Risk factors for neonatal hyperbilirubinemia: a systematic review and meta-analysis

Background: Hyperbilirubinemia is the most common cause of neonatal hospitalization and, although it generally has a good prognosis, a significant percentage of neonatal patients maintain a high bilirubin level, which can lead to severe complications, including lifelong disability such as growth retardation, encephalopathy, autism and hearing impairment. The study of risk factors for neonatal hyperbilirubinemia has been controversial. Therefore, we evaluated the risk factors of neonatal hyperbilirubinemia using a meta-analysis. Methods: Relevant English and Chinese studies that discussed risk factors for neonatal hyperbilirubinemia were retrieved from the PubMed, EMBASE, Medline, Central, China National Knowledge Infrastructure (CNKI), Wanfang and China Science Digital Library (CSDL). The literature took newborns as the research object, set up a control group, and observed the relationship between exposure factors and neonatal hyperbilirubinemia. The combined effect size was expressed by odds ratio (OR) and 95% confidence interval (CI). The Chi-square test was used to test heterogeneity of the studies, and if it existed, subgroup analyses were used to explore the source of heterogeneity, and the random-effects model was selected for the combined analysis. The fixed-effects model was chosen for the combined analysis if there was no heterogeneity. Publication bias was assessed using Egger's test and funnel plot. Results: Risk factors for neonatal hyperbilirubinemia were exclusive breastfeeding (BF: OR =1.74, 95% CI: 1.42, 2.12, Z=5.43, P<0.00001); glucose-6-phosphate dehydrogenase deficiency (G6PD: OR =1.62, 95% CI: 1.44, 1.81, Z=8.39, P<0.00001); maternal-fetal ABO blood group incompatibility (OR =1.64, 95% CI: 1.42, 1.89, Z=6.75, P<0.00001); and preterm birth (PTB: OR =1.31, 95% CI: 1.17, 1.47, Z=4.60, P<0.00001); there was no heterogeneity or publication bias among the studies (BF: chi(2) =5.34, P=0.25, I-2 =25%; G6PD: chi(2) =4. 40 , P=0.49, I-2 =0%; ABO: chi(2) =1.91, P=0.75, I-2 =0%; PTB: chi(2) =0.81, P=0.67, I-2 =0%). Conclusions: Exclusive breastfeeding, G6PD deficiency, ABO incompatibility and premature birth were confirmed as risk factors for neonatal hyperbilirubinemia. Pregnant women with risk factors should be monitored more closely and clinical intervention should be given in a timely manner.