Abstract
BackgroundHealth authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD).MethodsThe Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628).ResultsThe median total folate intake was 266 μg/d (interquartile range IQR 154–543) in the overall population and 540 μg/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.ConclusionsOur findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.
Highlights
Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects
The association of total dietary folate intake and spontaneous preterm delivery (PTD) was estimated as a hazard ratio (HR) with a 95% confidence interval (CI) by using Cox regression both in an unadjusted model and adjusted for the above-mentioned covariates
Dietary folate intake was higher in women who were older, did not smoke, had normal body mass index (BMI) (18.5-24.9 kg/m2), who were having their first child, were married/cohabitant, who had higher education levels and family incomes
Summary
Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. National health authorities in many countries recommend periconceptional folic acid supplementation, and some countries have introduced mandatory folate fortification of foods [1,3,4,9,10]. In Norway, folic acid supplementation of 400 μg/d is recommended from the time of planning a pregnancy to gestational week 12 [2,11], as is a daily folate intake of 500 μg/d. This is in line with the Nordic Nutrition Recommendations [2]
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