Bupropion and Specific Cardiovascular Malformations
Status:
Completed
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
The study is an extension of earlier work based on a retrospective epidemiologic study of
infants born to women who were exposed to bupropion in their estimated first trimester of
pregnancy using data from a large US health plan affiliated with i3 Drug Safety (Clinical
study ID WWE113694) (Cole JA, Oh KS, Chiang CC, Walker AM, Haight BR, Modell JG. Bupropion in
pregnancy and the prevalence of congenital malformations Pharmacoepidemiology and Drug
Safety, 2007; 16: 474-484). The cohorts developed for the earlier work consisted of all
infants born to women exposed to bupropion during the estimated first trimester and outside
the first trimester, and a random sample of infants born to women exposed to other
antidepressants during the first trimester between 01 January 1995 and 30 September 2004. The
objectives for this study include refining of both the original first trimester bupropion
cohort and the original bupropion outside the first trimester cohort into mono-therapy and
mono- or poly-therapy. Exposure to other antidepressants during the first trimester will also
be refined into mono-therapy and mono- or poly-therapy. With input from pediatric cardiology
expert, lists of specific cardiovascular malformations and malformation groupings will be
created. The groupings will be created among the refined first trimester bupropion cohort as
well as in two comparison cohorts of bupropion outside the first trimester and first
trimester antidepressant use (mono-therapy and mono-or poly-therapy). The prevalence in each
cohort will be calculated as the number of infants with a specific cardiovascular
malformation divided by the number of live born infants. Prevalence will be reported per
1,000 infants. Confidence intervals will be calculated using Wilson's approximation to exact
binomial intervals when the number of cases is five or greater and exact binomial intervals
when the number of cases is fewer than five. The appropriateness of further calculations will
be evaluated. Where numbers permit, adjusted odds ratios for specific cardiovascular
groups/malformations will be calculated and if appropriate, stratified according to maternal
dispensing of medications suspected to be teratogenic. The following comparisons, if numbers
permit, will be performed: 1) bupropion first trimester mono-therapy cohort versus other
antidepressant first trimester mono-therapy cohort; 2) bupropion first trimester mono- or
poly-therapy cohort versus other antidepressant first trimester mono- or poly-therapy cohort;
3) bupropion first trimester mono-therapy cohort versus bupropion outside of first trimester
mono-therapy cohort, and 4) bupropion first trimester mono- or poly-therapy cohort versus
bupropion outside of first trimester mono- or poly-therapy cohort. Adjusted odds ratios will
be calculated through a generalized estimated equations form of multivariate logistic
regression to account for births associated with multiple infants. The same covariates
identified in the original study will be included in this re-analysis. Covariates included:
diagnoses of bipolar disorder and eclampsia within one year before delivery; dispensings of
lithium, phenytoin, and fluconazole within one year before delivery through the end of the
first trimester; and the number of physician visits within 10 to 12 months before delivery,
maternal age, geographic region of the health plan, and infant gender. If generalized
estimating equation form of the logistic regression model does not converge, adjusted odds
ratios will be presented from a conventional multivariate logistic model. If the conventional
multivariate logistic model does not converge, only the crude odds ratio will be presented.