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Optimal interpregnancy interval in autism spectrum disorder: A multi-national study of a modifiable risk factor

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Open access
Authors
Pereira, Gavin
Francis, R.W.
Gissler, M.
Hansen, S.N.
Kodesh, A.
Leonard, H.
Levine, S.Z.
Mitter, V.R.
Parner, E.T.
Regan, Annette
Reichenberg, A.
Sandin, S.
Suominen, A.
Schendel, D.
Date
2021
Type
Journal Article

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Pereira, G. and Francis, R.W. and Gissler, M. and Hansen, S.N. and Kodesh, A. and Leonard, H. and Levine, S.Z. et al. 2021. Optimal interpregnancy interval in autism spectrum disorder: A multi-national study of a modifiable risk factor. Autism Research. 14 (11): pp. 2432-2443.
Source Title
Autism Research
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Faculty
Faculty of Health Sciences
School
Office of the Pro Vice Chancellor Health Sciences
Curtin School of Population Health
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This is the peer reviewed version of the following article: Pereira, G., Francis, R. W., Gissler, M., Hansen, S. N., Kodesh, A., Leonard, H., Levine, S. Z., Mitter, V. R., Parner, E. T., Regan, A. K., Reichenberg, A., Sandin, S., Suominen, A., & Schendel, D. (2021). Optimal interpregnancy interval in autism spectrum disorder: A multi-national study of a modifiable risk factor. Autism Research, 14(11), 2432–2443, which has been published in final form at https://doi.org/10.1002/aur.2599. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

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Abstract

It is biologically plausible that risk of autism spectrum disorder (ASD) is elevated by both short and long interpregnancy intervals (IPI). We conducted a retrospective cohort study of singleton, non-nulliparous live births, 1998–2007 in Denmark, Finland, and Sweden (N = 925,523 births). Optimal IPI was defined as the IPI at which minimum risk was observed. Generalized additive models were used to estimate relative risks (RR) of ASD and 95% Confidence Intervals (CI). Population impact fractions (PIF) for ASD were estimated under scenarios for shifts in the IPI distribution. We observed that the association between ASD (N = 9302) and IPI was U-shaped for all countries. ASD risk was lowest (optimal IPI) at 35 months for all countries combined, and at 30, 33, and 39 months in Denmark, Finland, and Sweden, respectively. Fully adjusted RRs at IPIs of 6, 12, and 60 months were 1.41 (95% CI: 1.08, 1.85), 1.26 (95% CI: 1.02, 1.56), and 1.24 (95% CI: 0.98, 1.58) compared to an IPI of 35 months. Under the most conservative scenario PIFs ranged from 5% (95% CI: 1%–8%) in Denmark to 9% (95% CI: 6%–12%) in Sweden. The minimum ASD risk followed IPIs of 30–39 months across three countries. These results reflect both direct IPI effects and other, closely related social and biological pathways. If our results reflect biologically causal effects, increasing optimal IPIs and reducing their indications, such as unintended pregnancy and delayed age at first pregnancy has the potential to prevent a salient proportion of ASD cases. Lay Summary: Waiting 35 months to conceive again after giving birth resulted in the least risk of autism. Shorter and longer intervals resulted in risks that were up to 50% and 85% higher, respectively. About 5% to 9% of autism cases might be avoided by optimizing birth spacing.