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


METHODS
The 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).


RESULTS
The 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.


CONCLUSIONS
Our 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.
Department of Obstetrics and Gynaecology, Sahlgrenska Academy, Sahlgrenska University Hospital/Östra, SE-416 85 Göteborg, Sweden. verena.sengpiel@obgyn.gu.se
Verena
V
Sengpiel
Jonas
J
Bacelis
Ronny
R
Myhre
Solveig
S
Myking
Aase Devold
AD
Pay
Margaretha
M
Haugen
Anne-Lise
AL
Brantsæter
Helle Margrete
HM
Meltzer
Roy M
RM
Nilsen
Per
P
Magnus
Stein Emil
SE
Vollset
Staffan
S
Nilsson
Bo
B
Jacobsson
D000328:Adult; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005865:Gestational Age; D006801:Humans; D009664:Norway; D018673:Nutrition Policy; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D014803:Vitamin B Complex / Q000008:administration & dosage*; D055815:Young Adult
D014803:Vitamin B Complex; D005492:Folic Acid