Is Intraventricular Hemorrhage Associated with Autism?

Background: Autism has been associated with perinatal cerebral white matter complications; however, many white matter diseases have yet to be studied. We examined the relationship between autism and intraventricular hemorrhage (IVH).

Objectives:  To determine whether children whose neonatal course is complicated by IVH are more likely to develop autism, and whether the relationship is influenced by prematurity or gender.

Methods:  This retrospective cohort study includes births drawn from the Office of Statewide Health Planning and Development PDD-Birth files from 01/01/1991-12/31/2008 that survived their first year of life. Children diagnosed with autism between 1991 and 2012 by the California Department of Developmental Services (DDS) were identified (n=42,423). The remainder of the birth cohort served as controls (n= 8,909,340). ICD-9-CM codes for IVH were identified with grade sub-categories available from 2001. A step-wise linear regression evaluated the relationship between IVH and autism, controlling for maternal age, race/ethnicity, delivery payer and birth year. Preeclampsia and birth mode did not alter the relationship.

Results:  IVH incidence was highest in infants with birthweight <1500 g or gestational age <31 weeks (16% and 20%, respectively). In adjusted analyses, children with IVH who survived their first year of life were 3 times more likely to develop autism (RR 2.97, 95% CI 2.61, 3.37). For those born in 2001-2008, the relative risk of autism increased proportional to severity for grades I-III (Figure 1). Girls with IVH were slightly more likely to develop autism compared with boys (RR 3.5,1, 95% CI 2.62, 4.71 vs RR 2.71, 95% CI 2.35, 3.13) and autism risk rose proportional to gestational age.

Conclusions:  The 3-fold increased autism risk in children whose neonatal course was complicated by IVH is concerning, as are the paradoxical findings of increased autism risk in IVH-affected girls and infants born later in gestation. IVH screening in infants born <30 weeks and in others with elevated risk improves early therapeutic potential. Our results underscore the importance of ASD screening in children with IVH and present considerable opportunity for interventions aimed at maximizing neurocognitive development and functional attainment.