DOI

10.17077/etd.l9rkcjrl

Document Type

Dissertation

Date of Degree

Fall 2015

Degree Name

PhD (Doctor of Philosophy)

Degree In

Epidemiology

First Advisor

Romitti, Paul A

First Committee Member

Burns, Trudy L

Second Committee Member

Carnahan, Ryan M

Third Committee Member

Lynch, Charles F

Fourth Committee Member

Shchelochkov, Oleg A

Abstract

Dextromethorphan and guaifenesin are the main active components in over-the-counter cough medications. Prenatal exposure to dextromethorphan has been shown to be teratogenic in animal models. Data from human studies for either dextromethorphan or guaifenesin are limited and inconclusive. We used data from the population-based National Birth Defects Prevention Study (NBDPS) to examine associations between maternal periconceptional (one month before through three months after conception) use of cough medications containing dextromethorphan, with or without guaifenesin, and isolated neural tube defects (NTDs). We also used NBDPS data to explore associations between such exposures and other isolated major birth defects, as well as associations between maternal periconceptional use of cough medications containing guaifenesin alone and isolated major birth defects.

Enrolled cases comprised 19,538 live births, still births, and elective terminations with isolated major birth defects, and enrolled controls comprised 10,200 live births without defects delivered from October 1997 through December 2009. Telephone interview reports of pregnancy exposures, including periconceptional use of cough medications, were obtained from mothers of case and control infants. Two approaches were used to build multivariable models: backward model selection and comparing the change in odds ratios (ORs) by adding each covariable individually into the main effect models. Adjusted ORs (aORs) and 95% confidence intervals (CIs) for maternal periconceptional exposure of cough medications containing dextromethorphan, with or without guaifenesin, or guaifenesin alone, respectively, and 22 types of birth defects were estimated using multivariable logistic regression analysis.

Applying our first multivariable model building approach, we observed that maternal periconceptional use of dextromethorphan, with or without guaifenesin, was marginally significantly associated with an increased risk of all NTDs combined (aOR=1.7, 95%CI=1.0-2.9), or spina bifida alone (aOR=1.9, 95%CI=1.0-3.5). Applying our second model-building approach confirmed the associations with all NTDs combined and spina bifida alone (aOR==1.9, 95% CI=1.2-3.0 and aOR=2.1, 95% CI=1.2-3.8; respectively). For other isolated birth defects, a positive, marginally significant association was observed for maternal periconceptional use of dextromethorphan, with or without guaifenesin, and cleft lip with or without cleft palate (aOR=1.3, 95%CI=1.0-1.7) applying our first model building approach. Our second model-building approach produced significant associations between such exposure and gastroschisis (aOR=1.8, 95%CI=1.2-2.8). With regard to maternal periconceptional use of cough medications containing guaifenesin alone, we observed marginally significant associations with all NTDs combined (aOR=1.9, 95%CI=1.1-3.5), spina bifida alone (aOR=2.3, 95%CI=1.1-4.4), or anorectal atresia (aOR=1.9, 95%CI=1.0-3.6) applying our first model-building approach. Applying our second model-building approach did not suggest significant associations between such exposure and birth defects.

Our findings suggest that maternal periconceptional use of cough medications containing dextromethorphan or guaifenesin may produce selected major structural birth defects in offspring. These findings provide important evidence to better understand the safety of these cough medications and informs about the potential of this modifiable exposure to cause isolated birth defects. Additional population-based research is necessary to validate these positive associations between cough medications and selected isolated birth defects identified in our study.

Keywords

Birth defects, Dextromethorphan, Guaifenesin, Pregnancy, Prevention

Pages

xiv, 133 pages

Bibliography

Includes bibliographical references (pages 119-133).

Copyright

Copyright © 2015 Yanyan Cao

Share

COinS