Antimycotic Azoles (all routes except local only)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bar-Oz - Itraconazole, 2000	prospective cohort	Details (timing and dose) of maternal drug therapy were reported by the treating physician.	Pregnancy outcome reports were sent to the manufacturer by the treating physician.	Subjects were matched for maternal age (within 2 years), last menstrual period (within 6 months), gravidity, parity, and alcohol and smoking status.
Berard - Fluconazole, 2019	nested case control	The Quebec Prescription Drug Insurance database. The filled prescription data were validated comparing them with maternal reports (the positive predictive value of prescription drug data to be ≥ 87% and the negative predictive value to be ≥ 92%).	Identification from the medical claims databases: Régie de l’assurance maladie du Québec (RAMQ) (outpatient diagnoses, procedures, women’s and physicians’ socioeconomic status), hospitalization archive database (MED-ÉCHO: diagnoses and procedures) and the Institut de la statistique du Québec (ISQ).	For intrauterine deaths: matched on gestational age at diagnosis of spontaneous abortion or stillbirth (index date) and the year of the last menstrual period. Adjusted OR obtained from multivariate conditional logistic regression model for maternal age, alcohol dependence, tobacco dependence, maternal comorbidities (hypertension, diabetes, epilepsy...), use of health services in 6 months before...
Carter - Miconazole, 2008	case control	Structured maternal interviews were conducted mainly by telephone in English or Spanish no later than 24 months after the expected date of delivery (EDD) to obtain data on maternal exposures during pregnancy.	Cases and controls were identified by the birth defects surveillance systems in 10 states of USA. Medical records were obtained for all cases and reviewed by clinical geneticists.	No adjustment for this group of exposure.
De Santis - Itraconazole, 2009	prospective cohort	A structured questionnaire used to collect information about maternal medical features and details of itraconazole therapy (dosage and timing).	A structured questionnaire administered to women by telephone to collect information about major congenital anomalies (presence and type), delivery (gestational age and type), birth weight and neonatal complications using .	Groups were matched according to maternal age, gravidity and parity, cigarette smoking, alcohol and illicit drug consumption.
Howley - Fluconazole, 2016	case control	Exposures before and during pregnancy were collected by trained interviewers conducted computer-assisted telephone interviews with the mothers of case and control infants between 6 weeks and 24 months after the estimated date of delivery.	Clinical information was abstracted from case medical records. The clinical record of each case was reviewed by a clinical geneticists.	Adjusted for mother’s state of residence at the time of birth, age, race/ethnicity, smoking, and gestational diabetes.
Inman - Fluconazole, 1994	retrospective cohort	The patients were identified by means of copies of prescriptions supplied to the Drug Safety Research Unit (DSRU) in confidence by the Prescription Pricing Authority.	Simple questionnaires (green forms) were posted to the doctors requesting notably diagnosis and any events that had occurred after the drug bad been prescribed. When the outcome of pregnancy was not recorded on the green form, a further questionnaire was sent to the prescribing doctor.	None.
Jick - Fluconazole and Itraconazole (Oral), 1999	retrospective cohort (claims database)	General Practice Research Database of prescription.	Computer record was reviewed to identify indications of a congenital anomaly. For those with a suspected anomaly, we requested relevant clinical records from the general practitioner.	Age- and practice-matched women.
Kazy - Ketoconazole, 2005	case control	The exposure data were obtained prospectively through antenatal care logbooks and other medical records, and retrospectively through questionnaires completed by the infants’ mothers.	The Hungarian Congenital Abnormality Registry (HCAR), in which notification by physicians of cases with Congenital anomalies is mandatory. Controls were selected from the National Birth Registry of the Central Statistical Office.	Controls matched according to sex, week of birth and district of parents’ residence. Adjusted for potential confounders evaluated in an unconditional logistic regression model (NOS).
Kerr - Miconazole, 2018	case control	Within 6 months of delivery, trained BDS nurse- interviewers contacted mothers to complete a roughly 1-hr computer-assisted telephone interview, including medications during pregnancy.	Cases and controls were ascertained at participating hospitals or birth defect registries in the same areas.	Adjusted models included maternal age, race/ethnicity, education, study center, and study year (aORs were calculated when there were five or more exposed cases).
Mastroiacovo - Fluconazole, 1996	prospective cohort	Staff physicians conduct a consultation that includes administering a structured interview with a detailed history of prescription and nonprescription drug use that included information on the commercial preparation, dosage, indication, and time during pregnancy when the drug was taken.	A structured interview administered by phone to women with questions related to pregnancy outcomes. The interviewing physicians were usually unaware of the exposure status of the women. If the mother reported an adverse outcome, additional information was requested from the attending physician.	The reference group was frequency-matched with the fluconazole-exposed group by region of residence. Possible confounders, including gestational age at the time of first contact with the Teratology Information Service, maternal age, parity, previous miscarriages, previous infants with congenital anomalies, maternal education, smoking, and alcohol use.
Molgaard-Nielsen - Fluconazole, 2013	population based cohort retrospective	Prescriptions for oral fluconazole that were filled by the women during pregnancy was obtained from the National Prescription Registry.	Cases of major birth defects were identified through the National Patient Register.	The covariates included calendar year; demographic characteristics; socioeconomic variables; and status with respect to smoking, previous births with malformation, selected coexisting conditions, and treatment with oral antibiotic agents, immunosuppressive agents, oral corticosteroids, antiepileptic agents, oral contraceptives, or drugs for in vitro fertilization
Molgaard-Nielsen - Fluconazole (Oral) (Controls exposed to pivmecillinam), 2016	population based cohort retrospective	Information on prescriptions for oral fluconazole (a prescription-only drug) was obtained from the National Prescription Register.	The Medical Birth Register and the National Patient Register.	Each fluconazole-exposed pregnancy was matched to up to 1 unexposed control pregnancies based on propensity scores, maternal age (5-year categories), calendar year, and gestational age.
Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016	population based cohort retrospective	Information on prescriptions for oral fluconazole (a prescription-only drug) was obtained from the National Prescription Register.	The Medical Birth Register and the National Patient Register.	Matched to unexposed control pregnancies based on propensity scores (age at pregnancy, place of birth, county of residence, marital status, level of education, household status, parity, history of spontaneous abortions, stillbirths, induced abortion, ectopic pregnancies, diabetes mellitus, immunodeficient states, drug prescriptions, hospital admission), maternal age, year and gestational age.
Norgaard - Fluconazole, 2008	retrospective cohort (claims database)	Prescription databases.	Data on congenital malformations were retrieved from the Danish National Registry of Patients.	Adjustment for maternal smoking, parity, maternal age and concurrent prescriptions for antiepileptics or maternal diabetes (either a diagnosis of diabetes or prescription on antidiabetics).
Pasternak - Fluconazole, 2018	population based cohort retrospective	Prescription database.	Not specified.	The cohorts for the analyses of stillbirth were matched (1:10 ratio) on maternal age, propensity score, and gestational age at fluconazole exposure. he cohorts for the analyses of neonatal death were matched (1:10 ratio) on maternal age and propensity score. No other details for propensity score.
Rosa - Miconazole, 1987	case control	Medicaid invoices for prescriptions.	Medicaid invoices for diagnoses.	None.
Ross - Miconazole, 2003	case control	Exposure information was collected from mothers using a structured telephone questionnaire. All prescription drugs recorded in the medical record were abstracted, including data for the trimester of pregnancy the drug was prescribed based upon gestational ages recorded in medical records.	Signed medical record release forms were obtained and complete copies of medical records were requested. Data were abstracted from medical records by two registered nurses using a structured protocol.	Controls matched to cases by birth date (within one year) and telephone area and exchange. Adjusted for maternal age, education, and income.
Santos - Fluconazole, 2011	nested case control	The Régie de l’assurance maladie du Québec (RAMQ) database, that provides information on prescriptions filled for residents insured by Québec’s Public Drug Insurance Plan. Data are available for physician-based diagnoses, therapeutic procedures, characteristics of patient, and healthcare providers.	The Med-Echo database that records hospitalisation data such as gestational age for deliveries for all Quebec residents. It also records the gestational age for planned abortions, miscarriages, and deliveries.	Adjusted for maternal age, maternal place of birth, gestational age, maternal RAMQ drug plan status; maternal health before and during pregnancy: comorbidities (infections, diabetes, hypertension, ...), number of medication used, number of different prescribers, emergency and doctor visits... Singletons only.
Sorensen - Fluconazole, 1999	retrospective cohort (claims database)	The population-based Pharmaco-Epidemiological Prescription Database of the County of North Jutland, Denmark was used to identify prescriptions. It includes the personal identification number, the drug prescribed according to ATC classification, and the date of the prescription.	Outcome data were obtained from the Danish Medical Birth Registry (birth weight, gestational age, ...) and the Regional Hospital Discharge Registry (to extract information on congenital malformations, classified according the ICD-8 or 10 versions).	Singletons only. The model was adjusted for maternal age, birth order and smoking.
Zhu - Fluconazole, 2020	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) including dispensing records for outpatient prescription drugs for reimbursement.	Malformations were identified with highly specific algorithms based on inpatient and outpatient diagnoses and procedure codes from ICD-9-CM (international classification of diseases, 9th revision, clinical modification), in the maternal and infant records.	Potential confounders included maternal age, delivery year, race/ethnicity, region, multiple gestation, vaginal candidiasis and related conditions, other maternal conditions (alcohol, tobacco use, drug abuse, chronic renal disease, obesity or overweight, pre-existing hypertension and diabetes), concomitant drug use (suspected teratogens…), general markers of disease burden…

master protocol