neonatal case presentation slideshare

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Original Author(s): Dr Phil Jordan and Dr Umberto Piaggio Last updated: 16th February 2021 Revisions: 19

• 1 Introduction
• 2.1 Physiological jaundice
• 2.2 Pathological jaundice
• 3 Risk factors and history
• 4 Clinical Presentation
• 5.1 Bilirubin
• 5.2 Further investigations
• 5.3 As needed
• 6.1 Phototherapy
• 6.2 Fluid intake
• 6.3 Exchange Transfusion
• 6.4 IV Immunglobulin
• 7 Complications
• 8 Prognosis
• 9 References

Introduction

Jaundice is t he yellow colouring of skin and sclera caused by the accumulation of bilirubin in the skin and mucous membranes.

Neonatal jaundice  occurs in 60% of term infants and 80% of preterm infants [1] and is caused by hyperbilirubinaemia that is unconjugated (divided into physiological or pathological) or conjugated (always pathological).  High levels of unconjugated bilirubin have acute harmful effects as well as long term damage if left untreated, such as kernicterus .

10% of breast fed babies are jaundiced at 1 month.

Types of Jaundice

Physiological jaundice.

Jaundice in a healthy baby, born at term, is normal and may result from:

• Increased red blood cell breakdown: in utero the fetus has a high concentration of Hb (to maximise oxygen exchange and delivery to the fetus) that breaks down releasing bilirubin as high Hb is no longer needed
• Immature liver not able to process high bilirubin concentrations

Starts at day 2-3, peaks day 5 and usually resolved by day 10.   The baby remains well and does not require any intervention beyond routine neonatal care.

Physiological jaundice can progress to pathological jaundice if the baby is premature or there is increased red cell breakdown e.g. Extensive bruising or cephalohaematoma following instrumental delivery.

Pathological jaundice

Jaundice which requires treatment or further investigation.

• Onset less than 24 hours
• ?previous siblings treated for jaundice/family history/maternal rhesus status
• Maternal blood group (type O most likely to produce enough IgG antibodies to cause haemolysis)
• Requires investigation and treatment
• Onset after 24 hours
• likely dehydrated ?breast fed baby establishing feeding
• increased haemolysis due to bruising/cephalohaematoma
• Unwell neonate: jaundice as a sign of congenital or post-natal infection
• Metabolic: Hypothyroid/pituitarism, galactosaemia
• Breast milk jaundice: well baby, resolves between 1.5-4 months
• GI: biliary atresia, choledhocal cyst

Risk factors and history

Risk factors for pathological hyperbilirubinaemia: to be asked in history

• Prematurity, low birth weight, small for dates
• Previous sibling required phototherapy
• Exclusively breast fed
• Jaundice <24 hours
• Infant of diabetic mother

Clinical Presentation

• Colour: All babies should be checked for jaundice with the naked eye in bright, natural light (if possible). Examine the sclera, gums and blanche the skin. Do not rely on your visual inspection to estimate bilirubin levels, only to determine the presence or absence of jaundice.
• Drowsy: difficult to rouse, not waking for feeds, very short feeds
• Neurologically: altered muscle tone, seizures-needs immediate attention
• Other: signs of infection , poor urine output, abdominal mass/organomegaly, stool remains black/not changing colour

Investigations

• Transcutaneous bilirubinometer (TCB) can be used in >35/40 gestation and >24 hours old for first measurement. TCB can be used for all subsequent measurements, providing the level remains <250 µmol/L and the child has not required treatment
• Serum bilirubin to be measured if <35/40 gestation, <24 hours old or TCB >250 µmol/L
• Infants that are not jaundice to the naked eye do not need routine bilirubin checking.  
• Total and Conjugated Bilirubin is important if suspected; liver or biliary disorder, metabolic disorder, congenital infection or prolonged jaundice. Do not subtract conjugated from total to make management decisions for hyperbilirubinaemia.

Further investigations

• Serum bilirubin for all subsequent levels
• Blood group (Mother and Baby) and DCT
• FBC for haemoglobin and haematocrit
• U&Es if excessive weight loss/dehydrated
• Infection screen if unwell or <24 hours including Microbiological cultures if infection suspected: blood, urine, CSF. Consider TORCH screen.
• Glucose-6-phosphate dehydrogenase especially if Mediterranean or African origin
• LFTs if suspected hepatobiliary disorder

Phototherapy

Figure 1 – NICE treatment threshold graph [3]

• Above: If level is on or above the phototherapy line for their gestation and age (in days) phototherapy should be initiated and bilirubin monitored
• >50µmol/L below, clinically well with no risk factors for neonatal jaundice do not routinely repeat level
• <50µmol/L below, clinically well repeat level within 18 hours (risk factors present) to 24 hours (no risk factors present)
• Repeat bilirubin 4-6 hours post initiation to ensure not still rising, 6-12 hourly once level is stable or reducing.
• NB. Maximum skin coverage, eye protection for babies, breaks for breastfeeding/nappy changes/cuddles to be coordinated to maximise phototherapy
• Stop phototherapy once level >50µmol/L below treatment line on the threshold graphs
• Check for rebound of hyperbilirubinaemia 12-18 hours after stopping phototherapy

Fluid intake

Do not give additional fluids with phototherapy unless indicated and if possible expressed maternal milk is preferred. If phototherapy intensified or feeding poorly consider NGT feeding or IV fluids.

Give consideration to underlying cause i.e. infection, biliary obstruction

Exchange Transfusion

This is the simultaneous exchange of the baby’s blood (hyperbilirubinaemic) with donated blood or plasma (normal levels of bilirubin) to prevent further bilirubin increase and decrease circulating levels of bilirubin.

Performed via umbilical artery or vein and is indicated when there are clinical features and signs of acute bilirubin encephalopathy or the level/rate of rise (>8.5µmol/L/hour) of bilirubin indicates necessity based on threshold graphs. This will require admission to an intensive care bed.

IV Immunglobulin

IVIG can be used as adjunct to intensified phototherapy in rhesus haemolytic disease or ABO haemolytic disease.

Complications

Kernicterus , billirubin-induced brain dysfunction, can result from neonatal jaundice. Bilirubin is neurotoxic and at high levels can accumulate in the CNS gray matter causing irreversible neurological damage . Depending on level of exposure, effects can range from clinically undetectable damage to severe brain damage.

Depends on underlying cause but if correctly and promptly treated prognosis is excellent.

Always refer to local trust guidelines.

1st Author: Dr Phil Jordan

Senior Reviewer: Dr Umberto Piaggio

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Respiratory distress in the neonate: Case definition & guidelines for data collection, analysis, and presentation of maternal immunization safety data

Leigh r. sweet.

a St. Mary’s Regional Medical Center, United States

Cheryl Keech

b Pharmaceutical Product Development, United States

Nicola P. Klein

c Kaiser Permanente Vaccine Study Center, United States

Helen S. Marshall

d Women’s and Children’s Health Network and Robinson Research Institute and School of Medicine, University of Adelaide, South Australia, Australia

Beckie N. Tagbo

e Institute of Child Health & Department of Paediatrics, University of Nigeria Teaching Hospital, Nigeria

David Quine

f Simpson’s Centre for Reproductive Health, Royal Infirmary Edinburgh, Scotland, United Kingdom

Pawandeep Kaur

g Clinical Development Services Agency, India

Ilia Tikhonov

h Sanofi Pasteur, United States

Muhammad Imran Nisar

i Aga Khan University, Pakistan

Sonali Kochhar

j Global Healthcare Consulting, India

l Erasmus University Medical Center, Rotterdam, The Netherlands

Flor M. Muñoz

k Baylor College of Medicine, United States

Associated Data

1. preamble, 1.1. need for developing case definitions and guidelines for data collection, analysis, and presentation for respiratory distress in the neonate as an adverse event following maternal immunization.

Definition of respiratory distress in the neonate

Every year, an estimated 2.9 million babies die in the neonatal period (the first 28 days of life), accounting for more than half of the under-five child deaths in most regions of the world, and 44% globally [1] . The majority (∼75%) of these deaths occur in the first week of life, with the highest risk of mortality concentrated in the first day of life [2] . Ninety-nine percent of neonatal deaths occur in low- and middle-income countries; south-central Asian countries experience the highest absolute numbers of neonatal deaths, while countries in sub-Saharan Africa generally have the highest rates of neonatal mortality [2] .

Respiratory distress is one of the most common problems neonates encounter within the first few days of life [3] . According to the American Academy of Pediatrics, approximately 10% of neonates need some assistance to begin breathing at birth, with up to 1% requiring extensive resuscitation [4] . Other reports confirm that respiratory distress is common in neonates and occurs in approximately 7% of babies during the neonatal period [3] , [5] . Respiratory disorders are the leading cause of early neonatal mortality (0–7 days of age) [6] , as well as the leading cause of morbidity in newborns [7] , and are the most frequent cause of admission to the special care nursery for both term and preterm infants [8] . In fact, neonates with respiratory distress are 2–4 times more likely to die than neonates without respiratory distress [9] .

Respiratory distress describes a symptom complex representing a heterogeneous group of illnesses [3] . As such, respiratory distress is often defined as a clinical picture based on observed signs and symptoms irrespective of etiology [7] , [10] . Clinical symptoms most commonly cited as indicators of respiratory distress include tachypnea [3] , [7] , [8] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , nasal flaring [3] , [7] , [8] , [10] , [11] , [12] , [13] , [14] , [15] , [17] , grunting [3] , [7] , [8] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , retractions [3] , [7] , [8] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] (subcostal, intercostal, supracostal, jugular), and cyanosis [3] , [7] , [8] , [10] , [11] , [13] , [17] . Other symptoms include apnea [3] , [8] , bradypnea [8] , irregular (seesaw) breathing [8] , inspiratory stridor [3] , [16] , wheeze [16] and hypoxia [8] , [14] .

Tachypnea in the newborn is defined as a respiratory rate of more than 60 breaths per minute [12] , [15] , bradypnea is a respiratory rate of less than 30 breaths per minute, while apnea is a cessation of breath for at least 20 s [18] . Apnea may also be defined as cessation of breath for less than 20 s in the presence of bradycardia or cyanosis [18] . Nasal flaring is a compensatory symptom that is caused by contraction of alae nasi muscles, increases upper airway diameter and reduces resistance and work of breathing [8] , [12] , [15] . Stridor is a high-pitched, musical, monophonic inspiratory breath sound that indicates obstruction at the larynx, glottis, or subglottic area [15] . Wheezing is a high-pitched, whistling, expiratory, polyphonic sound that indicates tracheobronchial obstruction [15] . Grunting is an expiratory sound caused by sudden closure of the glottis during expiration in an attempt to increase airway pressure and lung volume, and to prevent alveolar atelectasis [8] , [12] , [15] . Retractions occur when lung compliance is poor or airway resistance is high, result from negative intrapleural pressure generated by contraction of the diaphragm and accessory chest wall muscles, and are clinically evident by the use of accessory muscles in the neck, rib cage, sternum, or abdomen [8] , [15] . Finally, cyanosis is assessed by examining the oral mucosa for blue or gray discoloration and suggests inadequate gas exchange, while hypoxemia is signified by an oxygen saturation of less than 90% after 15 min of life [8] .

Pathophysiology of respiratory distress in the neonate

Most causes of respiratory distress result from an inability or delayed ability of a neonate’s lungs to adapt to their new environment [14] . In utero, the lungs are fluid filled, receive less than 10–15% of the total cardiac output, and oxygenation occurs through the placenta [8] , [19] , [20] , [21] . For the neonate to transition, effective gas exchange must be established [8] , [22] , alveolar spaces must be cleared of fluid and ventilated [20] , [21] , and pulmonary blood flow must increase to match ventilation and perfusion [14] , [23] . A small proportion of alveolar fluid is cleared by Starling forces and vaginal squeeze [14] , [23] , however the overall process is complex, and entails rapid removal of fluid by ion transport across the airway and pulmonary epithelium [8] , [20] , [23] . Peak expression of these ion channels in the alveolar epithelium is achieved at term gestation, leaving preterm infants with a reduced ability to clear lung fluid after birth [14] . If ventilation or perfusion is inadequate, the neonate develops respiratory distress [14] , [23] .

In utero, high pulmonary vascular resistance directs blood from the right side of the heart through the ductus arteriosus into the aorta [8] . When the umbilical vessels are clamped at birth the low-resistance placental circuit is removed, systemic blood pressure is increased, and the pulmonary vasculature relaxes [8] , [20] . Expansion of the lungs and increase in PaO2 results in increased pulmonary blood flow and constriction of the ductus arteriosus [8] , [21] . Cardiopulmonary transition is completed after approximately 6 h [8] . The neonate’s respiratory pattern may initially be irregular, but soon becomes rhythmic at a rate of 40–60 breaths per minute [8] . A neonate’s first breaths tend to be deeper and longer than subsequent breaths [19] , they are characterized by a short deep inspiration followed by a prolonged expiratory phase [24] . This breathing pattern helps the neonate develop and maintain functional residual capacity [24] .

Causes of respiratory distress in the neonate

Respiratory distress may be the clinical presentation of numerous conditions that affect the neonate (see Table 1 ). Specific causes of respiratory distress may be difficult to ascertain based on clinical presentation alone. The most common causes of respiratory distress in the newborn are pulmonary in origin and include transient tachypnea of the newborn, respiratory distress syndrome, meconium aspiration syndrome, pneumonia, sepsis, pneumothorax, persistent pulmonary hypertension of the newborn, and delayed transition [13] . Extrapulmonary etiologies, such as congenital heart defects, airway malformations, inborn errors of metabolism, neurologic, and hematologic causes are less common [13] .

Etiologies of respiratory distress in the neonate [8] , [12] , [13] , [15] , [17] .

Transient Tachypnea of the Neonate ( TTN ) is the most common etiology of respiratory distress in the neonatal period [8] , [13] . TTN occurs in near-term, term and late preterm infants, and affects 3.6–5.7 per 1000 term infants, and up to 10 per 1000 preterm infants [8] , [17] . TTN is a result of delayed resorption and clearance of alveolar fluid from the lungs [5] , [13] . Following delivery, the release of prostaglandins distends lymphatic vessels which remove lung fluid as pulmonary circulation increases following the first fetal breath [13] . Cesarean section prior to the onset of labor bypasses this process, and is therefore a risk factor for TTN [8] , [13] , [17] . Other risk factors include surfactant deficiency [13] , maternal asthma, diabetes, prolonged labor, and fetal distress requiring maternal anesthesia or analgesia [8] , [17] , [25] . TTN presents within the first two hours after birth and can persist for up to 72 h [13] . Clinical presentation includes rapid, shallow breathing with occasional grunting or nasal flaring [17] , and rarely respiratory failure [8] . Breath sounds may either be clear, or reveal rales on auscultation [13] . TTN is generally a self-limited disorder [5] , however, the higher the initial respiratory rate, the longer TTN is likely to last [13] .

Respiratory Distress Syndrome ( RDS ) is seen soon after birth, and worsens during the first few hours of life [8] , [17] . RDS occurs because of surfactant deficiency or dysfunction resulting in increased alveolar surface tension and alveolar collapse at the end of expiration [8] , [17] . The disease progresses rapidly [13] , with increased work of breathing, intrapulmonary shunting, ventilation perfusion mismatch, and hypoxia with eventual respiratory failure [8] , [17] . The risk of RDS is inversely proportional to gestational age; RDS occurs in approximately 5% of near-term infants, 30% of infants less than 30 weeks gestational age, and 60% of premature infants less than 28 weeks gestational age [8] , [17] . Additional factors associated with development of RDS are male sex in Caucasians, infants born to mothers with diabetes, perinatal asphyxia, hypothermia, multiple gestations, cesarean delivery without labor, and presence of RDS in a previous sibling [8] , [17] , [25] . Symptoms include tachypnea, grunting, retractions and cyanosis [8] , [13] .

Meconium Aspiration Syndrome ( MAS ) occurs in term or post-term infants born through meconium-stained amniotic fluid [17] , and is seen within a few hours after birth [8] . Although meconium-stained amniotic fluid is present in 10–15% of deliveries, most infants born to mothers with meconium-stained amniotic fluid are asymptomatic, and the incidence of MAS is only 1% [8] , [13] . Meconium excretion is representative of fetal maturity, therefore MAS is most commonly seen in term and post-term neonates [13] . Meconium is passed in utero when the fetus is distressed and relaxes the anal sphincter [17] . The resultant hypoxia and subsequent gasping lead to aspiration of meconium before birth [5] , [8] . Meconium consists of desquamated cells, skin, lanugo hair, vernix, bile salts, pancreatic enzymes, lipids, mucopolysaccharides, and water [8] , [17] . Chemical pneumonitis occurs when bile salts and other components of meconium deactivate pulmonary surfactant resulting in atelectasis [8] . Meconium also activates the complement cascade, causing inflammation and constriction pulmonary veins [8] , [17] . Risk factors include preeclampsia, maternal diabetes, chorioamnionitis, and illicit substance abuse [8] . MAS presents with tachypnea, grunting, retractions and cyanosis [13] . Affected neonates may have a barrel-shaped chest, rales and rhonchi heard on auscultation, and meconium staining of the nails and umbilical cord [8] , [13] , [17] .

Pneumonia is a significant cause of respiratory distress in the neonate and may be classified as early-onset (less than or equal to 7 days of age) or late-onset (greater than 7 days of age) [8] . Early-onset pneumonia most commonly occurs within the first three days of life, and is the result of placental transmission of bacteria or aspiration of infected amniotic fluid, while late-onset pneumonia occurs after hospital discharge and community exposure, resulting in various potential etiologies including viral and bacterial pathogens [13] . The clinical signs in neonatal pneumonia mimic other conditions like TTN, RDS or MAS, making it difficult to distinguish them [5] , [8] , [17] .

Assessment of respiratory distress in the neonate

Initial assessment of an infant with respiratory distress should focus on the physical examination and rapid identification of life-threatening conditions [8] , [17] . Assessment for respiratory distress may differ depending on clinical setting but should include at least some of the following parameters: (1) measurement of respiratory rate (normal 40–60); (2) observation for increased work of breathing: inspiratory sternal, intercostal and subcostal recession/in-drawing, tracheal tug; (3) assessment for airway noises such as expiratory grunting or inspiratory stridor; (4) assessment for nasal flaring or head bobbing; (5) assessment of color for cyanosis, ideally pulse oximetry measurement should be obtained if any concern about color/cyanosis. Apnea should prompt urgent medical assessment. Respiratory distress may be accompanied by increased, decreased, or normal respirations depending on the level of respiratory fatigue the infant is experiencing. Therefore, respiratory rate alone may not be indicative of the degree of distress. Utilizing a validated scoring system can improve the predictive value of the degree of respiratory distress and aid the practitioner in accessing additional support services in a timely fashion.

If providers are able to identify signs of respiratory distress prior to the onset of refractory disease, this may facilitate early intervention, and reduced morbidity and mortality [11] . Early warning tools may aid in the early identification of neonates at risk for clinical deterioration. These tools may also provide a standardized observation chart for monitoring clinical progress, and provide visual prompts to aid identification of abnormal parameters. Early identification of ill neonates and early intervention may facilitate early transfer to higher level care if necessary and available [26] .

Several scoring systems focused specifically on assessment of respiratory distress in the neonate are available. The World Health Organization provides the most simplified scoring system, which classifies breathing difficulty based on respiratory rate, grunting and chest in-drawing [27] (see Appendix A ). Other respiratory specific scoring systems include the ACoRN (Acute Care of at-Risk Newborns) Respiratory Score [11] , the Silverman Scoring System [15] , [28] , [29] , and the Downes Respiratory Distress Score (Downes RDS) [15] , [30] (see Appendix A and Table 2 ). These respiratory specific scoring systems are based on clinical criteria, and therefore can be implemented in most settings.

Comparison of validated neonatal scoring system measurements.

In addition to respiratory specific scoring systems, there are also general neonatal illness scoring systems. These include the Sick Neonate Score (SNS) [31] , the Score for Neonatal Acute Physiology II (SNAP-II) [32] , and the Neonatal Trigger Score (NTS) [33] (see Appendix B and Table 2 ). Although by definition these scores are more representative of overall neonatal illness, each does take respiratory symptoms into account, and therefore may also help determine the presence of respiratory distress in the neonate. SNS is a clinical score that was developed to assess neonatal illness in resource limited settings [31] . SNAP-II and NTS require 12 h of data collection, and SNAP-II requires assessment of urine output and a blood gas, which may make it more difficult to implement these scoring systems in some settings [11] , [32] , [33] .

Respiratory Distress in the Neonate following maternal immunization

Influenza vaccine is recommended for pregnant women in many countries at any time during pregnancy to prevent infection in both the pregnant woman and her neonate [34] . The safety of influenza vaccine during pregnancy has been studied with no evidence of safety concerns when administered in any trimester [34] , [35] , [36] . Although three systematic reviews have supported the evidence for no safety signal, there are limitations on the amount of evidence available, especially for more specific pregnancy outcomes such as congenital malformations, in women receiving influenza vaccine in the first trimester [35] . Respiratory symptoms in the neonate following maternal immunization are rarely reported [37] . In a large retrospective database review over 5 influenza seasons, Muñoz et al. reported on “respiratory problems” in the neonate within 2 days of birth. No infants had respiratory problems if their mother had received influenza vaccine during pregnancy, compared to 8 infants with respiratory problems whose mother had not received influenza vaccine, however this difference was not statistically significant (p = 0.2) [38] .

The evaluation of low APGAR scores (<7) as an adverse event following maternal influenza immunization, and which includes an assessment of respiratory effort, has been reported in six studies [39] , [40] , [41] , [42] , [43] , [44] . These studies mostly relate to pandemic influenza vaccine (influenza A H1N1 09 vaccine) with one reporting on influenza A Hsw1N1 vaccine [39] . Only the study by Håberg et al. had a point estimate that favored the unvaccinated cohort, although this was close to the null value and did not reach statistical significance (HR = 1.08 (95% CI, 0.91–1.28) [41] . The remainder of the cohort studies had a point estimate that favored the vaccinated cohort. A prospective cohort study reported an unadjusted OR = 0.88 (CI 95% 0.35–2.20) and a retrospective cohort study reported a RR = 0.97 (95% CI 0.82, 1.14) for APGAR < 7 [39] , [40] . A cross-sectional study indicated a protective effect against 5 min APGAR score <7, unadjusted OR = 0.7 (95% CI 0.47–1.05) [44] . None of the studies demonstrated any statistical or clinical association with decreased APGAR scores.

Pertussis-containing vaccines used in pregnant women often contain tetanus toxoid, diphtheria toxoid, acellular pertussis, and inactivated poliomyelitis antigens (Tdap or Tdap-IPV). In pregnant women, administration of a lower antigen pertussis-containing vaccine is recommended during the third trimester of pregnancy (or earlier in some countries), to ensure maximal and timely protection for neonates [45] , [46] . Large cohort studies examining the safety of Tdap/Tdap-IPV vaccine administered in pregnancy have not identified any safety concerns [47] , [48] , [49] , [50] , [51] , [52] . Morgan et al. provide the only published data on respiratory outcomes in neonates in pregnant women who have received Tdap vaccine. In this retrospective cohort study comparing women who did and did not receive Tdap vaccine in pregnancy, no difference was observed in infants with a 5-min APGAR score <4 [48] . No difference was observed between these groups in neonatal complications, including requirement for ventilation in the first 24 h. A subgroup analysis of multiparous women who received at least 2 doses of Tdap vaccine in the past 5 years compared to one dose of Tdap demonstrated comparable neonatal outcomes, including ventilation requirements [48] .

Existing case definitions for respiratory distress in the neonate

Respiratory distress in the newborn is a common clinical syndrome with many possible etiologies. Several definitions of respiratory distress are currently available from a variety of organizations and in the literature. These are summarized in Table 3 . If not cited, no specific definition was identified from certain organizations (e.g. American Academy of Pediatrics, CIOMS, MedDRA).

Existing case definitions of respiratory distress in the neonate.

Need for a harmonized definition of respiratory distress in the neonate

There is no uniformly accepted case definition of Respiratory Distress in the Neonate in the context of assessing adverse events following maternal immunization. There is variability in existing definitions, which decreases their specificity. Data comparability across trials or surveillance systems would facilitate data interpretation, improve harmonization across clinical and population studies, and promote the scientific understanding of Respiratory Distress in the Neonate.

1.2. Methods for the development of the case definition and guidelines for data collection, analysis, and presentation for respiratory distress in the neonate as an adverse event following maternal immunization

Following the process described in the overview papers [53] , [54] as well as on the Brighton Collaboration Website http://www.brightoncollaboration.org/internet/en/index/process.html , the Brighton Collaboration Respiratory Distress in the Neonate Working Group was formed in 2016 and included members of various clinical, academic, public health, and industry backgrounds. The composition of the working and reference group as well as results of the web-based survey completed by the reference group with subsequent discussions in the working group can be viewed at: http://www.brightoncollaboration.org/internet/en/index/working_groups.html .

To guide the decision-making for the case definition and guidelines, literature searches were performed using PubMed, Medline, Embase, Clinical Key and the Cochrane Libraries. One literature search focused on general descriptions of respiratory distress in the neonate, was conducted using PubMed, searched English language articles only, and used the search terms “respiratory distress” and “neonate”. The search resulted in 4000 articles from 2006 to present, all titles and abstracts were reviewed. Fifty-four articles with potentially relevant material were reviewed in full to identify case definitions, background rates, etiologies and pathophysiology of respiratory distress in the neonate.

Of the 54 articles reviewed on respiratory distress and the neonate, 33 were relevant, and a total of 16 definitions of respiratory distress in the neonate were identified ( Table 3 ). These case definitions were noted to contain similar elements, but there was variation in terminology used, number and type of symptoms considered, and application of the definition. An inventory of the 16 relevant case definitions of Respiratory Distress in the Neonate was made available to working group members.

An additional search was conducted to identify literature about maternal immunization in relation to respiratory distress in the neonate. This search utilized the terms “maternal immunization, vaccine, vaccines, vaccination, immunization, pregnancy, neonatal, neonate, newborn, infant, respiratory distress, respiratory insufficiency, apnoea, apnea, apneic attack, apnoeic attack, respiratory arrest, respiratory failure, respiratory acidosis, respiratory complications, difficulty breathing, increased work of breathing, labored respiration, pneumonia, pulmonary, respiratory tract, pulmonary edema, pulmonary oedema, alveolitis, lung infiltration, interstitial lung disease”. The search was limited to publications from 2005 to present, and concentrated on reviews or large clinical studies . The search resulted in the identification of 56 references, 9 of which were book chapters. All English language article abstracts were screened for possible reports of Respiratory Distress in the Neonate following maternal immunization. Forty-seven articles with potentially relevant material were reviewed in more detail, in order to identify studies using case definitions or, in their absence, providing clinical descriptions of the case material. This review resulted in a detailed summary of 47 articles, including information on the study type, the vaccine, the diagnostic criteria or case definition put forth, the time interval since time of immunization, and any other symptoms.

Of the 47 articles reviewed on immunization and respiratory distress, 17 focused on maternal immunization, while 30 focused on infant immunization. Most of the papers on maternal immunization did not mention Respiratory Distress in the Neonate as an adverse event that was considered in relation to maternal immunization. When respiratory distress was mentioned in a few of these articles it was not clearly defined. The 30 articles related to infant immunization were not relevant, as they focused on infants immunized outside of the neonatal age range, and were not related to maternal immunization.

1.3. Rationale for selected decisions about the case definition of respiratory distress in the neonate as an adverse event following maternal immunization

The term Respiratory Distress in the Neonate refers to a constellation of clinical findings that support the presence of breathing difficulty in the neonate (0 to 28 days of life), independent from etiology or severity, and independent from the infant’s gestational age or circumstances at the time of delivery. Respiratory distress is distinct from the clinical findings observed during normal transition from intra- to extra- uterine life in all newborns. Different terminology exists in the literature in relation to respiratory distress in the neonate, from a very broad characterization as “increased work of breathing” or “dyspnea”, to various measurable findings (e.g. respiratory rate), to observing for the presence of clinical findings consistent with difficulty breathing (e.g. expiratory grunting, chest retractions) or with the consequences of poor oxygenation (e.g. central cyanosis), to, in some cases, laboratory findings (e.g. arterial blood gas analysis).

Different terminologies in the literature that refer to the clinical syndrome of Respiratory Distress in the Neonate were identified, including: respiratory distress, difficulty breathing, labored breathing, shortness of breath, increased work of breathing, labored respirations, respiratory insufficiency, respiratory failure, respiratory arrest, respiratory acidosis, respiratory complications, respiratory disease, respiratory illness, and respiratory disorder. The term Respiratory Distress Syndrome is utilized specifically to designate hyaline membrane disease, and it is distinct from the term Respiratory Distress in the Neonate selected for this case definition.

Numerous related term(s) of Respiratory Distress in the Neonate exist in the literature. Some have the observed clinical findings associated with respiratory distress in neonates (e.g. apnea, apneic attack, bradypnea, tachypnea, dyspnea, retractions, recessions, use of accessory muscles, cyanosis, grunting, stridor, nasal flaring, wheezing), while others reflect the possible etiologies of respiratory distress (e.g. Respiratory Distress Syndrome, hyaline membrane disease, surfactant deficiency lung disease, meconium aspiration syndrome, transient tachypnea of the newborn, persistent pulmonary hypertension of newborn, hypoxia, pneumonia, pulmonary edema, alveolitis, lung infiltration, interstitial lung disease).

Disparity in the use of respiratory distress during the neonatal period may result in inconsistent classifications for adverse event reporting. It is important to highlight that when choosing to report on an adverse event associated with vaccination, the most precise definition or description of the event should be cataloged. Therefore, although respiratory distress may often present as a symptom of a disease, the more precise disease etiology should be the term chosen for the adverse event (e.g. meconium aspiration would be more precise than respiratory distress, although both would be present for the single situation).

Focus of brighton collaboration case definition

The focus of the Working Group was to identify all the necessary components to define Respiratory Distress in the Neonate, and to produce a harmonized definition to properly identify cases of respiratory distress in the neonate in the context of vaccination of mothers during pregnancy. Within the definition context, however, the three diagnostic levels must not be misunderstood as reflecting different grades of clinical severity. They instead reflect diagnostic certainty (see below). Furthermore, the definition may be applied to settings other than studies of vaccines in pregnancy.

The Brighton Collaboration case definition of respiratory distress in the neonate is based on clinical observation only, utilizing auscultation with stethoscope when available. However, supporting evidence from certain devices may be utilized in certain clinical settings, such as pulse oximetry or a cardiac and respiratory monitor. The definition based on clinical criteria is applicable in different settings, independent from resources. However, collection of additional information based on laboratory, imaging, or pathology results is encouraged to ascertain the cause of the syndrome manifesting as respiratory distress in the newborn. A summary of potential etiologies is described in Table 1 .

Formulating a case definition that reflects diagnostic certainty: weighing specificity versus sensitivity

It needs to be re-emphasized that the grading of definition levels is entirely about diagnostic certainty, not clinical severity of an event. Thus, a clinically very severe event may appropriately be classified as Level Two or Three rather than Level One if it could not reasonably be confirmed to fit within the case definition of Respiratory Distress in the Neonate. Detailed information about the severity of the event should additionally always be recorded, as specified by the data collection guidelines.

The number of symptoms and/or signs that will be documented for each case may vary considerably. The case definition has been formulated such that the Level 1 definition is highly specific for the condition. As maximum specificity normally implies a loss of sensitivity, two additional diagnostic levels have been included in the definition, offering a stepwise increase of sensitivity from Level One down to Level Three, while retaining an acceptable level of specificity at all levels. In this way it is hoped that all possible cases of Respiratory Distress in the Neonate can be captured.

The meaning of “Sudden Onset” and “Rapid progression” in the context of respiratory distress in the neonate

The term “sudden onset” refers to an event that occurred unexpectedly and without warning leading to a marked change in a subject’s previously stable condition.

The term “rapid progression” is a conventional clinical term. Respiratory distress may be classified as occurring unexpectedly and of being of “sudden onset”, and clinical progression can be assesses as “rapid” by the provider. An exact time-frame of what rapid progression is should not be offered since progression may be associated with wide range of potential etiologies. Documentation of these characteristics however, should be helpful during the evaluation of respiratory distress in the neonate, in order to correlate with potential etiologies and interventions.

Rationale for individual criteria or decision made related to the case definition

Pathology findings

Pathology is not necessary for the ascertainment of respiratory distress in the neonate, given that the diagnosis of respiratory distress is based on clinical observation. However, pathology findings are helpful for the identification of etiologic causes of respiratory distress in the newborn.

Radiology findings

Radiology findings are not necessary for the ascertainment of respiratory distress in the neonate, given that the diagnosis of respiratory distress is based on clinical observation. However, radiology findings are helpful for the identification of etiologic causes of respiratory distress in the newborn, specifically for the identification of pulmonary vs. extrapulmonary causes of respiratory distress.

Laboratory findings

Laboratory findings are not necessary for the ascertainment of respiratory distress in the neonate, given that the diagnosis of respiratory distress is based on clinical observation. However, laboratory findings are helpful for the identification of etiologic causes of respiratory distress in the newborn. For example, the result of arterial or venous blood gas analysis can confirm the presence of hypoxemia, and the presence of leukocytosis or a positive blood culture can identify an infectious etiology for respiratory distress.

Influence of treatment on fulfillment of case definition

The Working Group decided against using “treatment” or “treatment response” towards fulfillment of the Respiratory Distress in the Neonate case definition.

A treatment response or its failure is not in itself diagnostic, and may depend on variables like clinical status, time to treatment, and other clinical parameters.

An important consideration is that practically all newborns will require some form of reanimation after delivery (e.g. stimulation, suctioning of secretions, blow by oxygen, etc.), and that infants may present with clinical findings at birth that could be considered part of the clinical manifestations of Respiratory Distress (e.g. tachypnea, bradypnea, apnea, nasal flaring, retractions and cyanosis). However, these routine clinical findings and interventions should NOT be considered for the fulfillment of the case definition of respiratory distress in the neonate if they occur and then dissipate with standard delivery/post-delivery care in the first 10 min of life. Interventions that are beyond routine neonatal reanimation at birth needed to support an infant who meets the case definition of respiratory distress, should be documented.

Timing post maternal immunization

Specific time frames for onset of Respiratory Distress in the Neonate following maternal immunization are not included as a consideration when ascertaining the case definition. By our definition Respiratory Distress in the Neonate occurs after delivery to any time in the first 28 days of the infant’s life. The time interval between maternal immunization and delivery is variable depending on the study design and other events of pregnancy.

We postulate that a definition designed to be a suitable tool for testing causal relationships requires ascertainment of the outcome (e.g. Respiratory Distress in the Neonate) independent from the exposure (e.g. maternal immunizations). Therefore, to avoid selection bias, a restrictive time interval from maternal immunization to onset of Respiratory Distress in the Neonate should not be an integral part of such a definition. Instead, where feasible, details of this interval should be assessed and reported as described in the data collection guidelines.

Further, Respiratory Distress in the Neonate may occur outside the controlled setting of a clinical trial or hospital. In some settings it may be impossible to obtain a clear timeline of the event, particularly in less developed or rural settings. In order to avoid selecting against such cases, the Brighton Collaboration case definition avoids setting arbitrary time frames.

Differentiation from other (similar/associated) disorders

Respiratory Distress in the Neonate is distinct from normal signs and symptoms of transition to extrauterine life occurring immediately after delivery. These are transient and not associated with any pathology, typically resolving after stimulation and not requiring specific treatment. It is also distinct from Respiratory Distress Syndrome (RDS), a term used to describe a very specific condition, also known as surfactant deficiency or hyaline membrane disease of the newborn. See more detailed description in Section 1.1 .

1.4. Guidelines for data collection, analysis and presentation

As mentioned in the overview paper, the case definition is accompanied by guidelines which are structured according to the steps of conducting a clinical trial or conducting vaccine safety monitoring, i.e. data collection, analysis and presentation. Neither case definition nor guidelines are intended to guide or establish criteria for management of ill infants, children, or adults. Both were developed to improve data comparability.

1.5. Periodic review

Similar to all Brighton Collaboration case definitions and guidelines, review of the definition with its guidelines is planned on a regular basis (i.e. every three to five years) or more often if needed.

2. Case definition of respiratory distress in the neonate

For All Levels of Diagnostic Certainty

Respiratory Distress in the Neonate is a clinical syndrome occurring in Newborns 0 to 28 days of life , characterized by the presence of:

• Abnormal respiratory rate
• Measurement of number of breaths per minute consistent with:
• Tachypnea = respiratory rate of 60 or more breaths per minute
• Bradypnea = respiratory rate of less than 30 breaths per minute
• Apnea = cessation of respiratory effort (no breaths) for at least 20 s
• Clinical symptoms consistent with labored breathing

Clinical observation of:

• Nasal flaring (dilatation of alae nasi)
• Noisy respirations in the form of expiratory grunting, stridor, or wheeze
• Retractions or increased chest indrawings on respiration (subcostal, intercostal, sternal, suprasternal notch)
• Central cyanosis (whole body, including lips and tongue) on room air
• Low Apgar Score (<7 points) at 10 min, with respiration score <2

The ascertainment of respiratory distress in the neonate is independent from the newborn’s gestational age at the time of delivery and the circumstances of delivery, and distinct from the clinical manifestations of the immediate normal transition from intrauterine to extrauterine life. Clinical findings should therefore be persistent beyond the first 10 min of life (when Apgar scores are collected), or occur at any time after this transition period and before day of life 28. Clinical findings consistent with respiratory distress should be assessed prior to any intervention or assistance needed in response to the findings. Ascertainment of the diagnosis is not dependent on the need for, or results of, medical interventions or the type of intervention initiated (e.g. need for supplemental oxygen, positive pressure support, or mechanical ventilation). Provision of respiratory support (e.g. airway placement, oxygen supplementation) in itself is not always indicative of Respiratory Distress in the Neonate. Furthermore, the absence of an abnormal respiratory rate does not rule out the diagnosis of respiratory distress in infants who have had an abnormal respiratory rate, transiently appear normal, and continue to deteriorate. The case definition identifies cases of respiratory distress in the neonate, independently from the cause or the severity of the clinical findings of respiratory distress.

Additional supporting evidence of respiratory distress (but not required for case ascertainment) may include: Hypoxemia documented by pulse oximetry or arterial or venous blood gas analysis, presence of tachycardia or bradycardia, decreased muscular tone, flaccid/limp muscles, body or extremities, hypo-responsiveness, and obtundation.

Diagnostic levels of certainty

• Newborn 0 to 28 days of life
• Low Apgar Score (< 7 points) at 10 min, with respiration score < 2
• Examination and documentation by qualified, trained, health care provider appropriate for the clinical setting.
• Not measured, but reported as “rapid breathing”, “slow breathing”, having periods of “no breathing”, or “abnormal breathing”
• Retractions or increased chest indrawings on respiration (subcostal, intercostal, sternal, suprasternal notch) or seesaw respirations
• No medical record documentation, but reporting through either a non-medical observer (e.g. mother, father, community worker) or via standard census mechanisms (e.g. Demographic and Health Surveillance System)
• Collection of information from medical record review or billing codes.
• No need for a level 3 per working group .
• Not enough information to ascertain case of respiratory distress .
• Not a case of respiratory distress in the neonate .

3. Guidelines for data collection, analysis and presentation of respiratory distress in the neonate

It was the consensus of the GAIA-Brighton Collaboration Respiratory Distress in the Neonate Working Group to recommend the following guidelines to enable meaningful and standardized collection, analysis, and presentation of information about Respiratory Distress in the Neonate in studies of vaccines given during pregnancy. However, implementation of all guidelines might not be possible in all settings. The availability of information may vary depending upon resources, geographical region, and whether the source of information is a prospective clinical trial, a post-marketing surveillance or epidemiological study, or an individual report of Respiratory Distress in the Neonate. Also, these guidelines have been developed by this working group for guidance only, and are not to be considered a mandatory requirement for data collection, analysis, or presentation.

3.1. Data collection

These guidelines represent a desirable standard for the collection of data on availability following maternal immunization to allow for comparability of data, and are recommended as an addition to data collected for the specific study question and setting. The guidelines are not intended to guide the primary reporting of Respiratory Distress in the Neonate to a surveillance system or study monitor. Investigators developing a data collection tool based on these data collection guidelines also need to refer to the criteria in the case definition, which are not repeated in these guidelines.

Guidelines number 1–43 below have been developed to address data elements for the collection of adverse event information as specified in general drug safety guidelines by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use [55] , and the form for reporting of drug adverse events by the Council for International Organizations of Medical Sciences [56] . These data elements include an identifiable reporter and patient, one or more prior immunizations, and a detailed description of the adverse event, in this case, of Respiratory Distress in the Neonate following maternal immunization. The additional guidelines have been developed as guidance for the collection of additional information to allow for a more comprehensive understanding of Respiratory Distress in the Neonate following maternal immunization.

3.1.1. Source of information/reporter

For all cases and/or all study participants, as appropriate, the following information should be recorded:

• (1) Date of report.
• (2) Name and contact information of person reporting 3 and/or diagnosing Respiratory Distress in the Neonate as specified by country-specific data protection law.
• (3) Name and contact information of the investigator responsible for the subject, as applicable.
• (4) Relation to the patient (e.g. immunizer [clinician, nurse], family member [indicate relationship], other).

3.1.2. Vaccinee/control

3.1.2.1. demographics.

For all cases and/or all study participants (mothers and infants), as appropriate, the following information should be recorded:

• (5) Case/study participant identifiers (e.g. first name initial followed by last name initial) or code (or in accordance with country-specific data protection laws).
• (6) Date of birth, age, and sex.
• (7) For infants: Gestational age and birth weight.

3.1.2.2. Clinical and immunization history

• (8) Past medical history, including hospitalizations, underlying diseases/disorders, pre-immunization signs and symptoms including identification of indicators for, or the absence of, a history of allergy to vaccines, vaccine components or medications; food allergy; allergic rhinitis; eczema; asthma.
• (9) Any medication history (other than treatment for the event described) prior to, during, and after immunization including prescription and non-prescription medication as well as medication or treatment with long half-life or long term effect. (e.g. immunoglobulins, blood transfusion and immunosuppressants).
• (10) Immunization history (i.e. previous immunizations and any adverse event following immunization (AEFI)), in particular occurrence of Respiratory Distress in the Neonate after a previous maternal immunization. Of note, ascertainment of maternal immunization history might be challenging in different settings, and collection of data from different sources might be necessary to optimize data gathering.

3.1.3. Details of the immunization

• (11) Date and time of maternal immunization(s).
• (12) Description of vaccine(s) (name of vaccine, manufacturer, lot number, dose (e.g. 0.25 mL, 0.5 mL, etc.), name and lot number of any diluent used in the vaccine, and number of dose if part of a series of immunizations against the same disease).
• (13) The anatomical sites (including left or right side) of all immunizations (e.g. vaccine A in proximal left lateral thigh, vaccine B in left deltoid).
• (14) Route and method of administration (e.g. intramuscular, intradermal, subcutaneous, and needle-free (including type and size), other injection devices).
• (15) Needle length and gauge.

3.1.4. The adverse event

• (16) For all cases at any level of diagnostic certainty and for reported events with insufficient evidence, the criteria fulfilled to meet the case definition should be recorded.
• (17) Specifically document: Clinical description of signs and symptoms of Respiratory Distress in the Neonate, and if there was medical confirmation of the event (i.e. patient seen by physician).
• (18) Date/time of onset 4 , first observation 5 and diagnosis 6 , end of episode 7 and final outcome. 8
• (19) Concurrent signs, symptoms, and diseases.
• • Values and units of routinely measured parameters (e.g. respirations per minute, heart beats per minute, temperature) – in particular those indicating the severity of the event;
• • Method of measurement (e.g. respiratory monitor, pulse oximeter, duration of measurement, cardiac etc.);
• • Results of laboratory and radiographic examinations, surgical and/or pathological findings and diagnoses if present.
• (21) Treatment given for Respiratory Distress in the Neonate
• (22) Outcome 8 at last observation.
• (23) Objective clinical evidence supporting classification of the event as “serious”. 9
• (24) Exposures (e.g. food, environmental) considered potentially relevant to the reported event.

3.1.5. Miscellaneous/general

• (25) The duration of surveillance for Respiratory Distress in the Neonate is predefined based on the duration of the neonatal period of 28 days.
• (26) The duration of follow-up reported during the surveillance period should be predefined likewise. It should aim to continue to resolution of the event.
• (27) Methods of data collection should be consistent within and between study groups, if applicable.
• (28) Follow-up of cases should attempt to verify and complete the information collected as outlined in data collection guidelines 1–24.
• (29) Investigators of patients with Respiratory Distress in the Neonate should provide guidance to reporters to optimize the quality and completeness of information provided.
• (30) Reports of Respiratory Distress in the Neonate should be collected throughout the study period regardless of the time elapsed between maternal immunization and the adverse event. If this is not feasible due to the study design, the study periods during which safety data are being collected should be clearly defined.

3.2. Data analysis

The following guidelines represent a desirable standard for analysis of data on Respiratory Distress in the Neonate to allow for comparability of data, and are recommended as an addition to data analyzed for the specific study question and setting.

• (31) Reported events should be classified in one of the following five categories including the three levels of diagnostic certainty. Events that meet the case definition should be classified according to the levels of diagnostic certainty as specified in the case definition. Events that do not meet the case definition should be classified in the additional categories for analysis.

Event classification in 5 categories 10

Event meets case definition

• (1) Level 1: Criteria as specified in the Respiratory Distress in the Neonate case definition
• (2) Level 2: Criteria as specified in the Respiratory Distress in the Neonate case definition
• (3) Level 3: Criteria as specified in the Respiratory Distress in the Neonate case definition ( if applicable )

Event does not meet case definition

Additional categories for analysis

• (4) Reported Respiratory Distress in the Neonate with insufficient evidence to meet the case definition 11
• (5) Not a case of Respiratory Distress in the Neonate 12
• (32) The interval between maternal immunization and reported Respiratory Distress in the Neonate could be defined as the date/time of maternal immunization to the date/time of onset 4 of the first symptoms and/or signs consistent with the definition. In this case, it is probably important to distinguish cases of Respiratory Distress occurring in the immediate post-delivery period (within 10 min), those occurring in the first week after delivery (early neonatal period or 0–6 days of life), and those occurring at or after the 7th day and up to 28 days of life (late neonatal period). Determining the interval from maternal vaccination to the event is probably more relevant for those cases occurring immediately at the time of delivery. However, in all cases, the interval between maternal vaccination(s) and the date of birth should be recorded. For a large number of cases, data could be analyzed in the following increments:

Subjects with Respiratory Distress in the Neonate by Interval to Presentation

• (33) The duration of possible Respiratory Distress in the Neonate could be analyzed as the interval between the date/time of onset 3 of the first symptoms and/or signs consistent with the definition and the end of episode 7 and/or final outcome 8 . Whatever start and ending are used, they should be used consistently within and across study groups.
• (34) If more than one measurement of a particular criterion is taken and recorded, the value corresponding to the greatest magnitude of the adverse experience could be used as the basis for analysis. Analysis may also include other characteristics like qualitative patterns of criteria defining the event.
• (35) The distribution of data (as numerator and denominator data) could be analyzed in predefined increments (e.g. measured values, times), where applicable. Increments specified above should be used. When only a small number of cases is presented, the respective values or time course can be presented individually.
• (36) Data on Respiratory Distress in the Neonate obtained from infants of subjects receiving a vaccine should be compared with those obtained from one or more appropriately selected and documented control groups to assess background rates in non-exposed populations, and should be analyzed by study arm and dose where possible, e.g. in prospective clinical trials.

3.3. Data presentation

These guidelines represent a desirable standard for the presentation and publication of data on Respiratory Distress in the Neonate following maternal immunization to allow for comparability of data, and are recommended as an addition to data presented for the specific study question and setting. Additionally, it is recommended to refer to existing general guidelines for the presentation and publication of randomized controlled trials, systematic reviews, and meta-analyses of observational studies in epidemiology (e.g. statements of Consolidated Standards of Reporting Trials (CONSORT), of Improving the quality of reports of meta-analyses of randomized controlled trials (QUORUM), and of meta-analysis Of Observational Studies in Epidemiology (MOOSE), respectively) [57] , [58] , [59] .

• (37) All reported events of Respiratory Distress in the Neonate should be presented according to the categories listed in guideline 32.
• (38) Data on possible Respiratory Distress in the Neonate events should be presented in accordance with data collection guidelines 1–24 and data analysis guidelines 31–36.
• (39) Terms to describe Respiratory Distress in the Neonate such as “mild”, “moderate”, “severe” or “significant” are highly subjective, prone to wide interpretation, and should be avoided, unless clearly defined.
• (40) Data should be presented with numerator and denominator (n/N) (and not only in percentages), if available.

Although immunization safety surveillance systems denominator data are usually not readily available, attempts should be made to identify approximate denominators. The source of the denominator data should be reported and calculations of estimates be described (e.g. manufacturer data like total doses distributed, reporting through Ministry of Health, coverage/population based data, etc.).

• (41) The incidence of cases in the study population should be presented and clearly identified as such in the text.
• (42) If the distribution of data is skewed, median and range are usually the more appropriate statistical descriptors than a mean. However, the mean and standard deviation should also be provided.
• • The study design;
• • The method, frequency and duration of monitoring for Respiratory Distress in the Neonate;
• • The trial profile, indicating participant flow during a study including drop-outs and withdrawals to indicate the size and nature of the respective groups under investigation;
• • The type of surveillance (e.g. passive or active surveillance);
• • The characteristics of the surveillance system (e.g. population served, mode of report solicitation);
• • The search strategy in surveillance databases;
• • Comparison group(s), if used for analysis;
• • The instrument of data collection (e.g. standardized questionnaire, diary card, report form);
• • Whether the day of immunization was considered “day one” or “day zero” in the analysis;
• • Whether the date of onset 4 and/or the date of first observation 5 and/or the date of diagnosis 6 was used for analysis; and
• • Use of this case definition for Respiratory Distress in the Neonate, in the abstract or methods section of a publication. 13

The findings, opinions and assertions contained in this consensus document are those of the individual scientific professional members of the working group. They do not necessarily represent the official positions of each participant’s organization (e.g., government, university, or corporation). Specifically, the findings and conclusions in this paper are those of the authors and do not necessarily represent the views of their respective institutions.

Acknowledgements

The authors are grateful for the support and helpful comments provided by the Brighton Collaboration and the reference group (see https://brightoncollaboration.org/public/what-we-do/setting-standards/case-definitions/groups.html for reviewers), as well as other experts consulted as part of the process. The authors are also grateful to Jan Bonhoeffer, Jorgen Bauwens of the Brighton Collaboration Secretariat and Sonali Kochhar of Global Healthcare Consulting for final revisions of the final document. Finally, we would like to acknowledge the Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project, funded by the Bill and Melinda Gates Foundation – United States.

3 If the reporting center is different from the vaccinating center, appropriate and timely communication of the adverse event should occur.

4 The date and/or time of onset is defined as the time post immunization, when the first sign or symptom indicative of Respiratory Distress in the Neonate occurred. This may only be possible to determine in retrospect.

5 The date and/or time of first observation of the first sign or symptom indicative of Respiratory Distress in the Neonate can be used if date/time of onset is not known.

6 The date of diagnosis of an episode is the day post immunization when the event met the case definition at any level.

7 The end of an episode is defined as the time the event no longer meets the case definition at the lowest level of the definition.

8 E.g. recovery to pre-immunization health status, spontaneous resolution, therapeutic intervention, persistence of the event, sequelae, death.

9 An AEFI is defined as serious by international standards if it meets one or more of the following criteria: 1) it results in death, 2) is life-threatening, 3) it requires inpatient hospitalization or results in prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) is a congenital anomaly/birth defect, 6) is a medically important event or reaction.

10 To determine the appropriate category, the user should first establish, whether a reported event meets the criteria for the lowest applicable level of diagnostic certainty. If the lowest applicable level of diagnostic certainty of the definition is met, and there is evidence that the criteria of the next higher level of diagnostic certainty are met, the event should be classified in the next category. This approach should be continued until the highest level of diagnostic certainty for a given event could be determined. If the lowest level of the case definition is not met, it should be ruled out that any of the higher levels of diagnostic certainty are met and the event should be classified in additional categories four or five.

11 If the evidence available for an event is insufficient because information is missing, such an event should be categorized as “Reported Respiratory Distress in the Neonate with insufficient evidence to meet the case definition”.

12 An event does not meet the case definition if investigation reveals a negative finding of a necessary criterion (necessary condition) for diagnosis. Such an event should be rejected and classified as “Not a case of Respiratory Distress in the Neonate”.

13 Use of this document should preferably be referenced by referring to the respective link on the Brighton Collaboration website ( http://www.brightoncollaboration.org ).

Appendix A Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.vaccine.2017.01.046 .

Appendix A. Supplementary material

Neonatal Jaundice

Sep 23, 2014

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Neonatal Jaundice. Neonatal Ward Dr. Ziyu Hua. Classification of neonatal jaundice. Physiological jaundice. Pathological jaundice. Etiology of physiological jaundice. In the first few days after birth, haemoglobulin concentration falls rapidly.

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• conjugated hyperbilirubinemia
• unconjugated hyperbilirubinemia
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Presentation Transcript

Neonatal Jaundice Neonatal Ward Dr. Ziyu Hua

Classification of neonatal jaundice Physiological jaundice Pathological jaundice

Etiology of physiological jaundice In the first few days after birth, haemoglobulin concentration falls rapidly. Red cell life span of newborn infants is 70 days which is much shorter than that of adults(120 days). Hepatic bilirubin metabolism is less efficiency.

Jaundice is important as A sign of another disorder, e.g. infection, hemolysis Kernicterus: a severe complication of neonatal jaundice, indirect bilirubin (UB) deposited in the brain (basal ganglia).

Warning There are no bilirubin levels which are known to be safe or which will definitely cause kernicterus. Infants who experience severe hypoxia, hypothermia or any serious illness may be susceptible to damage from hyperbilirubinemia.

Severity of jaundice The jaundice starts on the head and face, spreads down the trunk and limbs. How to measure: Observation by eye: blanching the skin Transcutaneous jaundice meter Blood sample: minibilirubin meter

Gestation Preterm infants may be damaged by a lower bilirubin level than term infants. Age from birth is important, higher tolerance with increasing age.

Rate of change Rate of rise tends to be linear until reaching plateau. Rapid rise with increasing harm. Serial measurement of serum bilirubin, suitable intervention when necessary.

Etiology of pathological jaundice Age of onset is a useful guide to likely cause of jaundice. Within 24 hrs During 24 hrs to 2 wks After 2 wks

Jaundice within 24 hrs of age Hemolytic disorders: UB, rise rapidly, high level Rhesus hemolytic disease: jaundice, anemia, hydrops, hepatosplenomegaly; antenatal identify, fetal therapy. ABO incompatibility: less severe, more common, slight or without anemia, peak in the first 12—72hrs. G6PD deficiency: epidemiology; some drugs, infection, hypoxia.

Jaundice within 24 hrs of age Hemolytic disorders Spherocytosis: less common, family history; spherocytes found on the blood film. Congenital infection: conjugated bilirubin, other abnormal clinical signs.

Jaundice at 24 hrs to 2 wks of age Physiological jaundice Infection: unconjugated hyperbilirubinemia; abnormal metabolism of bilirubin; pneumonia, sepsis, hepatitis, urinary tract infection. Other causes: bruising, polycythaemia (venous hematocrit >65%); Crigler-Najjar syndrome (inherited deficiency of enzyme glucuronyl transferase)

Jaundice at 24 hrs to 2 wks of age Breast milk jaundice: prolonged, unconjugated hyperbilirubinemia; unknown cause; declined bilirubin with interruption of breast-feeding; may be harmless. It is unnecessary to stop breast-feeding when breast milk jaundice is diagnosed.

Jaundice at >2 wks of age(persistent) Unconjugated hyperbilirubinemia: Infection, particularly of urinary tract. Congenital hypothyroidism: neonatal biochemical screening; clinical manifestations (constipation, dry skin, coarse facies, hypotonia) Breast milk jaundice: most common, 15% affected; disappears by 3-4 wks of age.

Jaundice at >2 wks of age(persistent) Conjugated hyperbilirubinemia: Neonatal hepatitis syndrome(TORCH), biliary atresia; Dark urine and unpigmented pale stools; Biliary atresia should be diagnosed as soon as possible.

Management No study could prove that supplement with water or dextrose solution would reduce jaundice. Effective treatments: Phototherapy, intense phototherapy Exchange transfusion

Phototherapy Overhead light, blanket, and both of them Blue light: wavelength 450nm, visible Photodegradation: UB is converted into a water-soluble pigment, harmless, excreted in urine Side effects: Uncomfortable eyes, retinal damage in animal, dehydration, rash, diarrhoea, abnormal temperature Phototherapy should not be used indiscriminately.

Exchange transfusion(ET) Indications: Bilirubin rises to the dangerous level; Continues to rise above the recommended level in spite of intensive phototherapy. Transfusion via: cord vessels, peripheral vessels Blood volume: twice infant’s blood volume It should be consider seriously whether to use ET.

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• Case report
• Open access
• Published: 19 August 2024

Presentations of Waugh’s syndrome:intra-luminal cecal cyst and trans-anal prolapsing intussusception: a case report

• Mansoor Ahmed   ORCID: orcid.org/0009-0004-1041-9742 1 ,
• Murad Habib 1 ,
• Huma Memon 2 ,
• Rafee Raza Ahmad 1 &
• Muhammad Amjad Chaudhary 1  

Journal of Medical Case Reports volume  18 , Article number:  376 ( 2024 ) Cite this article

Metrics details

Intussusception with intestinal malrotation is termed as Waugh’s syndrome. The incidence of Waugh’s syndrome is less than 1%. There are very few reported cases. Once presented, it is a pediatric surgical emergency.

Case presentation

We present here two cases of Waugh’s syndrome: an 11-month-old male patient of Punjabi descent and a 4-month-old female patient of Afghan descent who presented to us with abdominal pain and bleeding per rectum. Abdominal sonography revealed an intussusception with a target sign. They were explored and perioperatively had intestinal malrotation alongside intussusception, thus a diagnosis of Waugh’s syndrome was made. A right hemicolectomy and Ladd’s procedure was performed.

Waugh syndrome is a rare congenital anomaly but can present with vague abdominal symptoms. Once presented, it is a pediatric surgical emergency. The patient should be optimized followed by surgical exploration.

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Introduction

Intussusception is a surgical emergency in which part of the gut telescopes into an adjacent part of the intestine [ 1 ]. It mostly occurs in the age range of 3 months to 3 years but can rarely occur in any age group. Patients usually present with a complaint of colicky abdominal pain with in-drawing of legs, red-currant jelly stool, and in some cases abdominal mass. Intussusception can be primary, where no lead point is observed, or secondary, due to a lead point. Waugh’s syndrome is the association of intussusception with intestinal malrotation [ 2 ]. Although intussusception is one of the most common causes of pediatric intestinal obstruction, there are very few reports on Waugh’s syndrome. It was first reported in 1911 by George E. Waugh and named after him by Brereton et al. in their study [ 7 ]. The incidence of Waugh’s syndrome is less than 1% in pediatric population [ 3 ]. Nonoperative management of intussusception may have masked many cases of Waugh’s syndrome, owing to which data on this anomaly are scarce; to date, very few cases have been reported in literature [ 4 ].

We report herein two cases of Waugh’s syndrome where the patient was diagnosed, operated upon, and managed at our facility. Both had uneventful postoperative course and were discharged home with instructions and remained on follow-up.

An 11-month-old male child of Punjabi descent presented to us with complaint of loose stool from last 5 days followed by excessive crying with in-drawing of legs and nongreenish vomiting from the last day with history of reflux since 3 months of life, for which he had multiple visits to local clinics and symptoms improved, and history of previous exploration for intussusception at 5 months of age. Perioperatively, previous exploration showed ileocecocolic intussusception with edematous terminal ileum; manual reduction of intussusception and appendectomy was performed (Fig.  1 ).

Waugh syndrome with intraluminal cyst

On examination, the patient’s vital signs were stable with soft abdomen and no distention, there was mild tenderness; on digital rectal examination, the patient passed watery stool with mucoid discharge.

X-ray of the abdomen was done and showed dilated gut loops, and ultrasound showed intussusception. The patient was explored following resuscitation, and basic laboratory investigations and perioperative ileocecocolic intussusception was found, which was reduced manually; on reduction, a cecal mass was observed with clear fluid in it, which might have acted as a lead point, hence a limited right hemicolectomy was performed with anastomosis and specimen was sent for histopathology. Perioperatively, duodenojujenal junction was also observed to be on right side, hence Ladd’s procedure was performed for intestinal malrotation. The postoperative course was uneventful, and the patient was discharged home on the sixth postoperative day with instructions and called for follow-up.

A 4-month-old female child of Afghani descent presented with history of loose stool from the last 10 days, per-rectal bleed from last 6 days, and something coming out of anus (prolapsed intussusceptum) from last 3 days, and also vomiting from last 3 days, which initially contained milk but later turned greenish. As the patient presented from a rural area where proper medical facilities were not available and owing to nonaffordability, the patient presented very late. There was no previous significant medical or surgical history.

On examination, the patient was very sick-looking, dehydrated with tachycardia and hypotension, immediate resuscitation was started, and we were able to optimize the patient for surgery. Basic laboratory investigations were carried out, and blood was arranged; as history and clinical examination was enough, we did not send the patient for ultrasound or X-ray, and the patient was explored (Fig.  2 ). Perioperative findings were ileocecocolic intussusception extending up to distal third transverse colon with gangrenous distal 13 cm of ileum and cecum, ascending colon perforated up to transverse colon, hence right extended hemicolectomy and end-to-end anastomosis was done.

Waugh syndrome with transanal prolapsing intussusception

Duodenojujenal junction was also observed to be on right side, and Ladd’s procedure was also performed. Postoperatively, the patient remained admitted for 5 days. He was allowed oral intake after gut functions returned, followed by discharge with instructions. He remained on follow-up.

Waugh’s syndrome is the combination of intussusception with intestinal malrotation, first reported in 1911 by George E. Waugh regarding three patients who presented with such. Brereton later found that 40% of his patients presenting with intussusception had duodenojujenal flexure on right side (15 out of 37) and thus named the syndrome after Waugh, giving it the name of Waugh’s syndrome [ 5 ]. The pathophysiology behind it is nonfixed cecum and ascending colon in children with malrotation, which provides an easy target to act as intussusception.

The age range of intussusception with or without malrotation is mostly between between 3 months and 3 years, but it can present in any age group, as Waugh’s syndrome has been reported in neonatal-age and school-age children too. The patients reported herein are also in the same age group as most others reported, that is, 11 months and 4 months [ 6 ].

The treatment of choice in Waugh’s syndrome is manual reduction of intussusception plus straightening of gut and division of bands with widening of mesentery, but our reported cases presented with rare problems [ 7 ]. The first case, where the patient was 11 months old, was a male child who presented with recurrence of intussusception, thus not being an ideal candidate for nonsurgical management; we explored the patient and following manual reduction found cystic mass within cecum, which might previously have acted as a lead point, hence we carried out a limited hemicolectomy, removing a small part of the terminal ileum, cecum, and part of ascending colon, thus removing the lead point to limit further such episodes, and sent the specimen for histopathology. The other case also had an unusual presentation: a transanal prolapsing intussusception. He was also operated upon, with a laparotomy being performed. Peroperative findings showed ileocecocolic intussusception extending up to distal third of transverse colon with gangrenous distal 13 cm of ileum and cecum, and ascending colon perforated, thus a right hemicolectomy was performed [ 8 ].

Whenever a case of Waugh’s syndrome presents, it is deemed a surgical and diagnostic dilemma [ 9 ]. Owing to advancements in imaging technology and surgical knowledge, we have become wise regarding nonsurgical management for intussusception, but one should still bear Waugh’s syndrome in mind for patients presenting with intussusception, as many cases go unnoticed because of this, while radiologists should be informed about also looking for malrotation in patients with intussusception to prevent recurrence [ 10 ].

Waugh syndrome is a rare anomaly but can present with vague abdominal symptoms. Once presented, it is a pediatric surgical emergency. The patient should be optimized followed by surgical exploration.

Data availability

The data that support the findings of this study are available from the corresponding author upon request to corresponding author.

Applegate KE. Intussusception in children: evidence-based diagnosis and treatment. Pediatr Radiol. 2009;39(Suppl 2):140–3.

Article   Google Scholar  

Rao P, Kumar V. Waugh’s syndrome. Indian J Pediatr. 2005;72(1):86.

Article   CAS   PubMed   Google Scholar  

Harper G, Hardy D, Howell C, Hatley R, Pipkin W. Laparoscopic approach to Waugh’s syndrome. Am Surg. 2011;77(4):E78.

Article   PubMed   Google Scholar  

Saxena R, Puri A, Pinnamaneni R. Waugh syndrome in preterm infant: diagnostic clues. Pediat Neonatol. 2015;56(3):203–4.

Al-Momani H. Waugh syndrome: a report of 7 patients and review of the published reports. Ann Saudi Med. 2014;34(6):527–31.

Article   PubMed   PubMed Central   Google Scholar  

Breckon V, Hadley GP. Waugh’s syndrome: a report of six patients. Pediatr Surg Int. 2000;16:370–3.

Brereton R, Taylor B, Hall CM. Intussusception and intestinal malrotation in infants: Waugh’s syndrome. J of Br Surg. 1986;73(1):55–7.

Article   CAS   Google Scholar  

Baltazar G, Sahyoun C, Sime J, Bitar M, Bitar J, Rao AC. Discovery of a case of Waugh’s syndrome during a mission to Haiti. Int J Surg Case Rep. 2012;3(1):22–4.

Inan M, Basaran UN, Ayvaz S, Pul M. Waugh’s syndrome: report of two cases. J Pediatr Surg. 2004;39(1):110–1.

Chukwubuike KE. Waugh syndrome in a child: a case report. J Med Case Rep Case Series. 2021;2(9).

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Department of Paediatric Surgery, The Children’s Hospital, Pakistan Institute of Medical Sciences, Islamabad/Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, 44000, Pakistan

Mansoor Ahmed, Murad Habib, Rafee Raza Ahmad & Muhammad Amjad Chaudhary

Department of Paediatric Medicine, The Children’s Hospital, Pakistan Institute of Medical Sciences Islamabad/Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, 44000, Pakistan

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Concept of study: MA, MH. Acquisition of data: HM, RR. Writing and drafting: MA, MH. Supervision: MAC.

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Correspondence to Mansoor Ahmed .

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Ahmed, M., Habib, M., Memon, H. et al. Presentations of Waugh’s syndrome:intra-luminal cecal cyst and trans-anal prolapsing intussusception: a case report. J Med Case Reports 18 , 376 (2024). https://doi.org/10.1186/s13256-024-04701-1

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Received : 06 November 2023

Accepted : 28 June 2024

Published : 19 August 2024

DOI : https://doi.org/10.1186/s13256-024-04701-1

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