Increased Risk of Autism Spectrum Disorders in Children Born to Women With Systemic Lupus Erythematosus: Results From a Large Population-Based Cohort

Objective: In utero exposure to maternal antibodies and cytokines are potential risk factors for autism spectrum disorders (ASDs). The aim of this study was to determine whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of ASD compared to children born to mothers without SLE.

Methods: The study population was derived from the Offspring of SLE Mothers Registry (OSLER), a large population-based cohort identified through healthcare databases in Quebec (1989-2009) comprising all women who had ≥1 hospitalization for a delivery (stillbirth or live birth) after SLE diagnosis. As general population controls, a randomly selected group of women without SLE was matched ≥4:1 to the mothers with SLE for age and year of delivery. Children born live to mothers with SLE and those born live to matched controls were identified, and a recorded diagnosis of ASD was ascertained for each child. Multivariate analyses were performed to adjust for parents' demographic characteristics, sex, birth order of the child, maternal comorbidities, and obstetric complications.

Results: In total, 509 women with SLE had 719 children, and 5,824 matched controls had 8,493 children. Children born to women with SLE were more frequently found to have a diagnosis of ASD compared to controls (frequency of recorded ASDs 1.4% [95% confidence interval (95% CI) 0.8-2.5] versus 0.6% [95% CI 0.5-0.8]), a difference of 0.8% (95% CI 0.1-1.9). The mean age at ASD diagnosis was younger in offspring of SLE mothers (mean 3.8 years, 95% CI 1.8-5.8) compared to offspring of controls (mean 5.7 years, 95% CI 4.9-6.5). In primary multivariate analysis, SLE offspring had a substantially increased risk of ASD compared to controls (odds ratio 2.19, 95% CI 1.09-4.39).

Conclusion: Compared to children from the general population, children born to women with SLE have an increased risk of ASD, although, in absolute terms, it represents a rare outcome. These hypothesis-generating data provide direction for additional studies of maternal autoimmunity and ASD risk.