EPID Multiple Sclerosis Pregnancy study - Pregnancy outcomes in Multiple Sclerosis populations exposed and unexposed to interferon beta - a register-based study in the Nordic countries

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• 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

• Anatomical Therapeutic Chemical (ATC) code:
  (L03AB07) interferon beta-1a

  interferon beta-1a

  (L03AB08) interferon beta-1b

  interferon beta-1b

  (L03AB13) peginterferon beta-1a

  peginterferon beta-1a
• Medical condition to be studied:
  Multiple sclerosis

Population studied

• Short description of the study population:
  The target study population consists of Finnish, Swedish and Norwegian women with MS who have been pregnant during the study period. The study population will be identified according to the inclusion and exclusion criteria below.; ; Inclusion criteria; • Women who have had a pregnancy with a recorded outcome consisting of an induced abortion, spontaneous abortion, ectopic pregnancy, or birth during the study period in FIN, SWE or NOR with the event being documented in the relevant databases. ; ; Exclusion criteria; • None
• Age groups:
  • Paediatric Population (< 18 years)

    • Adolescents (12 to < 18 years)
    • Infants and toddlers (28 days – 23 months)
    • 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)
      • Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  1671

Study design details

• Main study objective:
  The main objectives are to estimate and compare the prevalence of adverse pregnancy outcomes between women with MS exposed to IFN-β only vs. unexposed to any MSDMDs and women with MS exposed to IFN-β only vs. unexposed to IFN-β regardless of exposure to other MSDMDs.
• Outcomes:
  The primary outcome variable is a serious adverse pregnancy outcome defined as a composite endpoint including elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA), and stillbirth. Other outcome variables include live births, stillbirths, elective TOPFA or elective termination due to other reasons, MCA, spontaneous abortions, ectopic pregnancies and defect cases. The following perinatal health outcomes are also included: mode of delivery, preterm birth, birth weight and height, sex of the newborn, head circumference and Apgar scores.
• Data analysis plan:
  The characteristics of all pregnancies with respect to relevant covariates are described with number of events, mean, median, standard deviation, minimum, maximum and inter-quartile range for continuous variables and with number and percentage for categorical variables. The descriptive statistics (the number of events and prevalence) will be presented for each pregnancy outcome. Descriptive analyses of the pregnancy outcomes will be further stratified by e.g. maternal age at LMP, chronic diseases, exposure to any teratogenic medication, duration of MS treatment and gestational age. The prevalence of the pregnancy outcomes will be compared between the study cohorts using log-binomial regression with adjustments for relevant confounders. The RR estimates with 95% confidence intervals and associated p-values will be reported for these comparisons and for confounders used in the model. In indirect comparison between cohort 6 vs. cohort 3, standardized prevalence ratio will be used.