Neonatal hyperbilirubinemia in African American males: the importance of glucose-6-phosphate dehydrogenase deficiency

OBJECTIVE: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort. STUDY DESIGN: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight >/=4.0 kg, gestational age /=75(th) percentile. Hyperbilirubinemia was defined as any bilirubin value >/=95(th) percentile on the hour-of-life-specific bilirubin nomogram. RESULTS: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 +/- 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75(th) percentile 10.0 mg/dL, and 95(th) percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin >/=75(th) percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%). CONCLUSIONS: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.     

Neonatal jaundice and severity of glucose-6-phosphate dehydrogenase deficiency in Sardinian babies

We have investigated the association of neonatal jaundice (NNJ) and G6PD deficiency in consecutive births in a Northern Sardinian hospital. After excluding known causes for NNJ, and after correcting for the incidence of NNJ from unknown causes, we estimated that 20% of G6PD deficient male newborns develop NNJ resulting from their enzyme deficiency. By analyzing in detail 100 G6PD deficient babies we found no differences in birth weight or haemoglobin level between those without and those with NNJ, four of whom required exchange transfusion. We further showed by an accurate quantitative method that the residual G6PD enzyme activity was not significantly lower in G6PD deficient babies with NNJ compared to G6PD deficient babies without NNJ.     

Hyperbilirubinemia in healthy neonates with glucose-6-phosphate dehydrogenase deficiency

A cohort study was carried out to assess the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency, diagnosed by quantitative enzyme assay, and neonatal hyperbilirubinemia, defined as serum total bilirubin >/=15 mg/dl, in the well-baby nursery of Chang Gung Children's Hospital. Among 42,110 inborn infants, 757 male (3.54%) and 326 female (1.57%) newborns were G6PD-deficient. Compared to the occurrence of hyperbilirubinemia in G6PD-normal newborns (1.41% in male, 1.44% in female) in the well-baby nursery, a significantly higher incidence was observed in both G6PD-deficient male (11.36%) and female (7.06%) newborns. Further analyses demonstrated that the enzyme activity of G6PD in G6PD-deficient male newborns with hyperbilirubinemia (1.56+/-1.37 U/g Hb) were significantly lower than the subjects without hyperbilirubinemia (2.01+/-1.7 U/g Hb). No significant difference was observed in G6PD-deficient female newborns with hyperbilirubinemia (6.91+/-2.76 U/g Hb) compared to those without hyperbilirubinemia (7.81+/-2.84 U/g Hb). These data suggest that the G6PD-deficient neonates are at increased risk for hyperbilirubinemia even in the nursery free from agents that can potentially cause hemolysis to G6PD-deficient red cells. The lower G6PD enzyme activity was associated with the neonatal hyperbilirubinemia in G6PD-deficient male neonates.     

Massive acute haemolysis in neonates with glucose-6-phosphate dehydrogenase deficiency

Three neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency are described. All three patients suffered an episode of massive acute haemolysis, in the absence of blood group incompatibilities, infection, or ingestion of oxidising agents known to trigger haemolysis. One patient died, but the other two survived after an exchange transfusion. This highlights that G6PD deficiency in the neonatal period may present with severe anaemia in association with hyperbilirubinaemia.     

Neonatal jaundice and glucose-6-phosphate dehydrogenase deficiency in Basrah

In a study on a group of 186 newborn babies presenting with jaundice, erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency was detected in 95 (51%) of the patients. The incidence of severe hyperbilirubinaemia appeared to be much greater in G6PD-deficient infants (46%) than in infants who did not have the red cell defect (15%). No change was found in this association when ABO incompatibility was excluded. Phototherapy did not reduce the need for exchange transfusion, which was necessary in 27 babies. Eight babies developed kernicterus and one died. Early detection of G6PD deficiency and close surveillance of the affected newborns may be important in reducing the risk of severe neonatal jaundice and kernicterus associated with G6PD deficiency in Basrah.     

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: sex distribution.

Eight hundred and six newborn infants at high risk for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were screened; 30.2% of the boys and 10.4% of the girls had severe G-6-PD deficiency. Surprisingly, 14% of the enzyme deficient girls had a father from a low risk ethnic group. Girls of high risk mothers should be screened for G-6-PD deficiency regardless of paternal origin.     

Neonatal bilirubin production-conjugation imbalance: effect of glucose-6-phosphate dehydrogenase deficiency and borderline prematurity

OBJECTIVE: To evaluate relations between production and conjugation of bilirubin in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD) deficient neonates. METHODS: Term and borderline premature (35-37 weeks gestational age), healthy, male, G6PD deficient neonates were studied close to the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO (COHbc; an index of bilirubin production) and serum total conjugated bilirubin (TCB; a reflection of bilirubin conjugation) were measured in simultaneously drawn blood samples by gas chromatography and reverse phase high performance liquid chromatography respectively. A bilirubin production-conjugation index comprising COHbc/TCB was determined; a high index reflects imbalance between the bilirubin production and conjugation processes. COHbc and TCB individually and the production-conjugation index were studied in relation to serum total bilirubin (STB) concentration. RESULTS: Fifty one G6PD deficient neonates were sampled at 51 (8) hours. COHbc values did not correlate with STB (r=0.22, p=0.15). TCB did correlate inversely with STB (r=-0.42, p=0.004), and there was a positive correlation between the production-conjugation index and STB (r=0.45, p=0.002). The production-conjugation index (median (interquartile range)) was higher in the premature (n=8) than term neonates (2.31 (2.12-3.08) v 1.05 (0.53-1.81), p=0.003). This difference was the result of changes in TCB. CONCLUSIONS: The data show that jaundice in G6PD deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased haemolysis in its pathogenesis. Borderline premature infants are at special risk of bilirubin production-conjugation imbalance.     

Efficacy of phototherapy in neonatal hyperbilirubinaemia associated with glucose-6-phosphate dehydrogenase deficient status

The efficacy of phototherapy in a group of 427 infants with hyperbilirubinaemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency and a comparable group of 3924 G6PD normal infants with non-haemolhtic hyperbilirubinaemia was evaluated. Phototherapy was highly effective in reducing bilirubin levels in both groups of infants, being significantly more effective in the group with normal G6PD status. Failure rate was very low (2.03/1000) in the group with normal G6PD status and nil in the G6PD deficient group. Bilirubin rebound after phototherapy was unremarkable with very few infants requiring a second exposure —4.68/1000 in the G6PD deficient group and 6.37/1000 in the G6PD normal group. All the babies tolerated phototherapy well. Phototherapy would therefore seem to be a simple and effective method for the management of severe jaundice associated with G6PD deficiency.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Three mutations analysis of glucose-6-phosphate dehydrogenase deficiency in neonates in South-west China

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human enzymatic defects, is characterized by extreme molecular and biochemical heterogeneity. The underlying DNA changes associated with G6PD deficiency in Asian subjects have not been extensively investigated. METHODS: Three gene mutations (G1388A, G1376T, A95G, corresponding amino acid change: Arg463His, Arg459Leu, His32Arg, respectively) were examined in 240 G6PD-deficient subjects originating from South-west China using specific polymerase chain reaction. RESULTS: Of the 240 patients with G6PD deficiency, 190 were found to have the G1388A mutation, 48 had G1376T and two had A95G. There were no significant differences between the clinical manifestations caused by the former two gene mutations, which both cause acute hemolytic anemia and jaundice. Therefore the most common gene mutations of G6PD deficiency in neonates in South-west China are G1388A and G1376T mutations. CONCLUSION: It is suggested that G6PD deficiency screening be done in higher risk neonates with jaundice in qualified hospitals as soon as possible.     

Glucose-6-phosphate dehydrogenase deficiency in neonates

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited deficiency that may be the cause of neonatal hyperbilirubinemia, as has been found in several countries and among widely different ethnic groups, especially in Mediterranean region. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice.Methods : From March 1998 to April 2001 we studied 705 clinically icteric neonates who were admitted to Al-Zahra and Beheshti hospitals, two teaching hospitals in Isfahan, Iran. Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct coomb’s test, hemoglobin, blood smear, reticulocyte count and G6PD level.Results: In only 53(7.5%) of cases G6PD deficiency was diagnosed. In all G6PD deficient neonates no evidence of other factors known to cause hyperbilirubinemia were detected. The sex distribution was 13(24.5%)females and 40(75.5%)males in the G6PD deficient group. The mean bilirubin level in G6PD deficient and G6PD normal groups were 22.26 +/-8.36 and 18.14 +/-3.85 mg/dl, respectively (p=0.001). Phototherapy was required in G6PD deficient and other icteric neonates with duration of 3.76 +/-1.93 and 3.13 +/-2.14 days, respectively (p=0.045). Twenty-seven of the 53(50.9%) G6PD deficient infants required exchange transfusion. None of them developed kernicterus.Conclusions: Since the prevalence of severe hyperbilirubinemia among our neonates was relatively high and about half of them required exchange transfusion, early detection of this enzymopathy regardless of sex and close surveillance of the affected newborns may be important in reducing the risk of severe hyperbilirubinemia and exchange transfusion.