Duloxetine

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Anderson, 2020	case control	Information on exposure to SSRIs and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants, conducted 6 weeks to 24 months after the EDD.	Case infants were ascertained through population-based birth-defects surveillance systems in 10 U.S. states. Controls were selected randomly from the same geographic areas. Clinical data were abstracted from medical records and classified by clinician geneticists and other clinicians.	Adjusted for maternal race/ ethnicity, prepregnancy body mass index, education, and early pregnancy smoking and alcohol use
Ankarfeldt (Controls unexposed, NOS), 2023	population based cohort retrospective	Information about redeemed prescriptions obtained from the national prescription registers.	Information about preterm birth and small for gestational age was gathered from the medical birth registers.	Adjusted for age, education, household income, year, psychiatric hospital, psychiatric outpatient, gestational diabetes during index pregnancy, diabetes, hyper or hypothyroidism, hypertension, obesity, renal failure, depression, affective, anxiety or phobia, severe stress reaction, co-medication prescriptions (fluconazole, estradiol, thyroid, NSAID, antiepileptics, antipsychotics, ...).
Ankarfeldt (Controls unexposed, sick), 2023	population based cohort retrospective	Information about redeemed prescriptions obtained from the national prescription registers.	Information about preterm birth and small for gestational age was gathered from the medical birth registers.	Adjusted for age, education, household income, year, psychiatric hospital, psychiatric outpatient, gestational diabetes during index pregnancy, diabetes, hyper or hypothyroidism, hypertension, obesity, renal failure, depression, affective, anxiety or phobia, severe stress reaction, co-medication prescriptions (fluconazole, estradiol, thyroid, NSAID, antiepileptics, antipsychotics, ...).
Ankarfeldt a (Controls unexposed, NOS), 2021	population based cohort retrospective	The prescription registers containing electronically submitted information on prescriptions dispensed by pharmacies, classified according to the global ATC system.	The patient registers that include discharge diagnoses of all inpatients and outpatients in contact with a hospital. The medical birth registers included all live births and stillbirths from varying gestational ages with information on the mother, the neonate, and the father as well.	Major malfo: adjusted for country, age, household income, year, psychiatric hospital, psychiatric outpatient, smoking, previous spontaneous abortion, previous stillbirths, gestational diabetes, diabetes, obesity, mental illness, glucose-lowering, antihypertensive, estradiol, thyroid, NSAID, opioids, antiepileptics, antipsychotics, anxiolytics, ...
Ankarfeldt a (Controls unexposed, sick), 2021	population based cohort retrospective	The prescription registers containing electronically submitted information on prescriptions dispensed by pharmacies, classified according to the global ATC system.	The patient registers that include discharge diagnoses of all inpatients and outpatients in contact with a hospital. The medical birth registers included all live births and stillbirths from varying gestational ages with information on the mother, the neonate, and the father as well.	Major malfo: Adjusted for country, age, household income, year, psychiatric hospital, psychiatric outpatient, smoking, previous spontaneous abortion, previous stillbirths, gestational diabetes, diabetes, obesity, mental illness, glucose-lowering, antihypertensive, estradiol, thyroid, NSAID, opioids, antiepileptics, antipsychotics, anxiolytics, ...
Ankarfeldt b (Controls unexposed, sick), 2021	population based cohort retrospective	Information on maternal exposure to antidepressant drugs was based on redeemed prescriptions from community pharmacies using the Danish National Prescription Register.	Data on pregnancies ending with an abortion diagnosis (elective or spontaneous) were gathered from the National Patient Register which holds data on all procedures and diagnoses relating to hospital contact. Gestational age was identified in the medical birth register and the patient register.	Adjusted for age, education, household income, year, psychiatric hospital, psychiatric outpatient, gestational diabetes during index pregnancy, diabetes, hyper or hypothyroidism, hypertension, obesity, renal failure, depression, affective, anxiety or phobia, severe stress reaction, co-medication prescriptions (fluconazole, estradiol, thyroid, NSAID, antiepileptics, antipsychotics, ...).
Ankarfeldt b Controls unexposed, NOS), 2021	population based cohort retrospective	Information on maternal exposure to antidepressant drugs was based on redeemed prescriptions from community pharmacies using the Danish National Prescription Register.	Data on pregnancies ending with an abortion diagnosis (elective or spontaneous) were gathered from the National Patient Register which holds data on all procedures and diagnoses relating to hospital contact. Gestational age was identified in the medical birth register and the patient register.	Adjusted for age, education, household income, year, psychiatric hospital, psychiatric outpatient, gestational diabetes during index pregnancy, diabetes, hyper or hypothyroidism, hypertension, obesity, renal failure, depression, affective, anxiety or phobia, severe stress reaction, co-medication prescriptions (fluconazole, estradiol, thyroid, NSAID, antiepileptics, antipsychotics, ...).
Bahat, 2020	prospective cohort	Not specified.	Not specified.	Adjusted but potential confounders considered not specified.
Huybrechts (Controls unexposed, NOS), 2020	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) dataset that contains all filled outpatient drug prescriptions for Medicaid beneficiaries.	The Medicaid Analytic eXtract (MAX) dataset that contains all medical visits and hospital admissions, inpatient or outpatient diagnoses and procedure codes in the maternal (first month after delivery) or infant (first three months after date of birth) record.	Six groups of covariates: maternal demographic characteristics (age, ethnicity...), indications for duloxetine (depression, anxiety, specific pain conditions), comorbidities (chronic hypertension, diabetes, infections, alcohol dependence…), obstetric conditions (multifetal gestation), maternal drug treatments (antidiabetes, suspected teratogenic drugs...) and measures of healthcare utilization.
Huybrechts (Controls unexposed, sick), 2020	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) dataset that contains all filled outpatient drug prescriptions for Medicaid beneficiaries.	The Medicaid Analytic eXtract (MAX) dataset that contains all medical visits and hospital admissions, inpatient or outpatient diagnoses and procedure codes in the maternal (first month after delivery) or infant (first three months after date of birth) record.	Six groups of covariates: maternal demographic characteristics (age, ethnicity...), indications for duloxetine (depression, anxiety, specific pain conditions), comorbidities (chronic hypertension, diabetes, infections, alcohol dependence…), obstetric conditions (multifetal gestation), maternal drug treatments (antidiabetes, suspected teratogenic drugs...) and measures of healthcare utilization.
Källen, 2013	population based cohort retrospective	The exposure data are either based on midwife interviews from the first antenatal visit (usually during weeks 10–12) or on linkage with a prescribed drug register.	Medical Birth Register (MBR) supplemented with data from the Register of Birth Defects (RCM, previously Register of Congenital Malformations) and from a Hospital Discharge Register (HDR).	Adjustment was made for year of birth, maternal age (5-year class), parity (1–4), smoking in early pregnancy (unknown, none, <10 cigarettes/day, ≥10 cigarettes per day), and BMI (unknown, <18.5, 18.5–24.9, 25–29, 9. 30–34.9, ≥35).
Kjaersgaard (Controls unexposed, NOS), 2013	population based cohort retrospective	Information on all redeemed prescriptions was obtained from the Denmark Registry of Medicinal Product Statistics.	Clinically recognized abortions were identified in the Danish National Hospital Registry, that contains data on in- and outpatient contacts in Denmark coded according to a Danish version of the 10th revision of the International Classification of Diseases (ICD-10).	No adjustment for this group of exposure.
Kjaersgaard (Controls unexposed, sick), 2013	population based cohort retrospective	Information on all redeemed prescriptions was obtained from the Denmark Registry of Medicinal Product Statistics.	Clinically recognized abortions were identified in the Danish National Hospital Registry, that contains data on in- and outpatient contacts in Denmark coded according to a Danish version of the 10th revision of the International Classification of Diseases (ICD-10).	No adjustment for this group of exposure.
Marks (Controls exposed to Bupropion), 2021	retrospective cohort	Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis.	Diagnoses were extracted from the electronic database discharge summaries, delivery records, and/or International Classification of Diseases (ICD) codes. Clinical diagnosis were extracted from the delivery discharge summary written by the clinician caring for the infant.	All results reported as aOR (95% CI) controlling for maternal race, age, insurance, and gestational age at delivery.
Marks (Controls unexposed, sick), 2021	retrospective cohort	Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis.	Diagnoses were extracted from the electronic database discharge summaries, delivery records, and/or International Classification of Diseases (ICD) codes. Clinical diagnosis were extracted from the delivery discharge summary written by the clinician caring for the infant.	All results reported as aOR (95% CI) controlling for maternal race, age, insurance, and gestational age at delivery.
Martin, 2024	population based cohort retrospective	In the UK, prescription data were based on the prescriptions written by general practitioners (CPRD GOLD), whereas in Norway and Sweden, dispensation of prescription drugs from all ambulatory pharmacies was used (Norwegian Prescription Database, and Swedish Prescribed Drug Register).	The UK Clinical Practice Research Datalink that contains diagnoses made in primary care and secondary care data; Norway: Medical Birth Registry of Norway and the Norwegian Patient Registry; and Sweden: the Medical Birth Register of Sweden and the National Patient Register.	Singletons only. Adjusted for maternal age at delivery, early-pregnancy body mass index, parity, previous stillbirth, anti-seizure medication and antipsychotic use in the 12 months prior to pregnancy, smoking anytime during pregnancy, maternal depression or anxiety diagnosis prior to the start of pregnancy, proxy measures of socioeconomic position (SEP).
Martin - Norway, 2024	population based cohort retrospective	Dispensation of prescription drugs from all ambulatory pharmacies was used from the Norwegian Prescription Database.	The Medical Birth Registry of Norway and the Norwegian Patient Registry.	Singletons only. Adjusted for year of birth, maternal age, maternal educational attainment, previous stillbirth, parity, antipsychotic and antiseizure medication use in the 12 months before pregnancy, number of primary care consultations in the 12 months before pregnancy, depression ever before the start of pregnancy, anxiety ever before the start of pregnancy.
Martin - UK, 2024	population based cohort retrospective	In the United Kingdom, prescription data were based on the prescriptions written by general practitioners (CPRD GOLD).	The United Kingdom Clinical Practice Research Datalink that contains diagnoses made in primary care and secondary care data.	Singletons only. Adjusted for year of birth, maternal age, practice-level IMD quintile, maternal ethnicity (UK), smoking during pregnancy, previous stillbirth, parity, antipsychotic and antiseizure medication in the 12 months before pregnancy, primary care consultations in the 12 months before pregnancy, depression ever before the start of pregnancy, anxiety ever before the start of pregnancy.
Ozturk, 2016	prospective cohort	At the first contact, initiated via gynecologists, a detailed patient history form was used to notably record all drug exposures (dose, duration and timing in pregnancy).	Each newborn baby was checked at birth for signs of problems or complications.	None
Palmsten, 2013	retrospective cohort (claims database)	Outpatient pharmacy-dispensing data.	Medicaid enrollment information was linked to inpatient and outpatient procedures and diagnoses. Outcome validity was assessed by reviewing delivery hospital medical records for a sample of 183 women. Preeclampsia defined with ICD-9 code for preeclampsia or eclampsia (642.4x–642.7x).	Adjusted for delivery year, preeclampsia risk factors (age, race/ethnicity, primiparity, diabetes, multifetal gestation, pain-related diagnosis...), depression severity proxies, other antidepressant indications, other medications, and healthcare utilization.

master protocol