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

BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j4273 (Published 04 October 2017) Cite this as: BMJ 2017;359:j4273
  1. Elizabeth A DeVilbiss, postdoctoral researcher1,
  2. Cecilia Magnusson, adjunct professor2,
  3. Renee M Gardner, assistant professor2,
  4. Dheeraj Rai, consultant senior lecturer3,
  5. Craig J Newschaffer, professor1 4,
  6. Kristen Lyall, assistant professor4,
  7. Christina Dalman, professor2,
  8. Brian K Lee, associate professor1
  1. 1Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, 3215 Market St, Philadelphia, PA, 19104, USA
  2. 2Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
  3. 3Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
  4. 4AJ Drexel Autism Institute, Philadelphia, PA, USA
  1. Correspondence to: E A DeVilbiss ead77{at}drexel.edu
  • Accepted 3 September 2017

Abstract

Objective To determine whether nutritional supplementation during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) with and without intellectual disability in offspring.

Design Observational prospective cohort study using multivariable logistic regression, sibling controls, and propensity score matching.

Setting Stockholm County, Sweden.

Participants 273 107 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.

Exposures Multivitamin, iron, and folic acid supplement use was reported at the first antenatal visit.

Main outcome measure Diagnosis of ASD with and without intellectual disability in children determined from register data up to 31 December 2011.

Results Prevalence 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.

Conclusions Maternal 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.

Footnotes

  • Contributors: CM and CD provided the data used in the study. All authors designed the study. EAD performed the data analysis and drafted the manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. All authors interpreted data, critically revised, and approved the final manuscript.

  • Funding: This study was funded by the National Institutes of Health (1 R21 ES023760-01A1, “Early life vitamin D levels and risk of autism spectrum disorders”) Swedish Research Council, National Institute for Health Research Biomedical Research Centre Bristol. Funders facilitated EAD and BKL to perform their authorship responsibilities. Researchers were independent from funders.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This research has ethical approval as part of Psychiatry Sweden “Psykisk ohälsa, psykiatrisk sjukdom: förekomst och etiologi,” [Mental health and psychiatric disorders–prevalence and aetiology] approved by the Stockholm regional ethical review board (No 2010/1185-31/5).

  • Data sharing: The statistical code is available from the corresponding author.

  • Transparency: The lead author (EAD) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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