The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: the Japan environment and children's study

孕早期至孕中期补充叶酸对妊娠期高血压疾病风险的影响:日本环境与儿童研究

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Abstract

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are potentially life-threatening conditions for both the pregnant woman and fetus with long-term effects on maternal health, and while folic acid supplementation has been suggested to reduce the risk of HDP, current epidemiological evidence remains inconclusive. This study evaluated the impact of the frequency of folic acid supplementation on the risk of HDP and postpartum hypertension in a large-scale prospective cohort study within the Japanese population. METHODS: Data were obtained from the national birth cohort of the Japan Environment and Children's Study (JECS), collected between 2011 and 2014. Maternal folic acid supplementation during pregnancy was categorized into three groups (none, low frequency, and high frequency) based on self-reported intake frequency. Crude and adjusted binomial logistic regression analyses were performed to assess the association between maternal folic acid supplementation during pregnancy and HDP as well as postpartum hypertension. HDP was further classified according to onset timing as early-onset (Eo) or late-onset (Lo), and multinomial logistic regression was applied to examine these subtypes. RESULTS: A total of 91,069 pregnant women were included in the analysis. High frequency folic acid supplementation was associated with a lower risk of HDP compared with no supplementation (adjusted OR 0.86, 95% CI 0.78–0.94), whereas low frequency supplementation showed no significant association. For postpartum hypertension, both low and high frequency folic acid supplementation were associated with reduced risks (adjusted OR 0.88, 95% CI 0.79–0.97 and 0.85, 95% CI 0.79–0.92, respectively). In additional analyses stratified by HDP onset timing, high frequency folic acid supplementation was associated with a lower risk of Lo HDP (adjusted OR 0.86, 95% CI 0.78–0.96), but not Eo HDP. CONCLUSIONS: Folic acid supplementation during pregnancy was inversely associated with the incidence of HDP, particularly Lo HDP. Furthermore, it may contribute to the prevention of postpartum hypertension. In addition to its established role in preventing neural tube defects, continuous folic acid supplementation before conception may be beneficial for maintaining maternal health throughout pregnancy and the postpartum period. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-026-08898-5.

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