A1 Refereed original research article in a scientific journal
Optimal interpregnancy interval in autism spectrum disorder: A multi-national study of a modifiable risk factor
Authors: Pereira Gavin, Francis Richard W, Gissler Mika, Hansen Stefan N, Kodesh Arad, Leonard Helen, Levine Stephen Z, Mitter Vera R, Parner Eric T, Regan Annette K, Reichenberg Abraham, Sandin Sven, Suominen Auli, Schendel Diana
Publisher: WILEY
Publication year: 2021
Journal: Autism Research
Journal name in source: AUTISM RESEARCH
Journal acronym: AUTISM RES
Volume: 14
Issue: 11
First page : 2432
Last page: 2443
Number of pages: 12
ISSN: 1939-3792
eISSN: 1939-3806
DOI: https://doi.org/10.1002/aur.2599
Web address : https://doi.org/10.1002/aur.2599
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.
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.
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