Anti-thyroid Drug Use during pregnancy and risk of congenital anomalies: systematic review of observational studies and methodological considerations (Anti-thyroid drugs in pregnancy)

Study type

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

Non-interventional study

• Non-interventional study design:
  Systematic review and meta-analysis

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (H03BA02) propylthiouracil

  propylthiouracil

  (H03BB01) carbimazole

  carbimazole

  (H03BB02) thiamazole

  thiamazole
• Medical condition to be studied:
  Hyperthyroidism

Population studied

• Age groups:
  • 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:
  1000000

Study design details

• Main study objective:
  To measure the association between maternal exposure to methimazole, carbimazole and propylthiouracil and the risk of congenital anomalies in offspring from existing observational studies.
• Outcomes:
  Congenital anomalies in offspring
• Data analysis plan:
  The study characteristics and heterogeneity in confounding adjustment will first be described. Crude and adjusted effect estimates will be calculated on the natural log scale and pooled using the generic inverse variance method of analysis. Random-effects models will be generated analysis for each type of exposure and comparator group separately. A leave-one-out analysis will be undertaken to test the robustness of the results. Analyses will be conducted in Review Manager 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Publication bias will be assessed by testing for funnel-plot asymmetry and using the Egger test as appropriate.