Advances to diminish global newborn kernicterus mortality.

OBJECTIVE: Initiatives, "Every Newborn Action Plans" and "Sustainable Developmental Goals," are profoundly shaping global infant mortality trends. Concurrently, professional organizations recommended curricula to prevent extreme hyperbilirubinemia (EHB) sequelae. Therefore we assessed if these efforts have successfully decreased EHB-related mortality over time. STUDY DESIGN: We used the Global Burden of Diseases 2019 database to determine neonatal and infant mortality and the burden of kernicterus from 1990-2019. RESULTS: Globally, kernicterus accounted for 2.8 million infant deaths and trended downwards significantly from 1990 to 2019. By 2019, kernicterus-related mortality was 4 and 293 per million livebirths in high (HICs) and low income countries (LICs), respectively. 82% of deaths occurred in LICs and lower-middle income-countries. Average declines of mortality rates were 6.2% and 3.0% for HICs and LICs, respectively. CONCLUSIONS: Kernicterus-related mortality has been effectively reduced to <5 per million in HICs. Skills and knowledge transfer can potentially transform frontline services to bridge discordant kernicteric outcomes worldwide.

Neonatal Hyperbilirubinemia: Evaluation and Treatment.

Neonatal jaundice due to hyperbilirubinemia is common, and most cases are benign. The irreversible outcome of brain damage from kernicterus is rare (1 out of 100,000 infants) in high-income countries such as the United States, and there is increasing evidence that kernicterus occurs at much higher bilirubin levels than previously thought. However, newborns who are premature or have hemolytic diseases are at higher risk of kernicterus. It is important to evaluate all newborns for risk factors for bilirubin-related neurotoxicity, and it is reasonable to obtain screening bilirubin levels in newborns with risk factors. All newborns should be examined regularly, and bilirubin levels should be measured in those who appear jaundiced. The American Academy of Pediatrics (AAP) revised its clinical practice guideline in 2022 and reconfirmed its recommendation for universal neonatal hyperbilirubinemia screening in newborns 35 weeks' gestational age or greater. Although universal screening is commonly performed, it increases unnecessary phototherapy use without sufficient evidence that it decreases the incidence of kernicterus. The AAP also released new nomograms for initiating phototherapy based on gestational age at birth and the presence of neurotoxicity risk factors, with higher thresholds than in previous guidelines. Phototherapy decreases the need for an exchange transfusion but has the potential for short- and long-term adverse effects, including diarrhea and increased risk of seizures. Mothers of infants who develop jaundice are also more likely to stop breastfeeding, even though discontinuation is not necessary. Phototherapy should be used only for newborns who exceed thresholds recommended by the current AAP hour-specific phototherapy nomograms.

[Interpretation of the 2022 American Academy of Pediatrics guidelines for the management of hyperbilirubinemia in newborn infants]. / 2022ç‰ˆç¾Žå›½å„¿ç§‘å­¦ä¼šæ–°ç”Ÿå„¿é«˜èƒ†çº¢ç´ è¡€ç—‡ç®¡ç†æŒ‡å—è§£è¯».

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

Evidence Suggests a Decrease in the Incidence of Kernicterus in California.

We identified children diagnosed with kernicterus in the California Department of Developmental Services and estimated an incidence of 0.42 per 100 000 births from 1988 to 2014, significantly decreasing to 0.04 per 100 000 births after 2009. We also examined national infant kernicterus mortality from 1979 to 2016 using CDC data. It did not decrease significantly.

Chemoprevention of bilirubin encephalopathy with a nanoceutical agent.

BACKGROUND: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-Mn3O4 NP, the nanodrug) to degrade both systemic and neural bilirubin loads. METHOD: Severe neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine (PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated. RESULTS: Single oral dose (0.25 mg kg-1 bodyweight) of the nanodrug reduced both total serum bilirubin (TSB) and unconjugated bilirubin (UCB) in SNH rodents. Significant (p < 0.0001) UCB and TSB-degradation rates were reported within 4-8 h at 1.84 ± 0.26 and 2.19 ± 0.31 mg dL-1 h-1, respectively. Neural bilirubin load was decreased by 5.6 nmol g-1 (p = 0.0002) along with improved measures of neurobehavior, neuromotor movements, learning, and memory. Histopathological studies confirm that the nanodrug prevented neural cell reduction in Purkinje and substantia nigra regions, eosinophilic neurons, spongiosis, and cell shrinkage in SNH brain parenchyma. Brain oxidative status was maintained in nanodrug-treated SNH cohort. Pharmacokinetic data corroborated the bilirubin degradation rate with plasma nanodrug concentrations. CONCLUSION: This study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings. IMPACT: None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs), exhibits bilirubin reduction properties in rodents. Chemopreventive properties of this nano-formulation demonstrate an efficacious, efficient agent that appears to be safe in these early studies. Translation of C-Mn3O4 NPs to prospective preclinical and clinical trials in appropriate in vivo models should be explored as a potential novel pharmacotherapy for SNH.

Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.

CONTEXT: Severe hyperbilirubinemia is associated with kernicterus. Informed guidance on hyperbilirubinemia management, including preventive treatment thresholds, is essential to safely minimize neurodevelopmental risk. OBJECTIVE: To update the evidence base necessary to develop the 2022 American Academy of Pediatrics clinical practice guideline for management of hyperbilirubinemia in the newborn infant ≥35 weeks' gestation. DATA SOURCE: PubMed. STUDY SELECTION: English language randomized controlled trials and observational studies. Excluded: case reports or series, nonsystematic reviews, and investigations focused on <35-weeks' gestation infants. DATA EXTRACTION: Topics addressed in the previous clinical practice guideline (2004) and follow-up commentary (2009) were updated with new evidence published through March 2022. Evidence reviews were conducted for previously unaddressed topics (phototherapy-associated adverse effects and effectiveness of intravenous immune globulin [IVIG] to prevent exchange transfusion). RESULTS: New evidence indicates that neurotoxicity does not occur until bilirubin concentrations are well above the 2004 exchange transfusion thresholds. Systematic review of phototherapy-associated adverse effects found limited and/or inconsistent evidence of late adverse effects, including cancer and epilepsy. IVIG has unclear benefit for preventing exchange transfusion in infants with isoimmune hemolytic disease, with a possible risk of harm due to necrotizing enterocolitis. LIMITATIONS: The search was limited to 1 database and English language studies. CONCLUSIONS: Accumulated evidence justified narrowly raising phototherapy treatment thresholds in the updated clinical practice guideline. Limited evidence for effectiveness with some evidence of risk of harm support the revised recommendations to limit IVIG use.

Neonatal Hyperbilirubinemia.

Neonatal hyperbilirubinemia (NH) is a common phenomenon. In most cases, NH is benign and transient. However, in severe NH cases, neonates can develop encephalopathy and kernicterus. With appropriate screening and treatment, these adverse sequelae can be prevented. This article aims to provide the reader with an in-depth understanding of (1) bilirubin metabolism, (2) risk factors for severe NH, (3) NH screening and treatment, (4) various etiologies of severe NH, and (5) consequences of severe, untreated NH. [Pediatr Ann. 2022;51(6):e219-e227.].

Normalizing hyperactivity of the Gunn rat with bilirubin-induced neurological disorders via ketanserin.

BACKGROUND: Severe neonatal hyperbilirubinemia has been known to cause the clinical syndrome of kernicterus and a milder one the syndrome of bilirubin-induced neurologic dysfunction (BIND). BIND clinically manifests itself after the neonatal period as developmental delay, cognitive impairment, and related behavioral and psychiatric disorders. The complete picture of BIND is not clear. METHODS: The Gunn rat is a mutant strain of the Wistar rat with the BIND phenotype, and it demonstrates abnormal behavior. We investigated serotonergic dysfunction in Gunn rats by pharmacological analyses and ex vivo neurochemical analyses. RESULTS: Ketanserin, the 5-HT2AR antagonist, normalizes hyperlocomotion of Gunn rats. Both serotonin and its metabolites in the frontal cortex of Gunn rats were higher in concentrations than in control Wistar rats. The 5-HT2AR mRNA expression was downregulated without alteration of the protein abundance in the Gunn rat frontal cortex. The TPH2 protein level in the Gunn rat raphe region was significantly higher than that in the Wistar rat. CONCLUSIONS: It would be of value to be able to postulate that a therapeutic strategy for BIND disorders would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after onset of BIND manifestations. IMPACT: We demonstrated serotonergic dysregulation underlying hyperlocomotion in Gunn rats. This finding suggests that a therapeutic strategy for bilirubin-induced neurologic dysfunction (BIND) would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after the onset of the BIND manifestations. Ketanserin normalizes hyperlocomotion of Gunn rats. To our knowledge, this is the first study to demonstrate a hyperlocomotion link to serotonergic dysregulation in Gunn rats.

Acute bilirubin encephalopathy: Some lessons learned.

Acute bilirubin encephalopathy (ABE) is still an insufficiently addressed cause of mortality and long-term morbidity in low- and middle-income countries (LMICs). This article highlights that delayed or incorrect medical advice, inaccurate bilirubin measurements as well as ineffective phototherapy are some of the relevant causes predisposing jaundiced newborns to develop extreme hyperbilirubinemia [EHB, total serum/plasma bilirubin (TB) ≥ 25 mg/dL (428 µmol/L)] and subsequent ABE. Obstacles preventing state of the art management of such infants are also discussed. Prevention of ABE cannot occur without a system-based approach tailored to suit the needs and available resources of each community. Clear set protocols, rigorous training, monitoring, and accurate documentation together with simple innovative affordable technologies that can be locally produced, are essential to observe the change desired.

Combating the Hidden Health Disparity of Kernicterus in Black Infants: A Review.

Importance: Kernicterus is a devastating, permanently disabling neurologic condition resulting from bilirubin neurotoxicity. Black neonates account for more than 25% of kernicterus cases in the US, despite making up only approximately 14% of all births. This is a largely overlooked health disparity. Observations: The black kernicterus health disparity exists despite a lower overall incidence of clinically significant hyperbilirubinemia among black neonates, a paradox recently explained by a previously unrecognized risk for hazardous hyperbilirubinemia. Aligned with national and global health initiatives to reduce or eliminate health disparities, this review highlights the multiple biologic and nonbiologic factors contributing to kernicterus risk in black infants and approaches to reduce this health disparity. This includes both parent-level and clinician-level kernicterus prevention strategies, with an emphasis on improving parental health literacy on neonatal jaundice and acute bilirubin encephalopathy and clinician awareness of the key factors that contribute to hazardous hyperbilirubinemia risk in this vulnerable group. Parent-level prevention strategies include efforts to improve their health literacy on neonatal jaundice and acute bilirubin encephalopathy and empower care seeking for jaundice. Clinician-level prevention strategies include efforts to eliminate community and institutional barriers that impede access to care, heighten clinician awareness of the factors that contribute to kernicterus risk in this vulnerable patient group, and strengthen newborn hyperbilirubinemia management and bilirubin surveillance. Conclusions and Relevance: There are multiple opportunities for intervention to reduce black kernicterus risk. Although kernicterus is a rare disorder, the incidence among black infants is not a trivial matter nor are efforts to prevent kernicterus. While the multiple interacting biologic and nonbiologic contributors to increased kernicterus risk among black infants pose a considerable challenge to clinicians, there are opportunities for intervention to reduce this risk and health disparity. Continued study is imperative to understand the current scope of kernicterus and its occurrence in black neonates.

[An update on unconjugated neonatal hyperbilirubinaemia in Denmark].

Approximately 60% of term newborn infants are jaundiced during the first week of life, which is caused by unconjugated bilirubin. Bilirubin encephalopathy is seen with severe hyperbilirubinaemia, when unbound bilirubin crosses the blood-brain barrier. The chronic form is called kernicterus spectrum disorder. To avoid this devastating condition, the treatment of choice for neonatal hyperbilirubinaemia is phototherapy, which is most efficient with LED light of 478-nm wavelength. In this review, we argue, that a systematic approach to hyperbilirubinaemic infants as well as surveillance of extreme neonatal hyperbilirubinaemia is highly important.

Maternal Instruction About Jaundice and the Incidence of Acute Bilirubin Encephalopathy in Nigeria.

OBJECTIVE: To evaluate whether teaching mothers about neonatal jaundice will decrease the incidence of acute bilirubin encephalopathy among infants admitted for jaundice. STUDY DESIGN: This was a multicenter, before-after and cross-sectional study. Baseline incidences of encephalopathy were obtained at 4 collaborating medical centers between January 2014 and May 2015 (Phase 1). Structured jaundice instruction was then offered (May to November 2015; Phase 2) in antenatal clinics and postpartum. Descriptive statistics and logistic regression models compared 3 groups: 843 Phase 1 controls, 338 Phase 2 infants whose mothers received both antenatal and postnatal instruction (group A), and 215 Phase 2 infants whose mothers received no instruction (group B) either because the program was not offered to them or by choice. RESULTS: Acute bilirubin encephalopathy occurred in 147 of 843 (17%) Phase 1 and 85 of 659 (13%) Phase 2 admissions, which included 63 of 215 (29%) group B and 5 of 338 (1.5%) group A infants. OR for having acute bilirubin encephalopathy, comparing group A and group B infants adjusted for confounding risk factors, was 0.12 (95% CI 0.03-0.60). Delayed care-seeking (defined as an admission total bilirubin ≥18 mg/dL at age ≥48 hours) was the strongest single predictor of acute bilirubin encephalopathy (OR 11.4; 6.6-19.5). Instruction decreased delay from 49% to 17%. Other major risk factors were home births (OR 2.67; 1.69-4.22) and hemolytic disease (hematocrit ≤35% plus bilirubin ≥20 mg/dL) (OR 3.03; 1.77-5.18). The greater rate of acute bilirubin encephalopathy with home vs hospital birth disappeared if mothers received jaundice instruction. CONCLUSIONS: Providing information about jaundice to mothers was associated with a reduction in the incidence of bilirubin encephalopathy per hospital admission.

Improving the Bilirubin Management Program in the Newborn Nursery: Background, Aims, and Protocol.

BACKGROUND: Practices to detect and manage hyperbilirubinemia in newborn nurseries are highly variable. American Academy of Pediatrics guidelines in 1999, 2004, and 2009 have generated, perhaps unintentionally, divergent practices that might not all be of equivalent value. Evidence-based progress is needed to define less invasive, less expensive, uniform, and safe methods to reduce ER visits and hospital readmissions for jaundice treatment and bilirubin encephalopathy. OBJECTIVES: This research briefing is intended to inform readers of a new prospective quality improvement program aimed at testing the value of specific changes in newborn nursery hyperbilirubinemia detection and management. This new program includes predetermined means of assessing those specific changes, which relate to diagnosis, safety, outcomes, and cost. METHODS: In this briefing, we present the perceived problems in our present bilirubin management system, as voiced by stakeholders. We report our proposed means to test minimization of those problems utilizing already acquired data on approximately 400,000 well babies in the Intermountain Healthcare system of hospitals in the western USA. We then describe our methods of assessing specific outcomes in a pre- versus postpractice change analysis. RESULTS AND CONCLUSIONS: The University of Utah Newborn Nursery will implement a quality improvement project in bilirubin management during 2020 to test the feasibility and effectiveness of several changes to our current bilirubin management program. We maintain that the improved understanding generated by this project will be a step toward new evidence-based strategies for reducing ER visits and hospital readmissions for jaundice treatment and preventing bilirubin encephalopathy.

Review of bilirubin neurotoxicity II: preventing and treating acute bilirubin encephalopathy and kernicterus spectrum disorders.

Previously in Part I of this two-part review, we discussed the current and recent advances in the understanding of the molecular biology and neuropathology of bilirubin neurotoxicity (BNTx). Here in Part II, we summarize current treatment options available to treat the severely jaundiced infants to prevent significant brain damage and improve clinical outcomes. In addition, we review potential novel therapies that are in various stages of research and development. We will emphasize treatments for both prevention and treatment of both acute bilirubin encephalopathy (ABE) and kernicterus spectrum disorders (KSDs), highlighting the treatment of the most disabling neurological sequelae of children with mild-to-severe KSDs whose "rare disease" status often means they are overlooked by the clinical research community at large. As with other secondary dystonias, treatment of the dystonic motor symptoms in kernicterus is the greatest clinical challenge.

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria.

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7 days of age, and on the reference values for corrected gestational age at ≥7 days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.

Outcomes of neonatal jaundice in Taiwan.

OBJECTIVE: To investigate the burden of clinically significant neonatal jaundice (SNJ) in Taiwan, 2000-2010. STUDY DESIGN: The nationwide, population-based health insurance database in Taiwan was used to investigate the incidence, kernicterus rate and mortality rates of SNJ cohort born between 2000 and 2010. RESULTS: From 2000 to 2010, up to 242 546 patients admitted with neonatal jaundice (NJ) were identified. The incidence of SNJ was 5.9% in 2000 and increased to 13.7% in 2010 (P<0.001). The mortality rate significantly decreased from 0.51% in 2000 to 0.26% in 2010 (P<0.001) and the average incidence of kernicterus was 0.86 per 100 000 live births, indicating dramatically decreased rates compared with earlier rates in Taiwan. CONCLUSIONS: In spite of the increased incidence rates, the rates of mortality and kernicterus in patients with NJ significantly declined in Taiwan. The public health prevention programme, clinicians' awareness and effective management might contribute to the reduction of these acute severe sequelae.

Fluid supplementation for neonatal unconjugated hyperbilirubinaemia.

BACKGROUND: Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation. OBJECTIVES: To assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs). MAIN RESULTS: Out of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.There were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.In the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 µmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).One study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 µmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 µmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension. AUTHORS' CONCLUSIONS: There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.

Maternal Empowerment - An Underutilized Strategy to Prevent Kernicterus?

BACKGROUND: Kernicterus is a common cause of death and morbidity in many Low- Middle-income Countries (LMICs) and still occurs in affluent nations. In either case, the immediate cause is delayed treatment of severe hyperbilirubinemia. In the West, a provider driven "systems approach" has been widely adopted to identify babies at risk prior to discharge from birthing centers with follow up monitoring based on the serum bilirubin level at time of discharge. The situation is more complicated in regions of the world where kernicterus is endemic, especially in LMICs where Glucose-6-phosphate Dehydrogenase Deficiency (G6PDd) is common and the system of jaundice management is often fragmented. OBJECTIVE: To examine reasons for errors in jaundice management leading to kernicterus and the potential beneficial role of enlisting more parental participation in management decisions. METHOD: We searched world literature related to pitfalls in jaundice management including deficiencies in providers' and parents' knowledge and behavior. Perspectives from mothers of children with kernicterus supplemented the literature review. RESULT: System failures contributing to kernicterus in affluent countries include a lack of follow up planning, bad advice by providers, and a delay in care seeking by parents. In many LMICs, the majority of births occur at home with unskilled attendants. Traditional practices potentiate hemolysis in G6PDd babies. The danger of severe jaundice is frequently underestimated both by parents and care providers, and cultural and economic barriers as well as ineffective therapies delay care seeking. The failure to provide parents information about identifying severe jaundice and knowledge about the risks and treatment of hyperbilirubinemia has contributed to delayed treatment in both affluent and low-middle-income countries. A recent non-randomized clinical trial, supports teaching all parents skills to monitor jaundice, signs of early neurotoxicity, the importance of breast feeding, avoidance of ineffective or dangerous practices, and when/where to seek help. CONCLUSION: Empowering parents allow them to participate more fully in care decisions and to confront obstacles to care when provider services fail.