Associations of maternal folic acid supplementatio

Authors: Jolien Steenwegde Graaff Sabine J Roza Alette N Walstra Hanan El Marroun Eric A P Steegers Vincent W V Jaddoe Albert Hofman Frank C Verhulst Henning Tiemeier Tonya White

Publish Date: 2015/10/26

Volume: 56, Issue: 1, Pages: 65-75

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Abstract

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 offspringWithin a populationbased prospective cohort we measured maternal plasma folate concentrations at approximately 13 weeks of gestation 90  range 105–172 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 2002–2012In unadjusted models foetal head growth was 0006 SD 95  CI 0003 0009 P  0001 faster per week per 1SD higher maternal folate concentration After adjustment for confounders this association was attenuated to 0004 SD per week 95  CI 0000 0007 P = 002 estimated absolute difference at birth of 27 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 growthOur 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 longterm functioningSupplementation with folic acid during embryonic development reduces the risk of neural tube defects in infants 1 2 This protective effect has led to recommendations for daily supplementation with folic acid starting preconceptionally in women planning to become pregnant Additionally some countries have adopted fortification of flour with folic acid 3Emerging evidence from observational research has shown that maternal folic acid supplementation during pregnancy is associated with reduced risk of several other neurodevelopmental disorders in offspring including language delays 4 autism spectrum disorders 5 6 and problem behaviour 7 However the underlying neurobiology of low folate and these neurodevelopmental problems remains unclear Folic acid supplement use is strongly related to higher socioeconomic status and is a marker of good health literacy 8 9 which increases the susceptibility for confoundingTo further support a potential relationship between folic acid supplement use and neurodevelopmental disorders nutritional biomarkers and biological intermediates can be examined Blood folate concentration serves as a key nutritional biomarker This can be measured in maternal blood and can serve as the endpoint of the determinants of folate status ie after physiological absorption of folic acid supplements and folates from natural or fortified foods 10 Unlike folic acid supplementation folate concentrations are unaffected by recall bias thus serving as a better proxy for actual folate status

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