Am J Med Genet A. 2026 Aug 20. doi: 10.1002/ajmg.a.70287. Online ahead of print.
ABSTRACT
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common red blood cell enzymatic disorder worldwide. Although many heterozygotes are asymptomatic, affected neonates have an increased risk for hyperbilirubinemia and related complications. In the United States, detection of maternal G6PD heterozygous status often occurs incidentally during expanded carrier screening. We sought to characterize the diagnostic timing, clinical management, and neonatal outcomes among pregnancies complicated by maternal G6PD heterozygous status. We conducted a retrospective cohort study of pregnant individuals with a documented G6PD heterozygous diagnosis who received prenatal care at Baylor College of Medicine-affiliated hospitals between January 2013 and December 2025. Patients were identified through electronic health record queries and confirmed by manual chart review. Maternal demographics, diagnostic pathway, testing modality, medication exposures, and neonatal outcomes were abstracted. Descriptive statistics were used to summarize cohort characteristics. Thirty-six individuals with confirmed G6PD heterozygous status were included. Median maternal age was 31 years (IQR 27.5-38). Most patients identified as Black (66.7%) and non-Hispanic (88.9%), while four (11.1%) identified as Hispanic. Diagnosis occurred prior to the first pregnancy in 11.1% of patients, during pregnancy in 47.2%, and after pregnancy in 41.7%. Molecular testing alone was the most common diagnostic modality (55.6%), followed by enzymatic testing (27.7%) and combined testing (16.7%). Among molecularly characterized G6PD heterozygotes, the most frequent variant was c.202G>A (42.3%), followed by c.563C>T (19.2%). Genetic counseling related to G6PD status was documented for 75.0% of patients. Across 76 pregnancies, 82 neonates were delivered, including 71 singletons, four twin pregnancies, and one triplet pregnancy. Bilirubin measurements were available for 47 neonates, of which elevated bilirubin was documented in 16 (34.0%). Hyperbilirubinemia requiring phototherapy occurred in 12 neonates (25.5%). Infant G6PD enzyme testing was performed in 8 cases, of which 5 showed low enzyme levels. Neonatal hyperbilirubinemia occurred most frequently among pregnancies in which the mother carried the c.202G>A variant in G6PD. Maternal G6PD heterozygous status is often identified incidentally during pregnancy, yet subsequent newborn evaluation remains inconsistent. Although more than one-third of neonates born to heterozygote mothers developed hyperbilirubinemia, infant G6PD testing was infrequently performed. These findings highlight the variability in clinical management for individuals deficient in G6PD and demonstrate that identifying maternal heterozygotes provides an opportunity to improve targeted newborn screening as well as neonatal follow-up procedures.
PMID:42624797 | DOI:10.1002/ajmg.a.70287
