Bupropion and Specific Cardiovascular Malformations
Condition: Depressive Disorder; Pregnancy; Smoking Cessation
MeSH terms: Congenital Abnormalities; Depressive Disorder
Study type: Observational

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.
    

Detailed description: 
      Patients were not recruited for nor enrolled in this study. This study is a retrospective
      observational study. Data from medical records or insurance claims databases are anonymised
      and used to develop a patient cohort. All diagnoses and treatment are recorded in the course
      of routine medical practice.
    

Intervention name(s): 3. Exposure to other antidepressants during the first trimester comparison cohort; 2. Exposure to bupropion outside the first trimester comparison cohort; 1. Exposure to bupropion during the first trimester
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Exposure to other antidepressants during first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate dispensing of other antidepressants. Infants were classified according to maternal exposure to other antidepressants during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women who were exposed only to one type of an antidepressant ("other antidepressant monotherapy"), or more than one type of an antidepressant ("other antidepressant mono or polytherapy") during the first trimester. A woman was considered exposed if there is at least one dispensing of another antidepressant during the first trimester of pregnancy.; Exposure to bupropion outside the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. The comparison cohort ("bupropion exposure outside the first trimester") included women whose bupropion exposure occurred at least one month before the estimated date of conception and women whose bupropion exposure occurred after the first trimester, but before delivery. This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy") during the period outside the first trimester.; Exposure to bupropion during the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. Infants were classified according to maternal exposure to bupropion during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy"). A woman was considered exposed in the first trimester if there was at least one dispensing of bupropion during the first trimester of pregnancy.
Intervention MeSH terms: Bupropion; Antidepressive Agents
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The study population will be the same as that used previously in the 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. 1,213 infants born to 1,140 women (1,142 pregnancies) were exposed to
        bupropion during the first trimester. The comparison groups consisted of 4,753 infants born
        to 4,617 women (4,649 pregnancies) exposed to other anti-depressants during the first
        trimester, and 1,049 infants born to 1,009 women (1,009 pregnancies) exposed to bupropion
        outside of the first trimester. All medical and prescription claims data along with dates
        of health plan enrollment for these women were included. The other antidepressant sample
        was frequency-matched to the bupropion cohort by year of birth, and was selected
        irrespective of exposure to specific antidepressants.
      
Keywords: congenital malformation; cardiovascular malformation; cardiovascular defect; antidepressants; pregnancy; first trimester; Bupropion; prevalence