Risk factors for severe neonatal hyperbilirubinemia in low and middle-income countries: a systematic review and meta-analysis.

Bolajoko O Olusanya,Tina M Slusher,Folasade B Osibanjo,Waldemar A Carlo

doi:10.1371/journal.pone.0117229

Abstract

BackgroundAvailable evidence suggests that low- and middle-income countries (LMICs) bear the greatest burden of severe neonatal hyperbilirubinemia characterized by disproportionately high rates of morbidity, mortality and neurodevelopmental disorders compared to high-income countries. We set out to identify the risk factors that contribute to the burden of severe hyperbilirubinemia in the most developmentally disadvantaged LMICs to highlight areas for action and further research.MethodsWe systematically searched PubMed, Scopus, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), WHO Library Database (WHOLIS), African Index Medicus (AIM), African Journals Online (AJOL), LILACS, and IndMed for reports published between January 1990 and June 2014. We included only studies that controlled for the effects of confounding variables in determining maternal and infant risk factors for severe hyperbilirubinemia. We conducted meta-analysis of the eligible studies and computed the summary risk estimates with random effects models.ResultsA total of 13 studies with 1,951 subjects and 32,208 controls from India, Nigeria, Pakistan, Nepal and Egypt were identified and analyzed. The pooled data showed that primiparity (OR, 1.59; 95% CI:1.26-2.00), delivery outside public hospitals (OR, 6.42; 95% CI:1.76-23.36), ABO incompatibility (OR, 4.01; 95% CI:2.44-6.61), Rhesus hemolytic disease (OR, 20.63; 95% CI:3.95-107.65), G6PD deficiency (OR, 8.01; 95% CI:2.09-30.69), UGT1A1 polymorphisms (OR, 4.92; 95% CI:1.30-18.62), low gestational age (OR, 1.71; 95% CI:1.40-2.11), underweight/weight loss (OR, 6.26; 95% CI:1.23-31.86), sepsis (OR, 9.15; 95% CI:2.78-30.10) and high transcutaneous/total serum bilirubin levels (OR, 1.46; 95% CI:1.10-1.92) placed infants at increased risk of severe hyperbilirubinemia or bilirubin induced neurologic dysfunctions. Low social class was not associated with an increased risk of severe hyperbilirubinemia.ConclusionsInfants at risk of severe hyperbilirubinemia in LMICs are associated with maternal and neonatal factors that can be effectively addressed by available interventions to curtail the disease burden prevailing in the affected countries.

Highlights

Some degree of neonatal jaundice or hyperbilirubinemia is an unpreventable condition in 60%–80% of newborns worldwide [1,2]
Available evidence suggests that low- and middle-income countries (LMICs) bear the greatest burden of severe neonatal hyperbilirubinemia characterized by disproportionately high rates of morbidity, mortality and neurodevelopmental disorders compared to high-income countries
The pooled data showed that primiparity (OR, 1.59; 95% confidence intervals (CIs):1.26-2.00), delivery outside public hospitals (OR, 6.42; 95% CI:1.76-23.36), ABO incompatibility (OR, 4.01; 95% CI:2.44-6.61), Rhesus hemolytic disease (OR, 20.63; 95% CI:3.95-107.65), glucose-6-phosphate dehydrogenase (G6PD) deficiency (OR, 8.01; 95% CI:2.09-30.69), urine-diphosphateglucuronosyltransferase 1A1 gene (UGT1A1) polymorphisms (OR, 4.92; 95% CI:1.30-18.62), low gestational age (OR, 1.71; 95% CI:1.40-2.11), PLOS ONE | DOI:10.1371/journal.pone

Summary

Introduction

Some degree of neonatal jaundice or hyperbilirubinemia is an unpreventable condition in 60%–80% of newborns worldwide [1,2]. In a proportion of infants, jaundice may become severe, progressing to acute bilirubin encephalopathy (ABE) or kernicterus with a significant risk of neonatal mortality [3,4]. Suggests that low- and middle-income countries (LMICs) disproportionately bear the burden of severe neonatal hyperbilirubinemia [9,10]. This systematic review and meta-analysis set out to determine the risk factors for severe hyperbilirubinemia in LMICs in line with PRISMA guidelines [16] to inform health care policy and practice in and for the region. Available evidence suggests that low- and middle-income countries (LMICs) bear the greatest burden of severe neonatal hyperbilirubinemia characterized by disproportionately high rates of morbidity, mortality and neurodevelopmental disorders compared to high-income countries. We set out to identify the risk factors that contribute to the burden of severe hyperbilirubinemia in the most developmentally disadvantaged LMICs to highlight areas for action and further research

Methods

Results

Conclusion