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      Risk Factors for Severe Neonatal Hyperbilirubinemia in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis

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      1 , * , 2 , 3 , 4
      PLoS ONE
      Public Library of Science

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          Abstract

          Background

          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

          We 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.

          Results

          A 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.

          Conclusions

          Infants 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.

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          Most cited references27

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          Observational studies: cohort and case-control studies.

          Observational studies constitute an important category of study designs. To address some investigative questions in plastic surgery, randomized controlled trials are not always indicated or ethical to conduct. Instead, observational studies may be the next best method of addressing these types of questions. Well-designed observational studies have been shown to provide results similar to those of randomized controlled trials, challenging the belief that observational studies are second rate. Cohort studies and case-control studies are two primary types of observational studies that aid in evaluating associations between diseases and exposures. In this review article, the authors describe these study designs and methodologic issues, and provide examples from the plastic surgery literature.
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            Absence of evidence is not evidence of absence.

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              Incorporating variability in estimates of heterogeneity in the random effects model in meta-analysis.

              When combining results from separate investigations in a meta-analysis, random effects methods enable the modelling of differences between studies by incorporating a heterogeneity parameter tau 2 that accounts explicitly for across-study variation. We develop a simple form for the variance of Cochran's homogeneity statistic Q, leading to interval estimation of tau 2 utilizing an approximating distribution for Q; this enables us to extend the point estimation of DerSimonian and Laird. We also develop asymptotic likelihood methods and compared them with this method. We then use these approximating distributions to give a new method of calculating the weight given to the individual studies' results when estimating the overall mean which takes into account variation in these point estimates of tau 2. Two examples illustrate the methods presented, where we show that the new weighting scheme is between the standard fixed and random effects models in down-weighting the results of large studies and up-weighting those of small studies.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 February 2015
                2015
                : 10
                : 2
                Affiliations
                [1 ]Director, Centre for Healthy Start Initiative, Ikoyi, Lagos, Nigeria
                [2 ]Maternal and Child Health Unit, Centre for Healthy Start Initiative, Ikoyi, Lagos, Nigeria
                [3 ]Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, United States of America
                [4 ]Hennepin County Medical Center, Minneapolis, Minnesota, United States of America
                University of Alabama at Birmingham, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BOO. Performed the experiments: BOO FBO TMS. Analyzed the data: BOO. Contributed reagents/materials/analysis tools: FBO TMS. Wrote the paper: BOO FBO TMS. Reviewed and approved the final version: BOO FBO TMS.

                Article
                PONE-D-14-36696
                10.1371/journal.pone.0117229
                4326461
                25675342
                92f16517-dbf4-427b-9b47-6c5daaa233b1

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                Page count
                Figures: 2, Tables: 3, Pages: 16
                Product
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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