Leflunomide

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bérard, 2018	nested case control	The Quebec Prescription Drug Insurance database (drug name, start date, dosage, duration).	The medical service database (RAMQ: diagnoses, medical procedures, socio- economic status of women), the Hospital Records database (MedEcho: diagnoses and procedures, gestational age) and the Quebec Statistics database (ISQ: patient sociodemographic, birth weight).	Potential confounders considered: (1) socioeconomic variables; (2) maternal chronic comorbidities (diabetes, epilepsy,... ); (3) healthcare utilisation; (4) at least one diagnosis of autoimmune diseases (multiple sclerosis, …) in the year before; (5) pregnancy-related variables and other medications used during pregnancy (cholestyramine exposure during pregnancy stratified on trimester of use).
Chambers (Unexposed control, disease free), 2010	prospective cohort	Each woman completed 2 or 3 structured telephone interviews during pregnancy that included exposures. Each woman was provided with a diary in which she kept a record of any additional exposures that might occur before delivery. Medical records were examined for additional exposure data.	Birth outcome was recorded on a standard form completed via telephone interview of the mother. Medical records were examined and infant’s physician also asked to return a form reporting growth measures and any major structural defect. Liveborn infants were also examined by a dysmorphologist.	None
Chambers (Unexposed control, sick), 2010	prospective cohort	Each woman completed 2 or 3 structured telephone interviews during pregnancy that included exposures. Each woman was provided with a diary in which she kept a record of any additional exposures that might occur before delivery. Medical records were examined for additional exposure data.	Birth outcome was recorded on a standard form completed via telephone interview of the mother. Medical records were examined and infant’s physician also asked to return a form reporting growth measures and any major structural defect. Liveborn infants were also examined by a dysmorphologist.	Disease matched control group.
Karadag, 2013	retrospective cohort	Hospital files were used for selecting patients who used leflunomide before or during pregnancy.	Hospital files.	None
Langen, 2014	retrospective cohort	Data were collected from review of medical records and included medication use.	Data were collected from review of medical records and included pregnancy outcomes.	None
Viktil (Controls exposed to other treatments), 2012	population based cohort propective	Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).	The Medical Birth Registry of Norway (MBRN), a population based register that contains information about all births, including late abortion, from 12 weeks of gestation onwards.	None for this group of exposure. Singletons only.
Viktil (Controls unexposed, NOS), 2012	population based cohort propective	Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).	The Medical Birth Registry of Norway (MBRN), a population based register that contains information about all births, including late abortion, from 12 weeks of gestation onwards.	None for this group of exposure. Singletons only.

master protocol