Maternal and Newborn Safety profile of Progestogens in Early Pregnancy (PEARLY)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Observational Registry

Population studied

• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  11000

Study design details

• Main study objective:
  Assess the rate of major malformations in fetus and newborns by indication and by exposure to progestogens during the first trimester of pregnancy, with an emphasis on dydrogesterone versus non-dydrogesterone treatments.
• Outcomes:
  Rate of major malformations in fetus and newborns by indication and by exposure to progestogens during the first trimester of pregnancy, with an emphasis on dydrogesterone versus non-dydrogesterone treatments, • Describe the rate of other malformations by progestogen type and indication of use, • To describe demographic, reproductive, and maternal health data, as well as available information on prenatal diagnostics and pregnancy outcome for the mother and the newborn.
• Data analysis plan:
  The risk of major malformation as compared between treatment cohorts will be assessed by unconditional logistic regression. Potential factors of influence, potential confounding factors or risk factors, will be considered either in a pre-analysis step regarding cohort balancing using methods based on propensity scores, e.g. inverse probability of treatment weighting (IPTW) or by subsequent inclusion into the logistic model as cofactors for adjustment of the treatment effect. Crude and adjusted OR and 95% confidence intervals (CI) will be estimated. The primary analysis cohorts are defined as pregnant women using (I) dydrogesterone during the first trimester versus (II) other treatment and/or treatment combinations and/or no treatment during the first trimester of pregnancy. The overall incidence of major malformation will be calculated with respect to all pregnancies observed in the respective cohort and compared per indication area.