Venlafaxine

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
Bérard a, 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 (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 (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.
Calderon-Margalit, 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 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 (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 ...)...
Dandjinou, 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.
Einarson, 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, 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).
Furu, 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)).
Hanley, 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, 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...
Kieler, 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 (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.
Kolding (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 (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, 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.
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).
Nakhai-Pour, 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 (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 (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, 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, 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 (Controls 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 (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, 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 (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 (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 (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, 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.
Richardson, 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.
Te Winkel, 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.
Yaris, 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.

master protocol