{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:17:04Z","timestamp":1790209024874,"version":"4.1.0"},"reference-count":43,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,7,1]]},"abstract":"<jats:sec><jats:title>Objectives.<\/jats:title><jats:p>We assessed the incidence of hyperbilirubinemia, defined as serum total bilirubin \u226515 mg\/dL (256 \u03bcmol\/L), in a cohort of Sephardic Jewish female neonates at risk for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency with especial emphasis on the heterozygotes. We studied the roles of hemolysis by blood carboxyhemoglobin (COHb) determinations and of the variant promoter of the gene for the bilirubin-conjugating enzyme uridine 5\u2032-diphosphate glucuronosyltransferase 1 (UGT1A1) seen in Gilbert's syndrome in the pathogenesis of the hyperbilirubinemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Consecutively born, healthy, term, female neonates were screened for G-6-PD deficiency and observed clinically with serum bilirubin evaluations as indicated for hyperbilirubinemia. On day 3, blood was sampled for COHb, total hemoglobin (tHb), and a mandatory serum bilirubin determination. COHb, determined by gas chromatography, was expressed as percentage of tHb and corrected for inspired carbon monoxide (COHbc). DNA was analyzed for the G-6-PD Mediterranean563T mutation and for the variant UGT1A1 gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>The cohort included 54 G-6-PD-deficient heterozygotes, 19 deficient homozygotes, and 112 normal homozygotes. More heterozygotes (12\/54, 22%; relative risk: 2.26; 95% CI: 1.07\u20134.80) and deficient homozygotes (5\/19, 26.3%; relative risk: 2.68; 95% CI: 1.05\u20136.90) developed hyperbilirubinemia, than did normal homozygotes (11\/112, 9.8%). Third-day serum bilirubin values that were obtained from 144 neonates were significantly higher in both heterozygotes (11.2 \u00b1 3.7 mg\/dL [192 \u00b1 64 \u03bcmol\/L]) and G-6-PD-deficient homozygotes (12.0 \u00b1 3.0 mg\/dL [206 \u00b1 52 \u03bcmol\/L]) than in the G-6-PD normal homozygotes (9.4 \u00b1 3.4 mg\/dL [160 \u00b1 58 \u03bcmol\/L). In contrast, COHbc values were higher only in G-6-PD-deficient homozygotes (0.74% \u00b1 0.14%) and not in heterozygotes (0.69% \u00b1 0.19%, not statistically significant), compared with control values (0.63% \u00b1 0.19%). High COHbc values were not a prerequisite for the development of hyperbilirubinemia in any of the G-6-PD genotypes. A greater incidence of hyperbilirubinemia was found among the G-6-PD-deficient heterozygotes, who also had the variant UGT1A1 gene, in both heterozygous (6\/20, 30%) and homozygous (4\/8, 50%) forms, than was found in their counterparts with the normal UGT1A1 gene (2\/26, 7.7%). This effect was not seen in the G-6-PD normal homozygote group. A color reduction screening test for G-6-PD deficiency identified only 20.4% (11\/54) of the heterozygotes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>We showed that G-6-PD-deficient heterozygotes, categorically defined by DNA analysis, are at increased risk for neonatal hyperbilirubinemia. The screening test that was used was unable to detect most heterozygotes. Increased bilirubin production was not crucial to the development of hyperbilirubinemia, but presence of the variant UGT1A1 gene did confer increased risk. bilirubin, carbon monoxide, carboxyhemoglobin, females, gas chromatography, Gilbert's syndrome, glucose-6-phosphate dehydrogenase deficiency, hemolysis, hyperbilirubinemia, neonates, polymerase chain reaction, Sephardic Jews, screening test, uridine 5\u2032-diphosphate glucuronosyltransferase.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.104.1.68","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:45:45Z","timestamp":1092440745000},"page":"68-74","source":"Crossref","is-referenced-by-count":105,"title":["Neonatal Hyperbilirubinemia in Glucose-6-Phosphate Dehydrogenase-deficient Heterozygotes"],"prefix":"10.1542","volume":"104","author":[{"given":"Michael","family":"Kaplan","sequence":"first","affiliation":[{"name":"From the Department of Neonatology, the"},{"name":"Faculty of Medicine of the Hebrew University, Jerusalem, Israel; Department of Molecular and Experimental Medicine, the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Beutler","sequence":"additional","affiliation":[{"name":"Scripps Research Institute, La Jolla, California; and Neonatal and Developmental Metabolism Laboratory,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J.","family":"Vreman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University Medical Center, Stanford, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Hammerman","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, the"},{"name":"Faculty of Medicine of the Hebrew University, Jerusalem, Israel; Department of Molecular and Experimental Medicine, the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephrat","family":"Levy-Lahad","sequence":"additional","affiliation":[{"name":"Medical Genetics Service, and the"},{"name":"Department of Internal Medicine, Shaare Zedek Medical Center, and the"},{"name":"Faculty of Medicine of the Hebrew University, Jerusalem, Israel; Department of Molecular and Experimental Medicine, the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Renbaum","sequence":"additional","affiliation":[{"name":"Medical Genetics Service, and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University Medical Center, Stanford, 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