Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels

Activin A is Not a Reliable Prognostic Biomarker For Bilirubin Induced Neurotoxicity in Neonates

Background: Bilirubin induced neurological dysfunction (BIND) remains an important cause of disability in developing countries. Although high total serum bilirubin (TSB) is the main instigator for BIND, different babies may have different neurological outcomes at the same TSB level. This reflects the need for a more specific predictive factor for the neurological outcome, which would allow prompt intervention and prevention of kernicterus. Aim of the Work: To assess the value of serum activin A as a predictor for acute bilirubin neurotoxicity and adverse neurodevelopmental outcomes at one year of life. Materials and Methods: The study enrolled 84 term/near-term infants admitted with indirect hyperbilirubinemia requiring intervention to the Neonatal Intensive Care Unit of Cairo University Children’s Hospital. Clinical examination, BIND score and laboratory tests including activin A were performed. Neurodevelopmental outcome was assessed at 3, 6 and 12 months using the Bayley scale of Infant Development II. Correlations between serum activin A, TSB, BIND scores and Bayley scores were studied. Results: Mean TSB level at admission was 25.92±7.14 mg/dL. BIND score at admission ranged from 0-7, and mean serum activin A level was 109.92±55 pg/ml. Activin A did not show significant correlations with TSB or BIND scores. A negative correlation between activin A level and psychomotor developmental index (PDI) at 3 months was detected however all other neurodevelopmental outcomes showed no significant correlation with activin A. Conclusion: In cases of neonatal hyperbilirubinemia, activin A is not a reliable biomarker for predicting acute or chronic bilirubin induced neurotoxicity

Diagnostic Accuracy of S100B Urinary Testing at Birth in Full-Term Asphyxiated Newborns to Predict Neonatal Death

BACKGROUND: Neonatal death in full-term infants who suffer from perinatal asphyxia (PA) is a major subject of investigation, since few tools exist to predict patients at risk of ominous outcome. We studied the possibility that urine S100B measurement may identify which PA-affected infants are at risk of early postnatal death. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study between January 1, 2001 and December 1, 2006 we measured S100B protein in urine collected from term infants (n = 132), 60 of whom suffered PA. According to their outcome at 7 days, infants with PA were subsequently classified either as asphyxiated infants complicated by hypoxic ischemic encephalopathy with no ominous outcome (HIE Group; n = 48), or as newborns who died within the first post-natal week (Ominous Outcome Group; n = 12). Routine laboratory variables, cerebral ultrasound, neurological patterns and urine concentrations of S100B protein were determined at first urination and after 24, 48 and 96 hours. The severity of illness in the first 24 hours after birth was measured using the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP-PE). Urine S100B levels were higher from the first urination in the ominous outcome group than in healthy or HIE Groups (p<0.001 for all), and progressively increased. Multiple logistic regression analysis showed a significant correlation between S100B concentrations and the occurrence of neonatal death. At a cut-off >1.0 microg/L S100B had a sensitivity/specificity of 100% for predicting neonatal death. CONCLUSIONS/SIGNIFICANCE: Increased S100B protein urine levels in term newborns suffering PA seem to suggest a higher risk of neonatal death for these infants

Neonatal jaundice in low- and middle-income countries : lessons and future directions from the 2015 Don Ostrow Trieste Yellow Retreat

Severe neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥20 mg/dl, is associated with a higher risk of permanent neurological sequelae and death. Jaundice can and should be promptly diagnosed and treated. Reliable methods for TSB assay are not always readily available, particularly in low- and middle-income countries, making the true incidence of severe neonatal jaundice (NNJ) difficult to estimate. To gather a more comprehensive picture, a symposium addressing NNJ worldwide was organized during the 2015 Don Ostrow Trieste Yellow Retreat. Data collected by several researchers in different regions of the world were presented and differences/similarities discussed. This report points out the need for: (1) a coordinated worldwide effort to define the burden and the causes of severe NNJ and its consequences; (2) aggressive educational programs for families and health personnel to facilitate timely care-seeking, and (3) accurate diagnostics and effective phototherapy.9 page(s

Diagnostic Performance Analysis of the Point-of-Care Bilistick System in Identifying Severe Neonatal Hyperbilirubinemia by a Multi-Country ApproachResearch in context

Importance: The real prevalence and clinical burden of severe neonatal jaundice are undefined due to difficulties in measuring total serum bilirubin (TSB) outside secondary and tertiary clinical centers. Objective: To assess the diagnostic performance of the point-of care Bilistick System (BS) in identifying neonatal jaundice patients requiring treatment. Design: Between April 2015 and November 2016, 1911 neonates, were recruited to participate in the study. Blood samples were simultaneously collected for the TSB determination by BS and by hospital laboratory (Lab). Data were collected and sent to the Bilimetrix headquarter in Trieste where statistical analysis was performed. Newborns with neonatal jaundice were treated with phototherapy according to each center's guidelines. Setting: 17 hospitals from Nigeria, Egypt, Indonesia, and Viet Nam. Participants: 1911 newborns were included, of which 1458 (76·3%) fulfilled the inclusion criteria. Results: TSB level measured by BS agreed (p < .0001) with the lab result in all four countries. The diagnostic performance of BS showed a positive predictive value (PPV) of 92·5% and a negative predictive value (NPV) of 92·8%. Conclusions and Relevance: BS is a reliable system to detect neonatal jaundice over a wide range of bilirubin levels. Since Bilistick is a point-of-care test, its use may provide appropriate and timely identification of jaundiced newborns requiring treatment. Keywords: Neonatal jaundice, Severe hyperbilirubinemia, Neonatal screening, Bilirubin, Bilistick System, Point-of-care system, Diagnostic accuracy study, STARD, Low-medium income countrie