Related Experiment Videos
Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal
M Kaplan1, C Hammerman, P Renbaum
1Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel. kaplan@cc.huji.ac.il
Insights
This study compared how hemolysis and UGT gene variations affect newborn jaundice in glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and normal infants. Hemolysis significantly impacts bilirubin levels in G-6-PD deficient infants, especially by day 3.
Area of Science:
- Neonatal Medicine
- Genetics
- Biochemistry
Background:
- Perinatal bilirubinemia is a common concern in newborns.
- Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is a prevalent genetic condition affecting red blood cells.
- UDP-glucuronosyltransferase (UGT) gene promoter polymorphisms, like those in Gilbert's syndrome, can influence bilirubin metabolism.
Purpose of the Study:
- To compare the contributions of hemolysis and UGT gene promoter polymorphism to neonatal hyperbilirubinemia.
- To investigate these contributions in both G-6-PD deficient and G-6-PD normal neonates.
- To analyze the temporal changes in these contributions during the first three days of life.
Main Methods:
- Serum total bilirubin (STB) and blood carboxyhemoglobin corrected for inspired CO (COHbc) were measured in G-6-PD deficient (n=52) and normal (n=166) term male neonates.
- Samples were collected within 3 hours of delivery and on day 3.
- UGT promoter genotype was analyzed in relation to STB and COHbc values.
Main Results:
- G-6-PD deficient neonates exhibited higher COHbc levels, indicating increased hemolysis, at both sampling points.
- Second sample COHbc values correlated significantly with STB in G-6-PD normal neonates, but not in deficient ones.
- A higher frequency of variant UGT promoter alleles was observed in G-6-PD deficient neonates with elevated STB values on day 3.
Conclusions:
- Both hemolysis and UGT gene promoter polymorphism contribute to neonatal hyperbilirubinemia.
- The relative importance of hemolysis and UGT polymorphism varies between G-6-PD deficient and normal neonates.
- These factors show changing contributions to bilirubin levels during the initial three days of life.
Abstract:
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.