In utero rise of total serum bilirubin (TSB) occurs if the rate of
fetal TSB production exceeds the rate of elimination by the maternal
circulation, as in Rh iso-immunization. Recent reports indicate that
impaired hepatic conjugation is a more important cause of neonatal
jaundice in G6PD deficiency, than hemolysis due to post-natal
oxidative stress(1,2). This raises the possibility of TSB rise
starting in utero in G6PD deficiency. Kaplan et al(3) reported
that the TSB levels in G6PD deficient neonates are higher within 3
hours of life compared to their healthy counterparts [2.9 ± 0.7 mg/dL
vs 2.6 ± 0.6 mg/dL (P <0.05)](3). They concluded that TSB rise among
G6PD deficient patients most likely starts in utero, but in the
absence of cord bilirubin data, this conclusion could not be accepted
with certainty.
To address this issue, we performed a case-matched
cohort study. Cord blood samples of babies >34 wks and >1800 g were
screened for G6PD deficiency(4), TSB and hematocrit (Hct).
Congenitally malformed babies, Rh isoimmunized babies, those exposed
to antenatal phenobarbital and whose parents refused consent were
excluded. To identify a difference in mean cord TSB of 0.3 mg/dL (SD
0.5 mg/dL with an a error of 5% and 90% power, we recruited 44 cases
and 88 controls, who were matched for gestation and birth weight (± 50
g). The cases were G6PD-deficient patients, and controls were randomly
selected from among the matched subjects available in the
non-deficient group. The prevalence of maternal diabetes, distribution
of maternal ABO blood groups, use of oxytocin in labour, mode of
delivery and Apgar score at 1 minute were similar in the cases and
controls (all P >0.05). The mean cord TSB of cases did not differ
significantly from controls [1.26 ± 0.8 mg/dL vs 1.18 ± 0.6 mg/dL
respectively, P = 0.52]. Cord Hct of cases was also similar to
controls [48.8 ± 9 vs 48.9 ± 6 respectively, P = 0.94]. Our study
negates the possibility raised by Kaplan, et al. that in G6PD
deficient neonates jaundice commences most likely in utero.
Srinivas Murki,
Sourabh Dutta,
Neonatal Unit, Department of Pediatrics,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160 012, India.
E-mail:
[email protected]
1. Kaplan M, Muraca M , Hammerman C, Veleu MT,
Leiter C, Rudonsky B, et al. Bilirubin conjugation reflected
by conjugated bili- rubin fractions in glucose 6 phosphate
dehydrogenase deficient neonates. A determining factor in the
pathogenesis of hyperbilirubinemia. Pediatrics 1998; 102.
2. Kaplan M, Renbaum P, Levi-Lahas E, Hammerman
C, Lahad A, Beutler E. Gilberts syndrome and glucose 6 phosphate
dehydrogenase deficiency. A dose dependent genetic interaction
crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci USA 1997;
94: 12128-12132.
3. Kaplan M, Algur N, Hammerman C. On- set of
jaundice in glucose 6 phosphate dehydrogenase deficient neonates.
Pediatrics 2001; 108: 956-959.
4. Gall JC, Brewer GJ, Dem RJ. Studies of glucose-6-phosphate
dehydrogenase activity of individual erythrocytes: the methemoglobin
elution test for identification of female heterozygotes for G6PD
deficiency. Am J Hum Gen 1965; 17: 359.