Prenatal Vitamins and the Risk of Offspring Autism Spectrum Disorder: Systematic Review and Meta-Analysis

Abstract

Prenatal nutrition is associated with offspring autism spectrum disorder (herein referred to as autism), yet, it remains unknown if the association is causal. Triangulation may improve causal inference by integrating the results of conventional multivariate regression with several alternative approaches that have unrelated sources of bias. We systematically reviewed the literature on the relationship between prenatal multivitamin supplements and offspring autism, and evidence for the causal approaches applied. Six databases were searched up to 8 June 2020, by which time we had screened 1309 titles/abstracts, and retained 12 articles. Quality assessment was guided using Newcastle–Ottawa in individual studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) for the body of evidence. The effect estimates from multivariate regression were meta-analysed in a random effects model and causal approaches were narratively synthesised. The meta-analysis of prenatal multivitamin supplements involved 904,947 children (8159 cases), and in the overall analysis showed no robust association with offspring autism; however, a reduced risk was observed in the subgroup of high-quality observational studies (RR 0.77, 95% CI (0.62, 0.96), I2 = 62.4%), early pregnancy (RR 0.76, 95% CI (0.58; 0.99), I2 = 79.8%) and prospective studies (RR 0.69, 95% CI (0.48, 1.00), I2 = 95.9%). The quality of evidence was very low, and triangulation was of limited utility because alternative methods were used infrequently and often not robustly applied.

The Role of Dietary Patterns and Nutritional Supplements in the Management of Mental Disorders in Children and Adolescents: An Umbrella Review of Meta-Analyses: Le rôle des habitudes alimentaires et des suppléments nutritionnels dans la prise en charge des troubles mentaux chez les enfants et les adolescents : une méta-revue de méta-analyses

“…However, a reduced risk was observed in the subgroup of high-quality observational studies (RR = 0.77; 95% CI, 0.62 to 0.96; p < 0.05; I 2 = 62.4%), studies focused on early pregnancy (RR = 0.76; 95% CI, 0.58 to 0.99; I 2 = 79.8%), and prospective studies (RR = 0.69, 95% CI, 0.48 to 1.00; I 2 = 95.9%). 44 More specifically, folic acid supplementation during early pregnancy was associated with a lower risk of offspring's ASD (k = 10; n = 9,795 ASD cases; OR = 0.57; 95% CI, 0.41 to 0.78). The consumption of a daily amount of at least 400 μg folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD (k = 1; n = 466; OR = 0.55; 95% CI, 0.36 to 0.83).…”

“…In the field of nutritional psychiatry in children and adolescents, the most extensively studied mental disorders are ASD, [43][44][45][46][47][48][49][50][51][52][53] followed by ADHD. [34][35][36][37][38][39][40][41][42] These results are consistent with the observed increase in the prevalence of these disorders.…”

The social determinants of mental health and disorder: evidence, prevention and recommendations

“…Prenatal malnutrition following famine exposure has also been strongly associated with risk of psychotic disorders 65 , notwithstanding similar issues around causality. A systematic review also found evidence to support a protective effect of prenatal multivitamin supplementation on autism spectrum disorder 74 , but this was restricted to high‐quality studies. Surprisingly few studies have examined the association between prenatal nutrition and common mental disorders, with no systematic review available, although some longitudinal evidence exists for childhood mood and behavioural outcomes 75‐77 , with associations persisting after adjustment for maternal perinatal mental health, prenatal smoking and alcohol use.…”

Maternal Serum Vitamin B12 during Pregnancy and Offspring Autism Spectrum Disorder

“…There is a wide recognition that the etiology of ASD is multifactorial, involving the interplay of genetic and environmental factors [2]. Strong evidence has suggested that ASD is influenced by prenatal factors [3] including maternal nutrition [4]. Specific nutrients have been identified as potentially impacting the risk for ASD, for example, folate, vitamin D, iron and polyunsaturated fatty acids, but the findings are often mixed [5,6].…”

“…1 Data missing for 6 controls; 2 Data missing for 8 controls;3 Data missing for 6 controls;4 Data missing for 6 controls;5 Data missing for 8 controls.…”