Pregnancy outcome following maternal exposure to mirtazapine: a collaborative ENTIS study

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:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  MIRTAZAPINE
• Anatomical Therapeutic Chemical (ATC) code:
  (N06AB) Selective serotonin reuptake inhibitors

  Selective serotonin reuptake inhibitors
• Medical condition to be studied:
  Pregnancy

Population studied

• Short description of the study population:
  Pregnant women with or without exposure to mirtazapine.
• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  1071

Study design details

• Main study objective:
  The aim of the study is to assess the risk of mirtazapine exposure during pregnancy.
• Outcomes:
  The primary objective is to prospectively evaluate the rate of major birth defects after first trimester exposure to mirtazapine. Secondary objectives are to evaluate pregnancy outcome, birth weight, gestational age at delivery, and neonatal outcome of prospectively collected exposures to mirtazapine at any time during pregnancy.
• Data analysis plan:
  The birth defect rates will be calculated taking live births and anomalies in elective terminations of pregnancies (ETOPs) and miscarriages into account. Crude miscarriage rates will be calculated per exposed pregnancies or controls and after exclusion of ETOPs. Miscarriage rates will also be calculated applying the method of cumulative incidence function. Outcome endpoints of interests between the case and control groups will be compared using Chi Square or Fisher’s exact tests for categorical data and Kruskal-Wallis (for three groups) or Mann-Whitney tests (for two groups). Further multivariate explorations will rely on logistic regression analysis to account for a possible role of cofactors (dosage level, exposure time and duration, maternal age, alcohol, tobacco).