Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb;56(1):65-75.
doi: 10.1007/s00394-015-1058-z. Epub 2015 Oct 26.

Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study

Affiliations

Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study

Jolien Steenweg-de Graaff et al. Eur J Nutr. 2017 Feb.

Abstract

Purpose: Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal and postnatal head circumference in the offspring.

Methods: Within a population-based prospective cohort, we measured maternal plasma folate concentrations at approximately 13 weeks of gestation (90 % range 10.5-17.2) and assessed folic acid supplementation by questionnaire (2001-2005). Up to 11 repeated measures of head circumference were obtained during foetal life (20 and 30 weeks of gestation) and childhood (between birth and age 6 years) in 5866 children (2002-2012).

Results: In unadjusted models, foetal head growth was 0.006 SD (95 % CI 0.003; 0.009, P < 0.001) faster per week per 1-SD higher maternal folate concentration. After adjustment for confounders, this association was attenuated to 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; estimated absolute difference at birth of 2.7 mm). The association was independent of overall foetal growth. No associations were found between maternal folate concentrations and child postnatal head growth. Preconceptional start of folic acid supplementation was associated with larger prenatal head size, but not with prenatal or postnatal head growth.

Conclusions: Our results suggest an independent, modest association between maternal folate concentrations in early pregnancy and foetal head growth. More research is needed to identify whether specific brain regions are affected and whether effects of folate on foetal head growth influence children's long-term functioning.

Keywords: Foetal neurodevelopment; Folate; Folic acid supplementation; Head growth; Head size; Pregnancy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Similar articles

Cited by

References

    1. MRC Vitamin Study Research Group Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338(8760):131–137. doi: 10.1016/0140-6736(91)90133-A. - DOI - PubMed
    1. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327(26):1832–1835. doi: 10.1056/NEJM199212243272602. - DOI - PubMed
    1. Berry RJ, Bailey L, Mulinare J, Bower C, Folic Acid Working Group Fortification of flour with folic acid. Food Nutr Bull. 2010;31(1):S22–S35. doi: 10.1177/15648265100311S103. - DOI - PubMed
    1. Roth C, Magnus P, Schjolberg S, Stoltenberg C, Suren P, McKeague IW, Smith GD, Reichborn-Kjennerud T, Susser E. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011;306(14):1566–1573. doi: 10.1001/jama.2011.1433. - DOI - PMC - PubMed
    1. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case–control study. Am J Clin Nutr. 2012;96(1):80–89. doi: 10.3945/ajcn.110.004416. - DOI - PMC - PubMed

LinkOut - more resources