05 was considered to be statistically significant. The heterogeneity assumption was checked using an I2 statistic. An I2 value of > check details 50% signified “substantial heterogeneity”, and a random effects model was used. An I2 value of ≤ 50% showed the absence of heterogeneity and defaulted to the fixed effects model approach. Funnel plots and Egger’s linear regression test were used to identify potential publication bias, and p < 0.05 was considered indicative of statistically significant

publication bias. The literature search identified 546 articles on the association between genetic polymorphisms and neonatal hyperbilirubinemia. Of these, 536 were subsequently excluded after screening of abstracts or full texts. Ultimately, 10 articles were assessed as useful for the systematic review with meta-analysis,11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 and nine studies were included in the meta-analysis.11, 12, 13, 14, 15, 16, 17, 18 and 19 The flow diagram of study identification is shown in Fig. 1. These studies were conducted on six countries (China, Malaysia, Thailand, the United States, Brazil, and Turkey). They included 1,164 cases of neonatal hyperbilirubinemia and 1,416 controls. The characteristics of the included studies Hydroxychloroquine concentration are summarized in Table 1. In one study included in the systematic review, there were no statistically significant differences in the risk

of neonatal hyperbilirubinemia for the 388 G>A and 521 T>C variants of SLCO1B1.11 Nine studies were included in the meta-analysis, which assessed the association

between the SLCO1B1 388 G>A mutation and neonatal hyperbilirubinemia (Table 2).12, 13, 14, 15, 16, 17, 18, 19 and 20 Results of the meta-analysis indicated that there was no statistically significant difference in the risk of neonatal hyperbilirubinemia between SLCO1B1 388 G>A allele carriers (A/A+G/A) and G/G allele carriers (OR, 1.07; 95% CI: 0.90–1.28) (Fig. 2). A significant inter-study heterogeneity was observed (p = 0.00). Egger’s test provided no evidence for funnel plot asymmetry in the comparison of the SLCO1B1 388 G>A mutation and neonatal hyperbilirubinemia (t = 2.12, p = 0.07). Additionally, in the subgroup analyses based on ethnicity, no significant associations were found in white (OR, 1.01; 95% CI: 0.69–1.49), Asian, Thai, Latin American, or SB-3CT Malaysian populations (Table 3). However, significantly elevated risks were found in the SLCO1B1 388 G>A variant genotypes in Chinese neonates (OR, 1.39; 95% CI: 1.07–1.82). A significant inter-study heterogeneity was also observed in subgroup analysis of Asian populations (p = 0.02). Meta-analysis comparing the A allele to the G allele in the SLCO1B1 388 G>A mutation also showed an increased risk of neonatal hyperbilirubinemia (OR, 1.32; 95% CI: 1.06–1.64) in Chinese neonates, but not in white, Thai, Latin American, or Malaysian populations (Fig. 3 and Table 3).