Objectives: Severe neonatal jaundice is a common clinical manifestation of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and the most difficult to manage; kernicterus is not an uncommon outcome. We assessed in healthy, direct Coombs test-negative Greek newborns of >/=38 weeks' gestational age 1) the current burden of G-6-PD deficiency-associated severe jaundice, and 2) the efficacy of preventive use of Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase activity and thus of bilirubin production, in ameliorating jaundice in G-6-PD-deficient neonates.
Methods: The studies were conducted at Metera Maternity Hospital in Athens, Greece. Enrolled newborns had the plasma bilirubin concentration (PBC) determined in cord blood and daily thereafter until a declining level was obtained and the case was closed. Intervention with phototherapy was dictated at exact, age-specific PBC levels. In our initial study, we enrolled consecutive mature healthy G-6-PD-deficient newborns as well as a threefold excess of G-6-PD-normal neonates born at approximately the same time (control group). For the SnMP trial, G-6-PD-deficient neonates were administered SnMP as a single intramuscular dose of 6 micromol/kg birth weight within 24 +/- 12 hours of age.
Results: SnMP was administered at 26.7 +/- 6.1 hours of age to 172 G-6-PD-deficient newborns (group A); 168 G-6-PD-normal (group B) and 58 G-6-PD-deficient (group C) newborns who were enrolled earlier provided the comparison groups. Except for the expected excess of males in the G-6-PD-deficient groups (A and C), there were no differences in the demographic characteristics among the 3 groups. The incremental changes in PBC from cord blood to 24 hours of age also were similar (group A: 4.13 +/- 1.32 mg/dL; group B: 4.05 +/- 1.34 mg/dL; group C: 4.39 +/- 1.07 mg/dL), but there were significant differences in the next period, 24 to 48 hours of age (group A: 0.63 +/- 1.44 mg/dL; group B: 1.69 +/- 1.5 mg/dL; group C: 2.45 +/- 1.72 mg/dL). Peak PBC was significantly different (group A: 7.81 +/- 3.04 mg/dL; group B: 8.68 +/- 3.1 mg/dL; group C: 11.24 +/- 3.76 mg/dL) as was the age at which peak PBC was recorded (group A: 56 +/- 29 hours of age; group B: 69 +/- 26 hours of age; group C: 83 +/- 29 hours of age). These differences in favor of group A were observed despite the fact that phototherapy was used in 15% of the newborns in group B and 31% of those in group C, whereas none of those treated with SnMP required phototherapy. Finally, in one female, who was heterozygous for G-6-PD deficiency, in group C phototherapy failed and 2 exchange transfusions were performed.
Conclusions: In comparison with normal neonates, G-6-PD-deficient neonates experienced a twofold increase in the prevalence of significant hyperbilirubinemia requiring phototherapy. A single dose of SnMP administered in the 1st day of life to the G-6-PD-deficient newborns shifted the peak PBC distribution to the left (lower values) even in relation to normal neonates and entirely eliminated the need for phototherapy. Interdiction of bilirubin production by use of a heme oxygenase inhibitor such as SnMP represents a simple and highly effective means for the preventive management of jaundice in G-6-PD-deficient newborns.