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A Case-control Study

Lisa A. Croen, PhD; Judith K. Grether, PhD; Cathleen K. Yoshida, MS; Roxana Odouli, MSPH; Judy Van de Water, PhD

Arch Pediatr Adolesc Med. 2005;159:151-157.

Objective  To investigate the association between physician-documented diagnoses of maternal autoimmune diseases, allergies, and asthma around the time of pregnancy and subsequent diagnoses of autism in children.

Design  A case-control study nested within a cohort of infants born between January 1995 and June 1999.

Setting  Northern California Kaiser Permanente Medical Care Program.

Participants  Cases (n = 420) were children with at least 1 diagnosis of an autism spectrum disorder (ASD) recorded in Kaiser Permanente outpatient clinical databases. Controls (n = 2100) were children without an ASD diagnosis who were frequency matched to cases on sex, birth year, and hospital of birth.

Main Outcome Measures  Frequencies of maternal immunologic disorders were compared between cases and controls with a ² statistic, and relative risks were estimated by crude and adjusted odds ratios and 95% confidence intervals using logistic regression.

Results  The final study population included 407 cases and 2095 controls. A similar proportion of case and control mothers had a diagnosis of any autoimmune disease in the 4-year period surrounding pregnancy (10.3% vs 8.2%, P = .15). After adjustment for maternal factors, only 1 autoimmune condition, psoriasis, was significantly associated with ASDs (adjusted odds ratio, 2.7; 95% confidence interval, 1.3-5.8). A greater than 2-fold elevated risk of ASD was observed for maternal asthma and allergy diagnoses recorded during the second trimester of pregnancy.

Conclusions  These findings suggest that maternal autoimmune disorders present in women around the time of pregnancy are unlikely to contribute significantly to autism risk. Further etiologic investigations are needed to confirm these results and should include objective documentation of diagnoses and consider a larger set of maternal immune-related conditions, including asthma and allergies.

Author Affiliations: Division of Research, Kaiser Foundation Research Institute, Kaiser Permanente (Dr Croen and Mss Yoshida and Odouli), and Department of Health Services, Environmental Health Investigations Branch (Dr Grether), Oakland, Calif; and Division of Rheumatology/Allergy, University of California at Davis (Dr Van de Water).

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