Preconception and Prenatal Nutrition and Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

Abstract

Preconception and prenatal nutrition is critical for fetal brain development. However, its associations with offspring neurodevelopmental disorders are not well understood. This study aims to systematically review the associations of preconception and prenatal nutrition with offspring risk of neurodevelopmental disorders. We searched the PubMed and Embase for articles published through March 2019. Nutritional exposures included nutrient intake or status, food intake, or dietary patterns. Neurodevelopmental outcomes included autism spectrum disorders (ASD), attention deficit disorder-hyperactivity (ADHD) and intellectual disabilities. A total of 2169 articles were screened, and 20 articles on ASD and 17 on ADHD were eventually reviewed. We found an overall inverse association between maternal folic acid or multivitamin supplementation and children's risk of ASD; a meta-analysis including six prospective cohort studies estimated an RR of ASD of 0.64 (95% CI: 0.46, 0.90). Data on associations of other dietary factors and ASD, ADHD and related outcomes were inconclusive and warrant future investigation. Future studies should integrate comprehensive and more objective methods to quantify the nutritional exposures and explore alternative study design such as Mendelian randomization to evaluate potential causal effects.

Keywords: attention deficit disorder with hyperactivity; autism spectrum disorder; developmental origins of health and disease; meta-analysis; neurodevelopmental disorders; pregnancy nutrition; systematic review.

Figure 1

Proposed mechanisms in which preconception and prenatal nutrition affects the risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The neurodevelopmental timelines were adapted from the previous publications [3,28]. PUFA, polyunsaturated fatty acids.

Figure 2

Flow diagram of study selection process, intellectual disability (ID).

Figure 3

Adjusted relative risk (RRs) of offspring ASD risk associated with maternal intake of supplement containing folic acid, multivitamin or prenatal vitamin during pregnancy (with or without pre-pregnancy use). The overall effect size was estimated using random effects models weighted by inverse variance of each study. One data point was included for each study. Estimates covering any period during pregnancy were included. When estimates for folic acid and multivitamin were both available, the one for folic acid were selected. Notes: (a) Exposure during pregnancy; (b) Intake of supplement containing folic acid vs. no; (c) Exposure before and during pregnancy; (d) Folic acid intake ≥600 mcg/day vs. <600 mcg/day; (e) Intake of multivitamin vs. never/rarely. * p < 0.05.

Figure 4

Adjusted relative risk (RRs) of offspring risk of ASD associated with maternal intake of supplement containing folic acid, multivitamin or prenatal vitamin during (top) and before (bottom) pregnancy. The overall effect size was estimated using random effects models weighted by inverse variance of each study. Notes: (a) Intake of supplement containing folic acid vs. no; (b) Folic acid intake ≥600 mcg/day vs. <600 mcg/day; (c) Intake of multivitamin vs. never/rarely. * p < 0.05.