Tricyclic antidepressants

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Abadie, 2015	nested case control	From the first contact (most of the time, a telephone contact), the health professional informs the CRPV on the pregnancy progress and drug exposures. Then a questionnaire designed to complete data, notably on drug exposures is sent by the CRPV to the correspondent.	A second paper questionnaire is sent by the CRPV to the health professional when the woman is supposed to deliver in order to obtain pregnancy outcome.
Anderson, 2020	case control	Information on exposure to TCAs 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 estimated date of delivery (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.	No adjustment for this group of exposure.
Avalos (Controls exposed to SSRIs), 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 (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 (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, 2020	prospective cohort	Not specified.	Not specified.	Adjusted but potential confounders considered not specified.
Ban (Controls exposed to SSRIs), 2014	retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.	All diagnoses of major congenital anomalies (MCAs) were identified in the children’s medical records using Read codes that we classified into 14 system-specific groups according to the European Surveillance of Congenital Anomalies (EUROCAT) subgroups.	No adjustment for this group of comparison.
Ban (Controls exposed to SSRIs), 2012	population based cohort retrospective	Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records.	The Health Improvement Network (THIN), a database of computerised primary care medical records	No adjustment for this group of comparison.
Ban (Controls unexposed, disease free), 2014	retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.	All diagnoses of major congenital anomalies (MCAs) were identified in the children’s medical records using Read codes that we classified into 14 system-specific groups according to the European Surveillance of Congenital Anomalies (EUROCAT) subgroups.	Multivariable analyses were used to adjust for maternal age at the end of pregnancy, year of childbirth, Townsend deprivation quintile, maternal smoking history, body mass index before pregnancy, and maternal diabetes, hypertension, asthma, and epilepsy in the year before conception or during pregnancy.
Ban (Controls unexposed, disease free), 2012	population based cohort retrospective	Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records.	The Health Improvement Network (THIN), a database of computerised primary care medical records	Relative risk ratio adjusted for maternal age at the end of pregnancy, household socioeconomic status, maternal smoking status before delivery and body mass index before pregnancy.
Ban (Controls unexposed, sick), 2014	retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.	All diagnoses of major congenital anomalies (MCAs) were identified in the children’s medical records using Read codes that we classified into 14 system-specific groups according to the European Surveillance of Congenital Anomalies (EUROCAT) subgroups.	Multivariable analyses were used to adjust for maternal age at the end of pregnancy, year of childbirth, Townsend deprivation quintile, maternal smoking history, body mass index before pregnancy, and maternal diabetes, hypertension, asthma, and epilepsy in the year before conception or during pregnancy.
Ban (Controls unexposed, sick), 2012	population based cohort retrospective	Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records.	The Health Improvement Network (THIN), a database of computerised primary care medical records	Relative risk ratio adjusted for maternal age at the end of pregnancy, household socioeconomic status, maternal smoking status before delivery and body mass index before pregnancy.
Bérard (Controls exposed to SSRIs), 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 (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, 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 (Controls exposed to SSRIs), 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 (Controls exposed to SSRIs), 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 (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 (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.
Chan (Controls exposed to SSRIs), 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 ...)...
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 ...)...
Chen, 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.
Croen, 2011	case control	All inpatient and outpatient prescriptions for antidepressants dispensed at a KPNC pharmacy in the 3 months before the last menstrual period (LMP) through the date of delivery of the study child were identified from the Pharmacy Information Management System.	On the basis of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) recorded in the KPNC outpatient clinical databases.	Controls matched to case children by sex, birth year, and hospital of birth. No adjustment for this group of exposure.
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.
Davis, 2007	retrospective cohort (claims database)	Information on prescribed antidepressant medications was derived from the pharmacy database files available at each health system.	Information on patient age, health plan enrollment status, and inpatient and outpatient diagnoses and procedures was obtained from automated databases at each health system. Assessment of outcomes was limited to assigned ICD9 codes except for 3 malfo where medical charts were reviewed.	None.
De Vera, 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.
Greenberg, 1977	case control	Medical officers or community physicians were asked to identify the baby and the general practitioner, who was then interviewed by one of the Committee's medical field workers notably about drugs prescribed during the first trimester (only information obtained from written notes was used).	The doctor, midwife, or health visitor attending the birth of an abnormal baby may report the abnormality to the area health authority. This information is then passed to the OPCS. Though voluntary, it is believed that notification of visible and severe malformations is reasonably complete.	It was accepted as controls only babies born within three months of the case baby. Maternal age and parity similar in cases and controls.
Hagberg (Controls exposed to SSRIs), 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 (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 (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.
Hartwig, 2022	case control	Prescription database that contains prescription records include data on the date of dispensing, the amount dispensed, the dose regimen, the number of days the prescription is valid, the prescribing physician, and the Anatomical Therapeutic Chemical (ATC) code.	Drug prescription data was used as a proxy for Attention-deficit/hyperactivity disorder (ADHD) in offspring, as diagnostic information was not available: methylphenidate (MPH), dextroamphetamine or atomoxetine.	Singleton pregnancies. Adjusted for birth date of the child (as proxy for the date of pregnancy), age of the parent at birth, use of psychostimulants, opioids, and use of antiepileptic drugs in the 15 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...
Huybrechts (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 (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.
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).
Källén (Controls exposed to SSRIs), 2004	population based cohort retrospective	Data on first-trimester exposures are obtained by midwife interviews at the first antenatal care visit (usually week 10-12), while data on later exposures are obtained from the copies of the medical records of the antenatal care.	The Swedish Medical Birth Registry that contains data on delivery and the newborn, obtained from copies of the medical records used at delivery and at the pediatric examination of the newborn.	No adjustment for this group of comparison.
Källén (Controls unexposed, NOS), 2004	population based cohort retrospective	Data on first-trimester exposures are obtained by midwife interviews at the first antenatal care visit (usually week 10-12), while data on later exposures are obtained from the copies of the medical records of the antenatal care.	The Swedish Medical Birth Registry that contains data on delivery and the newborn, obtained from copies of the medical records used at delivery and at the pediatric examination of the newborn.	Adjusted for year of birth, maternal age, parity, and maternal smoking in early pregnancy.
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.
Kitchin, 2022	case control	Database for Pharmacoepidemiological Research in Primary Care, a computerized medical longitudinal population database of electronic medical records from 10.153 primary care practitioners and pediatricians distributed on nine Autonomous Regions (out of 17), which contains prescriptions.	Database for Pharmacoepidemiological Research in Primary Care, a computerized medical longitudinal population database of electronic medical records from 10.153 primary care practitioners and pediatricians, which contains medical diagnoses, medical visits, hospital admissions.	Controls individually matched to cases (maternal age, gestational age, and year of Last Menstrual Period date). Adjusted by number of GP visits, obesity, smoking, HTA, diabetes.
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.
Kullander - Imipramine, 1976	nested case control	Information on drug use was obtained mainly from the questionnaires administered to pregnant women, sometimes supplemented from hospital records etc. Information was usually collected before the outcome of the pregnancy was known. The (approximate) time of intake of each drug used was recorded.	All living children were carefully investigated by a pediatrician after birth and were followed to about 1 year old at the child health centres. Autopsy was performed and the age at death was recorded. The presence of major and minor malformations was recorded for all infants.	None.
Laugesen, 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 SSRI), 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...
Liu, 2015	population based cohort retrospective	Data on maternal or paternal antidepressants dispensed 1 year before or during the index pregnancy and dispensing date were extracted from the Danish National Prescription Registry.	Asthma in children was identified by using the Danish National Patient Register and the Danish National Prescription Registry. Asthma was defined as at least 2 prescriptions for antiasthmatic medications or 1 asthma hospital contact (based on ICD- 10 codes J45 and J46) after 3 years of age.	Adjusted for maternal country of origin, maternal age at delivery, maternal parity, maternal social status, maternal smoking during pregnancy, maternal history of asthma, gender of the child, and calendar year of birth.
Louik, 2014	case control	Mothers are invited to participate in a telephone interview after delivery, conducted by trained nurses who are unaware of the study hypotheses. It collects detailed data on all medications (prescription, over-the-counter, ...) used anytime from 2 months prior to conception through the pregnancy.	Research staff identify malformed subjects by reviewing hospital admission and discharge lists or from statewide birth-defect registries and mothers of non-malformed infants were identified at study hospitals and from a population-based random sample of newborns in Massachusetts.	Controls matched to cases on age within 2 months. Adjusted for study center, family history of birth defect and/or last menstrual period (LMP).
Lupattelli (Controls exposed to SSRIs), 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 (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.
Martin - Amitriptyline, 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.
Nijenhuis (Controls exposed to SSRIs), 2012	retrospective cohort (claims database)	The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.	The use of laxatives (ATC code = A06) and antidiarrhoeal medication (ATC code = A07C; A07D; A07F; A07X) in the newborn, regarded as a proxy for constipation and diarrhoea, respectively.	None.
Nijenhuis (Controls unexposed, NOS), 2012	retrospective cohort (claims database)	The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.	The use of laxatives (ATC code = A06) and antidiarrhoeal medication (ATC code = A07C; A07D; A07F; A07X) in the newborn, regarded as a proxy for constipation and diarrhoea, respectively.	None.
Nulman (Controls exposed to Fluoxetine), 1997	prospective cohort	During the initial assessment, at the diagnosis of pregnancy or within several weeks thereafter, the Service obtained a medical history of each woman, including use of medicinal drugs. Information concerning the time of drug therapy was recorded, as were the doses and of any concomitantly drugs.	All children were assessed by a psychometrician who did not know the nature of the intrauterine exposure.	None
Nulman (Controls unexposed, disease free), 2002	prospective cohort	During the initial consultation, during early pregnancy, Details concerning the time and duration of exposure to the antidepressant drugs, and the doses of any other concomitant medications were recorded was obtained from each mother.	The children were assessed by a psychometrist blinded to the exposure with the Bayley Scales of Infant Development-II or the McCarthy Scales of Children’s Abilities, the Toddler Temperament Scale or the Achenbach Child Behavior Checklist and the Reynell Developmental Language Scales.	None.
Nulman (Controls unexposed, NOS), 1997	prospective cohort	During the initial assessment, at the diagnosis of pregnancy or within several weeks thereafter, the Service obtained a medical history of each woman, including use of medicinal drugs. Information concerning the time of drug therapy was recorded, as were the doses and of any concomitantly drugs.	All children were assessed by a psychometrician who did not know the nature of the intrauterine exposure.	None
Nulman - Fluoxetine (Controls exposed to Fluoxetine), 2002	prospective cohort	During the initial consultation, during early pregnancy, Details concerning the time and duration of exposure to the antidepressant drugs, and the doses of any other concomitant medications were recorded was obtained from each mother.	The children were assessed by a psychometrist blinded to the exposure with the Bayley Scales of Infant Development-II or the McCarthy Scales of Children’s Abilities, the Toddler Temperament Scale or the Achenbach Child Behavior Checklist and the Reynell Developmental Language Scales.	None.
Ozturk - Amitriptyline, 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 SSRIs), 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 (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 (control exposed to SSRIs), 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 a (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.
Pastuszak (Controls exposed to Fluoxetine), 1993	prospective cohort	Drug exposure history was obtained from both the mother and biological father of the fetus, by an interview with a team physician.	All patients were contacted by telephone and asked details about the outcome of pregnancy, birth weight, and presence or absence of birth defects, and perinatal complications. All follow-up information was corroborated by written documentation from the child's physician.	Control group was age-matched (±2 years) to two controls, closest in date to the date of consultation of the fluoxetine case.
Pastuszak (Controls unexposed, NOS), 1993	prospective cohort	Drug exposure history was obtained from both the mother and biological father of the fetus, by an interview with a team physician.	All patients were contacted by telephone and asked details about the outcome of pregnancy, birth weight, and presence or absence of birth defects, and perinatal complications. All follow-up information was corroborated by written documentation from the child's physician.	Control group was age-matched (±2 years) to two controls, closest in date to the date of consultation.
Pearson (Controls exposed to SSRIs), 2007	retrospective cohort	Review of obstetrical and neonatal records.	Medical records were evaluated by 2 psychiatrists (K.H.P., M.B.) and an obstetrician (V.L.H.) blinded to the mother’s medication status in order to rate specific neonatal outcome measures.	No match/adjustment for this group of exposure.
Pearson (Controls unexposed, NOS), 2007	retrospective cohort	Review of obstetrical and neonatal records.	Medical records were evaluated by 2 psychiatrists (K.H.P., M.B.) and an obstetrician (V.L.H.) blinded to the mother’s medication status in order to rate specific neonatal outcome measures.	No match/adjustment for this group of exposure.
Pedersen, 2010	population based cohort retrospective	Information on medication use in early pregnancy was obtained partly through a self- administered questionnaire linked to the consent form. After consent was obtained, the women were contacted twice during pregnancy.	Information on developmental achievements in early childhood was collected mainly through computer-assisted telephone interviews with the mothers. Developmental milestones were reported by the mothers in the 2 postnatal interviews.	ORs were adjusted for maternal age, gender, age at interview, breastfeeding, problems during pregnancy, mother-child connection, and postnatal symptoms of depression.
Rai - Clomipramine only (Controls exposed to SSRIs), 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 - Clomipramine only (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 - Clomipramine only (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).
Reis (Controls exposed to SSRIs), 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 (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).
Simon (Controls exposed to SSRIs), 2002	retrospective cohort (claims database)	Pharmacy records were used to identify all antidepressant prescriptions filled or refilled during the 360 days before delivery.	The infants’ medical records were used to examine perinatal outcomes, congenital malformations, early childhood neurological illness, and developmental delay. All information regarding prenatal exposures were masked of the chart reviewers.	No adjustment or match for this group of comparison.
Simon (Controls unexposed, NOS), 2002	retrospective cohort (claims database)	Pharmacy records were used to identify all antidepressant prescriptions filled or refilled during the 360 days before delivery.	The infants’ medical records were used to examine perinatal outcomes, congenital malformations, early childhood neurological illness, and developmental delay. All information regarding prenatal exposures were masked of the chart reviewers.	Adjusted for maternal tobacco use, other substance use, race, and number of prior births. Unexposed selected taken into account to the following maternal characteristics: age, year of delivery, lifetime number of antidepressant prescriptions filled or refilled, lifetime history of psychiatric treatment, and length of Group Health Cooperative enrollment.
Solé, 2020	nested case control	Women were followed throughout pregnancy by a clinical researcher, who recorded the type and dosage of medications during pregnancy and information about concurrent medical illness.	Obstetric and medical histories were obtained for all women by systematic review of obstetric records and prenatal care.	None.
Song, 2023	nested case control	The data on medication history were screened from ATC codes in the Korea National Health Insurance claims.	The data on disease were screened from ICD-10 in the Korea National Health Insurance claims.	None.
Suarez (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 (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 (Controls exposed to SSRIs), 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 (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.
Ter Host (Controls exposed to SSRIs), 2013	retrospective cohort (claims database)	The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.	The drugs for pulmonary diseases in children were used as a proxy for developmental respiratory tract changes in children: beta-2 selective sympathomimetics (ATC: R03CC, R03AC), inhalation corticosteroids (ATC: R03BA), combined inhalation drugs (ATC: R03AK), and leucotriene antagonists (ATC: R03DC).	No adjustment for this group of comparison.
Ter Host (Controls unexposed, NOS), 2013	retrospective cohort (claims database)	The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.	The drugs for pulmonary diseases in children were used as a proxy for developmental respiratory tract changes in children: beta-2 selective sympathomimetics (ATC: R03CC, R03AC), inhalation corticosteroids (ATC: R03BA), combined inhalation drugs (ATC: R03AK), and leucotriene antagonists (ATC: R03DC).	Adjusted for maternal antibiotic use.
Tran (Controls exposed to SSRI), 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 (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).	Adjusted for maternal age, ethnicity, alcohol consumption, smoking during pregnancy, any endocrine disorders and concurrent use of vaso- constrictors.
Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013	retrospective cohort	Clinical records that described prescribed drugs from each clinical visit.	Computerized medical record that recorded all congenital anomalies noted in the patient’s clinical records.	No match nor adjustment for this group of comparison.
Vasilakis-Scaramozza (Controls unexposed, NOS), 2013	retrospective cohort (claims database)	Clinical records that described prescribed drugs from each clinical visit.	Computerized medical record that recorded all congenital anomalies noted in the patient’s clinical records.	Control group matched by age, year of pregnancy outcome, and general practice. Adjustment for potential confounders (prepregnancy body mass index, maternal age, cigarette smoking status, history of diabetes mellitus, insulin use, exposure to a teratogen during the first trimester, history of infertility and premature delivery) if its changed the crude relative risk estimate by more than 10%.
Wall-Wieler, 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, 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, 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.
Zakiyah, 2018	retrospective cohort (claims database)	The University of Groningen’s IADB.nl pharmacy prescription database, a longitudinal database containing pharmacy-dispensing data from community pharmacies in the Netherlands.	The outcome was determined by identifying dispensed antihypertensive drugs to treat gestational hypertension. A woman was considered to have gestational hypertension when she had at least one prescription for methyldopa, nifedipine, labetalol, ketanserin, or nicardipine.	Adjusted for maternal age and medications use during pregnancy i.e. prescriptions of benzodiazepines and antibiotics.

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