DARWIN EU® – Utilisation of commonly used benzodiazepines during pregnancy and the incidence of pregnancy losses

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Commonly used benzodiazepines

Population studied

• Short description of the study population:
  Participants in the study will be required to fulfil the following criteria: ; Inclusion criteria (Table 5): ; 1) Observation period within the study period (1st January 2010-31st December 2023, or latest data availability). ; 2) Female sex at birth. ; 3) At least one year of prior history recorded before start of pregnancy episode. ; 4) A pregnancy episode recorded during the study period (defined by the pregnancy start date), with a pregnancy start date on or before December 31, 2022 (to allow sufficient time between index date and last date of database data availability to cover a full-term pregnancy).(29); 5) Pregnancy end date follows pregnancy start date (in time). ; 6) Pregnancy duration (in days) is greater than 1 but less than 308 days (equivalent to 44 weeks of gestation). ; Exclusion criteria (Table 6): ; 1) Molar and ectopic pregnancies will be excluded (concept ids: 439083 and 437611). ; Disease Epidemiology (objective 5): Two approaches will be used: ; • No exclusion for prior history of pregnancy ; • Excluding anyone with a history of pregnancy in the -365 days.; • Excluding anyone with an unknown pregnancy outcome.;

Study design details

• Study design:
  Population-level cohort; Drug/s user cohort; Population-level cohort; Cohort analysis;
• Main study objective:
  1. To characterise users of benzodiazepine and alternative treatments (SSRIs, SNRIs, Z-hypnotics, and Melatonin) during pregnancy in terms of demographics, prior medications, history of mental illness and other comorbidities. ; 2. To characterise treatments with benzodiazepine and alternative treatments during pregnancy in terms of duration, posology, and indication of prescription during pregnancy.; 3. To describe the prevalence of benzodiazepine and alternative treatments’ use during pregnancy ; 4. To describe trajectories of prescriptions fills for benzodiazepine and alternative treatments throughout the year before pregnancy, pregnancy period, and one month following pregnancy end date. ; 5. To estimate the incidence of pregnancy loss among all pregnancies and in benzodiazepines and alternative treatment users during pregnancy (when numbers allow). ; 6. To characterise individuals with pregnancy loss in terms of demographics, comorbidities, and treatments of interest. ;