Reduced folate carrier 80A→G polymorphism, plasma folate, and risk of placental abruption

New Jersey-Placental Abruption Study (NJ-PAS), multicenter hospital-based case-control at Robert Wood Johnson University Hospital and Saint Peter's University Hospital, New Brunswick, NJ. Cases were women with clinically diagnosed placental abruption; controls were women without abruption. Matched on race/ethnicity and parity. Enrollment began August 2002. In-person interviews and blood draws were performed; most within 24 hours of delivery and all within 72 hours. Data included maternal smoking history and folate/multivitamin use. RFC-1 c.80A→G genotyping was performed; maternal plasma folate was measured. Of 218 cases and 210 controls enrolled, complete RFC-1 data were available for 196 cases and 191 controls, and folate assays for 136 cases and 140 controls.

RFC-1 c.80A→G polymorphism showed no association with placental abruption; allele frequencies were similar between cases and controls (G: 52.3% vs 50.5%; G/G OR 1.1, 95% CI 0.6–2.2). Plasma folate did not differ between cases and controls after censoring at 60 nmol/L (cases 63.6 ± 5.1 nmol/L vs controls 58.3 ± 4.7 nmol/L; P = 0.270); smoking did not modify this relationship (interaction P = 0.169). Among women with RFC-1 A/A genotype, low folate (<25th percentile, 31.0 nmol/L) was associated with a 2.7-fold higher odds of abruption (95% CI 1.2–8.4); no such association in A/G or G/G genotypes (interaction P = 0.365). Overall, no link between RFC-1 c.80A→G or low plasma folate and abruption; high prenatal folate/vitamin supplementation in this population may mask associations. Further research is needed to clarify potential genotype–folate interactions and abruption etiology.

Small sample sizes in sub-analyses; widespread prenatal folate/vitamin supplementation may mask folate-deficiency associations; plasma folate measured postpartum (within 1–2 days) may not reflect prenatal status; potential residual confounding and selection bias; limited race/ethnicity subgroup sizes; lack of dietary intake data; placental folate stores may differ from maternal plasma.