A single dose of Sn-mesoporphyrin prevents development of severe hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns

Objectives. Severe neonatal jaundice is a common clinical manifestation of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and the most difficul t to manage; kernicterus is not an uncommon outcome. We assessed in healthy , direct Coombs test-negative Greek newborns of greater than or equal to 38 weeks' gestational age 1) the current burden of G-6-PD deficiency-associat ed severe jaundice, and 2) the efficacy of preventive use of Sn-mesoporphyr in (SnMP), a potent inhibitor of heme oxygenase activity and thus of biliru bin 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) det ermined in cord blood and daily thereafter until a declining level was obta ined and the case was closed. Intervention with phototherapy was dictated a t exact, age-specific PBC levels. In our initial study, we enrolled consecu tive 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 gro up). For the SnMP trial, G-6-PD-deficient neonates were administered SnMP a s a single intramuscular dose of 6 mu mol/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-d eficient newborns (group A); 168 G-6-PD-normal (group B) and 58 G-6-PD-defi cient (group C) newborns who were enrolled earlier provided the comparison groups. Except for the expected excess of males in the G-6-PD-deficient gro ups (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 h ours 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 d ifferences in the next period, 24 to 48 hours of age (group A: 0.63 +/- 1.4 4 mg/dL; group B: 1.69 +/- 1.5 mg/dL; group C: 2.45 +/- 1.72 mg/dL). Peak P BC 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 hour s of age; group C: 83 +/- 29 hours of age). These differences in favor of g roup 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 he terozygous for G-6-PD deficiency, in group C phototherapy failed and 2 exch ange transfusions were performed. Conclusions. In comparison with normal neonates, G-6-PD-deficient neonates experienced a twofold increase in the prevalence of significant hyperbiliru binemia requiring phototherapy. A single dose of SnMP administered in the 1 st day of life to the G-6-PD-deficient newborns shifted the peak PBC distri bution to the left (lower values) even in relation to normal neonates and e ntirely eliminated the need for phototherapy. Interdiction of bilirubin pro duction by use of a heme oxygenase inhibitor such as SnMP represents a simp le and highly effective means for the preventive management of jaundice in G-6-PD-deficient newborns.