Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study

Abstract

BackgroundHealth authorities in numerous countries recommend periconceptional folic acid supplementation to prevent neural tube defects. The objective of this study was to examine the association of dietary folate intake and folic acid supplementation during different periods of pregnancy 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 66,014 women with singleton pregnancies resulting in live births in 2002–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until pregnancy week 24. 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 = 1,755).ResultsThe median total folate intake was 313 μg/d (interquartile range IQR 167–558) in the overall population and 530 μg/d (IQR 355–636) in the supplement users. Eighty-five percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while only 44% initiated folic acid supplementation before pregnancy. Cox regression analysis showed that the amount of dietary folate intake (hazard ratio HR 1.00; confidence interval 95% CI 0.61-1.65) and supplemental folate intake (HR 1.00; CI 1.00-1.00) 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 spontaneous PTD (HR 1.18; CI 1.05-1.32) compared to no folic acid supplementation preconception. There was no significant association with PTD when supplementation was initiated within 8 weeks preconception (HR 0.99; CI 0.87-1.13). 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. Preconceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of spontaneous PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-014-0375-1) contains supplementary material, which is available to authorized users.

Diet matters, particularly in pregnancy – Results from MoBa studies of maternal diet and pregnancy outcomes

“…This result differed from the result of a systematic review and meta-analysis including eight randomized controlled studies, which indicated a 2% increase in infant birth weight for every two-fold increase in folate intake (94). No association between intake of total folate and preterm delivery was found in MoBa (33), which is in line with the mentioned systematic review and meta-analysis (94).…”

“…[12][13][14], some testing hypotheses related to pregnancy outcomes (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), some testing hypotheses related to later health outcomes in mothers and children (e.g. [34][35][36][37], and some in which dietary factors were included as predictors or confounding variables (e.g.…”

Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects inNorway 1999–2009

“…A possible risk reduction of CHD by intake of folic acid or multivitamin supplements is likely determined by the extent of dietary vitamin insufficiency in the population. The dietary folate intake reported in pregnant Norwegian women, around 300 μg per day, 21 could be sufficient for fetal cardiac development, as opposed to certain Chinese provinces with a high prevalence of folate deficiency, where the risk of CHD has been significantly reduced when mothers had used periconceptional folic acid supplements. 22 Alternatively, the dose of folic acid supplement in the present study, 400 μg per day, is too small to prevent cardiac malformations, although plasma folate has been found to be significantly higher in women reporting folic acid supplement use.…”

Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

“…Observational studies showed that folic acid supplementation during conception was associated with the increased risk of wheezing in children through 18 months of age (dose was not reported) [60] and the increased risk of infant asthma (>72,000 μg∙day) [61]. Evidence from observational studies showed that folic acid supplementation was associated with the increased risk of infant clefts (dose was not reported) [62] and spontaneous preterm delivery (mean dose (interquartile range): 313 (167–558) μg/day) [63]. Valera-Gran et al found that high folic acid supplementation for mothers during conception (>5000 μg/day) had a detrimental effect on the psychomotor development of children [64].…”