam M. The effects of vitamin D supplementation on maternal and neonatal outcome: a randomized clinical trial. Iranian Journal of Reproductive Medicine 2015;13(11):687-96. - PMC - PubMed
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Mosalanejad N, IRCT2016121430612N2. Compare the effect of vitamin D and calcium plus vitamin D on pregnancy outcomes in pregnant women. en.search.irct.ir/view/34642 (first received 26 December 2016).

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Hosseinzadeh-Shamsi-Anar M, Mozaffari-Khosravi H, Salami MA, Hadinedoushan H, Mozayan MR. The efficacy and safety of a high dose of vitamin d in mothers with gestational diabetes mellitus: a randomized controlled clinical trial. Iranian Journal of Medical Sciences 2012;37(3):159-65. - PMC - PubMed
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Mozaffari-Khosravi H, Hosseinzadeh-Shamsi-Anar M, Salami MA, Hadinedoushan H, Mozayan MR. Effects of a single post-partum injection of a high dose of vitamin D on glucose tolerance and insulin resistance in mothers with first-time gestational diabetes mellitus. Diabetic Medicine 2012;29(1):36-42. - PubMed

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Mutlu GY, Ozsu E, Kalaca S, Yuksel A, Cizmecioglu FM, Hatun S. The evaluation of vitamin D supplementation dose during pregnancy in a high-risk population. Hormone Research in Paediatrics 2013;80(Suppl 1):92. - PubMed
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Nausheen S. Assessment of dose effectiveness of vitamin D supplementation during pregnancy. clinicaltrials.gov/ct2/show/NCT02215213 (first received 13 August 2014).

NCT02272387 (first received 2014) {published data only}

NCT02272387. Is vitamin D insufficiency and deficiency associated with antepartum and postpartum depression? http://clinicaltrials.gov/show/nct02272387 (first received 2014). [CENTRAL: CN-01549667] 4738441

NCT02706158 (first received 2016 March 11) {published data only}

NCT02706158. Dietary intervention program for pre-eclampsia in women at risk [Testing the effect of a dietary intervention program on the incidence of pre-eclampsia in women at risk]. https://clinicaltrials.gov/show/NCT02706158 (first received 2016 March 11). [CENTRAL: CN-01556455] 8307726

NCT02713009 (first received 2016 Jan 14) {published data only}

NCT02713009. Impact of maternal body weight on vitamin D status during pregnancy [Investigation of the impact of maternal body weight on vitamin D status during pregnancy: a randomised supplementation study]. https://clinicaltrials.gov/show/NCT02713009 (first received 14 January 2016). [CENTRAL: CN-01556667] 8307923

NCT03645109 (first received 2018 Aug 24) {published data only}

NCT03645109. Effect of supplementation of vitamin D in gestational diabetes mellitus [Effect of suplementation of 5,000 UI vitamin D3 on the glycemic profile in patients with gestational diabetes mellitus of the Hospital Civil de Guadalajara Dr. Juan I. Menchaca]. https://clinicaltrials.gov/show/nct03645109 (first received 24 August 2018). [CENTRAL: CN-01626434] 9158400

NCT04825093 (first received 2021 April 01) {published data only}

NCT04825093. Vitamin D supplementarion in pregnant women at risk and COVID-19 [Randomized clinical trial with vitamin D supplementation in pregnant women and prevalence of COVID-19]. https://clinicaltrials.gov/show/NCT04825093 (first received 1 April 2021). [CENTRAL: CN-02252261] 17132564

Niramitmahapanya 2017 {published data only}

Niramitmahapanya S, Kaoiean S, Sangtawesin V, Bordeerat NK, Deerochanawong C. Correlation of 25-hydroxyvitamin d levels in serum vs breastmilk in vitamin d-supplementation breastfeeding women during lactation: randomized double blinded control trial. Endocrine Reviews 2017;38(3). - PubMed

Pandey 2015 {published data only}

Pandey U, Divakar H. Role of vitamin D in iron metabolism, a pilot study. International Journal of Reproduction, Contraception, Obstetrics and Gynecology 2015;4(5):1494-8.

Qian 2015 {published data only}

Qian L, Wang H, Wu F, Li M, Chen W, Lv L. Vitamin D3 alters toll-like receptor 4 signaling in monocytes of pregnant women at risk for preeclampsia. International Journal of Clinical and Experimental Medicine 2015;8(10):18041-9. - PMC - PubMed

Rasmussen 2009 {published data only}

Mosekilde L, Sikjaer T, Vestergaard P, Heickendorff L, Uldbjerg N, Langdahl B, et al. Effects of high dose vitamin D supplementation on bone metabolism in pregnant women with hypovitaminosis D - a randomized controlled trial. Journal of Bone and Mineral Research 2015;30(Suppl 1). [CENTRAL: CN-01461769] 7882221 [EMBASE: 620769342]
Rasmussen G. Additional information on registered trial. Effects of vitamin D supplement before, during and after pregnancy on complications, birth weight and bone mineral density during lactation (gravita). Personal communication 2011.
Rasmussen GB. Effects of vitamin D supplement before and during pregnancy on birth weight (gravita). clinicaltrials.gov/ct2/show/NCT01038453 (first received 24 December 2009).

Razavi 2017 {published data only}

Razavi M, Jamilian M, Samimi M, Afshar Ebrahimi F, Taghizadeh M, Bekhradi R, et al. The effects of vitamin d and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes. Nutrition & Metabolism 2017;14:80. - PMC - PubMed

Rostami 2018 {published data only}

Rostami M, Ramezani Tehrani F, Simbar M, Bidhendi Yarandi R, Minooee S, Hollis BW, et al. Effectiveness of prenatal vitamin D deficiency screening and treatment program: a stratified randomized field trial. Journal of Clinical Endocrinology and Metabolism 2018;103(8):2936–48. - PubMed
Rostami M, Ramezani Tehrani F, Simbar M, Hosseinpanah F, Alavi Majd H. Rationale and design of Khuzestan vitamin D deficiency screening program in pregnancy: a stratified randomized vitamin D supplementation controlled trial. JMIR Research Protocols 2017;6(4):e54. - PMC - PubMed

Rostami 2020 {published data only}

IRCT20190618043927N1. Effect of vitamin D in pregnant women [The effect of vitamin D in third trimester of pregnancy on some maternal metabolic and neonatal anthropometric index in nulliparous pregnant woman]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20190618043927N1 (first received 2019). [CENTRAL: CN-01975388] 12077468
Rostami F, Moghaddam-Banaem L, Ghasemi N, Hantoushzadeh S. Treatment of vitamin d deficiency with high-dose vitamin d supplementation and its effect on hematological indices in pregnancy: a secondary analysis of a randomized clinical trial. Koomesh 2020;22(4):664-70. [CENTRAL: CN-02204268] 14984531 [EMBASE: 2005213588]

Shakiba 2013 {published data only}

Shakiba M, Iranmanesh MR. Vitamin D requirement in pregnancy to prevent deficiency in neonates: a randomised trial. Singapore Medical Journal 2013;54(5):285-8. - PubMed

Shi 2017 {published data only}

Shi DD, Wang Y, Guo JJ, Zhou L, Wang N. Vitamin d enhances efficacy of oral nifedipine in treating preeclampsia with severe features: a double blinded, placebo-controlled and randomized clinical trial. Frontiers in Pharmacology 2017;8:865. - PMC - PubMed

Simsek 2011 {published data only}

Simsek S. Vitamin D supplementation in gestational diabetes mellitus. trialregister.nl/trialreg/admin/rctview.asp?TC=3158 (first received 21 November 2011).

Singh 2021 {published data only}

Singh S, Garg R, Meena A, Kumar D. Perinatal outcome in vitamin d deficiency and effect of oral and intramuscular vitamin D3 supplementation in antenatal women on pregnancy outcomes. Journal of SAFOG 2021;13(3):86-9. [CENTRAL: CN-02325274] 19039129 [EMBASE: 2013582765]

SLCTR/2018/020 (first received 2018) {published data only}

SLCTR/2018/020. A randomized controlled clinical trial to compare the efficacy of vitamin D vs placebo to reduce high blood sugar during pregnancy [A randomized control trial comparing vitamin D supplementation versus placebo on glycemic control in gestational diabetes mellitus]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=SLCTR/2018/020 (first received 2018). [CENTRAL: CN-01907327] 10807012

Soheilykhah 2013 {published data only}

Soheilykhah S, Mojibian M, Moghadam MJ, Shojaoddiny-Ardekani A. The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy. Gynecological Endocrinology 2013;29(4):396-9. - PubMed
Soheilykhah S. Effect of different doses of vitamin D on insulin resistance in pregnant women attending in Shahid Sadoughi and Mojibian prenatal clinics. en.irct.ir/trial/3385 (first received 23 May 2011). [IRCT138811203312N1]

Stephensen 2011 {published data only}

Stephensen CB. Effects of vitamin D supplementation during pregnancy on clinical outcomes and immune function. clinicaltrials.gov/ct2/show/NCT01417351 (first received August 2011).
Zerofsky M, Jacoby B, Pedersen TL, Stephensen CB. Effects of a randomized, controlled trial of daily vitamin D3 supplementation during pregnancy on regulatory immunity and inflammation. FASEB Journal 2016;30(Suppl 1):296.7. - PubMed
Zerofsky M, Jacoby B, Stephensen C. A randomized controlled trial of vitamin D supplementation in pregnancy: Effects on vitamin D status and clinical outcomes. FASEB Journal 2014;28(1 Suppl 1):Abstract no. 1041.5.
Zerofsky MS, Jacoby BN, Pedersen TL, Stephensen CB. Daily cholecalciferol supplementation during pregnancy alters markers of regulatory immunity, inflammation, and clinical outcomes in a randomized controlled trial. Journal of Nutrition 2016;146(11):2388-97. - PubMed

Sudfeld 2017 {published data only}

NCT02305927. Trial of vitamin D in HIV progression, birth outcomes, and child health. https://clinicaltrials.gov/show/NCT02305927 (first received 29 October 2014). [CENTRAL: CN-02046217] 12584687
Sudfeld CR, Manji KP, Duggan CP, Aboud S, Muhihi A, Sando DM, et al. Effect of maternal vitamin d3 supplementation on maternal health, birth outcomes, and infant growth among HIV-infected Tanzanian pregnant women: study protocol for a randomized controlled trial. Trials 2017;18(1):411. - PMC - PubMed
Sudfeld CR, Manji KP, Muhihi A, Duggan CP, Aboud S, Alwy Al-Beity FM, et al. Vitamin D3 supplementation during pregnancy and lactation for women living with HIV in Tanzania: a randomized controlled trial. PLOS Medicine 2022;19(4):e1003973. [CENTRAL: CN-02395014] 20756988 [EMBASE: 637787204] [PMID: ] - PMC - PubMed

Taheri 2014 {published data only}

Taheri M, Baheiraei A, Rahimi A, Modarres M. Resolving vitamin D deficiency in the preconception period among high-risk reproductive women: a randomized controlled trial. Iranian Red Crescent Medical Journal 2014;16(1):e11175. - PMC - PubMed

Thiele 2014 {published data only}

Anderson CM, Thiele DK, Ralph JL, Perley D, OHM JE. Vitamin D supplementation and DNA methylation patterns during pregnancy in and lactation in mothers and infants. FASEB Journal 2016;30(Suppl 1):Abstract no: 1028.3.
Keesling Thiele D. The Impact of Continuous Prenatal and Early Postpartum Maternal Vitamin D Supplementation on The Vitamin D Status of Exclusively Breastfed Infants [Thesis]. University of North Dakota, 2013.
Thiele D, Anderson CM. CS_018. Maternal vitamin D supplementation increases infant vitamin D status at birth but the impact diminishes during breastfeeding. In: 17th Conference of the International Society for Research in Human Milk and Lactation (ISRHML); 2014 Oct 23-27; Kiawah Island, South Carolina, USA. 2014:122.
Thiele DK, Ralph J, El-Masri M, Anderson CM. Vitamin D3 supplementation during pregnancy and lactation improves vitamin D status of the mother-infant dyad. Journal of Obstetric, Gynecologic, and Neonatal Nursing: JOGNN 2017;46:135-47. - PubMed

Trivedi 2020 {published data only}

Trivedi M, Faridi MMA, Aggarwal A, Madhu SV, Malhotra RK. Oral vitamin D supplementation to mothers during lactation - effect of 25(OH)D concentration on exclusively breastfed infants at 6 months of age: a randomized double-blind placebo-controlled trial. Breastfeeding Medicine 2020;15(4):237-45. [CENTRAL: CN-02101804] 13649734 [EMBASE: 631505813] [PMID: ] - PubMed

Valizadeh 2016 {published data only}

Valizadeh M, Piri Z, Mohammadian F, Kamali K, Amir Moghadami HR. The impact of vitamin D supplementation on post-partum glucose tolerance and insulin resistance in gestational diabetes: a randomized controlled trial. International Journal of Endocrinology and Metabolism 2016;14(2):e34312. - PMC - PubMed

von Hurst 2009 {published data only}

Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial. British Journal of Nutrition 2010;103(4):549-55. - PubMed
Hurst PR, Stonehouse W, Matthys C, Conlon C, Kruger MC, Coad J. Study protocol--metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: a randomised, placebo-controlled, double-blind vitamin D intervention. BMC Public Health 2008;8:267. - PMC - PubMed
Hurst PR. The Role of Vitamin D in Metabolism and Bone Health. A Thesis Presented in Partial Fulfilment of The Requirements for The Degree of Doctor of Philosophy in Nutritional Science. Vol. 1. Albany: Massey University, 2009.

Wagner 2006 {published data only}

Appelgren KE, Nietert PJ, Hulsey TC, Hollis BW, Wagner CL. Analyzing adherence to prenatal supplement: does pill count measure up? International Journal of Endocrinology 2010;2010:1-8. - PMC - PubMed
Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. Journal of Bone and Mineral Research 2011;26(10):2341-57. - PMC - PubMed
Wagner CL, Johnson D, Hulsey TC, Ebeling M, Shary J, Smith PG, et al. Vitamin D supplementation during pregnancy part 2 NICHD/CTSA randomized clinical trial (RCT): outcomes. In: Pediatric Academic Societies' 2010 Annual Meeting; 2010 May 1-4; Vancouver, Canada. 2010.
Wagner CL, Johnson D, Hulsey TC, Ebeling M, Shary J, Smith PG, et al. Vitamin D supplementation during pregnancy Part I NICHD/CTSA randomized clinical trial (RCT): safety consideration. In: Pediatric Academic Societies Annual Meeting; 2010 May 1-4; Vancouver, Canada. 2010.
Wagner CL, McNeil R, Hamilton SA, Davis DJ, Prudgen C, Winkler J, et al. Vitamin D (vitD) supplementation during pregnancy: Thrasher Research Fund RCT in SC community center networks. In: Pediatric Academic Societies 2010 Annual Meeting; 2010 May 1-4; Vancouver, Canada. 2010.

Wagner 2013 {published data only}

Moore RS, Mulligan JK, Harmon H, Hollis BW, Wagner CL. Immune mediators and vitamin D status in the development of comorbidities of pregnancy. In: Pediatric Academic Societies Annual Meeting; 2016 April 30-May 3; Baltimore, USA. 2016:4109.85.
Schulz EV, Wagner CL, Cruze L, Wei W, Gehris J. Maternal vitamin d sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy. Journal of Steroid Biochemistry and Molecular Biology 2017;173:273-9. - PMC - PubMed
Wagner CL. Preventing health disparities during pregnancy through vitamin D supplementation. clinicaltrials.gov/ct2/show/NCT01932788 (first received 30 August 2013).

Wagner 2020 {published data only}

Wagner CL, Hulsey TC, Ebeling M, Shary JR, Asghari G, Howard CR, et al. Safety aspects of a randomized clinical trial of maternal and infant vitamin D supplementation by feeding type through 7 months postpartum. Breastfeeding Medicine 2020;15(12):765-75. [CENTRAL: CN-02176071] 14780713 [EMBASE: 632846646] [PMID: ] - PMC - PubMed

Weiss 2009 {published data only}

Al-Garawi A, Carey VJ, Chhabra D, Mirzakhani H, Morrow J, Lasky-Su J, et al. The role of vitamin D in the transcriptional program of human pregnancy. PLOS One 2016;11(10):e0163832. - PMC - PubMed
Al-Garawi A, Carey VJ, Chhabra D, Morrow J, Lasky-Su J, Koh A, et al. Differentially expressed genes during the course of pregnancy and their correlation with maternal vitamin D levels. American Journal of Respiratory and Critical Care Medicine 2015;191:A5994.
Al-Garawi A, Carey VJ, Qiu W, Mirzakhani H, Litonjua AA, Weiss ST. Cord blood vitamin D levels and gene expression profiles at birth are associated with wheezing in the first year of life: results from the vitamin D antenatal asthma reduction trial (VDAART). American Journal of Respiratory and Critical Care Medicine 2016;193:A3168.
Bhaskaran K, Smeeth L, Evans S. Prenatal vitamin D and offspring wheezing. JAMA 2016;315(24):2730. - PubMed
Blighe K, Chawes BL, Kelly RS, Mirzakhani H, McGeachie M, Litonjua AA, et al. Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y. American Journal of Clinical Nutrition 2017;106(4):1092-9. - PMC - PubMed

Wheeler 2017 {published data only}

Wheeler BJ, Taylor BJ, Herbison P, Haszard JJ, Mikhail A, Jones S, et al. Effect of high dose monthly maternal cholecalciferol supplementation during breastfeeding on infant and maternal vitamin d status at 5 months post-partum: a randomized controlled trial. International Journal of Pediatric Endocrinology 2017;2017(Suppl 1). [CENTRAL: CN-01461912] 8013461 [EMBASE: 620749158]

Xiaomang 2021 {published data only}

Xiaomang J, Yanling W. Effect of vitamin D3 supplementation during pregnancy on high risk factors - a randomized controlled trial. Journal of Perinatal Medicine 2021;49(4):480-4. [CENTRAL: CN-02347558] 19500816 [EMBASE: 2010575929] [PMID: ] - PubMed

Yap 2014 {published data only}

Yap C, Cheung NW, Gunton JE, Athayde N, Munns CF, Duke A, et al. Erratum. Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial. Diabetes care 2014;37:1837-1844. Diabetes Care 2015;38(10):1992. - PubMed
Yap C, Cheung NW, Gunton JE, Athayde N, Munns CF, Duke A, et al. Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial. Diabetes Care 2014;37(7):1837-44. - PubMed

Yazdchi 2016 {published data only}

Yazdchi R, Gargari BP, Asghari-Jafarabadi M, Sahhaf F. Effects of vitamin D supplementation on metabolic indices and hs-CRP levels in gestational diabetes mellitus patients: a randomized, double-blinded, placebo-controlled clinical trial. Nutrition Research and Practice 2016;10(3):328-35. - PMC - PubMed

Zhang 2016 {published data only}

Zhang Q, Cheng Y, He M, Li T, Ma Z, Cheng H. Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: a randomized controlled trial. Experimental and Therapeutic Medicine 2016;12(3):1889-95. - PMC - PubMed

Zhao 2019 {published data only}

Zhao Y, Teng Y, Wang J, Yang Z, Dong S, Hu J, et al. Effects of vitamin D supplementation in early pregnancy on high-risk groups of gestational diabetes mellitus. Wei Sheng Yan Jiu [Journal of Hygiene Research] 2019;48(2):226-31. [CENTRAL: CN-01981777] 12083238 [PMID: ] - PubMed

References to studies awaiting assessment

Asemi 2012 {published data only}.

Asemi Z, Tabassi Z, Heidarzadeh Z, Khorammian H, Sabihi SS, Samimi M. Effect of calcium-vitamin D supplementation on metabolic profiles in pregnant women at risk for pre-eclampsia: a randomized placebo-controlled trial. Pakistan Journal of Biological Sciences 2012;15(7):316-24. - PubMed

Basutkar 2020 {published data only}

Basutkar RS, Eipe T, Wilfred P, Sam KK, Varghese RC, Ponnusankar S, et al. Effect of daily oral supplementation of vitamin D3 in iron and 25 hydroxyvitamin d deficient pregnant women: a randomized placebo-controlled study. Latin American Journal of Pharmacy 2020;39(2):318-30. [CENTRAL: CN-02096616] 13304914 [EMBASE: 2004051607]

Brooke 1980 {published data only}

Brooke OG, Brown IR, Bone CD, Carter ND, Cleeve HJ, Maxwell JD, et al. Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. British Medical Journal 1980;1:751-4. - PMC - PubMed
Brooke OG, Butters F, Wood C. Intrauterine vitamin D nutrition and postnatal growth in Asian infants. British Medical Journal 1981;283:1024. - PMC - PubMed
Brown IR, Brooke OG, Cleeve HJ. Changes in mineral metabolism in the human foetus and newborns associated with maternal vitamin d supplements [proceedings]. Biochemical Society Transactions 1980;8(1):136-7. - PubMed
Maxwell JD, Ang L, Brooke OG, Brown IR. Vitamin D supplements enhance weight gain and nutritional status in pregnant Asians. British Journal of Obstetrics and Gynaecology 1981;88:987-91. - PubMed

Chen 2022 {published data only}

Chen Z, Chen J. The efficacy of calcium carbonate-vitamin D3 in pregnant women for the prevention of hypertensive disorders in pregnancy. Evidence-based Complementary and Alternative Medicine : ECAM 2022;2022:7971976. [CENTRAL: CN-02463131] 21608739 [PMID: ] - PMC - PubMed

ChiCTR1900024080 (first received 2019) {published data only}

ChiCTR1900024080. Effect on pregnancy outcomes of vitamin D nutritional status during perinatal period. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR1900024080 (first received 2019). [CENTRAL: CN-02434785] 21378424

ChiCTR‐IOQ‐16009309 (first received 2016) {published data only}

ChiCTR-IOQ-16009309. Effect of vitamin D supplementation on B.P, proteinuria and aldosterone to renin ratio in preecalmpsia [Effect of vitamin D supplementation on B.P, protein uria and ARR]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IOQ-16009309 (first received 2016). [CENTRAL: CN-01856705] 10756516

CTRI/2015/07/006039 (first received 2015) {published data only}

CTRI/2015/07/006039. Does vitamin D supplementation in pregnancy improves maternal and neonatal outcome? [The effect of vitamin D supplementation in pregnancy on maternal and neonatal outcome: a double blind randomised controlled trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2015/07/006039 (first received 2015). [CENTRAL: CN-01830636] 10730538

CTRI/2017/12/010850 (first received 2017) {published data only}

CTRI/2017/12/010850. Effect of oral vitamin D to pregnant mothers on vitamin D levels of their children at 6 months of age [Effect of oral vitamin D supplementation to pregnant mothers on vitamin D status of their exclusively breastfed infants at 6 months of age- a randomised triple blind placebo controlled trial]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2017/12/010850 (first received 2017). [CENTRAL: CN-01897281] 10796987

Dabbaghmanesh 2019 {published data only}

Dabbaghmanesh MH, Vaziri F, Najib F, Nasiri S, Pourahmad S. The effect of vitamin D consumption during pregnancy on maternal thyroid function and depression: a randomized, placebo-controlled, clinical trial. Jundishapur Journal of Natural Pharmaceutical Products 2019;14(2):e65328. [CENTRAL: CN-01958894] 11927469 [EMBASE: 628246206]
IRCT201508091312N2. Effects of vitamin D supplementation on thyroid function tests in pregnant women. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201508091312N2 (first received 2015). [CENTRAL: CN-01835527] 10735418

Delvin 1986 {published data only}

Delvin EE, Salle BL, Glorieux FH, Adeleine P, David LS. Vitamin D supplementation during pregnancy: effect on neonatal calcium homeostasis. Journal of Pediatrics 1986;109:328-34. - PubMed

IRCT20140317017034N6 (first received 2018) {published data only}

IRCT20140317017034N6. Effect of vitamin D in pregnant women [The effect of vitamin D supplementation on fetal antropometric parameters in pregnant ladies]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20140317017034N6 (first received 2018). [CENTRAL: CN-01904645] 10804343

Jelsma 2013 {published data only}ISRCTN70595832

Corcoy R, Mendoza LC, Simmons D, Desoye G, Adelantado JM, Chico A, et al. The DALI vitamin D randomized controlled trial for gestational diabetes mellitus prevention: no major benefit shown besides vitamin D sufficiency. Clinical Nutrition (Edinburgh, Scotland) 2020;39(3):976-84. [CENTRAL: CN-01937611] 11481172 [EMBASE: 2001891407] [PMID: ] - PubMed
Desoye G. Vitamin D and lifestyle intervention for gestational diabetes mellitus prevention. Diabetologe 2012;8(8):647-51. 12269152
Harreiter J, Mendoza LC, Simmons D, Desoye G, Devlieger R, Galjaard S, et al. Vitamin D3 supplementation in overweight/obese pregnant women: no effects on the maternal or fetal lipid profile and body fat distribution-a secondary analysis of the multicentric, randomized, controlled vitamin D and lifestyle for gestational diabetes prevention trial (DALI). Nutrients 2022;14(18):3781. [CENTRAL: CN-02466146] 21647960 [PMID: ] - PMC - PubMed
Jelsma JG, Poppel MN, Galjaard S, Desoye G, Corcoy R, Devlieger R, et al. DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomised trial - study protocol. BMC Pregnancy and Childbirth 2013;13:142. - PMC - PubMed
Simmons D, Van Poppel M, Corcoy R, Devlieger R, Kautzky-Willer A, Damm P, et al. DALI: vitamin D and lifestyle intervention to prevent gestational diabetes: early findings from the DALI pilot study. Diabetic Medicine 2015;32(Suppl 1):176. [CENTRAL: CN-01747204] 10372022 [EMBASE: 71821297]

Kaur 1991 {published data only}

Kaur J, Marya RK, Rathee S, lal H, Singh GP. Effect of pharmacological doses of vitamin D during pregnancy on placental protein status and birth weight. Nutrition Research 1991;11(9):1077-81.

Klar 2020 {published data only}

Klar M, Levi CS, Rozen GS, Solt I. 744: Dietary intervention program for women at risk for preeclampsia. American Journal of Obstetrics and Gynecology 2020;222(1):S470-1. [CENTRAL: CN-02129229] 13932209 [EMBASE: 2004455836]

Li 2000a {published data only}

Li X, Gou W. Study on prevention of pregnancy induced hypertension and effect of platelet intracellular free ca˜(2+) by calcium supplementation [补钙预防妊高征及对血小板细胞内游离钙浓度的影响]. Journal of Xi'an Medical University 2000;21(1):46-8.

Mallet 1986 {published data only}

Mallet E, Gugi B, Brunelle P, Henocq A, Basuyau JP, Lemeur H. Vitamin D supplementation in pregnancy: a controlled trial of two methods. Obstetrics & Gynecology 1986;68:300-4. - PubMed

Marya 1987 {published data only}

Marya RK, Rathee S, Manrow M. Effect of calcium and vitamin D supplementation on toxaemia of pregnancy. Gynecologic and Obstetric Investigation 1987;24(1):38-42. - PubMed

Marya 1988 {published data only}

Marya RK, Rathee S, Dua V, Sangwan K. Effect of vitamin D supplementation during pregnancy on foetal growth. Indian Journal of Medical Research 1988;88:488-92. - PubMed

Mazurkevich 2013 {published data only}

Mazurkevich M, Doronin G, Firsova T. State of placental complex during physiological pregnancy during correction of mineral insufficiency. Journal of Perinatal Medicine 2013;41(Suppl 1):Abstract no: 1213.

Mirghafourvand 2013 {published data only}

Mansouri A, Mirghafourvand M, Charandabi SM, Najafi M. The effect of vitamin D and calcium plus vitamin D on leg cramps in pregnant women: a randomized controlled trial. Journal of Research in Medical Sciences 2017;22(1):24. - PMC - PubMed
Mirghafourvand M, Mohammad-Alizadeh-Charandabi S, Mansouri A, Najafi M, Khodabande F. The effect of vitamin D and calcium plus vitamin D on sleep quality in pregnant women with leg cramps: a controlled randomized clinical trial. Journal of Isfahan Medical School 2015;32(320):2444-53.
Mirghafourvand M. The effect of vitamin D and calcium plus vitamin D for leg cramps in pregnant women: a randomised controlled trial. en.irct.ir/trial/10789 (first received 4 May 2013). - PMC - PubMed
Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Mansouri A, Najafi M, Khodabande F. The effect of vitamin D and calcium plus vitamin D during pregnancy on pregnancy and birth outcomes: a randomized controlled trial. Journal of Caring Science 2015;4(1):35-44. - PMC - PubMed

Naghshineh 2016 {published data only}

Naghshineh E, Sheikhaliyan S. Effect of vitamin D supplementation in the reduce risk of preeclampsia in nulliparous women. Advanced Biomedical Research 2016;5:7. [CENTRAL: CN-02129988] 11534554 [PMID: ] - PMC - PubMed
Naghshineh E, Sheikhaliyan S. Effect of vitamin D supplementation in the reduce risk of preeclampsia in nulliparous women. Advanced Biomedical Research 2016;5:7. - PMC - PubMed

NCT03743922 (first received 2018 Nov 16) {published data only}

NCT03743922. The effects of vitamin D2 supplement during pregnancy [The effects of vitamin D2 supplement during pregnancy on postpartum maternal and fetal vitamin D levels: the randomized controlled trial]. https://clinicaltrials.gov/show/nct03743922 (first received 16 November 2018). [CENTRAL: CN-01918396] 10848151

NCT04591847 (first received 2020 Oct 19) {published data only}

NCT04591847. Pregnancy outcome and vitamin D level among vitamin D supplementation during pregnancy [Pregnancy outcomes and vitamin D level among vitamin D supplementation during pregnancy: a double-blind randomized placebo controlled trial]. https://clinicaltrials.gov/show/NCT04591847 (first received 19 October 2020). [CENTRAL: CN-02182222] 14787863

Persad 2019 {published data only}

Persad MD, Staszewski C, Khan F, Adeyeye A, Day M, Ly V, et al. 143 Does vitamin D prophylaxis prevent adverse neonatal outcomes? American Journal of Obstetrics and Gynecology 2021;224(2):S98. [CENTRAL: CN-02247453] 16928887 [EMBASE: 2010867692]
Persad MD, Staszewski C, Khan F, Adeyeye A, Franz B, Ly V, et al. Does antepartum vitamin D3 supplementation prevent gestational diabetes mellitus? American Journal of Obstetrics and Gynecology 2021;224(2):S152. [CENTRAL: CN-02271217] 17632595 [EMBASE: 2010868187]
Persad MD, Staszewski C, Khan F, Adeyeye AF, Franz B, Ly V, et al. 31 Does vitamin D prophylaxis decrease the incidence of hypertensive disorders of pregnancy? In: American Journal of Obstetrics and Gynecology. Vol. 224. Netherlands: Mosby Inc, 2021:S22-3. [CENTRAL: CN-02247454] 16928888 [EMBASE: 2010867922]
Persad MD, Staszewski CL, Khan F, Chiu F, Perseleni T, Demishev M, et al. 562: Does antepartum vitamin D3 supplementation prevent preterm birth? American Journal of Obstetrics and Gynecology 2019;220(1):S374-5. [CENTRAL: CN-01925583] 10847421 [EMBASE: 2001405292]
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Sabet 2012 {published data only}

IRCT201104306335N1. Effects of monthly consumption of 100000 unit cholecalciferol during last third trimester of pregnancy on plasma iPTH and 25 (OH) D3 of the mother and cord blood [Determination of the effects of monthly consumption of 100000 unit cholecalciferol during third trimester on plasma iPTH and 25 (OH) D3 of the mother and offspring in a group of pregnant Tehranian women and a matched control group]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201104306335N1 (first received 2011). [CENTRAL: CN-01802354] 10702307
Sabet Z, Ghazi AA, Tohidi M, Oladi B. Vitamin D supplementation in pregnant Iranian women: effects on maternal and neonatal vitamin D and parathyroid hormone status. Acta Endocrinologica 2012;8(1):59-66.

Samimi 2016 {published data only}

Samimi M, IRCT201102135444N3. Effects of calcium and vitamin D co-supplementation on pre-eclampsia parameters, metabolic status and biomarkers of oxidative stress in pregnant women at risk for pre-eclampsia. en.search.irct.ir/view/5288 (first received 31 January 2015).
Samimi M, Kashi M, Foroozanfard F, Karamali M, Bahmani F, Asemi Z, et al. The effects of vitamin D plus calcium supplementation on metabolic profiles, biomarkers of inflammation, oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia. Journal of Human Nutrition and Dietetics 2016;29(4):505-16. - PubMed

Samimi 2017 {published data only}

Samimi M, Foroozanfard F, Amini F, Sehat M. Effect of vitamin D supplementation on unexplained recurrent spontaneous abortion: a double-blind randomized controlled trial. Global Journal of Health Science 2017;9(3):95.

Sasan 2017 {published data only}

IRCT2017010131695N1. The effect of vitamin D supplementation in the prevention of recurrence of preeclampsia in pregnant women with a history of preeclampsia. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2017010131695N1 (first received 2017). [CENTRAL: CN-01857837] 10757646
Sasan SB, Zandvakili F, Soufizadeh N, Baybordi E. The effects of vitamin d supplement on prevention of recurrence of preeclampsia in pregnant women with a history of preeclampsia. Obstetrics and Gynecology International 2017;2017:8249264. - PMC - PubMed

Shahgheibi 2016 {published data only}

Shahgheibi S, Farhadifar F, Pouya B. The effect of vitamin D supplementation on gestational diabetes in high-risk women: results from a randomized placebo-controlled trial. Journal of Research in Medical Sciences 2016;21(1):2. - PMC - PubMed

Singh 2015 {published data only}

Singh J, Hariharan C, Bhaumik D. Role of vitamin D in reducing the risk of preterm labour. International Journal of Reproduction, Contraception, Obstetrics and Gynecology 2015;1:86-93.

Sircar 2021 {published data only}

Sircar S. Role of vitamin D supplementation in preventing development of gestational diabetes mellitus. BJOG 2021;128(Suppl 2):90. [CENTRAL: CN-02285021] 18221131 [EMBASE: 635301955]

Taherian 2002 {published data only}

Taherian AA, Taherian A, Shirmani A. Prevention of preeclampsia with low-dose aspirin or calcium supplementation. Archives of Iranian Medicine 2002;5(3):151-6.

Tehrani 2014 {published data only}

IRCT201309277513N4. Comparison of effectiveness of vitamin D supplementation in decreasing the development of the gestational diabetes mellitus in pregnant women. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT201309277513N4 (first received 2012). 6731550
Tehrani HG, Mostajeran F, Banihashemi B. Effect of vitamin d supplementation on the incidence of gestational diabetes. Advanced Biomedical Research 2017;6:79. - PMC - PubMed
Tehrani HG. Comparison of effectiveness of vitamin D supplementation in decreasing the development of the gestational diabetes mellitus in pregnant women. en.irct.ir/trial/7997 (first received 3 January 2014).

Vaziri 2016 {published data only}

IRCT2015040910327N13. Effects of vitamin D supplement during pregnancy on umbilical cord vitamin D, bone mineral density and anthropometric measurements from birth to two months later. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2015040910327N13 (first received 2015). [CENTRAL: CN-01866730] 10766515
Vaziri F, Dabbaghmanesh MH, Samsami A, Nasiri S, Shirazi PT. Vitamin D supplementation during pregnancy on infant anthropometric measurements and bone mass of mother-infant pairs: a randomized placebo clinical trial. Early Human Development 2016;103:61-8. - PubMed
Vaziri F, Nasiri S, Tavana Z, Dabbaghmanesh MH, Sharif F, Jafari P. A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers. BMC Pregnancy and Childbirth 2016;16:239. - PMC - PubMed

References to ongoing studies

Baird 2016 {published data only}isrctn07227232.

Baird J, Barker M, Harvey NC, Lawrence W, Vogel C, Jarman M, et al. Southampton PRegnancy Intervention for the Next Generation (SPRING): protocol for a randomised controlled trial. Trials [Electronic Resource] 2016;17(1):493. - PMC - PubMed
EUCTR2013-002854-66-GB. SPRING â€“ Southampton PRegnancy Intervention for the Next Generation Randomised controlled trial of an intervention to improve diet and body composition of pregnant women and their offspring [Southampton Pregnancy Intervention for the Next Generation - a randomised controlled trial of vitamin D and nurse support in improving the diet and body composition of young women and their children. - SPRING Southampton Pregnancy Intervention for the Next Generation]. Http://www.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2013-002854-66-GB (first received 2013). [CENTRAL: CN-01876453] 10776211

ChiCTR2000032488 (first received 2020) {published data only}

ChiCTR2000032488. A multicenter randomized controlled study of vitamin D supplementation in pregnant women for the prevention of gestational diabetes. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR2000032488 (first received 2020). [CENTRAL: CN-02166077] 14772298

IRCT20190814044529N1 (first received 2020) {published data only}

IRCT20110807007244N3. Effect of vitamin D intake on maternal of delivery on retinopathy of prematurity in infants. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20110807007244N3 2020. [CENTRAL: CN-02169978] 14775939
IRCT20110807007244N4. The effect of vitamin D intake of mother in labor on the prognosis of premature children [The effect of vitamin D intake in mothers with preterm labor on prognosis of children at two years of age]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20110807007244N4 (first received 2020). [CENTRAL: CN-02169979] 14775940
IRCT20110807007244N5. The effect of vitamin D administration during labor on the incidence of transient rapid breathing of the newborn [The effect of vitamin D administration during labor on the incidence of transient tachypnea of the newborn]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20110807007244N5 (first received 2020). [CENTRAL: CN-02238090] 16904939
IRCT20110807007244N7. The effect of vitamin D intake in the mother during childbirth on the incidence of respiratory problems in infants. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20110807007244N7 (first received 2021). [CENTRAL: CN-02238088] 16904937
IRCT20190814044529N1. Effect of vitamin D on neonatal respiratory distress [Comparison of the incidence of respiratory distress syndrome in neonates of mothers receiving vitamin D with those who do not receive]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20190814044529N1 (first received 2020). [CENTRAL: CN-02170909] 14776834

ISRCTN46539495 (first received 2020) {published data only}

ISRCTN46539495. Prevention of pre-eclampsia through vitamin D supplementation: a single-blinded randomized clinical trial without placebo [Pre-eclampsia in Kivu: vitamin D levels and impacts of vitamin D supplementation on obstetric-neonatal outcomes in primigravida]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN46539495 (first received 2020). [CENTRAL: CN-02237407] 16904256

ISRCTN87262826 (first received 2022) {published data only}

ISRCTN87262826. Differences between sun exposure and vitamin D supplementation on blood pressure of pregnant women and size of newborn babies [Differences in the effect of sun exposure and vitamin D supplementation on blood pressure of pregnant women and anthropometric status of newborn babies]. https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN87262826 (first received 2022). [CENTRAL: CN-02378876] 20427680

NCT05208827 (first received 2022) {published data only}

NCT05208827. Vitamin D supplementation for the prevention of GDM [A multicenter randomized controlled study of vitamin D supplementation in pregnant women for the prevention of gestational diabetes]. https://clinicaltrials.gov/show/NCT05208827 (first received 2022). [CENTRAL: CN-02361713] 19872527

NCT05329428 (first received 2022) {published data only}

NCT05329428. PREDIN: pregnancy and vitamin D intervention study [PREDIN: pregnancy and vitamin D intervention study - a randomized controlled trial]. https://clinicaltrials.gov/show/NCT05329428 (first received 2022). [CENTRAL: CN-02392571] 20682618

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Open access
Published: 08 August 2024

Cerebral venous thrombosis at high altitude: more severe symptoms and specific predisposing factors than plain areas

Yuhui Sha 1 na1 ,
Junyi Zhang 1 na1 ,
Yang Ci 2 ,
Cidan zhuoga 2 ,
Yuhua Zhao 2 ,
Lixin Zhou 1 &

Thrombosis Journal volume 22 , Article number: 73 ( 2024 ) Cite this article

Metrics details

Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas.

We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People’s Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups.

A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*10 12 /L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively.

Conclusions

The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

Cerebral venous thrombosis (CVT) is an unusual but important component of cerebral vascular diseases, caused by thrombus in the dural venous sinuses or the cerebral veins [ 1 ]. The young and females are predominantly affected populations [ 1 ]. Other predisposing factors include oral contraception and pregnancy/puerperium, antiphospholipid syndrome, infections, dehydration, vaccine-induced thrombotic thrombocytopenia, genetic thrombophilia, and mechanical provoking factors [ 2 ]. The diagnosis of CVT is majorly based on conventional imaging techniques including computed tomography (CT) and magnetic resonance imaging (MRI), along with magnetic resonance venography (MRV) [ 3 ]. Gradient-recalled echo (GRE), susceptibility-weighted imaging (SWI) sequences, or contrast-enhanced MRV are also essential for the diagnosis [ 4 ], which challenges undeveloped areas with poor medical conditions.

The Qinghai-Tibet Plateau is the highest plateau in the world with an average altitude of over 4000 m. Its unique natural environment and its impact on human health are receiving increasing attention from the medical community. High altitude (HA) exposure comes with diverse environmental problems including hypoxia, low temperature, dehydration, and low atmospheric pressure [ 5 , 6 ], which may alter the hemodynamics and hemostasis states and further cause hypercoagulability [ 7 , 8 ]. People exposed to plateau areas are predisposed to have thromboembolic events such as deep vein thrombosis and pulmonary embolism [ 9 ], and one study demonstrated that long-term stay at high (> 3000 m) and extreme altitudes (> 5000 m) was associated with a 30 times higher risk of thromboembolic events [ 10 ].

Although CVT is relatively rare, it has been gradually identified as a severe complication of high-altitude exposure and might be related to volume depletion and ploycythaemia [ 11 ]. Our previous single-center retrospective study found that CVT patients in Tibet had various risk factors, of which recent infection was the most significant, indicating that altitude can also trigger CVT in individuals who are susceptible to hereditary and acquired thrombophilia [ 12 ]. However, the effect of HA on cerebral venous thrombosis and its mechanism remains ambiguous.

The aim of the present study is to explore the differences in the clinical, risk factors, and prognostic characteristics of cerebral venous thrombosis (CVT) patients from different altitudes, and further determine the role of high-altitude exposure in exacerbating predisposition towards CVT.

Study design and participants

We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People’s Hospital (altitude 3650 m) and Peking Union Medical College Hospital (PUMCH) (altitude 43.5 m) between January 2015 and December 2023. Tibet Autonomous Region People’s Hospital is the largest territory hospital in the Xizang plateau area and has received most CVT patients from Lhasa and other regions. PUMCH is a Class A tertiary comprehensive hospital reputed for its outstanding medical care, treating patients from all over China. The cases of CVT were reviewed and recruited in this study by thoroughly screening the electronic medical records in the hospital database via ICD-10 codes of I67.652, G08.X07 and G08.X09 for discharge diagnosis. Patients were required to be ≥ 18 years old. Patients from the plateau and the plain were considered two independent groups in this study. Demographic data and clinical, radiological, and laboratory findings were reviewed for each patient. The diagnosis of CVT was verified by two experienced physicians based on MRI or CT with MRV following established diagnostic criteria. A total of 48 patients with CVT from Tibet and 121 patients from PUMCH who met the diagnostic criteria of CVT were ultimately included in this study. Some cases from Tibet have been previously published in 2023 [ 12 ]. This retrospective study was approved by the ethical review board of Tibet Autonomous Region People’s Hospital and PUMCH.

Baseline clinical data

Demographic data, clinical manifestations, risk factors, radiological and laboratory characteristics of CVT were collected in all patients. Demographic data included age, gender, ethnicity and body mass index (BMI). Clinical manifestations included the type of onset (acute < 2 days, subacute 2–30 days, or chronic > 30 days), and symptoms of CVT (headache, hemiplegia, seizure and altered consciousness). Risk factors of CVT in this study included history of deep vein thrombosis (DVT), family history of CVT, malignant tumor, hematological disorders, kidney diseases, autoimmune diseases, infection in the past 4 weeks, cerebral trauma in the past 4 weeks, intracranial hypotension in the past 4 weeks, taking oral contraceptive in recent days, and pregnancy or puerperium.

The “infection in the past 4 weeks” included two main types: (1) systemic infections including pneumonia, upper respiratory tract infection, septic shock, acute gastroenteritis, and reproductive tract infections. (2) infections of central nervous system (CNS) and neighboring tissues including viral meningitis, tuberculous meningitis, hypertrophic cranial pachymeningitis caused by infection, acute mastoiditis, and acute sinusitis or paranasal sinusitis.

The “autoimmune diseases” included: Behcet’s disease, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), granulomatosis with polyangiitis, sicca syndrome, IgG4-related disease, psoriasis and other connective tissue diseases.

The “hematological disorders” included: iron deficiency anemia, idiopathic thrombocytopenic purpura, hereditary thrombophilia, acute leukemia, paroxysmal nocturnal hemoglobinuria, essential thrombocythemia, POEMS syndromes, myelodysplastic syndrome, aplastic anemia, autoimmune hemolytic anemia, hemolytic uremic syndrome, and eosinophilia.

The “kidney diseases” included: nephrotic syndrome, chronic renal insufficiency, and nephritis of Schonlein-Henoch purpura.

Imaging and laboratory data

All patients underwent brain imaging (CT scan and MRI) and were reviewed by two experienced physicians. Radiological factors of CVT were collected including: (1) venous infarction and hemorrhage on brain MRI or CT; (2) involvement of venous sinus on MRI and MRV (superior sagittal sinus, transverse/sigmoid sinus, cerebral deep venous system, cortical veins and dural arteriovenous fistulas).

Laboratory examinations included coagulopathy panels (antiphospholipid antibodies, protein C (P-C), protein S (P-S), antithrombin III (anti-III)), levels of D-Dimer (0-0.55 mg/L FEU), fibrinogen (Fbg) (1.8–3.5 g/L), hemoglobin (HGB) (120–160 g/L), white blood cells (WBC) (4–10*10 9 /L) and highly sensitive C reactive protein (hsCRP) (0-8 mg/L).

The data of anticoagulant therapy for CVT including low-molecular-weight heparin (LMWH), heparin, warfarin, and direct oral anticoagulants (DOACs) was collected.

We conducted a unified telephone or face-to-face interview retrospectively for all patients with CVT from high altitude and plain areas in January 2024. Follow-up data was modified Rankin Scale (mRS).

The outcome data recorded at discharge and during follow-up were disability and death based on mRS. The outcome was defined as favorable (mRS 0–2) and unfavorable (mRS 3–6) both at discharge and during follow-up.

Statistical analysis

The continuous variables were described as median (interquartile range, IQR) given the skewed distribution. The categorical variables were expressed as proportions. Chi-square test was used for categorical variables. We used the Mann–Whitney U-test for continuous variables. All tests were two-tailed, and statistical significance was determined at an alpha level of 0.05. Statistical analyses were performed using SPSS (v 28.0).

A total of 169 patients with CVT were included in this study, with 48 patients from plateau and 121 patients from plain. The baseline characteristics of the cohort were summarized in Table 1 . The median age was 27 (IQR: 23.0-55.8) years old of highlanders, with 16 (33.3%) male patients, and 33 (68.8%) of them were Tibetan. The median altitude of the patients’ residence is 3800 (IQR: 3657–4085) meters. The median age was 34 (IQR: 26.0-46.5) years old of lowlanders, with 55 (45.5%) male patients, and 110 (90.0%) of them were Han. The median BMI of highland people was 23.0 (IQR: 20.0-27.3) kg/m 2 , while the median BMI of lowland people was 22.5 (IQR: 20.7–26.0) kg/m 2 . There was no significant difference in age, gender and BMI between CVT patients at different altitudes.

Clinical characteristics and risk factors

Table 1 showed clinical manifestations and risk factors of patients with CVT from plateau and plain. CVT patients from plateau were more likely to present acute or subacute onset (77.1% vs. 51.2%, P = 0.002). Headache (91.7% vs. 71.1%, P = 0.004) and altered consciousness (31.3% vs. 16.5%, P = 0.033) were more common in patients from plateau than those from plain, and headache was the most frequent symptom in both groups. There was no significant difference in hemiplegia and seizure between the two groups.

Among the risk factors for CVT, autoimmune diseases were more frequently detected in CVT patients in the plain than those in the plateau (39.7% vs. 2.1%, P < 0.001), while pregnancy or puerperium was more common in patients from plateau (25% vs. 5.8%, P < 0.001). There was no significant difference in the proportion of recent infections, hematological disorders, kidney diseases, malignant tumor, history of deep vein thrombosis, family history of CVT and taking oral contraceptive between patients from plateau and plain. Three patients had intracranial hypotension in the past 4 weeks, two from plain and one from plateau, two of them were caused by epidural anesthesia for painless labor.

Diagnostic findings and treatment

Table 2 showed diagnostic findings, treatment and outcome at discharge of CVT patients from plateau and plain. The imaging characteristics of CVT at different altitudes were different, with a higher incidence of hemorrhage (41.7% vs. 19.0%, P = 0.002) and venous infarction (50.0% vs. 25.6%, P = 0.002) for patients at plateau. The involvement of lateral sinus was both the most common in patients from plateau and plain (70.8% vs.73.6%, P = 0.72), followed by superior sagittal sinus (54.2% vs. 46.3%, P = 0.355), cerebral deep venous system (16.7% vs. 22.3%, P = 0.414) and cortical veins. There was no significant difference in the involved sinus or veins between the two groups other than cortical veins, which accounted for 14.0% in CVT patients from plain but only 2.1% in those from plateau ( P = 0.023). In addition, we also found that dural arteriovenous fistulas co-existed in 5 (4.1%) CVT patients from plain.

There was no significant difference in abnormal antiphospholipid antibodies or decreased P-C, P-S or anti-III between the two groups, although the frequency of patients receiving tested was far lower in patients from plateau. The average levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), Fbg (3.7 vs. 3.0 g/L, P < 0.001) and HGB (157 vs. 129 g/L, P = 0.01) were significantly higher in patients from plateau than plain. Besides, the amount of WBC (9.6 vs. 7.5*10 12 /L, P < 0.001) and the levels of hsCRP (20.2 vs. 3.2 mg/L, P = 0.005) were greatly higher in highland patients.

The percentage of patients receiving anticoagulant therapy for CVT was lower in plateau than that in plain (70.8% vs. 93.4%, P < 0.001). Favorable outcome at discharge was observed in 81.3% of highland patients and 88.4% of patients at plain ( P = 0.22). All three plateau patients who died in hospital had recent infections, and two patients from plain underwent in-hospital death because of severe pneumonia and cerebral hernia respectively.

Outcome at follow-up

Table 3 showed the outcome at follow-up of CVT patients from plateau and plain. Two patients from plateau and one from plain were lost to follow-up. Favorable outcome at follow-up was observed in 81.4% of patients in plateau and 90.7% of those in plain with no significant difference between the two groups ( P = 0.106), with a median follow-up time of 330 days and 703 days respectively. One patient in plateau and four in plain died during the follow-up.

To our knowledge, this was the first study to enroll the largest sample of CVT patients at HA and revealed the characteristic distinctions between plateau and plain regions as well. The more severe clinical and imaging manifestations along with prominent inflammation and hypercoagulable state were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at HA. Pregnancy or puerperium were more common in patients at HA. The overall prognosis of CVT patients from both groups were favorable.

In our study, no significant difference was found in the demographic characteristics of CVT between highlands and plains, with female patients and young patients being more common, which was consistent with other studies [ 13 ]. Headache was the most frequent symptom in both groups, in accordance with previous studies [ 1 , 14 ]. Patients at HA majorly presented as acute or subacute onset and altered consciousness was more common. In addition, the imaging of CVT patients at HA showed a remarkably higher incidence of bleeding and venous infarction. The results suggested that the overall symptoms and radiological manifestations were more severe in high-altitude patients. One possible explanation is that exposure to high-altitude environments may lead to a higher substantial thrombus burden for CVT, which needs to be confirmed in future clinical and imaging studies. Another reason is that the diagnosis of CVT might be more difficult at HA, as some specific neurological disorders arising at HA can mimic CVT, including acute mountain sickness and high-altitude cerebral edema. Patients with mild clinical symptoms, such as isolated headache, might be misdiagnosed because brain imaging is not routinely performed. We also found that cortical veins were less frequently involved in HA areas. Since the identification of cortical vein thrombosis requires experienced physicians and largely relies on SWI or GRE sequences [ 15 , 16 ], we suspect that inadequate imaging diagnostic workup and lack of experience may lead to some missed diagnosis of cortical vein thrombosis in high-altitude patients.

HA exposure is an important risk factor for venous thromboembolism, including deep venous thrombosis, pulmonary thromboembolism, CVT etc. [ 11 , 17 ]. Although the mechanism of HA on venous thromboembolism remains unclear, so far, it is believed that multiple physiological alterations induced by hypobaric hypoxia such as vascular endothelial damage, polycythemia, inflammation and hypercoagulable states, are associated with an increased probability of thrombosis [ 11 ]. In our study, coagulation markers including D-Dimer and Fbg as well as HGB were significantly higher in patients at HA compared with those at plains, further confirming the presence of more severe hypercoagulable state in CVT patients at HA, similar to previous studies [ 8 ]. One recent study has found that harmful environmental factors in high-altitude areas can upregulate transferrin, leading to hypercoagulable states and thromboembolic events, which suggests that targeting the transferrin pathway is a potentially powerful strategy against thromboembolic events at HA [ 7 ]. More studies are required in the future to clarify the mechanism of hypercoagulation related to HA and provide promising strategies for the treatment of thromboembolic disorders at HA.

In addition to high-altitude exposure, other established risk factors of CVT should be systematically studied, including genetic or acquired prothrombotic conditions, infections, malignancy, oral contraceptives, and pregnancy, to better understand the etiology of CVT at HA and provide more effective prevention. We have found various risk factors of CVT at HA, including infection, hematological disorders, pregnancy or postpartum, etc. The spectrum of risk factors is quite different from that at plain. Among the major findings in this study, the notable one was that patients with CVT at HA exhibited a significantly higher inflammatory state, reflected by higher levels of leukocytes and hsCPR in blood test. Recently increasing evidence supports the important role of inflammation in the occurrence and development of CVT. Several studies have reported that leukocytes, proinflammatory cytokines, and adherence molecules had significant effect on the CVT-related inflammatory process [ 18 ]. Several identified risk factors of CVT, such as infection and systematic autoimmune diseases, are linked with inflammatory condition, also indicating that inflammation is involved in cerebral venous thrombogenesis. Although about one-third of CVT patients at HA are complicated with recent infections, there is no significant difference in the proportion of infections compared to patients at plains. In addition, the prevalence of autoimmune diseases in CVT patients at plateau is significantly lower than that in plain areas, although the prevalence might be underestimated considering incomplete etiological workup. The above results seem insufficient to explain the high inflammatory status in high-altitude areas. Therefore, we speculate that the inflammation induced by exposure to the high-altitude environment itself is probably involved in the pathogenesis of high-altitude CVT. Although the mechanism of high inflammatory state in CVT at HA has not yet been clear, we believe that detecting potential infections and autoimmune diseases through a standardized etiological diagnosis workup and implementing effective treatment are essential strategies to improve the prognosis of CVT at HA. Further exploration of the effectiveness and safety of anti-inflammatory therapy is also needed.

Previous studies have rarely focused on the clinical characteristics and risk factors of female patients with CVT in high-altitude areas, mainly because most studies included soldiers and mountaineers at high altitudes, with almost all of them being males. In our study, the rate of pregnant or postpartum patients was notably higher in plateau (25%) than in plain areas (5.8%), also higher than that reported in ASCVT (17%) [ 14 ]. Pregnancy may induce alterations in the coagulation state and elevate the risk of CVT [ 19 ]. Exposure to highland climate may aggravate the hypercoagulable state and increase the susceptibility to CVT in pregnant and postpartum women [ 11 ]. Therefore, early detection and management of high-risk pregnant and postpartum women in plateau areas are quite important.

With the improvement of medical conditions, the treatment of CVT has been improving gradually, especially in high-altitude regions, however, the proportion of anticoagulation therapy was significant lower in plateau areas in our study. Further investigation is needed to develop targeted treatment and prevention strategies in CVT at HA. Meantime, follow-up should be strengthened to improve adherence with anticoagulant drug usage in patients at HA. Overall, the outcomes at discharge and at follow-up were favorable in both groups, indicating that the prognosis of CVT is generally benign, even in patients at HA with more severe clinical and imaging manifestations. This favorable prognosis is likely due to a good response to timely anticoagulant and other comprehensive therapies. Future prospective cohort studies are needed to provide more reliable evidence regarding the prognosis of CVT at HA.

Limitations

However, there are several limitations in this study. As an observational and retrospective study, the sample is not large enough to completely represent plateau and plain areas and some selection bias may exist. Some laboratory tests were incomplete in plateau patients due to poor medical conditions. We did not differentiate travelers and long-term residents in plateau concerning the small sample. We conducted retrospective follow-up in January 2024. However, the time of patient inclusion spanned from 2015 to 2023, leading to the variation of follow-up periods as well as the difference of that between the two groups, which could potentially impact the prognosis assessment. In the future, a large sample prospective cohort study is required to further investigate the impact of HA on CVT and its mechanisms.

CVT is more common in young women patients in both plateau and plain areas. The clinical and imaging manifestations are more severe in patients exposed to HA. The risk factors for CVT in plateau areas are different from those in plain areas, with a significant increase in the proportion of pregnant or postpartum patients, indicating the need to strengthen the management of high-risk pregnant women in plateau areas. The inflammatory and hypercoagulable state might remarkably affect the severity and prognosis of CVT patients at HA. Although the proportion of anticoagulant therapy in patients with high-altitude CVT is lower, the prognosis of CVT remains favorable, similar to that at sea level. Apart from anticoagulant therapy, treatment and prevention for all causes of hypercoagulability such as inflammation are likely to be treatment strategies and directions for CVT at HA. This study shows that CVT in HA areas has unique clinical, imaging, and risk factor characteristics, and lacks targeted standardized diagnosis and treatment strategies. Therefore, more relevant research is needed in the future.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

The authors would like to express our gratitude to all patients for participating in the project and to all the staff for the time and effort they devoted.

This study was supported by grants from National High Level Hospital Clinical Research Funding (2022-PUMCH-A-257) and the Natural Science Foundation of Xizang Autonomous Region (XZ2022ZR-ZY14(Z)).

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Yuhui Sha and Junyi Zhang contributed equally to this work.

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Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Dongdan, Dongcheng District, Beijing, 100730, China

Yuhui Sha, Junyi Zhang, Lixin Zhou & Jun Ni

Department of Neurology, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, China

Yang Ci, Cidan zhuoga & Yuhua Zhao

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JN, LZ contributed to study concept and design. YC, YS, JZ, Ci, YZ made contributions to data collection and analysis. YS and JZ contributed to manuscript drafting. Critical revision of the manuscript for intellectual content was completed by JN and LZ.

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Correspondence to Lixin Zhou or Jun Ni .

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Sha, Y., Zhang, J., Ci, Y. et al. Cerebral venous thrombosis at high altitude: more severe symptoms and specific predisposing factors than plain areas. Thrombosis J 22 , 73 (2024). https://doi.org/10.1186/s12959-024-00643-2

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Walz, Throwing Punches at Republicans, Makes His Big Entrance With Harris

As the vice president introduced her new running mate at an energetic rally in Philadelphia, he quickly demonstrated his ability to deliver searing attacks against Donald Trump and JD Vance.

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Harris and Walz Hold First Campaign Rally Together

Vice president kamala harris and her newly announced running mate, gov. tim walz of minnesota, went on the attack against the trump-vance republican ticket during a raucous rally in philadelphia..

“To his former high school students, he was Mr. Walz. And to his former high school football players, he was Coach. And in 91 days, the nation will know Coach Walz by another name: Vice President of the United States.” “Thank you, Madam Vice President, for the trust you put in me, but maybe more so, thank you for bringing back the joy. Now, Donald Trump sees the world a little differently than us. First of all, he doesn’t know the first thing about service. He doesn’t have time for it because he’s too busy serving himself. Like all regular people I grew up with in the heartland, JD [Vance] studied at Yale, had his career funded by Silicon Valley billionaires, and then wrote a best seller trashing that community. Come on. That’s not what middle America is. And I got to tell you, I can’t wait to debate the guy.”

By Reid J. Epstein Erica L. Green and Katie Glueck

Reid J. Epstein and Erica L. Green reported from Philadelphia, and Katie Glueck from New York.

Aug. 6, 2024

America’s introduction to Gov. Tim Walz of Minnesota began with a half-hour of cheering for Vice President Kamala Harris and ended with some of the sharpest attacks Democrats have leveled against former President Donald J. Trump and his running mate, Senator JD Vance of Ohio.

Before a raucous crowd in Philadelphia, Ms. Harris and Mr. Walz presented the Minnesotan as a folksy former schoolteacher and football coach who had inspired his students, served in the military and improved his constituents’ lives.

But it was his ability to deliver searing yet accessible attacks against their Republican opponents that won Mr. Walz a place on the national ticket, and during his first rally, he did not miss his marks.

“Donald Trump sees the world a little differently than us,” he said. “First of all, he doesn’t know the first thing about service. He doesn’t have time for it because he’s too busy serving himself.”

Then came the dagger. “Violent crime was up under Donald Trump,” he said, before pausing for effect. “That’s not even counting the crimes he committed.”

The Harris campaign’s presentation of Mr. Walz brought an end to its two-week sprint to find a running mate, a process that typically takes months and involves a series of public tryouts. Instead, Ms. Harris’s search for a partner took place largely behind closed doors.

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IMAGES

Cephalic presentation of baby in pregnancy
Cephalic Presentation of Baby During Pregnancy
presentation breech in pregnancy
Fetal Presentations Medical Illustration Medivisuals
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Fetal Presentation, Position, and Lie (Including Breech Presentation)

Position and Presentation of the Fetus

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