Closely spaced pregnancies are associated with increased odds of autism in California sibling births

Abstract

Objective: To determine whether the interpregnancy interval (IPI) is associated with the risk of autism in subsequent births.

Methods: Pairs of first- and second-born singleton full siblings were identified from all California births that occurred from 1992 to 2002 using birth records, and autism diagnoses were identified by using linked records of the California Department of Developmental Services. IPI was calculated as the time interval between birth dates minus the gestational age of the second sibling. In the primary analysis, logistic regression models were used to determine whether odds of autism in second-born children varied according to IPI. To address potential confounding by unmeasured family-level factors, a case-sibling control analysis determined whether affected sibling (first versus second) varied with IPI.

Results: An inverse association between IPI and odds of autism among 662 730 second-born children was observed. In particular, IPIs of <12, 12 to 23, and 24 to 35 months were associated with odds ratios (95% confidence intervals) for autism of 3.39 (3.00-3.82), 1.86 (1.65-2.10), and 1.26 (1.10-1.45) relative to IPIs of ≥ 36 months. The association was not mediated by preterm birth or low birth weight and persisted across categories of sociodemographic characteristics, with some attenuation in the oldest and youngest parents. Second-born children were at increased risk of autism relative to their firstborn siblings only in pairs with short IPIs.

Conclusions: These results suggest that children born after shorter intervals between pregnancies are at increased risk of developing autism; the highest risk was associated with pregnancies spaced <1 year apart.

FIGURE 1

Cumulative distribution of the IPIs for full-sibling pairs with 0 or 1 autism case subjects, among California singleton births, 1992–2002. Autism diagnoses were identified by using records of the California DDS.

FIGURE 2

ORs and 95% CIs for autism according to IPI preceding conception, among 662 730 second-born singletons from full-sibling pairs born between 1992 and 2002 in California, where the first child was not diagnosed with autism. Calculated using logistic regression models adjusted for sex, birth year, parental ages, maternal education, ethnicity, birth place and Medi-Cal use. IPIs were modeled using indicator variables for 3-month intervals. Autism diagnoses were identified using records of the California DDS.

FIGURE 3

ORs and 95% CIs for the association of autism and birth order (second versus first) according to IPI among 5327 singleton full-sibling pairs born in California between 1992 and 2002. Model adjusted for the child's sex, birth year, maternal and paternal ages (categorical variables), Medi-Cal use, and maternal education. Autism diagnoses were identified using records of the California DDS.