Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal neonates.

The objective was to compare the contribution to perinatal bilirubinemia of hemolysis and UDP-glucuronosyltransferase (UGT) gene promoter polymorphism, seen in Gilbert's syndrome, between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal neonates. Serum total bilirubin (STB) values from 52 G-6-PD-deficient and 166 G-6-PD-normal term, male neonates, sampled within 3 h of delivery (first sample) and on d 3 (second sample), were analyzed in relation to blood carboxyhemoglobin corrected for inspired CO (COHbc), an accurate index of hemolysis, and UGT promoter genotype. COHbc values (% total Hb) were greater in G-6-PD-deficient neonates than controls: first sample 1.00 +/- 0.25% versus 0.84 +/- 0.24%, p < 0.0001; second sample 0.83 +/- 0.20% versus 0.76 +/- 0.19%, p = 0.002. First sample COHbc and STB values did not correlate in either the G-6-PD-deficient or control groups, whereas second sample COHbc values correlated significantly with corresponding STB values in the control population only (r = 0.28, p = 0.0007). At second sampling, there was a higher allele frequency of the variant UGT promoter among those with STB values > or =75th percentile than those <75th among the G-6-PD-deficient neonates (0.60 versus 0.33, respectively, p = 0.025), but not controls (0.31 versus 0.40, respectively, p = 0.24). Among those infants with at least one variant UGT promoter allele, STB values were higher in the G-6-PD-deficient neonates than controls at second sampling only (181 +/- 56 microM versus 149 +/- 46 microM, respectively, p = 0.03). Both within and between the G-6-PD-deficient and control groups, our data demonstrate changing and differing contributions of hemolysis and UGT promoter polymorphism to bilirubinemia during the first 3 d of life.