CONTROL OF HYPERBILIRUBINEMIA IN GLUCOSE-6-PHOSPHATE DEHYDROGENASE-DEFICIENT NEWBORNS USING AN INHIBITOR OF BILIRUBIN PRODUCTION, SN-MESOPORPHYRIN

Background. Hyperbilirubinemia in newborns with glucose-6-phosphate de hydrogenase (G6PD) deficiency is a serious clinical problem because of the severity and unpredictability of its course. An innovative approa ch to this problem is suggested by previous experience with Sn-mesopor phyrin (SnMP), a potent inhibitor of bilirubin production, in moderati ng neonatal hyperbilirubinemia caused by ABO incompatibility, immaturi ty, and unspecified mechanisms. Objective. To compare the effectivenes s of the preventive and therapeutic uses of SnMP in ameliorating the c ourse of bilirubinemia of G6PD-deficient neonates. Methods. Neonates b orn at the Metera Maternity Hospital, Athens, Greece, and found to be G6PD-deficient by cord blood testing were stratified by sex and gestat ional age (210-265 days and >265 days) and randomized in pairs to rece ive SnMP (6 mu mol/kg birth weight, intramuscularly) either on the fir st day of life (preventive use) or if and when the plasma bilirubin co ncentration (PBC) level reached an age-specific threshold level for in tervention (therapeutic use). In the case of failure of SnMP to contro l the rise of PBC levels, the protocol defined precisely the threshold PBC levels for switchover to phototherapy (PT) and, if necessary, exc hange transfusion. PBC was measured daily until a declining value was obtained and the case was closed. Results. A total of 86 G6PD-deficien t neonates were randomized: 42 in the preventive arm and 44 in the the rapeutic arm. Of the latter, 20 (45%) reached PBC levels requiring the rapeutic intervention and thus received SnMP. Regardless of the trial arm, none of the 86 neonates required PT, whereas in a previous study in the same population, 33% of G6PD-deficient neonates required PT. In the intrapair sequential analysis, the favored arm was decided on the criterion of the age at closure of the case being shorter by at least 1 day. After plotting 30 untied pairs in the sequential analysis grap h, the preventive use of SnMP proved to be the favored arm, and the tr ial was stopped. At this point, there were 2 unpaired neonates, 12 tie d pairs, 22 pairs in which the preventive use of SnMP was favored and 8 pairs in which the therapeutic use of SnMP was favored. In the group analysis, infants in the preventive group, compared with those in the therapeutic group, had a lower maximum PBC level (8.2 +/- 3.1 and 10. 9 +/- 2.8 mg/dL, respectively), which was reached at an earlier age (6 3.5 +/- 34.8 and 82.2 +/- 24.7 hours, respectively) as well as a lower closing PBC level (7.2 +/- 2.9 and 9.6 +/- 2.5 mg/dL, respectively) a nd an earlier age at closing (89.1 +/- 35.6 and 110.8 +/- 23.6 hours, respectively). Moreover, a PBC level of greater than or equal to 8.0 m g/dL, a level at which jaundice is clearly visible, was not reached by 52% of the neonates in the preventive arm and 16% of the neonates in the therapeutic arm. Conclusions. In G6PD-deficient neonates, a single dose of SnMP administered preventively or therapeutically entirely su pplanted the need for PT to control hyperbilirubinemia. The preventive use of SnMP offers practical advantages in populations with a high en ough prevalence of G6PD deficiency to justify cord blood screening.