The Effects of Prenatal Use of Folic Acid and Other Dietary Supplements on Early Child Development

George L. Wehby; Jeffrey C. Murray


Matern Child Health J. 2008;12(2):180-187. 

In This Article

Abstract and Background

Objective: Our objective was to evaluate in an exploratory framework the effects of prenatal use of folic acid and other dietary supplements on child development at around 3 years of life.
Methods: Data from the 1988 National Maternal Infant Health Survey and the 1991 follow-up supplement is used. Performance indicators are formed based on 16 developmental assessment items completed by the mother to measure overall as well as domain specific (language, personal-social, gross-motor and fine-motor) development. Pooled as well as separate analyses by child race are performed. Multinomial and binary outcome logistic regression is used and several maternal and household characteristics are included as covariates.
Results: Folic acid use was associated with improved gross-motor development with a more pronounced effect among African-American children, but there was marginally significant poorer performance for the personal-social domain. Zinc and calcium use were associated with increased risks on the overall development scale and two other developmental domains. The negative effects of Zinc on overall development were only observed among white children. On the contrary, vitamin A was associated with decreased risks on the overall development scale only among white children.
Conclusions: Study results suggest that while prenatal folic acid supplementation may improve development at 3 years of age, further research is needed in this regard. The results also emphasize the importance of further research into the use of prenatal calcium and zinc supplementation in a US population.

Folic acid intake has been shown to decrease the occurrence and recurrence of neural tube defects (NTDs) at doses of 0.4 mg for primary occurrence and 4 mg for recurrence prevention.[1,2] This evidence has encouraged initiation of folic acid fortification of flour and cereals in some countries. In the US, the fortification dose is about 140 μg/100 g of cereal grain product.[3] The use of multivitamins (including folic acid) has also been shown to reduce NTDs.[4] A preventive role for multivitamins and/or folic acid has also been suggested for other congenital anomalies such as oral clefts and congenital heart disease yet the evidence remains less consistent compared to NTDs.[5,6,7,8,9] The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommend that women of childbearing age consume 0.4 mg of folic acid per day (with intake of a multivitamin containing folic acid being commonly suggested as one approach to meet this goal).[10,11,12]

Folic acid plays a vital role in DNA synthesis and methylation (silencing of gene expression), and thus contributes to the development and expression of genes. Metabolic forms of folate are involved in synthesis of nucleotides and in the methionine cycle, which generates methyl groups that are essential for DNA methylation.[13] Folic acid deficiency at conception and during pregnancy may contribute to abnormal development. However, excessive exposure could have negative effects on development, through, for instance, silencing genes that should remain active.

Little is known about the effect of prenatal intake of folic acid and multivitamins on child development. Beneficial or neutral effects on perinatal outcomes including birth weight and gestational age have been reported.[14] Recently, no effect was reported for low serum and RBC folate levels during the second half of pregnancy on neurological development at 5 years of age in a sample of low socio-economic African-American children, although the results are limited by a lack of folate measures early in pregnancy.[15] It is therefore important to further understand the effects of taking folic acid earlier in pregnancy on child development.

Other vitamin and mineral supplements including vitamin A, vitamin C, zinc and calcium also have biological effects on fetal and infant health either directly or indirectly. Some studies have found positive or no effect of maternal supplement use on fetal and infant health outcomes yet there are limited studies of these effects on child developmental outcomes.[16,17,18,19,20,21,22]

In this study we evaluate the effects of regular use of folic acid, multivitamin/minerals, vitamin A, vitamin C, zinc, calcium and iron at preconception and/or the first trimester of pregnancy on child development at 3 years of age. We assess these effects using a two-sided hypothesis and exploratory framework.


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