Mom's Multivitamin Use May Cut Comorbid Autism, Intellectual Disability Risk

Batya Swift Yasgur, MA, LSW

October 16, 2017

Use of multivitamins during pregnancy may reduce the risk for co-occurring autism spectrum disorder (ASD) and intellectual disability, new research suggests.

Investigators from Drexel University in Philadelphia, Pennsylvania, found that maternal multivitamin supplementation, with or without additional iron or folic acid, was associated with a 31% reduced risk for ASD plus intellectual disability in children.

By contrast, supplementation did not affect the odds of developing ASD without intellectual disability.

"It was very interesting that our findings differed by presence or absence of intellectual disability," lead author Elizabeth DeVilbiss, MPH, PhD, postdoctoral researcher, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, told Medscape Medical News.

"The associations between multivitamin use and ASD could be related to ASD, intellectual disability, or both. This could not be examined in the present study, but we plan on looking at this in future work," she said.

The study was published online October 4 in the BMJ.

Maternal Diet, Autism Risk

Although previous research suggests that ASD develops antenatally and that maternal nutrition could influence the risk for ASD, results from population-based studies have been "inconsistent," the authors note.

Moreover, "clarifying the potential role of nutritional supplements is difficult, given the potential for the cause of ASD to differ by the presence of intellectual disability" ― an issue that has "not been well studied in the context of nutritional supplementation," they add.

Maternal differences in socioeconomic factors, disease status, healthy behaviors, or pregnancy characteristics may be potential confounders of observed associations between dietary supplementation and ASD in offspring.

"Not much is known about how diet during pregnancy affects the risk of autism and/or intellectual disability," said Dr DeVilbiss.

"There have been studies in recent years about varied aspects of diet during pregnancy and autism risk involving multivitamins, iron, folic acid, vitamin D, and more, but the evidence is still inconclusive," she said.

To address the limitations of prior studies, the researchers analyzed sibling control persons to account for familial, environmental, and genetic confounding, and they utilized propensity score matching to ensure balanced comparisons between exposed and unexposed children.

The researchers also used multivariable regression analysis of the whole sample to adjust for a large number of covariates.

The analytic strategy was intended to lend "robustness" to the findings.

Self-reported supplement and drug use were assessed at the first antenatal visit, which occurred at a median of 10.7 weeks' gestation (interquartile range, 9.0 - 12.7 weeks).

Maternal covariates included use of inpatient services, outpatient services, prescription drugs. Maternal covariates also included psychiatric data, as well data regarding age, parity, smoking status, and weight. Maternal sociodemographic data included country of birth, education, and family income.

The data were drawn from a register of children residing in Stockholm County, Sweden, for a minimum of 4 years between 2001 and 2011. Only children aged 4 to 15 years at the end of 2011 and only children with siblings born within the study period to the same mother were included in the study.

The researchers divided the mother-child pairs (n = 273,107) into five nonoverlapping groups on the basis of their use of supplements: multivitamins (n = 62,840; 23.0%), iron only (n = 90,138; 33.0%), iron and folic acid (n = 25,445; 9.3%), folic acid only (n = 2789; 1.0%), and none of the above (n = 91,895; 33%).

The multivitamin groups were further subdivided into those who took multivitamins only (n = 17,539; 6.4%), those who took multivitamins and iron (n = 37,046; 13.6%), those who took multivitamins and folic acid (n = 1602; 0.6%), and those who took multivitamins, iron, and folic acid (n = 6653; 2.4%).

Regression analyses revealed that multivitamin use was significantly associated with a lower likelihood of ASD with intellectual disability, compared with nonuse of multivitamins, iron, and folic acid (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.57 - 0.84) in all analyses.

Similar findings were seen in the point estimates from the propensity score analyses (OR, 0.68; 95% CI, 0.54 - 0.86) and sibling control analyses (OR, 0.77; 95% CI, 0.52 - 1.15), although the latter finding was not statistically significant.

Notably, multivitamin use was not associated with lower ASD without intellectual disability in any analysis.

For women who used multivitamins without additional iron or folic acid, the odds ratio estimate was 0.60 (95% CI, 0.44 - 0.84).

Analyses using indicator variables for supplement use, adjusted for the other supplements, yielded estimates for multivitamins and ASD with intellectual disability in the regression and sibling analyses that were similar to estimates from primary analyses.

Findings Still Not Definitive

There were differences between the groups of supplement users with respect to several health and socioeconomic characteristics. Multivitamin users tended to be older, primiparous, more educated, have higher family incomes, be less likely to smoke, and be more likely to be born in Sweden compared to those who did not use multivitamins.

Although folic acid users were on the whole similar to multivitamin users, they were more likely to be immigrants, smokers, and to have epilepsy.

Mothers taking iron or iron plus folic acid tended to be younger, multiparous, less educated, immigrants, smokers, and to have lower incomes.

These observed differences between mothers were potential confounders.

The researchers suggest that it is likely that there were additional unobserved confounders. However, they note, the three types of "advanced analytic methods," taken together, "appeared to point toward a potential inverse association between multivitamin use and ASD with intellectual disability."

On the other hand, the type, timing, and dose of supplements could not be determined, and the data did not indicate whether there is a "critical window" for exposure to the supplements.

Dr DeVilbiss noted other concerns. "A single observational study cannot establish cause and effect, and prior studies have reported conflicting findings."

Moreover, "while we did not find consistent relationships for folic acid and iron taken on their own, we cannot rule out potential contributions by iron and folic acid, as there is folic acid and iron in multi- and prenatal vitamins, and we also did not assess dietary intake," she added.

Clinical Applicability Debatable

Commenting on the study for Medscape Medical News, Joseph M. Braun, MSPH, PhD, assistant professor of public health and epidemiology, Brown University School of Public Health, Providence, Rhode Island, described the study as "well-designed in a very large cohort."

He added that the ability to identify a large number of cases of ASD and to classify them on the basis of intellectual disability status was "a strength."

The study makes an important contribution to the field because it "adds to a growing body of evidence showing that nutritional and environmental factors during pregnancy influence a child's risk of ASD," he said.

The study's finding that the association between maternal multivitamin use and ASD in offspring only applied to the risk for ASD with intellectual disability is "novel," he said.

"In contrast to prior studies, the results from this work suggest that other micronutrients besides folic acid or iron may play a role in influencing the development of ASD or other neurobehavioral disorders."

He added that the study has important practical applicability because it "reinforces the message that clinicians should advise women of childbearing age to take prenatal vitamins, which is especially important since the micronutrient intake very early in pregnancy reduces the risk of ASD and some women do not know that they are pregnant until several weeks into their pregnancy."

Dr DeVilbiss was more cautious about the role of the study findings in informing clinical decisions.

"In light of the current understanding and strength of evidence that supports the importance of nutritional supplementation during pregnancy, these results on their own should not change current clinical practice."

She emphasized that women who are pregnant or are hoping to become pregnant should "make decisions regarding supplement usage in consultation with their healthcare providers."

This study was funded by the National Institutes of Health, the Swedish Research Council, and the National Institute for Health Research Biomedical Research Center Bristol.

The authors and Dr Braun have disclosed no relevant financial relationships.

BMJ. Published online October 4, 2017. Full text

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