Association of combined folic acid and progesterone use with congenital malformations in women with vaginal bleeding during early pregnancy: a multicenter cohort study
Year: 2025
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Progesterone supplementation is used for miscarriage prevention. Animal studies have showed that folic acid supplementation (FAS) improves progesterone profiles. However, little is known about the interaction between progesterone supplementation and FAS in women with early pregnancy bleeding. METHODS: We conducted a multicenter prospective study of 17,713 women recruited at 11-13 weeks' gestation in 23 tertiary hospitals from 12 provinces in China. The interaction between the treatment (e.g., injection or oral administration of progesterone) and FAS was investigated. RESULTS: Women with bleeding in early pregnancy were more likely to have a baby with malformations than those without bleeding (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.05-1.78; P = 0.0208). Treatment for bleeding was not associated with malformations compared to no treatment (HR, 1.05; 95% CI 0.65-1.72). An insignificant interaction between FAS and progesterone injection was observed in total sample (HR, 1.55, 95% CI 0.19-12.61) and in women with bleeding (HR, 3.22, 95% CI 0.30-34.70). Among women without a history of adverse pregnancy outcomes, progesterone injection was not associated with malformations compared with untreated women (HR, 1.18, 95% CI 0.63-2.22). However, the association approached borderline statistical significance when compared with no bleeding women (HR, 1.61, 95% CI 1.00-2.60, P = 0.051). CONCLUSIONS: Bleeding in early pregnancy was associated with a higher risk of malformations. The use of progesterone injection should be caution in women without a history of adverse pregnancy outcomes. Further studies are warranted to study the potential interactive effect of FAS and progesterone injection on malformation.
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W4415783793