Inter-Pregnancy Intervals and Risk of Autism in a Population-Based Study

Background: Numerous studies have found associations between perinatal factors and an increased risk for autism.  While some factors, such as pre-term birth or low-birth weight, are not clearly controllable based on current knowledge, other reported risk factors may be modifiable.  A large and recent study of children from California reported a three-fold increased risk of autism for second-born children whose mothers became pregnant within 12 months after having a previous child, compared to children conceived at least 36 months since their mother last gave birth.

Objectives: The aim of this study was to evaluate the relationship between inter-pregnancy intervals (IPIs) and autism risk in a population-based cohort of Wisconsin children. If the finding that shorter IPIs substantially increase the risk of autism in second-born children is confirmed, this would strengthen the case for a potentially modifiable risk factor for autism. 

Methods: The Wisconsin site of the Autism and Developmental Disabilities Monitoring (ADDM) Network performed a population-based surveillance among 8-year-old children in 2002, 2006 and 2008. Autism case status was determined through the review of medical records by experienced clinicians. Birth certificate information for the autism cases was compared to that for all children born in the same regions of Wisconsin for the birth years corresponding to the cases.  Additionally, for comparability with the California study, the analysis was restricted to second-born children who were not multiples, yielding a final sample size of 154 children with autism, and 31,561 controls. IPIs were calculated as the interval between births of the first and second-born, minus the gestational age of the second-born child. This sample had 80% power to detect an odds ratio of 1.7 for autism between the shortest and longest IPI categories. Multivariable logistic regression was used to determine the odds of autism among second-born children in various IPIs.  The covariates included in the model were birth year, sex of child, maternal age, paternal age, maternal education, and maternal race. 

Results: Among second-born children, the risk of autism among those with IPIs <12 months was not significantly different from children with IPIs ≥36 months (OR=1.2, 95% Confidence Interval: 0.79, 1.91).  After adjusting for confounding variables, this OR increased to 1.6 (95% Confidence Interval: 0.97, 2.60).  While IPIs were not statistically significant predictors of autism, later year of birth, male sex, and white race were associated with increased odds of autism.

Conclusions: We were unable to replicate the finding that shorter IPIs increase the risk for autism among second-born children; if an association is present in this sample, it is likely much smaller in magnitude than what was previously reported in the literature. Additional studies are needed to clarify whether pregnancy intervals are independent risk factors for autism.