Onset of jaundice in glucose-6-phosphate dehydrogenase-deficient neonates

We asked whether neonatal jaundice associated with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency commences either in utero or in the immediate postnatal period and whether this perinatal bilirubinemia is the precursor of the subsequent neonatal jaundice and hyperbilirubinemia.

Mandatory serum total bilirubin (STB) determinations were performed within 3 hours of birth, to reflect the in utero state (first STB), and on the third day of life (second STB), with additional determinations as clinically necessary, on healthy, term male neonates at high risk for G-6-PD deficiency. G-6-PD Mediterranean mutation was determined by molecular means. G-6-PD-deficient neonates were compared with control participants. The relationship of first STB values to second STB and subsequent hyperbilirubinemia (defined as STB >/=256 micromol/L [15.0 mg/dL]) was determined.

Both first and second STB values were significantly higher in the G-6-PD-deficient neonates (n = 52) than in control participants (n = 166; 50 +/- 12 micromol/L vs 44 +/- 10 micromol/L [2.9 +/- 0.7 mg/dL vs 2.6 +/- 0.6 mg/dL] and 174 +/- 52 micromol/L vs 152 +/- 52 micromol/L [10.2 +/- 3.1 mg/dL vs 8.9 +/- 3.0 mg/dL] for the first and second STB values, respectively). The rate of rise between these 2 points was greater in the G-6-PD-deficient neonates (2.6 +/- 0.9 micromol/L/h vs 2.2 +/- 0.9 micromol/L/h [0.15 +/- 0.05 mg/dL/h vs 0.13 +/- 0.05 mg/dL/h). Sixteen (30.8%) of the G-6-PD-deficient neonates developed hyperbilirubinemia compared with 10 (6%) of control participants (relative risk: 5.11; 95% confidence interval: 2.47-10.56). In both G-6-PD-deficient and normal populations, first STB values correlated significantly with both second STB values and with those who subsequently developed hyperbilirubinemia. Significantly more G-6-PD-deficient neonates with a first STB value greater than or equal to the mean developed hyperbilirubinemia compared with those with first STB less than the mean: 13 of 28 neonates versus 3 of 24 (relative risk: 3.7; 95% confidence interval: 1.20-11.51). This difference did not reach statistical significance in the control group.

Higher first STB values, an increased risk of hyperbilirubinemia in G-6-PD-deficient neonates with first STB value greater than or equal to the mean, and significant correlation between first STB values and second STB values and hyperbilirubinemia suggest that jaundice in G-6-PD-deficient neonates commences in the immediate perinatal period, most likely in utero.