Prenatal Vitamins, One-carbon Metabolism Gene Variants, and Risk for Autism

Abstract

Background Causes of autism are unknown. Associations with maternal nutritional factors and their interactions with gene variants have not been reported. Methods Northern California families were enrolled from 2003–2009 in the CHARGE (CHildhood Autism Risks from Genetics and Environment) population-based case-control study. Children aged 24–60 months were evaluated and confirmed to have autism (n = 288), autism spectrum disorder (n = 141), or typical development (n = 278) at the University of California–Davis Medical Investigation of Neurodevelopmental Disorders Institute using standardized clinical assessments. We calculated adjusted odds ratios (ORs) for associations between autism and retrospectively collected maternal vitamin intake before and during pregnancy. We explored interaction effects with functional genetic variants involved in one-carbon metabolism (MTHFR, COMT, MTRR, BHMT, FOLR2, CBS, and TCN2) as carried by the mother or child. Results Mothers of children with autism were less likely than those of typically developing children to report having taken prenatal vitamins during the three months before pregnancy or the first month of pregnancy (OR = 0.62 [95% confidence interval = 0.42–0.93]). Significant interaction effects were observed for maternal MTHFR 677 TT, CBS rs234715 GT+TT, and child COMT 472 AA genotypes, with greater risk for autism when mothers did not report taking prenatal vitamins periconceptionally (4.5 [1.4–14.6]; 2.6 [1.2–5.4]; and 7.2 [2.3–22.4], respectively). Greater risk was also observed for children whose mothers had other one-carbon metabolism pathway gene variants and reported no maternal prenatal vitamin intake. Conclusions Periconceptional use of prenatal vitamins may reduce the risk of having children with autism, especially for genetically susceptible mothers and children. Replication and mechanistic investigations are warranted.

Folate status and health: challenges and opportunities

“…A recent case-control study on 429 children with autism and 278 controls reported that maternal prenatal intake of FA ≥ 600 μg/day (vs. < 600 μg/day) was associated with a lower probability of autism in the offspring [49]. The association was more impressive in mothers with the MTHFR677 TT genotype [49], in accordance with an earlier study showing an increased risk for autism in the offspring of MTHFR677 TT mothers who were not supplemented with FA prenatally [50]. The Norwegian Mother and Child Cohort (MoBa) study, a prospective study on 85,176 children born between 2002 and 2008 in Norway [51], showed that autistic disorders were found in 0.10% of children whose mothers took FA (starting before conception and lasting at least up to the 8 th gestational week) but in 0.21% of those unexposed [adjusted OR 0.61 (95%CI 0.41-0.90] [51].…”

The association between the interpregnancy interval and autism spectrum disorder in a Canadian cohort

“…Prenatal nutritional status has been linked to brain development in the offspring, [8][9][10][11] which supports a potential biologic basis for the association between short IPIs -which may contribute to maternal nutritional depletion 12 -and autism/ASD. If this or some other biologic mechanism underlies the observed associations, rather than confounding or chance, it would open up opportunities for modifying risk.…”

Research Letter: Folic acid supplementation and intake of folate in pregnancy in relation to offspring risk of autism spectrum disorder

“…Recent studies (Schmidt et al 2011(Schmidt et al , 2012de Steenweg et al 2015), including results from the large Norwegian MoBa Cohort, suggest that prenatal folic acid supplement use may protect the child against developing autism (Suren et al 2013). Folate is necessary for normal fetal development (Morse, 2012), and plays a key role in DNA methylation (Reynolds, 2006) and could therefore impact risk of ASD.…”

“…Folate is necessary for normal fetal development (Morse, 2012), and plays a key role in DNA methylation (Reynolds, 2006) and could therefore impact risk of ASD. Previous studies have for the most part been casecontrol studies (Schmidt et al 2011(Schmidt et al , 2012, or have had incomplete ascertainment of ASD due to a relatively short follow-up period (Suren et al 2013).…”