Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study

Abstract

ObjectiveTo determine whether nutritional supplementation during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) with and without intellectual disability in offspring.DesignObservational prospective cohort study using multivariable logistic regression, sibling controls, and propensity score matching.SettingStockholm County, Sweden.Participants273 107 mother-child pairs identified through population registers. The study sample was restricted to children who were aged 4 to 15 years by the end of follow-up on 31 December 2011 and were born between 1996 and 2007.ExposuresMultivitamin, iron, and folic acid supplement use was reported at the first antenatal visit.Main outcome measureDiagnosis of ASD with and without intellectual disability in children determined from register data up to 31 December 2011.ResultsPrevalence of ASD with intellectual disability was 0.26% (158 cases in 61 934) in the maternal multivitamin use group and 0.48% (430 cases in 90 480) in the no nutritional supplementation use group. Maternal multivitamin use with or without additional iron or folic acid, or both was associated with lower odds of ASD with intellectual disability in the child compared with mothers who did not use multivitamins, iron, and folic acid (odds ratio 0.69, 95% confidence interval 0.57 to 0.84). Similar estimates were found in propensity score matched (0.68, 0.54 to 0.86) and sibling control (0.77, 0.52 to 1.15) matched analyses, though the confidence interval for the latter association included 1.0 and was therefore not statistically significant. There was no consistent evidence that either iron or folic acid use were inversely associated with ASD prevalence.ConclusionsMaternal multivitamin supplementation during pregnancy may be inversely associated with ASD with intellectual disability in offspring. Further scrutiny of maternal nutrition and its role in the cause of autism is recommended.

Review and meta‐analysis found that prenatal folic acid was associated with a 58% reduction in autism but had no effect on mental and motor development

“…The ASD diagnoses were made using the Autism Diagnostic Interview – Revised and the Autism Diagnostic Observation Schedule in most cases . Diagnoses were reported according to the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases Criteria . The Social Responsiveness Scale was used to assess autistic traits in one study .…”

“…We felt that 31 papers were potentially relevant, although 15 of them were later excluded because they focused on other nutrients, other disparate results of neurological development or lacked relevant data. Finally, 16 papers with a combined cohort size of 756 365 children were considered in the present study: seven on mental development (12,14,19,20,24,34,35) and, or on motor development (14,19,20,24), and nine on ASD (17,18,23,(35)(36)(37)(38)(39)(40). As can be seen in Tables 1 and 2, two studies were RCTs (34,35), three were case-control studies (36,37,41) and the other 11 were from population-based cohorts (12,14,(17)(18)(19)(20)23,24,(38)(39)(40).…”

“…The Bayley Scales of Infant and Toddler Development -Third Edition (42) was the test most commonly used to evaluate the mental and motor development of children (14,19,24) but the McCarthy Scales of Children's Abilities (43), the Kaufman Assessment Battery for Children (44), the Popper-Szondy Functional Development Test and the Brunet-Lezine test (45) were also used. The ASD diagnoses were made using the Autism Diagnostic Interview -Revised (46) and the Autism (18,(35)(36)(37) and the International Classification of Diseases Criteria (17,18,39,40). The Social Responsiveness Scale (48) was used to assess autistic traits in one study (23).…”

“…Most of the studies were of high (14,(17)(18)(19)(20)23,24,37) or moderate quality (12,36,37,41). Only two studies were of low quality (34,35) and probably had a high risk of selection bias, according to the Cochrane Collaboration's tool, because there was insufficient detail about sequence generation and allocation concealment.…”

“…The effect of prenatal folic acid supplements on the risk of ASD in children is another controversial issue. Although a meta‐analysis published in 2017 showed that folic acid supplements were associated with a decreased risk of ASD, other authors did not find a clear inverse association. The use of high doses of folic acid has also raised concerns and some authors have assessed its effects on the neurodevelopment of children and the risk of ASD , recommending caution with over supplementation.…”