Serotonin and Noradrenaline Reuptake Inhibitors (SNRI)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Anderson - SNRI, 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 - Duloxetine (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 - Duloxetine (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 - Duloxetine (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: exclusion mothers with teratogenic drug; 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 - Duloxetine (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: exclusion of teratogenic drug exposures; 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 - Duloxetine (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, ...).
Ankarfeldt b - Duloxetine (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, ...).
Avalos - SNRI (Controls exposed to TCA), 2015	retrospective cohort (claims database)	Women exposed to antidepressant medications during pregnancy were identified through linkage to information on dates of drug dispensation and days of supply from the pharmacy database.	The diagnoses of preeclampsia and birth delivery data are available through KPNC's well-established automated clinical and pharmacy databases. Preeclampsia was defined as any of the following ICD-9 codes occurring after 20 weeks gestation: 642.4, 642.5, 642.6, or 642.7.	No adjustment for this group of comparison.
Avalos - SNRI (Controls unexposed, disease free), 2015	retrospective cohort (claims database)	Women exposed to antidepressant medications during pregnancy were identified through linkage to information on dates of drug dispensation and days of supply from the pharmacy database.	The diagnoses of preeclampsia and birth delivery data are available through KPNC's well-established automated clinical and pharmacy databases. Preeclampsia was defined as any of the following ICD-9 codes occurring after 20 weeks gestation: 642.4, 642.5, 642.6, or 642.7.	Adjusted for Pre-pregnancy BMI, maternal age, race/ethnicity, marital status, parity, alcohol use, smoking, diabetes, other indications for antidepressant medications, other mental health diagnoses.
Avalos - SNRI (Controls unexposed, sick), 2015	retrospective cohort (claims database)	Women exposed to antidepressant medications during pregnancy were identified through linkage to information on dates of drug dispensation and days of supply from the pharmacy database.	The diagnoses of preeclampsia and birth delivery data are available through KPNC's well-established automated clinical and pharmacy databases. Preeclampsia was defined as any of the following ICD-9 codes occurring after 20 weeks gestation: 642.4, 642.5, 642.6, or 642.7.	No adjustment for this group of comparison.
Bahat - Duloxetine, 2020	prospective cohort	Not specified.	Not specified.	Adjusted but potential confounders considered not specified.
Benevent - SNRI, 2023	retrospective cohort (claims database)	Prescriptions obtained from the French Health Insurance database (Haute Garonne), that included all drug prescriptions dispensed at pharmacies by patients receiving outpatient care, prior to and during pregnancy (names, ATC codes, dispensing dates, etc).	Child outcomes obtained from the compulsory health certificates registered with the Maternal and Child Protection, from the Prenatal Diagnostic Center and the French National Uniform Hospital Discharge Data Set Database (PMSI) for maternal medical discharge diagnosis codes from hospital.	G. hypertension: Adjusted for maternal age maternel, multiple grossesse, gestational diabete (prescription of antidiabetics during 2nd and/or 3rd trimester), pregestational diabete, folic acid before pregnancy, prescription of drugs that could induce hypertension (NSAIDs, triptans and nasal vasoconstrictors) and Medically assisted reproduction (clomifene prescription). Other outcomes: none.
Bérard a - Venlafaxine, 2017	population based cohort propective	The Quebec Public Prescription Drug Insurance database (drug name, start date, dosage, duration).	The Régie de l’assurance maladie du Québec (RAMQ) (diagnoses, medical procedures, ...), the hospitalization archive database (MedEcho: in-hospital diagnoses and procedures). PPHN defined as ICD-9: 416, 747.8 or ICD-10: I27, I521, P293.	Adjusted for maternal depression, use of antidepressants in the first 20 weeks of pregnancy and other potential confounders (sociodemographic variables, maternal chronic comorbidities during the 12 months prior to and during the first trimester of pregnancy).
Bérard b - SNRI=Venlafaxine (Controls exposed to TCA), 2017	retrospective cohort (claims database)	Prescription fillings dispensed to women identified in the cohort from the Quebec public prescription drug insurance database	Major congenital malformations were identified in the Régie de l’assurance maladie du Québec (RAMQ) and the Quebec hospitalization archives (MedEcho) databases defined according to International Classification of Diseases (9th-10th).	Adjusted for maternal age, welfare status, diabetes, hypertension, asthma and other medication uses including benzodiazepines as well as healthcare usage in the year prior and during the first trimester.
Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017	retrospective cohort (claims database)	Prescription fillings dispensed to women identified in the cohort from the Quebec public prescription drug insurance database	Major congenital malformations were identified in the Régie de l’assurance maladie du Québec (RAMQ) and the Quebec hospitalization archives (MedEcho) databases defined according to International Classification of Diseases (9th-10th).	Adjusted for maternal age, welfare status, diabetes, hypertension, asthma and other medication uses including benzodiazepines as well as healthcare usage in the year prior and during the first trimester.
Bernard - SNRI, 2019	prospective cohort	Documentation on antidepressant medication was obtained following delivery from a standardized prenatal follow-up form filled at each prenatal visit by the nurse and the physician and included in the hospital records.	Diagnosis of hypertensive disorders of pregnancy was made by a senior obstetrician based on information retrieved from medical records.	Adjusted for pre-pregnancy BMI, pre-pregnancy hypertension, maternal age, ethnicity, parity, smoking during pregnancy, mean arterial pressure (MAP) at the first visit, past history of hypertensive disorders of pregnancy, presence of gestational diabetes (GDM).
Boukhris - SNRI (Controls exposed to TCA), 2016	retrospective cohort (claims database)	The Public Prescription Drug Insurance database of Québec (drug name, start date, dose, and duration). Data on prescription filling for AD were validated against medical records and maternal reports.	The medical service databases: The Régie de l’assurance maladie du Québec (RAMQ): diagnoses, medical procedures, prescribers, and socioeconomic status of women and children), the Québec centralized hospitalization archives (MedEcho) and the Québec Statistics database.	No adjustment for this group of comparison.
Boukhris - SNRI (Controls exposed to TCA) , 2017	retrospective cohort (claims database)	The Quebec’s Public Prescription Drug Insurance database (drug name, start date and duration), MedEcho database (diagnoses and procedures).	Administrative databases: the medical service database (RAMQ: diagnoses, therapeutic procedures), the Quebec Statistics database (ISQ) and prescription database. ADHD diagnosis was defined as a medical service claim or hospitalisation with a diagnosis of ADHD according to the ICD-9, ICD-10.	No adjustment for this group of comparison.
Boukhris - SNRI (Controls unexposed, NOS), 2016	retrospective cohort (claims database)	The Public Prescription Drug Insurance database of Québec (drug name, start date, dose, and duration). Data on prescription filling for antidepressant were validated against medical records and maternal reports.	The medical service databases: The Régie de l’assurance maladie du Québec (RAMQ): diagnoses, medical procedures, prescribers, and socioeconomic status of women and children), the Québec centralized hospitalization archives (MedEcho) and the Québec Statistics database.	Adjusted for use of antidepressants 1 year before the first day of gestation, use of ADs in the first trimester, infant characteristics (sex, year of birth), and maternal variables (maternal age at first day of gestation, high school completed, recipient of social assistance, living alone, chronic or gestational hypertension, chronic or gestational diabetes, and other psychiatric disorders).
Boukhris - SNRI (Controls unexposed, NOS), 2017	retrospective cohort (claims database)	The Quebec’s Public Prescription Drug Insurance database (drug name, start date and duration), MedEcho database (diagnoses and procedures).	Administrative databases: the medical service database (RAMQ: diagnoses, therapeutic procedures), the Quebec Statistics database (ISQ) and prescription database. ADHD diagnosis was defined as a medical service claim or hospitalisation with a diagnosis of ADHD according to the ICD-9, ICD-10.	Adjusted for use of AD classes in the 1st trimester of pregnancy, infant characteristics (sex, year of birth), maternal variables (maternal age, level of education, recipient of social assistance, living alone, area of residence, chronic/gestational hypertension, chronic/gestational diabetes, other psychiatric disorders, maternal history of depression/anxiety, and maternal history of ADHD.
Calderon-Margalit - Venlafaxine, 2009	prospective cohort	Participants were interviewed during a prenatal visit prior to 20 weeks of gestation by trained research personnel using a structured questionnaire. Data on medications used during pregnancy were retrieved from both questionnaires and medical records.	Information on pregnancy outcome was ascertained by reviewing hospital labor and delivery medical records and clinic records after delivery.	Adjustments for maternal age, race, years of education, marital status, smoking during pregnancy, preeclampsia, parity, and singleton/multiple pregnancy.
Chan (Controls unexposed, sick), 2024	retrospective cohort (claims database)	Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.	Diagnoses of malformations were determined by pediatricians, and were ascertained using the ICD-9-CM codes from specialist outpatient and inpatient records.	Exclusion of malfo due to maternal infection or exposure to known teratogens. Adjusted for age, parity, maternal pre-existing diseases (diabetes, hypertension, epilepsy...), gestational diabetes, hypertension, placental abnormalities, caesarean delivery, preterm delivery, maternal psychiatric disorders, substance/alcohol use disorders, medications (suspected teratogens, anticonvulsivant ...)...
Chan - SNRI (Controls exposed to TCA), 2024	retrospective cohort (claims database)	Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.	Diagnoses of malformations were determined by pediatricians, and were ascertained using the ICD-9-CM codes from specialist outpatient and inpatient records.	Exclusion of abnormalities due to maternal infection or exposure to known teratogens. No adjustment for this group of comparison.
Chan - SNRI (Controls unexposed, general pop), 2024	retrospective cohort (claims database)	Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.	Diagnoses of malformations were determined by pediatricians, and were ascertained using the ICD-9-CM codes from specialist outpatient and inpatient records.	Exclusion of malfo due to maternal infection or exposure to known teratogens. Adjusted for age, parity, maternal pre-existing diseases (diabetes, hypertension, epilepsy...), gestational diabetes, hypertension, placental abnormalities, caesarean delivery, preterm delivery, maternal psychiatric disorders, substance/alcohol use disorders, medications (suspected teratogens, anticonvulsivant ...)...
Chen - SNRI, 2021	population based cohort retrospective	The National Health Insurance Research Database (NHIRD) which is a medical claims database and that includes drug prescription.	The National Health Insurance Research Database (NHIRD) which is a medical claims database coding with ICD-9-CM codes.	Adjusted for age, income-related insurance premium, hospital types, urbanization levels, parity, multiple gestation, diabetes mellitus, hypertension, dyslipidemia, uteroplacental ischemia or hemorrhage, reproductive tract infection, (pre)eclampsia, placenta previa, abruptio placenta, polycystic ovaries, hypo- hypergonadism, history of infertility, morbid obesity or overweight, anxiety disorders.
Dandjinou - SNRI, 2019	nested case control	The Quebec Prescription Drug Insurance Database (drug name, start date, dosage and duration).	The medical service database (RAMQ: diagnoses and medical procedures), the Hospitalisation Archive Database (MedEcho: in-hospital diagnoses and procedures) and the Quebec Statistics Database (Institut de la statistique du Québec (ISQ):patient sociodemographic information).	Matched for gestational age and year of pregnancy. Adjusted for maternal age, area of residence, receipt of social assistance during pregnancy, physician-based diagnoses or filled prescriptions of medications for chronic comorbidities; physician-based diagnoses of maternal diseases; medication use other than antidepressants; history of antidepressant use and health service utilisation.
De Ocampo - SNRI, 2016	prospective cohort	After enrollment, the women completed a comprehensive intake interview and use of prescription and over-the-counter medications were collected. Information on exposures collected at intake was updated at each successive interview (every 3 months until the end of the pregnancy).	Outcomes were self-reported by the participants at any interview after 20 weeks of gestation and for a minimum of 1 year after birth. Additional data, such as birth outcomes, were also collected from medical records obtained from the obstetrician, birth hospital, and the child’s pediatrician.	Adjusted for race/ethnicity, parity, diabetes status, asthma status, autoimmune disease status, cigarettes smoked per day, maternal age, pre- pregnancy BMI, gravidity, cohort study, and enrollment year
De Vera - SNRI, 2012	nested case control	The Quebec’s Public Prescription Drug Insurance Plan.	Linkage of three administrative databases: (i) Régie de l’Assurance Maladie du Québec (RAMQ), (ii) MED-ECHO and (iii) Institut de la Statistique du Québec (ISQ).	Cases and controls matched on gestational age. Multivariable models were adjusted for sociodemographic variables, depression, anxiety, other comorbid medical conditions, medication use and health care utilization.
Einarson - Venlafaxine, 2009	prospective cohort	During the initial telephone contact, details of exposure and concurrent exposures are recorded on a standardized questionnaire.	At the follow-up interview, gestational findings, fetal outcomes, and neonatal health are documented on a structured form by telephone interview with each mother. The details are then corroborated with the report of the physician caring for the baby.	No adjustment/no matching for this group of exposure (the 2 whole groups were matched for maternal age, smoking, and alcohol use).
Einarson - Venlafaxine, 2001	prospective cohort	On successful contact, information on each woman’s exposure history and pregnancy outcome were obtained, along with other measures of interest, with the aid of a structured questionnaire.	At follow-up, women were questioned regarding the course of their pregnancy, the health of their child. Outcomes were confirmed by sending a letter to the child’s primary care physician to corroborate the mother’s information.	None. No significant differences in maternal characteristics (age, smoking status, and alcohol use).
Frayne - SNRI, 2021	retrospective cohort	Psychotropic medication usage was extracted from the medical records and included information for first trimester and third trimester exposure as well as dosage.	Data were extracted from a large dataset utilising the hospital medical records.	Adjusted for maternal age, Body mass index (BMI) and comorbid gestational diabetes mellitus (GDM).
Furu - Venlafaxine, 2015	population based cohort retrospective	The Nordic prescription registers include data on dispensed drugs, substance, brand name, and formulation, together with date of dispensing.	From the medical birth, patient, and malformation registers data on maternal characteristics, the pregnancy and delivery, and major birth defects were retrieved.	Adjusted for maternal age, year of birth, birth order, smoking, maternal diabetes, country, and use of other prescribed drugs (antiepileptics (atC code n03), anxiolytics and hypnotics (n05b and n05C), and angiotensin converting enzyme inhibitors (C09)).
Hagberg - SNRI (Controls exposed to TCA), 2018	retrospective cohort (claims database)	The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs.	Diagnosis in the UK Clinical Practice Research Datalink (CPRD) with at least one Read diagnostic code indicating ASD recorded at any time, including codes for autism, Asperger’s syndrome, and pervasive developmental disorder (PDD).	No adjustment for this group of comparison.
Hagberg - SNRI (Controls unexposed, disease free), 2018	retrospective cohort (claims database)	The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs.	Diagnosis in the UK Clinical Practice Research Datalink (CPRD) with at least one Read diagnostic code indicating ASD recorded at any time, including codes for autism, Asperger’s syndrome, and pervasive developmental disorder (PDD).	Adjusted for maternal BMI, smoking status, parity, anxiety, or other psychiatric dis- orders. Matched on mother’s year of birth (±2 years), baby’s year of birth (±2 years), and general practice attended.
Hagberg - SNRI (Controls unexposed, sick), 2018	retrospective cohort (claims database)	The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs.	Diagnosis in the UK Clinical Practice Research Datalink (CPRD) with at least one Read diagnostic code indicating ASD recorded at any time, including codes for autism, Asperger’s syndrome, and pervasive developmental disorder (PDD).	No adjustment for this group of comparison.
Hanley - SNRI, 2016	retrospective cohort (claims database)	The British Columbia PharmaNet (a prescription dispensation database into which all prescriptions dispensed must be entered by law).	The Population Data British Columbia with all medical services records, all hospital discharge records. Hospital records over the period of study included diagnostic codes based on the ICD-9 and ICD-10: Women with diagnostic codes for postpartum hemorrhage (ICD-9 666.x and ICD- 10 O72.x).	Adjusted for year of birth, maternal age, parity, preterm birth, multifetal pregnancy, diabetes, coagulopathy, smoking during pregnancy, blood thinner use in the month before delivery, anxiolytic use in the month before delivery, antipsychotic use in the month before delivery, a diagnosis of mood disorder, any psychiatric visits, or any psychiatric hospitalization in the 5 months before delivery.
Heuvelman - Venlafaxine, 2023	retrospective cohort (claims database)	The Clinical Practice Research Datalink (CPRD) contains an extensive code list to identify the name, formulation and dose of medications, which are mandatory fields in the prescription electronic record (according to protocol).	For child outcomes, the primary care clinical and referral records were examined for presence of disorders based on Read codes and for ADHD: prescription of ADHD medication (methylphenidate, dexamphetamine, atomoxetine, dextroamphetamine, amphetamine with dexamphetamine, or lisdexamphetamine).	Adjusted for maternal age, Charlson Comorbidity Index score, maternal disorders (alcohol-related, psychosis, anxiety, self-harm, bipolar disorder, eating disorders, personality disorders, sleep disorders and neuropathic pains), medications (for physical health problems, central nervous system agents, multiple antidepressants ...) smoking, any recorded severity of past depressive symptoms...
Huybrechts - Duloxetine (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 - Duloxetine (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.
Huybrechts - SNRI (Controls unexposed, NOS), 2014	cohort	The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions.	The Medicaid Analytic eXtract data set that contains data on all physician services and hospitalizations and the accompanying diagnoses and procedures. Congenital cardiac malformations were identified on the basis of International Classification of Diseases (ICD-9) codes.	None.
Huybrechts - SNRI (Controls unexposed, sick), 2014	cohort	The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions.	The Medicaid Analytic eXtract data set that contains data on all physician services and hospitalizations and the accompanying diagnoses and procedures. Congenital cardiac malformations were identified on the basis of International Classification of Diseases (ICD-9) codes.	Adjusted for the high-dimensional propensity score: including year of delivery, age, race, multiple gestation, antidepressant indications, proxies for depression severity, other chronic maternal illness, other psychotropic medication use, antidiabetic, antihypertensive and residual confounding for proxies of unmeasured confounders.
Jackson - SNRI, 2024	retrospective cohort (claims database)	Medication exposure was determined by its presence or absence in the medication reconciliation document completed during hospital admission.	Clinical data were obtained from the inpatient electronic medical record system. Outcome was determined by the presence of an ICD-10 diagnosis code for postpartum hemorrhage (PPH) and a procedure code for blood transfusion.	Adjustment on induction of labor, multiple gestation, >4 previous vaginal births, prior cesarean or uterine incision, large uterine fibroids, fetal demise, polyhydramnios, placental abruption, placenta accreta, placenta previa, known coagulopathy, anemia (hematocrit <30%), and thrombocytopenia, advanced maternal age, obesity, public health insurance, and race and ethnicity group.
Kieler - Venlafaxine, 2015	nested case control	The prescription registers include data on dispensed item, substance, brand name, and formulation, together with date of dispensing for over 95% of the total outpatient population.	In the registers the diagnoses and pregnancy complications are classified according to the national version of the International Classification of Diseases (ICD).	Controls were matched with cases by country of residence, calendar year of pregnancy end point, age, and parity. Model 2 also adjusting for use of antidiabetics, antiepileptics, or other teratogenic drugs.
Kjaersgaard - Venlafaxine (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 - Venlafaxine (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.
Kolding - Venlafaxine (Controls unexposed, disease free), 2021	population based cohort retrospective	Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.	Data on prenatally diagnosed cardiac malformations came from the Danish Fetal Medicine Database and data on cardiac malformations diagnosed up to 1 year postnatally came from the Danish National Patient Registry.	Variables included in the analysis with propensity score fine stratification: ethnicity, civil status, parity, age, BMI, smoking, exposure to teratogens, antihypertensives, antidiabetics, use of other psychotropic drugs, depression diagnosis, diabetes diagnosis.
Kolding - Venlafaxine (Controls unexposed, sick), 2021	population based cohort retrospective	Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.	Data on prenatally diagnosed cardiac malformations came from the Danish Fetal Medicine Database and data on cardiac malformations diagnosed up to 1 year postnatally came from the Danish National Patient Registry.	Adjusted for smoking and age at conception.
Laspro - Venlafaxine, 2024	nested case control	Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy.	Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records.	None.
Laugesen - SNRI, 2013	population based cohort retrospective	Prescription identified through the Danish National Prescription.	ADHD was detected either as a diagnosis of ADHD or redemption of a prescription for ADHD medication. Using the Danish Psychiatric Registry and the Danish National Registry of Patients (identified with inpatient and outpatient hospital diagnoses of ADHD, with ICD codes).	Adjusted for gender of the child, calendar time at birth, birth order, maternal age at birth, maternal smoking status, maternal psychiatric diagnoses, paternal psychiatric diagnoses, maternal diseases during pregnancy (infections, epilepsy) and maternal medication (anxiolytics/ hypnotics/sedatives) use during pregnancy.
Lee (Controls exposed to TCAs), 2025	retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including clinical information like diagnoses, clinic attendances, hospital admissions.	Singleton. No adjustment for this group of comparison.
Lee (Controls unexposed, general pop), 2025	retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including clinical information like diagnoses, clinic attendances, hospital admissions.	Singleton. Adjusted for age, parity, maternal diabetes, hypertension, dyslipidaemia, epilepsy, physical comorbidity burden, gestational diabetes and hypertensive disorders, maternal psychiatric disorders, substance/alcohol use disorders, drugs during pregnancy (antipsychotics, lithium, valproate, lamotrigine, carbamazepine, benzodiazepines, z-hypnotics, opioid), history of psychiatric admission...
Lupattelli - SNRI (Controls exposed to TCA), 2017	prospective cohort	Data about antidepressant exposure were gathered prospectively from 2 self‐completed questionnaires at Gestational weeks 17 (Q1) and 30 (Q3). Women reported the name of the medication taken along with timing of use (6 months before pregnancy and during pregnancy by 4‐week intervals).	Outcomes as registered in the Medical Birth Registry of Norway (MBRN).	No adjustment for this group of exposure and comparison.
Lupattelli - SNRI (Controls unexposed, sick), 2017	prospective cohort	Data about antidepressant exposure were gathered prospectively from 2 self‐completed questionnaires at Gestational weeks 17 (Q1) and 30 (Q3). Women reported the name of the medication taken along with timing of use (6 months before pregnancy and during pregnancy by 4‐week intervals).	Outcomes as registered in the Medical Birth Registry of Norway (MBRN).	No adjustment for this group of exposure.
Marks - Duloxetine (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 - Duloxetine (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 - Venlafaxine, 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).
Nakhai-Pour - Venlafaxine, 2010	nested case control	The Régie de l’assurance maladie du Québec (RAMQ) database which provides prospectively collected data on filled prescriptions.	The Régie de l’assurance maladie du Québec (RAMQ) (physician-based diagnoses according to the ICD-9), the Med-Echo database (data on acute care hospital admissions) and the Institut de la statistique du Québec database (data on all births and deaths in Quebec).	Match. Adjusted for maternal age, social assistance status and place of residence; gestational age at index date; comorbidities (diabetes mellitus, cardiac disease, asthma, untreated thyroid disease, depression, anxiety, bipolar disorder); history of abortions; visits to physicians; duration of antidepressants; prenatal visits and other medication use in the year before and during pregnancy.
Nulman - Venlafaxine (Controls unexposed, disease free), 2012	prospective cohort	At the time of the first contact with Motherisk during pregnancy, information about medications was collected.	A psychometrist masked to group affiliation tested all children individually using a battery of age-appropriate standardized psychological tests.	None.
Nulman - Venlafaxine (Controls unexposed, sick), 2012	prospective cohort	At the time of the first contact with Motherisk during pregnancy, information about medications was collected.	A psychometrist masked to group affiliation tested all children individually using a battery of age-appropriate standardized psychological tests.	None
Oberlander - Venlafaxine, 2008	retrospective cohort (claims database)	PharmaNet, a province-wide network recording all prescriptions dispensed by British Columbian pharmacists outside hospitals.	Five administrative sources housed in the BC Linked Health Database: British Columbia registry of births, hospital separation records, the PharmaCare registry of subsidized prescriptions; the Medical Services Plan physician billing records; and the registry of Medical Services Plan subscribers.	None (adjustment provided for risk difference but not for relative risk or odd ratio).
Ozturk - Venlafaxine, 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 - SNRI (Controls exposed to TCA), 2012	retrospective cohort (claims database)	PharmaNet database, which contains all non-hospital pharmacy dispensings.	Province-wide health-care utilization databases which contain diagnostic and procedural information from all physician services and hospitalizations.	No adjustment for this group of comparison.
Palmsten - SNRI (Controls unexposed, sick), 2012	retrospective cohort (claims database)	PharmaNet database, which contains all non-hospital pharmacy dispensings.	Province-wide health-care utilization databases which contain diagnostic and procedural information from all physician services and hospitalizations.	Adjusted for delivery year, age, diabetes, multifetal gestation, obesity, primiparity, and physician visits, number of depression claims, number of psychiatrist visits/mental health hospitalizations, and dispensing of benzodiazepines, anticonvulsants, and antipsychotics.
Palmsten a - SNRI (control exposed to TCA), 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).	No adjustment for this group of comparison.
Palmsten a - SNRI (Controls unexposed, sick), 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.
Palmsten b - SNRI, 2013	retrospective cohort (claims database)	Data of prescription.	Women with an ICD-9 code for 666.x during the admission to hospital for delivery, or within three days after the delivery date, were classified as having postpartum hemorrhage. Atonic postpartum hemorrhage only (666.1x) and inpatient postpartum hemorrhage only, also considered.	Adjusted for delivery year, age, race, multiple pregnancy, diabetes, coagulopathy, number of outpatient and inpatient mood/anxiety disorder diagnoses, other mental health disorder, pain indication, sleep disorder, anticonvulsant, benzodiazepine, aspirin, heparin, low molecular weight heparin and warfarin dispensing, and number of outpatient visits and days in hospital during baseline.
Rai - Venlafaxine (Controls exposed to TCA), 2017	prospective cohort	Information on maternal use of antidepressants in pregnancy is derived from the medical birth register (as reported by pregnant women at their antenatal interview, at a median of 10 weeks’ gestation) and supplemented it with the prescribed drug register (available from July 2005).	Diagnostic information of autism were collected the national patient register, the Stockholm child and adolescent mental health register, and the habilitation registers (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes).	No adjustment for this group of comparison.
Rai - Venlafaxine (Controls unexposed, disease free), 2017	prospective cohort	Information on maternal use of antidepressants in pregnancy is derived from the medical birth register (as reported by pregnant women at their antenatal interview, at a median of 10 weeks’ gestation) and supplemented it with the prescribed drug register (available from July 2005).	Diagnostic information of autism were collected the national patient register, the Stockholm child and adolescent mental health register, and the habilitation registers (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes).	No adjustment for this group of comparison.
Rai - Venlafaxine (Controls unexposed, sick), 2017	prospective cohort	Information on maternal use of antidepressants in pregnancy is derived from the medical birth register (as reported by pregnant women at their antenatal interview, at a median of 10 weeks’ gestation) and supplemented it with the prescribed drug register (available from July 2005).	Diagnostic information of autism were collected the national patient register, the Stockholm child and adolescent mental health register, and the habilitation registers (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes).	Models are adjusted for birth year, maternal depression, and antidepressant polypharmacy (binary variable for use of 2 or more antidepressants).
Rampono - SNRI=Venlafaxine, 2009	prospective cohort	The antidepressant and dose for each individual patient was determined by the prescriber (JR) according to the patients needs. The analyses of medicines and metabolites in maternal and infant plasma were carried out by high performance liquid chromatography.	Infant behaviour in relation to medication intolerance/ withdrawal was assessed daily by the midwives while the infants were in the postnatal wards using the Finnegan neonatal abstinence scoring system (NAS). The assessors were blinded to the treatment or control group classification.	None.
Reis - SNRI (Controls exposed to TCA), 2010	population based cohort retrospective	Information on drug use is partly based on an interview conducted by the midwife at the first antenatal visit (in 90% of cases before the end of the first trimester) and partly on information from the antenatal care with respect to drugs prescribed later during the pregnancy by the attending doctor.	The Swedish Medical Birth Register, the Register of Birth Defects (previously known as the Register of Congenital Malformations) and the Patient Register (previous the Hospital Discharge Register).	No adjustment for this group of comparison.
Reis - SNRI (Controls unexposed, NOS), 2010	population based cohort retrospective	Information on drug use is partly based on an interview conducted by the midwife at the first antenatal visit (in 90% of cases before the end of the first trimester) and partly on information from the antenatal care with respect to drugs prescribed later during the pregnancy by the attending doctor.	The Swedish Medical Birth Register, the Register of Birth Defects (previously known as the Register of Congenital Malformations) and the Patient Register (previous the Hospital Discharge Register).	Adjusted for pertinent variables, always including year of delivery, maternal age, parity, smoking, and body mass index (BMI).
Richardson - Venlafaxine, 2019	prospective cohort	Upon contact with the service, relevant information is collected from the health professional to allow accurate fetal risk assessment. Subsequently, all enquiries which involve maternal exposures in pregnancy are included in the prospective surveillance system.	This system utilises postal questionnaires sent shortly after the estimated date of delivery (EDD) to collect pregnancy and fetal outcome data from the healthcare professional who originally contacted the service.	Controls matched to the venlafaxine exposed pregnancies by both calendar year and maternal age (each ± 2 years). Additional adjusted analyses were conducted using binomial logistic regression to assess the impact of co-variates (tobacco, alcohol, recreational drug and folic acid use) on adverse pregnancy outcome risk estimates.
Robinson-Wolrath - SNRI, 2016	retrospective cohort	Retrospective review of all pregnancies at King Edward Memorial Hospital, using midwifery and neonatal databases and case records.	Retrospective review of all pregnancies at King Edward Memorial Hospital, using midwifery and neonatal databases and case records.	Adjustment (NOS).
Suarez - SNRI (Controls unexposed, discontinuers), 2022	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications.	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on diagnoses, and procedures received dur- ing all health care encounters, including all inpatient, out- patient, or emergency department visits.	Illness. Adjusted for age, race/ethnicity (MAX only), delivery year, antidepressant indications, proxies for severity of mental conditions, smoking, alcohol/substance abuse, other medications, overweight/obesity, pregestational diabetes, pregestational hypertension, county-level socioeconomic indicators (MAX only), prenatal vitamin use, multiple gestation pregnancy, parity (MAX only), ...
Suarez - SNRI (Controls unexposed, general pop), 2022	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications.	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on diagnoses, and procedures received dur- ing all health care encounters, including all inpatient, out- patient, or emergency department visits.	Adjusted for age, race/ethnicity (MAX only), delivery year, antidepressant indications, proxies for severity of mental conditions, smoking, alcohol/substance abuse, other medications, overweight/obesity, pregestational diabetes, pregestational hypertension, county-level socioeconomic indicators (MAX only), prenatal vitamin use, multiple gestation pregnancy, parity (MAX only), ...
Sørensen - SNRI (Controls exposed to TCA), 2013	population based cohort retrospective	The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist.	Diagnoses are reported to the Danish Psychiatric Central Register (DPCR) from Danish child and adolescent psychiatric clinics where clinical assessment is made by a specialized team including child psychiatrists and psychologists.	No adjustment for this group of comparison.
Sørensen - SNRI (Controls unexposed, NOS), 2013	population based cohort retrospective	The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist.	Diagnoses are reported to the Danish Psychiatric Central Register (DPCR) from Danish child and adolescent psychiatric clinics where clinical assessment is made by a specialized team including child psychiatrists and psychologists.	Hazard ratios were adjusted for maternal age at conception, paternal age at conception, parental psychiatric history (except maternal affective disorder), gestational age, birth weight, sex, and parity.
Te Winkel - Venlafaxine, 2016	prospective cohort	Information about the exposure was collected after individual risk counseling. Standardized procedures for data collection and follow up were used by each center.	Information about pregnancy data and pregnancy outcome were collected after individual risk counseling. Standardized procedures for data collection and follow up were used by each center.	None.
Tran - SNRI (Controls exposed to TCA), 2022	retrospective cohort (claims database)	The PHARMO Database Network, a population-based network of healthcare databases combining data from hospital and community pharmacies in the Netherlands, including the ATC classification of the drug, start and end date of use, strength, dosage regimen and route of administration.	The Netherlands Perinatal Registry (PRN, or named PERINED)	No adjusted for this group of comparison.
Tran - SNRI (Controls unexposed, NOS), 2022	retrospective cohort (claims database)	The PHARMO Database Network, a population-based network of healthcare databases combining data from hospital and community pharmacies in the Netherlands, including the ATC classification of the drug, start and end date of use, strength, dosage regimen and route of administration.	The Netherlands Perinatal Registry (PRN, or named PERINED)	No adjustment for this group of exposure.
Wall-Wieler - SNRI, 2020	retrospective cohort (claims database)	Antidepressant prescriptions were identified from outpatient pharmacy files through National Drug Codes (NDC) from outpatient pharmaceutical claims.	IBM databases with link between inpatient services, outpatient services, outpatient pharmacy prescription claims, and healthcare plan enrollment information.	High-dimensional propensity score adjustments including 500 variables, notably the year of pregnancy, women’s age at the end of the pregnancy, and 5 predefined conditions identified as being risk factors for ectopic pregnancy: pelvic infections, sexually transmitted infections, assisted reproductive technology, intrauterine devices, and smoking in the year before a woman’s last menstrual period.
Yang - SNRI, 2021	retrospective cohort (claims database)	The Health and Welfare Database (HWD), administrative claims database that incorporates prescription drug utilization.	The Health and Welfare Database (HWD) and the Birth Certificate Application (BCA) administrative databases that incorporates patient diagnoses (coded according to ICD-9 or 10).	Characteristics (demographic variables (as age and region), the presence of comorbid diseases (included obesity, diabetes, renal diseases, liver diseases, epilepsy, substance use disorder, autoimmune diseases, ...), medication-related variables, and severity of depression) considered imbalanced between the 2 groups were further adjusted for in the regression analyses.
Yaris - Venlafaxine, 2005	prospective cohort	Data surveyed by the interviews.	Examinations were made by obstetric ultrasound for the mothers and birth weight and height, gestational age, APGAR scores, congenital malformation and developmental problems for the babies. Periodic checks of all the babies in the neonatal period, were made the first year, and following years.	None for this group of exposure.
Yeh - SNRI, 2021	retrospective cohort (claims database)	The Taiwan National Health Insurance Research Database (THIRD) provides prescriptions information about insured individuals.	The THIRD provides diagnosis information about insured individuals. Psychiatric disorders were diagnosed based on clinical judgement and interviews by psychiatrists. In this study, the diagnosis of ADHD and ASD required at least twice outpatient visits within each year for these ICD-9 codes.	Adjusted for demographic characteristics (the level of urbanization, monthly income, and other demographics).

master protocol