International Meeting for Autism Research: Maternal Infection During Pregnancy and Risk of Autism Spectrum Disorders

Maternal Infection During Pregnancy and Risk of Autism Spectrum Disorders

Thursday, May 20, 2010: 11:30 AM
Grand Ballroom AB Level 5 (Philadelphia Marriott Downtown)
10:00 AM
L. A. Croen , Division of Research, Kaiser Permanente, Oakland, CA
Y. Qian , Division of Research, Kaiser Permanente, Oakland, CA
Background: Converging evidence points towards an immunologic component in an unknown proportion of children with autism.  An initiating role for immune factors during the critical period of neurodevelopment has been suggested.  Gestational exposure to viral infections has been associated with higher autism risk in a few previous studies.
Objectives: To investigate the association between maternal infection during pregnancy and risk of delivering an infant subsequently diagnosed with an autism spectrum disorder (ASD). 
Methods: We conducted a large case-control study nested within the cohort of infants born from 1995-1999 in Kaiser Permanente Northern California (KPNC) hospitals.  Cases (n=407) were children with an ASD diagnosis recorded in KPNC outpatient databases; controls (n=2075) were children without an ASD diagnosis, randomly sampled at a 5:1 ratio and frequency-matched to cases on sex, birth year, and birth hospital.  Information on maternal infection during pregnancy was ascertained from KPNC clinical databases which document all diagnoses recorded by health care providers at every inpatient and outpatient encounter.  Multivariable unconditional logistic regression analysis was conducted to estimate the risk of ASD associated with maternal infection during pregnancy.  Separate models were run for all infections combined, and organism-specific infections (bacterial, viral, parasitic, and mycosal).  For each exposure definition, we examined ASD risk associated with trimester of exposure.  Risks associated with infections documented only during hospitalizations were also examined.  Women with no inpatient or outpatient infection diagnoses for the entire pregnancy period were considered unexposed for all analyses. 
Results:     Nearly 50% of both case and control mothers had at least one diagnosed infection at some point during pregnancy (48.9% vs. 46.6%, P=0.4).  After controlling for covariates (maternal race, age, education, parity, and plurality), the risk of delivering a child later diagnosed with an ASD was somewhat higher for women with diagnosed bacterial infections (inpatient or outpatient) in the 2nd trimester (6.3% vs. 3.4%, P=0.04; ORadj=1.9, 95% CI 1.0-3.7), and 3rd trimester (16.5% vs. 12.3%, P=0.07; ORadj=1.5, 95% CI 1.0-2.2) of pregnancy.  Mycosal infections during pregnancy were also associated with a borderline increased risk (13.3% vs. 9.5%, P=0.07; OR=1.5, 95% CI 1.0-2.3).  The frequency of maternal viral infections anytime during pregnancy did not differ between cases and controls (17.1% vs. 14.9%, P=0.4; ORadj=1.1, 95% CI 0.8-1.6).  Women who were diagnosed with an infection during a hospitalization (inpatient only) in the 2nd trimester of pregnancy had a significantly increased risk of delivering a child who was subsequently diagnosed with an ASD (2.8% vs. 1%, P=0.03; OR=3.7, 95% CI 1.3-10.5).  Inpatient diagnoses of maternal bacterial infections in the 2nd trimester occurred more often among cases than controls, but the difference was not statistically significant.   
Conclusions: These results suggest that maternal infection in the second half of pregnancy, particularly bacterial infection, is associated with a modest increase in risk of having a child with an autism spectrum disorder.  Possible pathogenic mechanisms include direct trans-placental infection of the fetus, hyperthermia, medications used to treat the infection, or the maternal inflammatory response.  Additional studies are needed to clarify the underlying biology accounting for this observed association.
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