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Dissertation
Effect of in utero exposure to beta-2 adrenergic receptor agonists and selective serotonin reuptake inhibitors on the risk for autism spectrum disorders
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2013
DOI:
https://doi.org/10.17918/etd-6132
Abstract
Objective: This dissertation explored associations between two specific classes of drug exposures, beta-2 adrenergic receptor (B2AR) agonists and selective serotonin reuptake inhibitors (SSRIs) and the risk for ASD. Study Design: This project had two components: 1) a case-control study focused on estimation of exposure main effects from Denmark's population-registers and 2) a candidate gene-environment interaction analysis using both exposure and genotype data from a large ongoing US autism case-control study. Methods: From the Danish registers, one case per ten controls was individually matched on birth month and year. Conditional logistic regression was used to estimate unadjusted and adjusted drug exposure odds ratios (OR) and 95% confidence intervals (CI). Estimates were calculated in each drug class for any exposure, any exposure by preconception or trimester, dose, and duration. Special attention was paid to confounding by indication, as well as a sensitivity analysis for exposure and indicating condition misclassification. The gene-environment interaction analysis was based on unmatched case-control data and explored whether effects of in utero B2AR agonist drugs used during pregnancy are modified by polymorphisms in the ADRB2 gene (Gly16 and Glu27 polymorphisms). Logistic regression was used to estimate adjusted ORs and 95% CI. Results: In parental age and child sex adjusted models we observed an increased risk for ASD associated with any in utero B2AR agonist drugs exposure (OR 1.3, 95% CI: 1.1- 1.5). Similarly, any exposure to SSRIs during pregnancy was associated with ASD (OR 2.0 [95% CI, 2.0 [1.6-2.6]) compared to the unexposed reference group. Lastly, for the gene-environment interaction analysis we found some suggestion that the ASD risk associated with prenatal B2AR exposure may be modified by ADRB2 genotype; although estimates were imprecise. Conclusion: The combination of low exposure prevalence during pregnancy and modest odds ratios we had observed for these two classes of drugs implies that the population attributable risks associated with both exposures will be fairly small. The possible increase in ASD risk from exposure to these medications must be weighed against effects of uncontrolled indications during pregnancy and the growing concern over the potential risk for the developing fetus and the mother as well as benefits of medication to mother and fetus despite possible ASD risk.
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Details
- Title
- Effect of in utero exposure to beta-2 adrenergic receptor agonists and selective serotonin reuptake inhibitors on the risk for autism spectrum disorders
- Creators
- Nicole Bondad Gidaya - DU
- Contributors
- Craig J. Newschaffer (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Public Health (2002-2015); Drexel University
- Other Identifier
- 6132; 991014632173504721