Increased Risk of Autism Spectrum Disorders at Short and Long Interpregnancy Intervals in a Finnish Population-Based Study

Background: The time interval between completion of one pregnancy and conception of the next has the potential to influence prenatal exposures. Both short and long interpregnancy intervals (IPI) are believed to present possible adverse conditions for fetal development of the subsequent pregnancy. Short IPI has recently been associated with increased risk of autism, but whether long IPI increases risk for autism spectrum disorders (ASD) has not been thoroughly investigated.

Objectives: To test the hypotheses that both short and long IPI are associated with increased risk of ASD.

Methods:  This study was conducted in the Finnish Prenatal Study of Autism, which is based in a national birth cohort. Children born in Finland in 1987-2005 and diagnosed with childhood autism, Asperger syndrome, or pervasive developmental disorder, not otherwise specified (PDD-NOS) by 2007 were identified through the Finnish Hospital Discharge Register. Matched controls were selected for each case using the Finnish Medical Birth Register. Non-firstborn subjects (2208 ASD cases and 5163 matched controls) were included in the primary analysis. IPI was calculated as the difference between the birthdates of each subject and their preceding sibling, minus gestational age of the subject. The association between IPI and ASD was determined using conditional logistic regression and adjusted for potential confounders. Analyses were also conducted stratified by ASD subtype and by presence of intellectual disability (ID) in the case.

Results: Relative to births with an IPI of 24-59 months, those with the shortest IPI (<12 months) had an increased risk of ASD (OR (95% CI), 1.50 (1.28, 1.74)) in confounder-adjusted models, while the ORs (95% CI) for longer IPI births (60-119 months and >120 months) were 1.28 (1.08, 1.52) and 1.44 (1.12, 1.85), respectively. Upon stratifying by ASD subtypes, the association of shorter IPI with ASD appeared to be accounted for by childhood autism and PDD-NOS, but not Asperger syndrome. However, the association of longer IPI with ASD was strongest and statistically significant only for Asperger syndrome. The association between IPI and ASD did not differ significantly between cases with versus without ID.

Conclusions: This study provides evidence that risk of ASD is increased at long as well as short IPI.