Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study

Background: Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. Aim: The aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. Study design: Women were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 +/- 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. Subjects: Nulliparous women with singleton pregnancies. Outcome measures: SGA (< 10th customised birthweight centile). Results: 5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67-01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (beta 2.56 (95% CI: 0.87-4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. Conclusions: In this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.