Demonstrating solutions for studying intermittent medication exposures in diseases with episodic manifestations during pregnancy: application to medication for migraine in pregnancy

Study type

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

  Disease epidemiology

  Drug utilisation

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N02CC) Selective serotonin (5HT1) agonists

  Selective serotonin (5HT1) agonists
• Medical condition to be studied:
  Migraine

  Vomiting

  Gestational diabetes

  Maternal hypertension affecting foetus

  Premature baby

  Low birth weight baby

  Small for dates baby

  Live birth

  Congenital anomaly

Population studied

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

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Adolescents (12 to < 18 years)
  • 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:
  5000000

Study design details

• Main study objective:
  To study the association between prenatal exposure to triptans/migraine medications and adverse maternal and pregnancy outcomes. The potential impact of exposure misclassification on exposure-outcome associations will be assessed under a range of scenarios. Further, to describe drug utilization patterns in women with migraine, and identify event finding algorithms for migraine and maternal events.
• Outcomes:
  Major congenital anomalies in offspring, maternal preeclampsia and gestational diabetes mellitus, - non-live birth (y/n) - preterm birth (y/n), GA (cont. in days) - low birth weight (y/n), BW (cont. in gram, z-scores) - small for gestational age/ intrauterine growth restriction
• Data analysis plan:
  We will estimates prevalence of migraine medication use in the drug utilisation part. In the safety part of the study, risk ratios/hazard ratios/mean differences of the various outcomes by exposure status are estimated using regression models. We will account for confounding using methods within the causal inference framework (eg, marginal structural models). Absolute risk difference and population attributable fractions will also be computed.