Drug transporter protein -mediated drug interactions during pregnancy and offspring outcome; with special emphasis on second-generation antipsychotics and
SSRIs (PgP and BCRP interactions and pregnancy)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  BUPROPION
• Anatomical Therapeutic Chemical (ATC) code:
  (N05A) ANTIPSYCHOTICS

  ANTIPSYCHOTICS

  (N06AB) Selective serotonin reuptake inhibitors

  Selective serotonin reuptake inhibitors
• Medical condition to be studied:
  Congenital anomaly

Population studied

• Short description of the study population:
  Women exposed one month before pregnancy or during the first trimester to P-gp/BCRP polytherapy; P-gp/BRCP monotherapy; non-P-gp/BCRP polytherapy, and unexposed.
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  1000000

Study design details

• Main study objective:
  To investigate if concomitant use of two or more drug transporter substrates or a substrate and an inhibitor during first trimester is associated with an increased risk of offspring major congenital malformations. Specifically, we will assess the risk of overall malformations in offspring of women using SGAs, and the risk of cardiac malformations in offspring of women using SSRIs or bupropion.
• Outcomes:
  Major congenital malformations and major cardiac malformations, according to EUROCAT coding (www.eurocat-network.eu ). Neonatal outcomes: Apgar score <7, need for respirator treatment, need for treatment in neonatal (intensive) care unit, need for care outside home at the age of one week
• Data analysis plan:
  All data are anonymized and coded prior to statistical analysis. The prevalence of specific outcomes is compared between the different exposure groups of pregnant women and their offspring. Crude and adjusted odds ratios (cOR and aOR) and 95% confidence intervals (CI) were calculated. Statistical significance was set at a P value of less than 0.05. Univariate analyses are used to study demographic differences between the study cohorts. Univariate and logistic regression are used to calculate crude and adjusted odds ratios (cOR and aOR), and 95% confidence intervals (CI) and to assess the association between exposures during pregnancy and major congenital malformations and other perinatal outcomes. Covariates will be tested using a P -value of < 0.1 to detect associations with exposure and outcome. If associated with both exposure and outcome, the covariate will be included as a true confounder in the analysis.