Background & Objectives: The WHO regards glucose-6-phosphate dehydrogenase (G6PD) deficient female heterozygotes as being at low risk for neonatal hyperbilirubinemia. Because of difficulty in identifying this genotype, this concept may have been based on inadequate data as to the frequency of hyperbilirubinemia. We assessed hyperbilirubinemia, defined as serum bilirubin >15 mg/dL, and hemolysis, by blood carboxyhemoglobin (COHb) determinations, in females categorized for G-6-PD genotype.

Methods: Consecutively born, healthy, term, Sephardic Jewish female neonates, were screened for G6PD deficiency and observed for hyperbilirubinemia until stabilization of the jaundice. On day three, blood was sampled for COHb, total hemoglobin (tHb), and serum bilirubin. Additional bilirubin values were obtained as clinically indicated. COHb was determined by gas chromatography, expressed as percentage of tHb, and corrected for inspired CO (COHbc).A color reduction kit (Sigma Diagnostics) was used to screen for G6PD deficiency. DNA was analysed for the G6PD Mediterranean563T mutation.

Results: 54 heterozygotes and 19 homozygotes for G6PD Mediterranean were found. 112 were homozygous normal. The screening test identified 107 (95.5%) of the normal homozygotes, 16 (84%)of the G6PD deficient homozygotes, but only 11 (20.4%) of the heterozygotes. Significantly more heterozygotes (12/54 [22%], relative risk 2.26, 95% CI 1.07 to 4.80) and deficient homozygotes (5/19 [26.3%], relative risk 2.68, 95% CI 1.05 to 6.90) developed hyperbilirubinemia than normal homozygotes (11/112, [9.8%], defined as relative risk=1.0). Third day serum bilirubin values were greater in both the deficient homozygotes (12.0 ± 3.0 mg/dL) and heterozygotes (11.2±3.7 mg/dL) than in normal homozygotes (9.4 ± 3.4 mg/dL), p<0.01). COHbc values were higher in deficient homozygotes (0.74 ± 0.14%, p=0.02), but not in heterozygotes (0.69 ± 0.19%, NS) than controls (0.63 ± 0.19%). COHbc values were similar in hyperbilirubinemic and non-hyperbilirubinemic neonates of the same G-6-PD genotype. tHb was similar throughout.

Conclusions: Surprisingly, not only homozygous G6PD deficient females, but heterozygotes as well, are at significantly increased risk for neonatal hyperbilirubinemia. Increased hemolysis can not entirely explain the jaundice. As few heterozygotes could be diagnosed by the screening test, females of population groups with a high incidence of G-6-PD deficiency must be regarded as being at high risk for neonatal jaundice, even if screening tests read normal.