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.

Exploring Eating and Nutritional Challenges for Children with Autism Spectrum Disorder: Parents’ and Special Educators’ Perceptions

“…The experts were always updated with recent development pertaining to the new findings in nutrition among children with autism. Based on the latest studies, there are associations between micronutrient deficiencies with neurodevelopmental disorders, and low nutritional status of pregnant mothers can be a risk for such disorders including ASD [60]. Recently, there was a study linking low iodine levels in the first trimester of pregnancy and processing disorders of the child including children with ASD [61].…”

Significant Effects of Maternal Diet During Pregnancy on the Murine Fetal Brain Transcriptome and Offspring Behavior

“…Deficiencies in B vitamins and Vitamin D have also been linked to increased ADHD risk in children (Morales et al, 2015;Altun et al, 2018;Fasihpour et al, 2019;Kotsi et al, 2019), although some studies have failed to find these associations (Gustafsson et al, 2015). Inconsistent with our finding of hyperactivity in the powder-chow exposed offspring, recent human and rodent studies have reported that increased cord blood n-6/n-3 fatty acid ratio or relative maternal deficiency of n-3 fatty acids is associated with increased risk for ADHD in offspring (Fedorova and Salem, 2006;Sakayori et al, 2016;Lopez-Vicente et al, 2019), A recent systematic meta-analysis concluded that maternal omega-3 fatty acid intake has not been consistently associated with offspring ADHD risk, however (Li et al, 2019). Poor maternal dietary quality, particularly diets high in sugar, fat and processed foods (which may in some cases be a marker for micronutrient deficiency), has been more consistently linked to ADHD risk in offspring (Rijlaarsdam et al, 2017;Galera et al, 2018).…”

“…With respect to the finding of hyperactivity/increased locomotion in powdered-chow exposed offspring, human studies evaluating the impact of vitamin and micronutrient deficiencies on offspring attention deficit hyperactivity disorder (ADHD) risk have reported mixed results (Li et al, 2019). For example, maternal multivitamin and folate intake were associated with a lower risk of ADHD diagnosis and medication use in the Danish National Birth Cohort, but not in a New Zealand birth cohort (Virk et al, 2018;D'Souza et al, 2019).…”

“…While the impact of maternal macronutrient and micronutrient intake in pregnancy has been examined in several human observational studies, these focus primarily on the impact of maternal intake on pregnancy outcomes such as preeclampsia and preterm birth, on fetal growth trajectory, and on neonatal outcomes such as small-and large-for-gestational age, and incidence of congenital anomalies (Mousa et al, 2019). Fewer studies have focused directly on the impact of maternal pregnancy and lactational nutrition on fetal brain development and offspring behavior (Prado and Dewey, 2014;Li et al, 2019). There remains a knowledge gap regarding the impact of maternal micro-and macronutrient intake specifically on fetal brain development and offspring behavior.…”

Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers

“…Maternal defects in one-carbon metabolism have also been proposed to influence ASD risk [49][50][51][52]. So far, however, no single factor has been identified to play a leading role in the development of ASD [53][54][55], giving support to the notion that autism has a complex and multifactorial origin [56].…”