Neonatal glucose-6-phosphate dehydrogenase activity by gestational age and sex: evidence-based cut-offs for newborn screening in Saudi Arabia

Objective To characterise quantitative glucose-6-phosphate dehydrogenase (G6PD) activity in term and preterm neonates, compare activity by gestational age (GA) and sex and derive neonatal screening cut-offs using percentile and WHO methods. Design Retrospective cross-sectional analysis of cord blood screening programme. Setting King Abdulaziz Medical City, Riyadh, Saudi Arabia, January 2016 to May 2022. Participants All live births with cord blood G6PD and GA. Of 59 465 births, 58 139 (97.8%) were screened. For reference range derivation only, results below the adult threshold (70% normal). Secondary measures were stratum medians and the male share among detected cases. Results Mean activity was 15.33±2.67 U/g Hb, higher in preterm than term. Sex differences were absent in preterm strata but present at term (males lower than females; p=0.002). The neonatal 2.5th percentile cut-off was 9.9 U/g Hb. Using the adult cut-off, 2.00% (1163/58 139) were deficient, 80.9% male. Using the neonatal cut-off, prevalence rose to 4.97% (2888/58 139), adding 1725 infants (+583 males, +1142 females) and reducing the male share to 52.8%. WHO bands identified a small <30% group and a female intermediate (30–70%) group across strata. Medians were 15.0 (≥37 weeks), 16.0 (33–36), 17.0 (29–32) and 17.6 (≤28) U/g Hb. Conclusions G6PD activity in neonates shows clear GA and sex effects. Adult cut-offs underestimate deficiency, especially in females. Neonatal thresholds (2.5th percentile plus GA-specific WHO bands) improve detection. Adoption within newborn screening, with reporting of a female intermediate band, should strengthen follow-up; external validation and linkage to bilirubin outcomes are needed.