Given the low cost (approximately .20 dollars for a course of therapy) and technologic simplicity of the intervention and the effect size observed in this study, a clinical trial with increased numbers of subjects is indicated to evaluate the potential of topical therapy to reduce infections and save newborn lives in developing countries.
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.
WHAT'S KNOWN ON THIS SUBJECT: Hemolytic disease, sepsis, and low gestational age are thought to increase the risk for bilirubin encephalopathy in term/near-term newborns with severe hyperbilirubinemia, but data describing relative risks of these factors are lacking. WHAT THIS STUDY ADDS: Infants with no neurotoxicity risk factors may tolerate high bilirubin levels without adverse effects (31 mg/dL in this study). Beyond a threshold bilirubin of 25 mg/dL, the risk for encephalopathy in infants with Rh hemolytic disease or sepsis depends primarily on unidentified modifying factors. abstract OBJECTIVE: To evaluate the importance of total serum bilirubin (TSB) and neurotoxicity risk factors in predicting acute bilirubin encephalop-athy (ABE) at admission or posttreatment bilirubin encephalopathy (BE) in infants with severe hyperbilirubinemia. METHODS: We analyzed the interaction of TSB and risk factors as determinants of ABE and BE in 249 newborns admitted with a TSB level of 25 mg/dL (427 mol/L) to Cairo University Children's Hospital during a 12-month period. RESULTS: Admission TSB values ranged from 25 to 76.4 mg/dL. Forty-four newborns had moderate or severe ABE at admission; 35 of 249 infants (14%) had evidence of BE at the time of discharge or death. Rh incompatibility (odds ratio [OR]: 48.6) and sepsis (OR: 20.6) greatly increased the risk for ABE/BE, but TSB levels correlated poorly with the presence or absence of ABE or BE in these patients. The OR for ABO incompatibility with anemia (1.8) was not statistically significant. Low admission weight (OR: 0.83 per 100 g) increased the risk for BE, especially when other risk factors were present. The threshold TSB level that identified 90% of infants with ABE/BE was 25.4 mg/dL when neuro-toxicity risk factors were present. In contrast, neurotoxicity was first observed at a TSB level of 31.5 mg/dL in 111 infants without risk factors. CONCLUSIONS: Newborns without risk factors for neurotoxicity have a higher tolerance for hyperbilirubinemia than recognized in management guidelines. The risk for BE in hemolytic disease varies with etiol-ogy. The great variation in response to TSB indicates that biological factors other than TSB values are important in the pathogenesis of BE. KEY WORDS kernicterus, neonatal hyperbilirubinemia, bilirubin encephalopathy, acute bilirubin encephalopathy, BIND score, risk factors for kernicterus ABBREVIATIONS AAP-American Academy of Pediatrics TSB-total serum bilirubin BE-bilirubin encephalopathy ABE-acute bilirubin encephalopathy BIND-bilirubin-induced neurologic dysfunction OR-odds ratio PPV-positive predictive value ROC-receiver operator characteristic FPR-false-positive rate
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-015-0358-z) contains supplementary material, which is available to authorized users.
WHAT'S KNOWN ON THIS SUBJECT: Jaundiced newborns without additional risk factors rarely develop kernicterus if the total serum bilirubin is ,25 mg/dL. Measuring the bilirubin/albumin ratio might improve risk assessment, but the relationships of both indicators to advancing stages of neurotoxicity are poorly documented.WHAT THIS STUDY ADDS: Both total serum bilirubin and bilirubin/albumin ratio are strong predictors of advancing stages of acute and post-treatment auditory and neurologic impairment. However, bilirubin/albumin ratio, adjusted to the same sensitivity, does not improve prediction over total serum bilirubin alone. abstract BACKGROUND AND OBJECTIVE: Bilirubin/albumin ratio (B/A) may provide a better estimate of free bilirubin than total serum bilirubin (TSB), thus improving identification of newborns at risk for bilirubin encephalopathy. The objective of the study was to identify thresholds and compare specificities of TSB and B/A in detecting patients with acute and posttreatment auditory and neurologic impairment. METHODS:A total of 193 term/near-term infants, admitted for severe jaundice to Cairo University Children's Hospital, were evaluated for neurologic status and auditory impairment (automated auditory brainstem response), both at admission and posttreatment by investigators blinded to laboratory results. The relationships of TSB and B/A to advancing stages of neurotoxicity were compared by using receiver operating characteristic curves.RESULTS: TSB and B/A ranged from 17 to 61 mg/dL and 5.4 to 21.0 mg/g, respectively; 58 (30%) of 193 subjects developed acute bilirubin encephalopathy, leading to kernicterus in 35 infants (13 lethal). Auditory impairment was identified in 86 (49%) of 173 infants at admission and in 22 of 128 at follow-up. In the absence of clinical risk factors, no residual neurologic or hearing impairment occurred unless TSB exceeded 31 mg/dl. However, transient auditory impairment occurred at lower TSB and B/A (22.9 mg/dL and 5.7 mg/g, respectively). Intervention values of TSB and B/A set at high sensitivity to detect different stages of neurotoxicity had nearly the same specificity. CONCLUSIONS:
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