Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the Nurses' Health Study II

Abstract

The authors examined pregnancy and obstetric complications in association with autism spectrum disorders (ASD) in children of participants from the Nurses' Health Study II, a prospective national cohort with information collected through biennial mailed questionnaires since 1989. Logistic regression was used to obtain crude and adjusted odds ratios for ASD, and by diagnostic subgroup. Seven hundred and ninety-three cases were reported among 66,445 pregnancies. Pregnancy complications and obstetric suboptimality factors were assessed by maternal report of occurrence in first birth and, in secondary analyses, in any birth. Complications and a suboptimality score were significantly associated with having a child with ASD (OR 1.49, 95% CI 1.26, 1.77, P<0.0001 for pregnancy complications in first birth and 2.76, 95% CI 2.04, 3.74, P<0.0001 comparing individuals with four or more obstetric suboptimality factors in first birth to those with none; results similar when assessed in any birth). In particular, gestational diabetes was associated with a significantly increased risk of ASD in results of primary and sensitivity analyses (OR in primary analysis = 1.76, 95% CI 1.34, 2.32, P<0.0001); suboptimal parity and suboptimal age-at-first-birth were also individual factors associated with ASD. Associations were similar by diagnostic subgroup, suggesting autism, Asperger syndrome, and other Pervasive Developmental Disorders are all associated with pregnancy complications. Consistent with previous research, the general class of pregnancy complications was associated with ASD as a whole. Additional work will be required to more fully assess the role of gestational diabetes.

Figure 1

Summary of study groups, exposures, and outcome definitions used in primary and sensitivity analyses. Abbreviations: NHS II = Nurses Health Study II. Due to the way in which the NHS II question was asked, we did not know year of birth for the ASD children, except for those women with 1 child (uniparous group); however, using information on age at first and last birth when available (for most women) identified a known period of time in which the child was born, which for most women was within 5 years, and was similar in cases and controls.

Figure 2

The graph shows the odds of ASD (Y axis) associated with value of obstetric suboptimality score (X axis). ORs on the Y axis represent values from fully adjusted models, as in Tables 3 and 4. The horizontal dotted line represents the null OR value of no association, while dashed lines flanking the solid line indicate 95% confidence intervals.