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Friday, May 8, 2009: 10:30 AM
Northwest Hall Room 5 (Chicago Hilton)
Background: Abnormal outcomes in brain and tissue function have been reported following prenatal administration of β2-adrenergic receptor (B2AR) agonists in animals. Prenatal exposure to terbutaline, a B2AR agonist, has been previously linked to autism in dizygotic twins, and the prevalence of more active B2AR polymorphisms has been reported to be increased in families with autistic individuals.
Objectives: To investigate the association between maternal exposure to B2AR agonists 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 at northern California Kaiser Permanente (KPNC) hospitals. Cases (n=398) were children with an ASD diagnosis recorded in KPNC outpatient databases; controls (n=410) were children without an ASD diagnosis, randomly sampled and frequency-matched to cases on sex, birth year, and birth hospital. Information on maternal exposure to B2AR agonists and drugs with similar postnatal cell signaling effects after prenatal exposure (mimics) was ascertained from the KPNC pharmacy database, which records all dispensed prescriptions for KPNC members, and abstracted from prenatal medical records using a standardized form. All inpatient and outpatient prescriptions in the 3 months before conception through the end of the pregnancy with the study child were identified.
Results: The frequency of exposure to B2AR agonists or mimics anytime during pregnancy was somewhat higher for the mothers of children with autism (21.4%) compared with the mothers of control children (17.3%), but differences were not statistically significant. After controlling for covariates (birth order, plurality, maternal age, maternal education, and birth weight), the risk of delivering a child later diagnosed with an ASD was over 3 times higher for women with B2AR agonist exposure in the 3 months before conception (OR=3.48, 95% CI 1.2-10.3), and approximately twice as high for women with 1st trimester (OR=1.94, 95% CI 0.87-4.30) or 2nd trimester (OR=2.1, 95% CI 1.0-4.1) exposure. Albuterol was the most frequently used B2AR agonist among mothers of both cases and controls during the preconception period (2.3% vs. 1.2%), as well as in the 1st trimester (3.8% vs. 2.2%) and 2nd trimester (5.3% vs. 3.4%). Frequency of maternal exposure to any B2AR agonist was highest in the 3rd trimester, but did not differ between cases and controls (17.6% vs. 15.6%, P=0.45, OR=1.1, 95% CI 0.71-1.6). Terbutaline accounted for the majority of 3rd trimester exposure in both case and control mothers (10.3% vs. 7.2%, P=0.13, OR=1.34, 95% CI 0.81-2.25).
Conclusions: These results suggest that B2AR agonist exposure in the first half of pregnancy may be associated with an increase in risk of having a child with autism spectrum disorders.
Objectives: To investigate the association between maternal exposure to B2AR agonists 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 at northern California Kaiser Permanente (KPNC) hospitals. Cases (n=398) were children with an ASD diagnosis recorded in KPNC outpatient databases; controls (n=410) were children without an ASD diagnosis, randomly sampled and frequency-matched to cases on sex, birth year, and birth hospital. Information on maternal exposure to B2AR agonists and drugs with similar postnatal cell signaling effects after prenatal exposure (mimics) was ascertained from the KPNC pharmacy database, which records all dispensed prescriptions for KPNC members, and abstracted from prenatal medical records using a standardized form. All inpatient and outpatient prescriptions in the 3 months before conception through the end of the pregnancy with the study child were identified.
Results: The frequency of exposure to B2AR agonists or mimics anytime during pregnancy was somewhat higher for the mothers of children with autism (21.4%) compared with the mothers of control children (17.3%), but differences were not statistically significant. After controlling for covariates (birth order, plurality, maternal age, maternal education, and birth weight), the risk of delivering a child later diagnosed with an ASD was over 3 times higher for women with B2AR agonist exposure in the 3 months before conception (OR=3.48, 95% CI 1.2-10.3), and approximately twice as high for women with 1st trimester (OR=1.94, 95% CI 0.87-4.30) or 2nd trimester (OR=2.1, 95% CI 1.0-4.1) exposure. Albuterol was the most frequently used B2AR agonist among mothers of both cases and controls during the preconception period (2.3% vs. 1.2%), as well as in the 1st trimester (3.8% vs. 2.2%) and 2nd trimester (5.3% vs. 3.4%). Frequency of maternal exposure to any B2AR agonist was highest in the 3rd trimester, but did not differ between cases and controls (17.6% vs. 15.6%, P=0.45, OR=1.1, 95% CI 0.71-1.6). Terbutaline accounted for the majority of 3rd trimester exposure in both case and control mothers (10.3% vs. 7.2%, P=0.13, OR=1.34, 95% CI 0.81-2.25).
Conclusions: These results suggest that B2AR agonist exposure in the first half of pregnancy may be associated with an increase in risk of having a child with autism spectrum disorders.