Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border
Issued Date
2022-06-01
Resource Type
eISSN
27673375
Scopus ID
2-s2.0-85135740238
Journal Title
PLOS Global Public Health
Volume
2
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLOS Global Public Health Vol.2 No.6 (2022)
Suggested Citation
Bancone G., Gornsawun G., Peerawaranun P., Penpitchaporn P., Paw M.K., Poe D.D., Win D., Cicelia N., Mukaka M., Archasuksan L., Thielemans L., Nosten F., White N.J., McGready R., Carrara V.I. Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border. PLOS Global Public Health Vol.2 No.6 (2022). doi:10.1371/journal.pgph.0000475 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/100581
Title
Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border
Corresponding Author(s)
Other Contributor(s)
Abstract
Very high unconjugated bilirubin plasma concentrations in neonates (neonatal hyperbilirubinaemia; NH) may cause neurologic damage (kernicterus). Both increased red blood cell turn-over and immaturity of hepatic glucuronidation contribute to neonatal hyperbilirubinaemia. The incidence of NH requiring phototherapy during the first week of life on the Thailand-Myanmar border is high (approximately 25%). On the Thailand-Myanmar border we investigated the contribution of genetic risk factors to high bilirubin levels in the first month of life in 1596 neonates enrolled in a prospective observational birth cohort study. Lower gestational age (<38 weeks), mutations in the genes encoding glucose-6-phosphate dehydrogenase (G6PD) and uridine 50-diphospho-glucuronosyltransferase (UGT) 1A1 were identified as the main independent risk factors for NH in the first week, and for prolonged jaundice in the first month of life. Population attributable risks (PAR%) were 61.7% for lower gestational age, 22.9% for hemi or homozygous and 9.9% for heterozygous G6PD deficiency respectively, and 6.3% for UGT1A1*6 homozygosity. In neonates with an estimated gestational age ≥ 38 weeks, G6PD mutations contributed PARs of 38.1% and 23.6% for “early” (≤ 48 hours) and “late” (49–168 hours) NH respectively. For late NH, the PAR for UGT1A1*6 homozygosity was 7.7%. Maternal excess weight was also a significant risk factor for “early” NH while maternal mutations on the beta-globin gene, prolonged rupture of membranes, large haematomas and neonatal sepsis were risk factors for “late” NH. For prolonged jaundice during the first month of life, G6PD mutations and UGT1A1*6 mutation, together with lower gestational age at birth and presence of haematoma were significant risk factors. In this population, genetic factors contribute considerably to the high risk of NH. Diagnostic tools to identify G6PD deficiency at birth would facilitate early recognition of high risk cases.