Tricyclic antidepressants

Exposed non-exposed, cohort studies

Study	Country Study period Study design	Data source	Exposure definition	Non-exposure definition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks
Avalos (Controls exposed to SSRIs) 2015	USA 2010 - 2012 retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC).	Pregnant women with at least one pharmacy dispensing of tricyclic antidepressants (TCAs) only between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnant women with at least one pharmacy dispensing of selective serotonin reuptake inhibitors (SSRIs) between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	during pregnancy (anytime or not specified)	116 / 1262	Results of SSRI only and TCA only reported rather than 'SSRI only and SSRI plus other antidepressant' or 'TCA only and TCA plus other antidepressant'.
Avalos (Controls exposed to SSRIs) 2015	USA 2010 - 2012 retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC).	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.		during pregnancy (anytime or not specified)	116 / 1262
Avalos (Controls unexposed, disease free) 2015	USA 2010 - 2012 retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC).	Pregnant women with at least one pharmacy dispensing of tricyclic antidepressants (TCAs) only between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnant women without depression.	during pregnancy (anytime or not specified)	116 / 16402	Results of TCA only reported rather than 'TCA only and TCA plus other antidepressant'.
Avalos (Controls unexposed, disease free) 2015	USA 2010 - 2012 retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC).	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.		during pregnancy (anytime or not specified)	116 / 16402
Avalos (Controls unexposed, sick) 2015	USA 2010 - 2012 retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC).	Pregnant women with at least one pharmacy dispensing of tricyclic antidepressants (TCAs) only between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with untreated depression (diagnosed between 6 months prior to the woman's last menstrual period (LMP) and 20 completed weeks of gestation).	during pregnancy (anytime or not specified)	116 / 1345	Results of SSRI only and TCA only reported rather than 'SSRI only and SSRI plus other antidepressant' or 'TCA only and TCA plus other antidepressant'.
Avalos (Controls unexposed, sick) 2015	USA 2010 - 2012 retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC).	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.		during pregnancy (anytime or not specified)	116 / 1345
Bahat 2020	Israel 2001 - 2015 prospective cohort	The Israeli Teratology Information Service (TIS).	Pregnant women counseled for tricyclic antidepressants (TCA) exposure in the first trimester.	unexposed (general population or NOS) Pregnant women counseled for non-teratogenic exposure in pregnancy.	1st trimester	83 / 511	Major congenital anomalies excluding genetic or cytogenetic not reported because number of cases, exposures and exclusions not provided.
Bahat 2020	Israel 2001 - 2015 prospective cohort	The Israeli Teratology Information Service (TIS).	Not specified.		1st trimester	83 / 511
Ban (Controls exposed to SSRIs) 2012	The United Kingdom (UK). 1990 - 2009 population based cohort retrospective	The Health Improvement Network (THIN), a nationally representative database of computerised primary care medical records collected at 446 general practices (primary health care units).	Pregnant women with prescriptions for any tricyclic antidepressants (TCAs) (alone - i.e. no other psychotropic medication of interest) during the first trimester.	exposed to other treatment, sick Pregnant women with prescriptions for any selective serotonin reuptake inhibitors (SSRIs) (alone - i.e. no other psychotropic medication of interest) during the first trimester.	during pregnancy (anytime or not specified)	4349 / 14191	Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status.
Ban (Controls exposed to SSRIs) 2012			Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records.		during pregnancy (anytime or not specified)	4349 / 14191
Ban (Controls exposed to SSRIs) 2014	United Kingdom 1990 - 2009 retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database of computerised primary care records.	Pregnant women with tricyclic antidepressants (TCAs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnant women with selective serotonin reuptake inhibitors (SSRIs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	1st trimester	2428 / 7683	Exclusion of 9096 children (2.5% of the study population) whose mothers had bipolar disorder, schizophrenia, other serious psychotic disorders, or prescriptions for antimanic and antipsychotic drugs. Overlapping: with Petersen 2016, Ban 2013 (abstract).
Ban (Controls exposed to SSRIs) 2014			The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.		1st trimester	2428 / 7683
Ban (Controls unexposed, disease free) 2014	United Kingdom 1990 - 2009 retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database of computerised primary care records.	Pregnant women with tricyclic antidepressants (TCAs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnant women without diagnosis of depression.	1st trimester	2428 / 325294	Exclusion of 9096 children (2.5% of the study population) whose mothers had bipolar disorder, schizophrenia, other serious psychotic disorders, or prescriptions for antimanic and antipsychotic drugs. Overlapping: with Petersen 2016, Ban 2013 (abstract).
Ban (Controls unexposed, disease free) 2014			The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.		1st trimester	2428 / 325294
Ban (Controls unexposed, disease free) 2012	The United Kingdom (UK). 1990 - 2009 population based cohort retrospective	The Health Improvement Network (THIN), a nationally representative database of computerised primary care medical records collected at 446 general practices (primary health care units).	Pregnant women with prescriptions for any tricyclic antidepressants (TCAs) (alone - i.e. no other psychotropic medication of interest) during the first trimester.	unexposed, disease free Pregnant women without any indication of current or prior depression or anxiety.	during pregnancy (anytime or not specified)	4349 / -9	Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status. Number of unexposed women not provided.
Ban (Controls unexposed, disease free) 2012			Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records.		during pregnancy (anytime or not specified)	4349 / -9
Ban (Controls unexposed, sick) 2014	United Kingdom 1990 - 2009 retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database of computerised primary care records.	Pregnant women with tricyclic antidepressants (TCAs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with depression diagnosed in the year before conception up to the end of the first trimester, but with no antidepressant drug prescriptions in the first trimester.	1st trimester	2428 / 13432	Exclusion of 9096 children (2.5% of the study population) whose mothers had bipolar disorder, schizophrenia, other serious psychotic disorders, or prescriptions for antimanic and antipsychotic drugs. Overlapping: with Petersen 2016, Ban 2013 (abstract).
Ban (Controls unexposed, sick) 2014			The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.		1st trimester	2428 / 13432
Ban (Controls unexposed, sick) 2012	The United Kingdom (UK). 1990 - 2009 population based cohort retrospective	The Health Improvement Network (THIN), a nationally representative database of computerised primary care medical records collected at 446 general practices (primary health care units).	Pregnant women with prescriptions for any tricyclic antidepressants (TCAs) (alone - i.e. no other psychotropic medication of interest) during the first trimester.	unexposed, sick Pregnant women with un-medicated depression or anxiety, i.e with current depression or anxiety but no prescriptions during the first trimester.	during pregnancy (anytime or not specified)	4349 / -9	Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status. Number of unexposed women not provided.
Ban (Controls unexposed, sick) 2012			Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records.		during pregnancy (anytime or not specified)	4349 / -9
Bérard (Controls exposed to SSRIs) 2017	Canada 1998 - 2009 retrospective cohort (claims database)	A register-based cohort study using data from the Quebec Pregnancy Cohort (QPC).	Depressed/anxious pregnancies with prescription fillings for Tricyclic antidepressants (TCA) dispensed during the first trimester of gestation.	exposed to other treatment, sick Depressed/anxious pregnancies with prescription fillings for selective serotonin reuptake inhibitors (SSRIs) dispensed during the first trimester of gestation.	1st trimester	382 / 2327	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Bérard (Controls exposed to SSRIs) 2017	Canada 1998 - 2009 retrospective cohort (claims database)		Prescription fillings dispensed to women identified in the cohort from the Quebec public prescription drug insurance database		1st trimester	382 / 2327
Bérard (Controls unexposed, sick) 2017	Canada 1998 - 2009 retrospective cohort (claims database)	A register-based cohort study using data from the Quebec Pregnancy Cohort (QPC).	Depressed/anxious pregnancies with prescription fillings for Tricyclic antidepressants (TCA) dispensed during the first trimester of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnancies with a diagnosis or were treated with antidepressants in the year before their pregnancy but with no exposure to antidepressants during the first trimester of gestation.	1st trimester	382 / 14847	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Bérard (Controls unexposed, sick) 2017	Canada 1998 - 2009 retrospective cohort (claims database)		Prescription fillings dispensed to women identified in the cohort from the Quebec public prescription drug insurance database		1st trimester	382 / 14847
Bernard 2019	Canada 2005 - 2010 prospective cohort	The CHU de Québec-Université Laval.	Pregnant women exposed to Tricyclic antidepressant (TCA) before the 16th week of pregnancy.	unexposed, disease free Pregnant women not exposed to the antidepressant/anxiolytic medication, depression or anxiety.	at least 1st trimester	8 / 6502
Bernard 2019	Canada 2005 - 2010 prospective cohort	The CHU de Québec-Université Laval.	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.		at least 1st trimester	8 / 6502
Boukhris (Controls exposed to SSRIs) 2016	Canada 1998 - 2009 retrospective cohort (claims database)	The Québec Pregnancy Children Cohort (QPC), a register-based study of an ongoing population-based cohort.	Infants whose mother having at least 1 prescription of Tricyclic antidepressants filled at any time during pregnancy or before pregnancy that overlapped the first day of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Infants whose mother having at least 1 prescription of Selective serotonin reuptake inhibitor (SSRIs) filled at any time during pregnancy or before pregnancy that overlapped the first day of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	2nd and/or 3rd trimester	229 / 1583	'Exposure to a single class was defined as the filling of prescriptions for only 1 AD class in the time window of interest.'
Boukhris (Controls exposed to SSRIs) 2016	Canada 1998 - 2009 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.		2nd and/or 3rd trimester	229 / 1583
Boukhris (Controls exposed to SSRIs) 2017	Canada 1998 - 2009 retrospective cohort (claims database)	A register-based cohort study using data from the Quebec Pregnancy/Children Cohort (QPC).	Having at least one prescription filled of tricyclic antidepressants (TCAs) during the 2nd/3rd trimesters of pregnancy. (This is a subgroup of exposure among the whole exposed group considered).	exposed to other treatment, sick Having at least one prescription filled of selective serotonin reuptake inhibitors (SSRIs) during the 2nd/3rd trimesters of pregnancy. (This is a subgroup of exposure among the whole exposed group considered).	2nd and/or 3rd trimester	227 / 1561	‘Single class exposure was defined as the filling of prescriptions for only one antidepressant class in the time window of interest.'
Boukhris (Controls exposed to SSRIs) 2017	Canada 1998 - 2009 retrospective cohort (claims database)		The Quebec’s Public Prescription Drug Insurance database (drug name, start date and duration), MedEcho database (diagnoses and procedures).		2nd and/or 3rd trimester	227 / 1561
Boukhris (Controls unexposed, NOS) 2016	Canada 1998 - 2009 retrospective cohort (claims database)	The Québec Pregnancy Children Cohort (QPC), a register-based study of an ongoing population-based cohort.	Infants whose mother having at least 1 prescription of tricyclic antidepressants (TCAs) filled at any time during pregnancy or before pregnancy that overlapped the first day of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Infants who were not exposed in utero to antidepressants.	2nd and/or 3rd trimester	229 / 142924	'Exposure to a single class was defined as the filling of prescriptions for only 1 antidepressant class in the time window of interest.'
Boukhris (Controls unexposed, NOS) 2016	Canada 1998 - 2009 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.		2nd and/or 3rd trimester	229 / 142924
Boukhris (Controls unexposed, NOS) 2017	Canada 1998 - 2009 retrospective cohort (claims database)	A register-based cohort study using data from the Quebec Pregnancy/Children Cohort (QPC).	Having at least one prescription filled of tricyclic antidepressants (TCAs) during the 2nd/3rd trimesters of pregnancy. (This is a subgroup of exposure among the whole exposed group considered).	unexposed (general population or NOS) Infants who were not exposed in utero to any antidepressants during the 2nd/3rd trimesters of pregnancy.	2nd and/or 3rd trimester	227 / 141905	‘Single class exposure was defined as the filling of prescriptions for only one antidepressant class in the time window of interest.'
Boukhris (Controls unexposed, NOS) 2017	Canada 1998 - 2009 retrospective cohort (claims database)		The Quebec’s Public Prescription Drug Insurance database (drug name, start date and duration), MedEcho database (diagnoses and procedures).		2nd and/or 3rd trimester	227 / 141905
Chan (Controls exposed to SSRIs) 2024	China 2003 - 2018 retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents.	Infants of women with prescription of tricyclic-antidepressants (TCA) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	exposed to other treatment, sick Infants of women with prescription of Selective-serotonin-reuptake-inhibitors (SSRI) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	1st trimester	322 / 956
Chan (Controls exposed to SSRIs) 2024	China 2003 - 2018 retrospective cohort (claims database)		Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.		1st trimester	322 / 956
Chan (Controls unexposed, general pop) 2024	China 2003 - 2018 retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents.	Infants of women with prescription of tricyclic-antidepressants (TCA) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	unexposed (general population or NOS) Infants of pregnant women who were not prescribed with any antidepressant within 90 days before the last menstrual period and during the first trimester.	1st trimester	322 / 462377
Chan (Controls unexposed, general pop) 2024	China 2003 - 2018 retrospective cohort (claims database)		Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.		1st trimester	322 / 462377
Chan (Controls unexposed, sick) 2024	China 2003 - 2018 retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents.	Infants of women with depression/anxiety who were prescribed with tricyclic-antidepressants (TCA) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	unexposed, sick Infants of pregnant women with depression/anxiety who were not prescribed with any antidepressant within 90 days before the last menstrual period and during the first trimester.	1st trimester	181 / 4413
Chan (Controls unexposed, sick) 2024	China 2003 - 2018 retrospective cohort (claims database)		Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.		1st trimester	181 / 4413
Chen 2021	Taiwan 2000 - 2013 population based cohort retrospective	The Taiwanese National Health Insurance Research Database (NHIRD).	Pregnant patients with perinatal depression with tricyclic antidepressant prescription. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant patients with perinatal depression with no antidepressant treatment 90 days before the date of their first pregnancy.	during pregnancy (anytime or not specified)	380 / 1789	Tricyclic antidepressants (TCAs; imipramine, clomipramine, desipramine, trimipramine, amitriptyline, nortriptyline, amoxapine, doxepin, maprotiline, and protriptyline). Meta-analysis of adjusted HR provided by authors according to defined daily doses.
Chen 2021	Taiwan 2000 - 2013 population based cohort retrospective		The National Health Insurance Research Database (NHIRD) which is a medical claims database and that includes drug prescription.		during pregnancy (anytime or not specified)	380 / 1789
Davis 2007	USA 1996 - 2000 retrospective cohort (claims database)	A population-based cohort based on five health maintenance organizations (HMOs) participating in the HMO Research Network’s Center for Education and Research on Therapeutics (CERTs).	Fullterm infants exposed in utero to tricyclic antidepressants (TCAs) (trimester of exposure according to outcomes). (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Fullterm infants born to mothers who were not prescribed antidepressants at any time during pregnancy, but who might have had other medications prescribed.	1st trimester, 3rd trimester, during pregnancy (anytime or not specified)	339 / 81146	Polyhydramnios, Oligohydramnios, Poly- and/or oligo-hydramnios not reported because not sure that the 3rd trimester exposure occurred before outcome.
Davis 2007	USA 1996 - 2000 retrospective cohort (claims database)		Information on prescribed antidepressant medications was derived from the pharmacy database files available at each health system.			339 / 81146
Hagberg (Controls exposed to SSRIs) 2018	United Kingdom 1989 - 2011 retrospective cohort (claims database)	The UK Clinical Practice Research Datalink (CPRD), a large, population-based electronic medical database.	Pregnant women with depression treated with tricyclic antidepressants (TCAs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered).	exposed to other treatment, sick Pregnant women with depression treated with Selective serotonin reuptake inhibitors (SSRIs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered).	during pregnancy (anytime or not specified)	4856 / 17362	For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept.
Hagberg (Controls exposed to SSRIs) 2018			The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs.		during pregnancy (anytime or not specified)	4856 / 17362
Hagberg (Controls unexposed, disease free) 2018	United Kingdom 1989 - 2011 retrospective cohort (claims database)	The UK Clinical Practice Research Datalink (CPRD), a large, population-based electronic medical database.	Pregnant women with depression treated with tricyclic antidepressants (TCAs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered).	unexposed, disease free Pregnant women who had neither depression nor prescriptions for antidepressants prior to the baby’s delivery date.	during pregnancy (anytime or not specified)	4856 / 154107	For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept.
Hagberg (Controls unexposed, disease free) 2018			The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs.		during pregnancy (anytime or not specified)	4856 / 154107
Hagberg (Controls unexposed, sick) 2018	United Kingdom 1989 - 2011 retrospective cohort (claims database)	The UK Clinical Practice Research Datalink (CPRD), a large, population-based electronic medical database.	Pregnant women with depression treated with tricyclic antidepressants (TCAs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered).	unexposed, sick Pregnant women with untreated depression (recent history of treated depression but no antidepressants during the exposure period).	during pregnancy (anytime or not specified)	4856 / 12994	For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept.
Hagberg (Controls unexposed, sick) 2018			The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs.		during pregnancy (anytime or not specified)	4856 / 12994
Heuvelman 2023	United Kingdom 1995 - 2017 retrospective cohort (claims database)	The UK Clinical Practice Research Datalink, a large, ongoing database of anonymised primary care medical records for patients registered with a general practice in the United Kingdom.	Women who had initiated or continued tricyclic antidepressants (TCAs) for the treatment of depressive symptoms during pregnancy.	unexposed, sick Women who did not initiate or who discontinue antidepressants during pregnancy.	during pregnancy (anytime or not specified)	2148 / 16330	For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept.
Heuvelman 2023			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).		during pregnancy (anytime or not specified)	2148 / 16330
Huybrechts (Controls unexposed, NOS) 2014	USA 2000 - 2007 cohort	Cohort study nested in the nationwide Medicaid Analytic eXtract.	Pregnant women who have had exposure to tricyclic antidepressants (TCAs) with the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women without exposure to antidepressants during the first trimester.	1st trimester	5954 / 885115	Exclusion of pregnancies with a diagnosis of a chromosomal abnormality and pregnancies in which the mother had been treated with known teratogens during the first trimester (i.e., lithium, antineoplastic agents, retinoids, and thalidomide).
Huybrechts (Controls unexposed, NOS) 2014	USA 2000 - 2007 cohort		The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions.		1st trimester	5954 / 885115
Huybrechts (Controls unexposed, sick) 2014	USA 2000 - 2007 cohort	Cohort study nested in the nationwide Medicaid Analytic eXtract.	Pregnant women who have had exposure to tricyclic antidepressants (TCAs) with the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with a diagnosis of depression without exposure to antidepressants during the first trimester.	1st trimester	5954 / 180564	Use of High-dimensional propensity-score data (Supplementary Table S15). Exclusion of pregnancies in which the mother had been treated with known teratogens during the first trimester (i.e., lithium, antineoplastic agents, retinoids, and thalidomide).
Huybrechts (Controls unexposed, sick) 2014	USA 2000 - 2007 cohort		The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions.		1st trimester	5954 / 180564
Källen 2013	Sweden 1996 - 2011 population based cohort retrospective	Swedish Medical Birth Register	Infants whose mothers used Tricyclic antidepressants (TCA) in early or late pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Infants in population whose mothers used at least one of a central nervous system active drugs (less than 3%) or weren't exposed in early pregnancy.	2nd and/or 3rd trimester, early pregnancy	2139 / 1575847	Overlapping: For major malfo, cardiac malfo, septal defects, hypospadias : this publication included data of Reis 2010. But for late exposure, Reis 2010 included more pregnancies, thus outcomes also provided by Reis 2010 not reported here.
Källen 2013	Sweden 1996 - 2011 population based cohort retrospective	Swedish Medical Birth Register	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.		2nd and/or 3rd trimester, early pregnancy	2139 / 1575847
Källén (Controls exposed to SSRIs) 2004	Sweden 1995 - 2001 population based cohort retrospective	The Swedish Medical Birth Registry.	Infants whose mothers received Tricyclic drugs after the first antenatal care center visit. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Infants whose mothers received selective serotonin reuptake inhibitors (SSRIs) after the first antenatal care center visit. (This is a subgroup of exposure among the whole exposed group considered in the study).	late pregnancy	395 / 558	Overlapping: Preterm, LBW, SGA, LGA and neonat outcomes not reported here because these data (1995-2001) have been updated by a larger study published by Reis 2010 (1995-2007). Only 19/395 (5%) used TCA and an other antidep => considered as TCA only.
Källén (Controls exposed to SSRIs) 2004	Sweden 1995 - 2001 population based cohort retrospective	The Swedish Medical Birth Registry.	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.		late pregnancy	395 / 558
Källén (Controls unexposed, NOS) 2004	Sweden 1995 - 2001 population based cohort retrospective	The Swedish Medical Birth Registry.	Infants whose mothers received Tricyclic drugs after the first antenatal care center visit. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) All infants in the registry.	late pregnancy	395 / 581787	Overlapping: Preterm, LBW, SGA, LGA and neonat outcomes not reported here because these data (1995-2001) have been updated by a larger study published by Reis 2010 (1995-2007). Only 19/395 (5%) used TCA and an other antidep => considered as TCA only.
Källén (Controls unexposed, NOS) 2004	Sweden 1995 - 2001 population based cohort retrospective	The Swedish Medical Birth Registry.	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.		late pregnancy	395 / 581787
Kjaersgaard (Controls unexposed, NOS) 2013	Denmark 1997 - 2008 population based cohort retrospective	Danish administrative health registries.	Mother that had redeemed a prescription for tricyclic antidepressants (TCA) at any time from 30 days before conception up to 1 day before the end of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Mother that had not redeemed any prescription for antidepressant medication from 6 months before conception up to 1 day before the end of the pregnancy.	during pregnancy (anytime or not specified)	-9 / 983258	Molar or ectopic pregnancies (ICD-10: O00.0– O01.9) were excluded from the main analyses. Unexposed cohort: 1843 plus 981415 = 983258.
Kjaersgaard (Controls unexposed, NOS) 2013	Denmark 1997 - 2008 population based cohort retrospective	Danish administrative health registries.	Information on all redeemed prescriptions was obtained from the Denmark Registry of Medicinal Product Statistics.		during pregnancy (anytime or not specified)	-9 / 983258
Kjaersgaard (Controls unexposed, sick) 2013	Denmark 1997 - 2008 population based cohort retrospective	Danish administrative health registries.	Mother with a registry-based diagnosis of depressive disorder that had redeemed a prescription for tricyclic antidepressants (TCA) at any time from 30 days before conception up to 1 day before the end of pregnancy.	unexposed, sick Mother with a registry-based diagnosis of depressive disorder that had not redeemed any prescription for antidepressant medication from 6 months before conception up to 1 day before the end of the pregnancy.	during pregnancy (anytime or not specified)	-9 / -9	Molar or ectopic pregnancies (ICD-10: O00.0– O01.9) were excluded from the main analyses.
Kjaersgaard (Controls unexposed, sick) 2013	Denmark 1997 - 2008 population based cohort retrospective	Danish administrative health registries.	Information on all redeemed prescriptions was obtained from the Denmark Registry of Medicinal Product Statistics.		during pregnancy (anytime or not specified)	-9 / -9
Kolding (Controls unexposed, disease free) 2021	Denmark 2007 - 2014 population based cohort retrospective	Five nationwide registries and databases: the Danish Fetal Medicine Database, the Danish National Patient Registry, the Danish Medical Birth Registry and the Danish Health Services Prescription Database.	Pregnant women with two or more redeemed prescriptions of Tricyclic antidepressants (TCA) from 28 days before through 70 days after the conception date. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnant women with absence of redemptions for an antidepressant in the same time window, combined with absence of former use.	1st trimester	254 / 353581	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Kolding (Controls unexposed, disease free) 2021	Denmark 2007 - 2014 population based cohort retrospective		Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.		1st trimester	254 / 353581
Kolding (Controls unexposed, sick) 2021	Denmark 2007 - 2014 population based cohort retrospective	Five nationwide registries and databases: the Danish Fetal Medicine Database, the Danish National Patient Registry, the Danish Medical Birth Registry and the Danish Health Services Prescription Database.	Pregnant women with two or more redeemed prescriptions of Tricyclic antidepressants (TCA) from 28 days before through 70 days after the conception date. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with untreated- or well treated depression or anxiety without antidepressant use in the pregnancy (one or more redeemed prescription of an antidepressant from 365 to 183 days preconception and no redemptions between 182 days preconception through the first trimester).	1st trimester	254 / 6326	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Kolding (Controls unexposed, sick) 2021	Denmark 2007 - 2014 population based cohort retrospective		Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.		1st trimester	254 / 6326
Laugesen 2013	Denmark 1996 - 2009 population based cohort retrospective	Nationwide Danish medical registries	Children born to mother with redemption of a Tricyclic antidepressive agent (TCA) prescription by the mother 30 days prior to or during pregnancy. (This is a subgroup of exposure among the whole exposed group considered).	unexposed (general population or NOS) Children born to mother who had never redeemed a prescription on antidepressants.	during pregnancy (anytime or not specified)	716 / 816792
Laugesen 2013	Denmark 1996 - 2009 population based cohort retrospective	Nationwide Danish medical registries	Prescription identified through the Danish National Prescription.		during pregnancy (anytime or not specified)	716 / 816792
Lee (Controls exposed to SSRI) 2025	China 2003 - 2018 retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority, Hong Kong.	Women filling at least one prescription of any tricyclic antidepressants (TCA) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery.	exposed to other treatment, sick Women filling at least one prescription of any selective serotonin reuptake inhibitors (SSRI) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery.	during pregnancy (anytime or not specified)	613 / 1465
Lee (Controls exposed to SSRI) 2025	China 2003 - 2018 retrospective cohort (claims database)		The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.		during pregnancy (anytime or not specified)	613 / 1465
Lee (Controls unexposed, general pop) 2025	China 2003 - 2018 retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority, Hong Kong.	Women filling at least one prescription of any tricyclic antidepressants (TCA) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery.	unexposed (general population or NOS) Women who were not prescribed with any antidepressant during index pregnancy.	during pregnancy (anytime or not specified)	613 / 463440
Lee (Controls unexposed, general pop) 2025	China 2003 - 2018 retrospective cohort (claims database)		The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.		during pregnancy (anytime or not specified)	613 / 463440
Liu 2015	Denmark 1996 - 2007 population based cohort retrospective	Linkage of several national registers in Denmark, including the Danish Medical Birth Registry (DMBR), the Danish Psychiatric Central Register and the Danish National Patient Register.	Children born to mothers who had prenatal depression and who used Tricyclic antidepressants (TCAs) only during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Children born to mothers who had prenatal depression and who did not take antidepressants during pregnancy.	during pregnancy (anytime or not specified)	409 / 12476	Number of women exposed to Tricyclic antidepressants (TCAs) based on % provided by authors (81%*505).
Liu 2015	Denmark 1996 - 2007 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.		during pregnancy (anytime or not specified)	409 / 12476
Lupattelli (Controls exposed to SSRIs) 2017	Norway 1999 - 2008 prospective cohort	The Norwegian Mother and Child Cohort (the MoBa study), a prospective population‐based study, and the Medical Birth Registry of Norway	Depressed pregnant women that reported use of tricyclic antidepressants (TCAs) monotherapy during pregnancy.	exposed to other treatment, sick Depressed pregnant women that reported use of selective serotonin reuptake inhibitors (SSRIs) monotherapy during pregnancy.	during pregnancy (anytime or not specified)	21 / 654	Data for Early‐onset preeclampsia cannot be reported because nb of exposure to TCA in gestational weeks 0‐16 is not reported. 'Women on antidepressant polytherapy, ie, exposed to multiple antidepressant groups in pregnancy, were excluded'
Lupattelli (Controls exposed to SSRIs) 2017	Norway 1999 - 2008 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).		during pregnancy (anytime or not specified)	21 / 654
Lupattelli (Controls unexposed, sick) 2017	Norway 1999 - 2008 prospective cohort	The Norwegian Mother and Child Cohort (the MoBa study), a prospective population‐based study, and the Medical Birth Registry of Norway	Depressed pregnant women that reported use of Tricyclic antidepressants (TCAs) monotherapy during pregnancy.	unexposed, sick Depressed pregnant women nonmedicated.	during pregnancy (anytime or not specified)	21 / 5106	Data for Early‐onset preeclampsia cannot be reported because nb of exposure to TCA in gestational weeks 0‐16 is not reported. 'Women on antidepressant polytherapy, ie, exposed to multiple antidepressant groups in pregnancy, were excluded'
Lupattelli (Controls unexposed, sick) 2017	Norway 1999 - 2008 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).		during pregnancy (anytime or not specified)	21 / 5106
Martin - Amitriptyline 2024	Norway, Sweden and United Kingdom. 1996 - 2020 population based cohort retrospective	The UK’s Clinical Practice Research Datalink (CPRD), the Norway’s Medical Birth Registry and the Sweden’s Medical Birth Register.	Singleton deliveries with maternal Amitriptyline (without concurrent prescriptions for different antidepressants) use during pregnancy proxied by prescriptions in the United Kingdom and dispensations in Norway and Sweden.	unexposed (general population or NOS) Singleton deliveries without maternal antidepressants use during pregnancy proxied by prescriptions in the United Kingdom and dispensations in Norway and Sweden.	during pregnancy (anytime or not specified)	4773 / 2408707	A group ‘multiple’ (i.e drug switching or concurrent prescriptions for different antidepressants) is available => thus individual antidepressant considered as monotherapy. Unexposed numbers: Table S4.
Martin - Amitriptyline 2024			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).		during pregnancy (anytime or not specified)	4773 / 2408707
Nijenhuis (Controls exposed to SSRIs) 2012	The Netherlands 1995 - 2009 retrospective cohort (claims database)	The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl	Children of mothers exposed to tricyclic antidepressants (TCAs) during pregnancy.	exposed to other treatment, sick Children of mothers exposed to selective serotonin re-uptake inhibitors (SSRIs) during pregnancy.	1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy	76 / 527	The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. SSRI: Paroxetine (n = 310), fluoxetine (n = 105), citalopram (n = 60), fluvoxamine (n = 60), sertraline (n = 19), escitalopram (n = 2).
Nijenhuis (Controls exposed to SSRIs) 2012			The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.			76 / 527
Nijenhuis (Controls unexposed, NOS) 2012	The Netherlands 1995 - 2009 retrospective cohort (claims database)	The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl	Children of mothers exposed to tricyclic antidepressant (TCA) during pregnancy.	unexposed (general population or NOS) Children of mothers who did not use any selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) during pregnancy and during a period of 7 days before pregnancy.	1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy	76 / 34908	The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. The most commonly used TCA was clomipramine (n = 40), followed by amitriptyline (n = 26).
Nijenhuis (Controls unexposed, NOS) 2012			The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.			76 / 34908
Nulman (Controls exposed to Fluoxetine) 1997	Canada Since 1985 prospective cohort	The Motherisk Program, an information and consultation service regarding exposure to drugs, chemicals, radiation, and infectious agents during pregnancy and lactation.	Pregnant women who took a tricyclic antidepressant drug at least during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnant women who took fluoxetine at least during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	at least 1st trimester	80 / 55	Overlapping of some outcomes (language development) with Nulman 2002 (with more relevant period of exposure), thus not reported here. For Cognitive Index: the nb of infants examined by Bayley or McCarthy scales not provided. => data not extractable.
Nulman (Controls exposed to Fluoxetine) 1997	Canada Since 1985 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.		at least 1st trimester	80 / 55
Nulman (Controls unexposed, disease free) 2002	Canada Until 1985 prospective cohort	The Motherisk Program	Pregnant women diagnosed as having major depression who had been counseled by the program regarding therapy with Tricyclic antidepressants and who had continued taking these medications throughout gestation.	unexposed, disease free Pregnant women who had no history of a psychiatric disorder or depressive symptoms and were unexposed to any drug, chemical, radiation, or infection known to affect the fetus adversely.	throughout pregnancy	46 / 36	'Eighteen mother-child pairs exposed to fluoxetine and 36 exposed to tricyclic antidepressants who were part of our original study (Nulman 1997) and who were exposed to these drugs throughout gestation were included in the present study.'
Nulman (Controls unexposed, disease free) 2002	Canada Until 1985 prospective cohort	The Motherisk Program	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.		throughout pregnancy	46 / 36
Nulman (Controls unexposed, NOS) 1997	Canada Since 1985 prospective cohort	The Motherisk Program, an information and consultation service regarding exposure to drugs, chemicals, radiation, and infectious agents during pregnancy and lactation.	Pregnant women who took a tricyclic antidepressant drug at least during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women not exposed to any drug, chemical, radiation, or infection known to affect the fetus adversely.	at least 1st trimester	80 / 84	Overlapping of some outcomes (language development) with Nulman 2002 (with more relevant period of exposure), thus not reported here. For Cognitive Index: the nb of infants examined by Bayley or McCarthy scales not provided. => data not extractable.
Nulman (Controls unexposed, NOS) 1997	Canada Since 1985 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.		at least 1st trimester	80 / 84
Nulman - Fluoxetine (Controls exposed to Fluoxetine) 2002	Canada Until 1985 prospective cohort	The Motherisk Program	Pregnant women diagnosed as having major depression who had been counseled by the program regarding therapy with tricyclic antidepressants and who had continued taking these medications throughout gestation.	exposed to other treatment, sick Pregnant women diagnosed as having major depression who had been counseled by the program regarding therapy with fluoxetine and who had continued taking these medications throughout gestation.	throughout pregnancy	46 / 40	'Eighteen mother-child pairs exposed to fluoxetine and 36 exposed to tricyclic antidepressants who were part of our original study (Nulman 1997) and who were exposed to these drugs throughout gestation were included in the present study.'
Nulman - Fluoxetine (Controls exposed to Fluoxetine) 2002	Canada Until 1985 prospective cohort	The Motherisk Program	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.		throughout pregnancy	46 / 40
Ozturk - Amitriptyline 2016	Turkey 2007 - 2012 prospective cohort	An observational cohort study based on a prenatal consultation service.	Pregnant women exposed to Amitriptyline during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women selected from the non-teratogen exposed pregnancies in the same year.	at least 1st trimester	4 / 275	This study assessed several Tricyclics antidepressants (TCA), with potential co-exposures => data of all TCAs cannot be added. To avoid redundancy of control, only the substance with the higher number of exposure was used in the meta-analysis.
Ozturk - Amitriptyline 2016	Turkey 2007 - 2012 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).		at least 1st trimester	4 / 275
Palmsten (Controls exposed to SSRIs) 2012	Canada 1997 - 2006 retrospective cohort (claims database)	Population-based health-care utilization databases from the province of British Columbia.	Pregnant women with at least 1 pharmacy dispensing record for a tricyclic antidepressant (TCA) during estimated gestational weeks 10–20 (Monotherapy).	exposed to other treatment, sick Pregnant women with at least 1 pharmacy dispensing record for a selective serotonin reuptake inhibitor (SSRI) during estimated gestational weeks 10–20 (Monotherapy).	2nd trimester	146 / 3169	'Exposure was classified as monotherapy if dispensings for only 1 antidepressant class were present during pregnancy and as polytherapy otherwise.'
Palmsten (Controls exposed to SSRIs) 2012	Canada 1997 - 2006 retrospective cohort (claims database)		PharmaNet database, which contains all non-hospital pharmacy dispensings.		2nd trimester	146 / 3169
Palmsten (Controls unexposed, sick) 2012	Canada 1997 - 2006 retrospective cohort (claims database)	Population-based health-care utilization databases from the province of British Columbia.	Pregnant women with at least 1 pharmacy dispensing record for a tricyclic antidepressant (TCA) during estimated gestational weeks 10–20 (Monotherapy).	unexposed, sick Pregnant women with no antidepressant dispensings between the year prior to the last menstrual period and gestational week 20.	2nd trimester	146 / 65392	'Exposure was classified as monotherapy if dispensings for only 1 antidepressant class were present during pregnancy and as polytherapy otherwise.'
Palmsten (Controls unexposed, sick) 2012	Canada 1997 - 2006 retrospective cohort (claims database)		PharmaNet database, which contains all non-hospital pharmacy dispensings.		2nd trimester	146 / 65392
Palmsten a (control exposed to SSRIs) 2013	USA 2000 - 2007 retrospective cohort (claims database)	The US nationwide Medicaid Analytic eXtract (MAX).	Pregnant women with a depression diagnosis and a dispensation of tricyclic antidepressant in monotherapy during the exposure window.	exposed to other treatment, sick Pregnant women with a depression diagnosis and a dispensation of selective serotonin reuptake inhibitor (SSRI) in monotherapy during the exposure window.	2nd and/or 3rd trimester	441 / 19000	Women who received only one antidepressant class during the window were classified as having either SSRI, SNRI, tricyclic, bupropion or other antidepressant (mirtazapine, nefazodone, trazodone) monotherapy.
Palmsten a (control exposed to SSRIs) 2013	USA 2000 - 2007 retrospective cohort (claims database)	The US nationwide Medicaid Analytic eXtract (MAX).	Outpatient pharmacy-dispensing data.		2nd and/or 3rd trimester	441 / 19000
Palmsten a (Controls unexposed, sick) 2013	USA 2000 - 2007 retrospective cohort (claims database)	The US nationwide Medicaid Analytic eXtract (MAX).	Pregnant women with a depression diagnosis and a dispensation of tricyclic antidepressant in monotherapy during the exposure window.	unexposed, sick Pregnant women with a depression diagnosis and no antidepressant exposure between the LMP and the end of the window.	2nd and/or 3rd trimester	441 / 59219	Women who received only one antidepressant class during the window were classified as having either SSRI, SNRI, tricyclic, bupropion or other antidepressant (mirtazapine, nefazodone, trazodone) monotherapy.
Palmsten a (Controls unexposed, sick) 2013	USA 2000 - 2007 retrospective cohort (claims database)	The US nationwide Medicaid Analytic eXtract (MAX).	Outpatient pharmacy-dispensing data.		2nd and/or 3rd trimester	441 / 59219
Palmsten b 2013	USA 2000 - 2007 retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) data	Women with a supply of Tricyclic antidepressants (TCAs) monotherapy that overlapped with the delivery date. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Women who had no supply of antidepressants in the five months before delivery.	late pregnancy	175 / 69044	Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Palmsten b 2013	USA 2000 - 2007 retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) data	Data of prescription.		late pregnancy	175 / 69044
Pastuszak (Controls exposed to Fluoxetine) 1993	USA and Canada Not specified prospective cohort	Four Teratogen Information Services (TIS): Motherisk (Toronto, Ontario), Pregnancy Healthline (Philadelphia, Pa), Pregnancy Risk Information Service (Camden,NJ) and Pregnancy Risk Line (Salt Lake City, Utah).	Pregnant women exposed to tricyclic antidepressants (TCAs) during the first trimester.	exposed to other treatment, sick Pregnant women exposed to fluoxetine during the first trimester.	1st trimester	74 / 74	The matched data were taken into consideration. Authors made comparison TCAs versus Fluoxetine, thus considered as mono-exposure.
Pastuszak (Controls exposed to Fluoxetine) 1993	USA and Canada Not specified prospective cohort		Drug exposure history was obtained from both the mother and biological father of the fetus, by an interview with a team physician.		1st trimester	74 / 74
Pastuszak (Controls unexposed, NOS) 1993	USA and Canada Not specified prospective cohort	Four Teratogen Information Services (TIS): Motherisk (Toronto, Ontario), Pregnancy Healthline (Philadelphia, Pa), Pregnancy Risk Information Service (Camden,NJ) and Pregnancy Risk Line (Salt Lake City, Utah).	Pregnant women exposed to tricyclic antidepressants (TCAs) during the first trimester.	unexposed (general population or NOS) Pregnant women who sought counseling at Motherisk regarding exposure to a nonteratogen.	1st trimester	74 / 74	The matched data were taken into consideration. Authors made comparison TCAs versus Fluoxetine, thus considered as mono-exposure.
Pastuszak (Controls unexposed, NOS) 1993	USA and Canada Not specified prospective cohort		Drug exposure history was obtained from both the mother and biological father of the fetus, by an interview with a team physician.		1st trimester	74 / 74
Pearson (Controls exposed to SSRIs) 2007	USA 1996 - 2000 retrospective cohort	The Perinatal and Reproductive Psychiatry Program at the Massachusetts General Hospital.	Infants whose mothers with primary major affective or anxiety disorders used Tricyclic antidepressants (TCAs) during any portion of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Infants whose mothers with primary major affective or anxiety disorders used serotonin reuptake inhibitor (SRIs) during any portion of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	during pregnancy (anytime or not specified)	37 / 42	TCA: nortriptyline (N = 13), imipramine (N = 11), desipramine (N = 7), clomipramine (N = 4), amitriptyline (N = 2). SRI: fluoxetine (N = 17), sertraline (N = 13), paroxetine (N = 12).
Pearson (Controls exposed to SSRIs) 2007	USA 1996 - 2000 retrospective cohort		Review of obstetrical and neonatal records.		during pregnancy (anytime or not specified)	37 / 42
Pearson (Controls unexposed, NOS) 2007	USA 1996 - 2000 retrospective cohort	The Perinatal and Reproductive Psychiatry Program at the Massachusetts General Hospital.	Infants whose mothers with primary major affective or anxiety disorders used Tricyclic antidepressants (TCAs) during any portion of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Infants whose mothers were not exposed to an antidepressant drug during pregnancy.	during pregnancy (anytime or not specified)	37 / 168	TCA: nortriptyline (N = 13), imipramine (N = 11), desipramine (N = 7), clomipramine (N = 4), amitriptyline (N = 2).
Pearson (Controls unexposed, NOS) 2007	USA 1996 - 2000 retrospective cohort		Review of obstetrical and neonatal records.		during pregnancy (anytime or not specified)	37 / 168
Pedersen 2010	Denmark 1996 - 2002 population based cohort retrospective	The Danish National Birth Cohort, a nationwide, ongoing, follow-up study of pregnant women and their offspring.	Live-born singletons of pregnant women that reported use of tricyclic antidepressants (TCAs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Live-born singletons of pregnant women depressed during pregnancy but did not report use of any psychotropic medication (untreated depression).	1st trimester, during pregnancy (anytime or not specified)	28 / 479	Among the 415 women treated with antidepressants, 336 used 1 type of SSRI only, 12 used >1 SSRI, 28 used only TCAs, and 29 used other types of antidepressants only (eg, venlafaxine). Ten used combinations of SSRIs, TCAs, and other antidepressants.
Pedersen 2010	Denmark 1996 - 2002 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.		1st trimester, during pregnancy (anytime or not specified)	28 / 479
Rai - Clomipramine only (Controls exposed to SSRIs) 2017	Sweden 2001 - 2011 prospective cohort	The Stockholm youth cohort, an observational prospective cohort study of Stockholm County.	Children of mothers who used Clomipramine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Children of mothers who used Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	during pregnancy (anytime or not specified)	235 / 2710	Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy.
Rai - Clomipramine only (Controls exposed to SSRIs) 2017	Sweden 2001 - 2011 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).		during pregnancy (anytime or not specified)	235 / 2710
Rai - Clomipramine only (Controls unexposed, disease free) 2017	Sweden 2001 - 2011 prospective cohort	The Stockholm youth cohort, an observational prospective cohort study of Stockholm County.	Children of mothers who used Clomipramine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free No maternal psychiatric disorder and unexposed to antidepressants	during pregnancy (anytime or not specified)	235 / 238943	Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy.
	Sweden 2001 - 2011 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).		during pregnancy (anytime or not specified)	235 / 238943
Rai - Clomipramine only (Controls unexposed, sick) 2017	Sweden 2001 - 2011 prospective cohort	The Stockholm youth cohort, an observational prospective cohort study of Stockholm County.	Children of mothers who used Clomipramine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Children of mothers with psychiatric disorders (any time before the birth of the child) who did not take antidepressants during pregnancy.	during pregnancy (anytime or not specified)	235 / 12325	Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy.
Rai - Clomipramine only (Controls unexposed, sick) 2017	Sweden 2001 - 2011 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).		during pregnancy (anytime or not specified)	235 / 12325
Reis (Controls exposed to SSRIs) 2010	Sweden 1995 - 2007 population based cohort retrospective	The Swedish Medical Birth Register (MBR), Register of Birth Defects and the Patient Register (previous the Hospital Discharge Register).	Pregnant women who reported the use of tricyclic antidepressant (TCA) in late pregnancy or were prescribed TCAs during pregnancy.	exposed to other treatment, sick Pregnant women who reported the use of selective serotonin receptor inhibitors (SSRIs) in late pregnancy or were prescribed SSRIs during pregnancy.	1st trimester, 2nd and/or 3rd trimester	784 / 4809	Overlapping: Major malfo, cardiac malfo, septal defects and hypospadias not reported here because updated by Kallen 2013. This publication included data of Kallen 2012 (Preterm), Källén 2003 (Cardiac malfo) and Källén 2004 and 2013 (neonatal outcomes).
Reis (Controls exposed to SSRIs) 2010	Sweden 1995 - 2007 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.		1st trimester, 2nd and/or 3rd trimester	784 / 4809
Reis (Controls unexposed, NOS) 2010	Sweden 1995 - 2007 population based cohort retrospective	The Swedish Medical Birth Register (MBR), Register of Birth Defects and the Patient Register (previous the Hospital Discharge Register).	Pregnant women who reported the use of tricyclic antidepressant (TCA) in late pregnancy or were prescribed TCAs during pregnancy.	unexposed (general population or NOS) All other pregnant women in the register (not exposed to antidepressants during pregnancy).	1st trimester, 2nd and/or 3rd trimester	784 / 1062190	Overlapping: Major malfo, cardiac malfo, septal defects and hypospadias not reported here because updated by Kallen 2013. This publication included data of Kallen 2012 (Preterm), Källén 2003 (Cardiac malfo, Källén 2004 and 2013 (neonatal outcomes).
Reis (Controls unexposed, NOS) 2010	Sweden 1995 - 2007 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.		1st trimester, 2nd and/or 3rd trimester	784 / 1062190
Simon (Controls exposed to SSRIs) 2002	USA 1986 - 1998 retrospective cohort (claims database)	The Group Health Cooperative, a prepaid health plan serving approximately 400,000 members in Washington State.	Mothers with any tricyclic antidepressants prescriptions during the 270 days before delivery. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Mothers with any selective serotonin reuptake inhibitor (SSRI) prescriptions during the 270 days before delivery. (This is a subgroup of exposure among the whole exposed group considered in the study).	during pregnancy (anytime or not specified)	209 / 185	Tricyclic antidepressants: 66 exposed to amitriptyline, 49 exposed to imipramine, 36 exposed to doxepin, 33 exposed to nortriptyline, and 22 exposed to desipramine. No infant exposed to more than one antidepressant in the tricyclic antidepressant group.
Simon (Controls exposed to SSRIs) 2002	USA 1986 - 1998 retrospective cohort (claims database)		Pharmacy records were used to identify all antidepressant prescriptions filled or refilled during the 360 days before delivery.		during pregnancy (anytime or not specified)	209 / 185
Simon (Controls unexposed, NOS) 2002	USA 1986 - 1998 retrospective cohort (claims database)	The Group Health Cooperative, a prepaid health plan serving approximately 400,000 members in Washington State.	Mothers with any tricyclic antidepressants prescriptions during the 270 days before delivery. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Mothers with no antidepressant prescriptions during the 360 days before delivery.	during pregnancy (anytime or not specified)	209 / 209	Tricyclic antidepressants: 66 exposed to amitriptyline, 49 exposed to imipramine, 36 exposed to doxepin, 33 exposed to nortriptyline, and 22 exposed to desipramine. No infant exposed to more than one antidepressant in the tricyclic antidepressant group.
Simon (Controls unexposed, NOS) 2002	USA 1986 - 1998 retrospective cohort (claims database)		Pharmacy records were used to identify all antidepressant prescriptions filled or refilled during the 360 days before delivery.		during pregnancy (anytime or not specified)	209 / 209
Suarez (Controls unexposed, discontinuers) 2022	USA 2000 - 2015 retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), USA.	Individuals with at least 1 dispensing of tricyclic antidepressants (TCAs) from 127 days after LMP (week 19 of gestation) to delivery.	unexposed, sick Individuals that having a dispensing for tricyclic antidepressants (TCAs) in the window from 90 to 31 days prior to LMP but not during the window of 30 days prior to LMP through delivery.	2nd and/or 3rd trimester	4307 / 5710	The Medicaid Analytic eXtract (MAX): 2000 to 2014 and the MarketScan Commercial Claims Database (MarketScan): 2003 to 2015.
Suarez (Controls unexposed, discontinuers) 2022	USA 2000 - 2015 retrospective cohort (claims database)		The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications.		2nd and/or 3rd trimester	4307 / 5710
Suarez (Controls unexposed, general pop) 2022	USA 2000 - 2015 retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), USA.	Individuals with at least 1 dispensing of tricyclic antidepressants (TCAs) from 127 days after LMP (week 19 of gestation) to delivery.	unexposed (general population or NOS) Individuals with no antidepressant dispensing from 90 days prior to pregnancy start through the day prior to delivery.	2nd and/or 3rd trimester	4357 / 2965988	The Medicaid Analytic eXtract (MAX): 2000 to 2014 and the MarketScan Commercial Claims Database (MarketScan): 2003 to 2015.
Suarez (Controls unexposed, general pop) 2022	USA 2000 - 2015 retrospective cohort (claims database)		The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications.		2nd and/or 3rd trimester	4357 / 2965988
Sørensen (Controls exposed to SSRIs) 2013	Denmark 1996 - 2006 population based cohort retrospective	The Danish Civil Registration System (CRS), the Danish National Prescription Registry (DNPR) and the Danish Psychiatric Central Register (DPCR).	Children of women who filled a prescription for Tricyclic antidepressants (TCA) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Children of women who filled a prescription for Selective serotonin reuptake inhibitor (SSRI) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study).	during pregnancy (anytime or not specified)	642 / 7506	Overlapping between Gidaya 2014, Hviid 2013 and Sorensen 2013: same outcomes, same dataset, same period (not the same research team). The study of Sorensen 2013 included a larger study period and more pregnancies and was the only one reported.
Sørensen (Controls exposed to SSRIs) 2013	Denmark 1996 - 2006 population based cohort retrospective		The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist.		during pregnancy (anytime or not specified)	642 / 7506
Sørensen (Controls unexposed, NOS) 2013	Denmark 1996 - 2006 population based cohort retrospective	The Danish Civil Registration System (CRS), the Danish National Prescription Registry (DNPR) and the Danish Psychiatric Central Register (DPCR).	Children of women who filled a prescription for Tricyclic antidepressants (TCA) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Children of women who not filled antidepressant drugs during pregnancy.	during pregnancy (anytime or not specified)	642 / 646782	Overlapping between Gidaya 2014, Hviid 2013 and Sorensen 2013: same outcomes, same dataset, same period. Sorensen 2013 included more pregnancies=> the only one reported. Low nb of co-exposure SSRI/SNRI/TCS (<5%) => considered as monotherapies.
Sørensen (Controls unexposed, NOS) 2013	Denmark 1996 - 2006 population based cohort retrospective		The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist.		during pregnancy (anytime or not specified)	642 / 646782
Ter Host (Controls exposed to SSRIs) 2013	The Netherlands 1995 - 2009 retrospective cohort (claims database)	The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl	Children of mothers exposed to tricyclic antidepressant (TCA) during pregnancy.	exposed to other treatment, sick Children of mothers exposed to selective serotonin re-uptake inhibitors (SSRIs) during pregnancy.	1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy	67 / 436	The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. The most commonly used TCA was clomipramine (n=43), followed by amitriptyline (n=31).
Ter Host (Controls exposed to SSRIs) 2013			The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.			67 / 436
Ter Host (Controls unexposed, NOS) 2013	The Netherlands 1995 - 2009 retrospective cohort (claims database)	The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl	Children of mothers exposed to tricyclic antidepressant (TCA) during pregnancy.	unexposed (general population or NOS) Children of mothers who did not use any selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) during pregnancy and during a period of 7 days before pregnancy.	1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy	67 / 35033	The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. The most commonly used TCA was clomipramine (n=43), followed by amitriptyline (n=31).
Ter Host (Controls unexposed, NOS) 2013			The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands.			67 / 35033
Tran (Controls exposed to SSRI) 2022	The Netherlands 2000 - 2010 retrospective cohort (claims database)	The Netherlands Perinatal Registry (PERINED) and the PHARMO Database Network.	Pregnant women who received a dispensing of tricyclic antidepressants (TCAs) between weeks 0–20 of gestation or received before pregnancy, but the treatment duration lasted into pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnant women who received a dispensing of Selective serotonin reuptake inhibitors (SSRIs) between weeks 0–20 of gestation or received before pregnancy, but the treatment duration lasted into pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	1st and 2nd trimester, at least 1st trimester	214 / 1488
Tran (Controls exposed to SSRI) 2022			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.		1st and 2nd trimester, at least 1st trimester	214 / 1488
Tran (Controls unexposed, NOS) 2022	The Netherlands 2000 - 2010 retrospective cohort (claims database)	The Netherlands Perinatal Registry (PERINED) and the PHARMO Database Network.	Pregnant women who received a dispensing of tricyclic antidepressants (TCAs) between weeks 0–20 of gestation or received before pregnancy, but the treatment duration lasted into pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women who did not receive antidepressants in 15 months before delivery.	1st and 2nd trimester, at least 1st trimester	214 / 95376
Tran (Controls unexposed, NOS) 2022			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.		1st and 2nd trimester, at least 1st trimester	214 / 95376
Vasilakis-Scaramozza (Controls exposed to SSRIs) 2013	United Kingdom 1991 - 2002 retrospective cohort	The United Kingdom’s General Practice Research Database (GPRD) containing data from 368 general practices.	Pregnant women with a diagnosis of depression and with at least one prescription for Tricyclic antidepressants during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period.	exposed to other treatment, sick Pregnant women with a diagnosis of depression and with at least one prescription for selective serotonin reuptake inhibitor (SSRI) during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period.	1st trimester	1608 / 1825	'Antidepressant exposure categories (tricyclics or SSRI) are not mutually exclusive.' but only 157 women were exposed to both tricyclics and SSRI (< 10%) => thus it is considered that comparison between tricyclics and SSRI can be made.
Vasilakis-Scaramozza (Controls exposed to SSRIs) 2013	United Kingdom 1991 - 2002 retrospective cohort		Clinical records that described prescribed drugs from each clinical visit.		1st trimester	1608 / 1825
Vasilakis-Scaramozza (Controls unexposed, NOS) 2013	United Kingdom 1991 - 2002 retrospective cohort (claims database)	The United Kingdom’s General Practice Research Database (GPRD) containing data from 368 general practices.	Pregnant women with a diagnosis of depression and with at least one prescription for Tricyclic antidepressants during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period.	unexposed (general population or NOS) Pregnant women not exposed to any antidepressant during the first trimester of pregnancy.	1st trimester	1608 / 6617	'Antidepressant exposure categories (tricyclics or SSRI) are not mutually exclusive.' but only 157 women were exposed to both tricyclics and SSRI (< 10%) => thus it is considered as monotherapy exposure.
Vasilakis-Scaramozza (Controls unexposed, NOS) 2013			Clinical records that described prescribed drugs from each clinical visit.		1st trimester	1608 / 6617
Wall-Wieler 2020	USA 2008 - 2015 retrospective cohort (claims database)	The nationwide (American) IBM® MarketScan® Databases, a large administrative claims database.	Pregnant women having a tricyclic antidepressant (TCA) prescription that had at least a 1-day supply in the 3 weeks after a woman’s estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women who had a prepregnancy depression diagnosis and did not have Selective serotonin reuptake inhibitor (SSRI) prescription, but that could they could be exposed to an antidepressant (but not that class).	early pregnancy	1037 / 105751	Non exposed group: a majority is non exposed to antidepressant (n=66501) whereas the other one are exposed to an other class of antidepressants.
Wall-Wieler 2020	USA 2008 - 2015 retrospective cohort (claims database)		Antidepressant prescriptions were identified from outpatient pharmacy files through National Drug Codes (NDC) from outpatient pharmaceutical claims.		early pregnancy	1037 / 105751
Yang 2021	Taiwan 2010 - 2016 retrospective cohort (claims database)	The Health and Welfare Database (HWD) in Taiwan, administrative claims database that incorporates information from the Taiwan National Health Insurance Program, which covers more than 99.6% of Taiwan's population.	Pregnant women with depression and at least 1 prescription for an oral tricyclic antidepressants (TCA) from the day of pregnancy initiation up to the start of 20 weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women with depression without antidepressant prescription.	1st and 2nd trimester	105 / 2832	'In addition, we restricted the cohort of antidepressant users to patients who were only prescribed 1 consistent antidepressant during the exposure period.'
Yang 2021	Taiwan 2010 - 2016 retrospective cohort (claims database)		The Health and Welfare Database (HWD), administrative claims database that incorporates prescription drug utilization.		1st and 2nd trimester	105 / 2832
Yaris 2005	Turkey 1999 - 2004 prospective cohort	Toxicology Information and Follow-up Service	Women who were exposed to Tricyclics during pregnancy for depression, anxiety, and psychotic disorders. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Women who did not use any drug while pregnant.	during pregnancy (anytime or not specified)	51 / 248	Tricyclics: addition of Clomipramine (13), Amytriptiline (27), Maprotilin (3), Opipramol (8). Raw data for Intrauterine exitus not reported because the nb of cases in the unexposed group not clearly stated.
Yaris 2005	Turkey 1999 - 2004 prospective cohort	Toxicology Information and Follow-up Service	Data surveyed by the interviews.		during pregnancy (anytime or not specified)	51 / 248
Zakiyah 2018	The Netherlands 1994 - 2015 retrospective cohort (claims database)	A retrospective cohort study performed with a large mother-infant subset from the University of Groningen’s IADB.nl pharmacy prescription database, referred to as 'pregnancy database'.	At least one dispensing record of tricyclic antidepressants (TCAs) between the theoretical conception date and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women that were without antidepressant prescriptions in the period of 6 months prior to the theoretical conception date until 20 completed weeks of gestation.	1st and 2nd trimester	89 / 27481	TCA (Amitriptyline 66; Clomipramine 31; Imipramine 3; Nortriptyline 3; Dosulepin 2; Trimipramine 1; Maprotiline 1; Doxepin 1). 70 women used 1 type of antidepressant and 19 women used 2 different types of antidepressants from TCAs class.
Zakiyah 2018			The University of Groningen’s IADB.nl pharmacy prescription database, a longitudinal database containing pharmacy-dispensing data from community pharmacies in the Netherlands.		1st and 2nd trimester	89 / 27481

Case-control studies

Study	Country Study period Study design	Data source	Case	Control	Exposition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks
Abadie 2015	France 1984 - 2010 nested case control	TERAPPEL database shared by several French Regional PharmacoVigilance Centers (CRPVs).	All the women registered in the database whose pregnancy outcome was “spontaneous abortion” (before the 22nd week of amenorrhea).	All the women registered in the database whose pregnancy outcome was 'birth'.	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.	1st trimester	838 / 4508
Abadie 2015	France 1984 - 2010 nested case control		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.			1st trimester	838 / 4508
Anderson 2020	USA 1997 - 2011 case control	The National Birth Defects Prevention Study (NBDPS), a US population-based, multisite case-control study.	The case infants were infants born alive or died at 20 SG or more and who had received a diagnosis of at least one selected birth defect.	The controls were live-born infants with no major birth defects who were randomly selected from hospital or state birth-certificate records from the same geographic areas.	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).	1st trimester	30630 / 11478	'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.'
Anderson 2020	USA 1997 - 2011 case control		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.			1st trimester	30630 / 11478
Croen 2011	USA 1995 - 1999 case control	The Childhood Autism Perinatal Study, a large case-control study within the Kaiser Permanente Medical Care Program in Northern California.	Children with at least 1 diagnosis of autism (ICD-9-CM code 299.0), Asperger syndrome (ICD-9-CM code 299.8), or pervasive developmental disorder not otherwise specified (ICD-9-CM code 299.8).	Children without an Autism spectrum disorder diagnosis randomly sampled from the remaining cohort of live births.	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.	3 months (or more) before pregnancy or during pregnancy	298 / 1507
Croen 2011	USA 1995 - 1999 case control		On the basis of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) recorded in the KPNC outpatient clinical databases.			3 months (or more) before pregnancy or during pregnancy	298 / 1507
Dandjinou 2019	Canada 1998 - 2015 nested case control	The Quebec Pregnancy Cohort (QPC), a Canadian provincial database.	Pregnant women with a diagnosis of gestational diabetes mellitus (GDM) identified using diagnosis codes ICD-9: 250.0–250.9, 648.0, 648.8, 790.2, 775.1 or ICD-10: E10–E14, O24, R73.0) or at least one filled prescription for an antidiabetic drug allowed during pregnancy (insulin, glyburide or metformin), both after week 20 of gestation, whichever occurred first.	Pregnant women that did not have a diagnosis of gestational diabetes mellitus (GDM) at the index date.	The Quebec Prescription Drug Insurance Database (drug name, start date, dosage and duration).	during pregnancy (anytime or not specified)	20905 / 209050	The 10 categories of exposure were mutually exclusive.
Dandjinou 2019	Canada 1998 - 2015 nested case control		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).			during pregnancy (anytime or not specified)	20905 / 209050	The 10 categories of exposure were mutually exclusive.
De Vera 2012	Canada 1997 - 2003 nested case control	The Quebec Pregnancy Registry (QPR), a longitudinal cohort established with the linkage of three administrative databases.	Women with a diagnosis of gestational hypertension (ICD-9: 642.3, 642.0), pre-eclampsia (ICD-9: 642.4, 642.5) or eclampsia (ICD-9: 642.6) after the 20th week of gestation.	Women who did not have a diagnosis of pregnancy-induced hypertension at or before the same gestational age.	The Quebec’s Public Prescription Drug Insurance Plan.	during pregnancy (anytime or not specified)	1216 / 12160	Tricyclic antidepressants (amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline and trimipramine).
De Vera 2012	Canada 1997 - 2003 nested case control		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).		The Quebec’s Public Prescription Drug Insurance Plan.	during pregnancy (anytime or not specified)	1216 / 12160
Greenberg 1977	United Kingdom (England and Wales). 1969 - 1974 case control	The information passed in the Office of population censuses and surveys (OPCS), United Kingdom.	Children with congenital abnormalities (all minor malformations were eliminated).	Children without congenital abnormalities born in the same practice within 3 months of the date of birth of an abnormal baby.	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).	1st trimester	836 / 836
Greenberg 1977			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.			1st trimester	836 / 836
Hartwig 2022	The Netherlands 1995 - 2016 case control	The IADB.nl database, a prescription database from the University of Groningen in the Netherlands.	Children receiving at least two consecutive prescriptions for Attention-deficit/hyperactivity disorder (ADHD) medication (i.e., methylphenidate, dextroamphetamine, or atomoxetine) before the age of 16, with 'consecutive' meaning the second prescription being received within 6 months.	Sibling of a case, being born from the same womb, with no prescriptions for MPH, dextroamphetamine, or atomoxetine during follow-up until the 16th birthday.	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.	during pregnancy (anytime or not specified)	1304 / 1529
Hartwig 2022	The Netherlands 1995 - 2016 case control		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.			during pregnancy (anytime or not specified)	1304 / 1529
Kieler 2015	Denmark, Finland, and Norway 1996 - 2007 nested case control	National registers of Denmark, Finland, and Norway.	Women with elective termination of pregnancy at 12–23 weeks of gestation.	Women that continued their pregnancy, randomly selected and matched with cases on key factors.	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.	3 months (or more) before pregnancy or during pregnancy, during pregnancy (anytime or not specified)	14902 / 148929	TCAs (imipramine, klomipramine, trimipramine, amitriptylin, nortriptyline, doxepine, dosulepine, amoxapine, and maproteline). The (ORs) are presented for women exposed to only one type of antidepressant during the exposure period.
Kieler 2015		National registers of Denmark, Finland, and Norway.	In the registers the diagnoses and pregnancy complications are classified according to the national version of the International Classification of Diseases (ICD).				14902 / 148929
Kitchin 2022	Spain 2002 - 2015 case control	The Spanish database BIFAP (Base de Datos para la Investigacion Farmacoepidemiologica en Atencion Primaria, Database for Pharmacoepidemiological Research in Primary Care)	Pregnant woman suffering a miscarriage.	Pregnant woman randomly selected from the whole cohort among women who were still at risk within follow-up, by risk-set sampling and individually matched to cases.	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.	1st trimester	18070 / 54209
Kitchin 2022	Spain 2002 - 2015 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, which contains medical diagnoses, medical visits, hospital admissions.			1st trimester	18070 / 54209
Kullander - Imipramine 1976	Sweden 1963 - 1965 nested case control	The Department of Gynecology and Obstetrics and the Department of Embryology, University of Lund, Sweden.	Infants with different kinds of malformations.	Infants without malformations.	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.	1st trimester	751 / 5002
Kullander - Imipramine 1976	Sweden 1963 - 1965 nested case control		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.			1st trimester	751 / 5002
Louik 2014	USA and Canada 1992 - 2011 case control	The Slone Epidemiology Center’s Birth Defects Study (BDS), a multi-center case-control surveillance program for birth defects.	Infants with any of a wide range of malformations (infants with isolated minor defects are excluded)..	Infants without malformations.	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.	1st trimester	2734 / 8611
Louik 2014	USA and Canada 1992 - 2011 case control		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.			1st trimester	2734 / 8611
Nakhai-Pour 2010	Canada 1998 - 2003 nested case control	The Quebec Pregnancy Registry, built with the linkage of three administrative databases: the Régie de l’assurance maladie du Québec (RAMQ), the Med-Echo database and the Institut de la statistique du Québec database.	Pregnant women with a diagnosis or a procedure for spontaneous abortion between the first day and the 20th week of gestation.	Randomly selected pregnant women who did not have a spontaneous abortion at or before the same gestational age as their matched case did.	The Régie de l’assurance maladie du Québec (RAMQ) database which provides prospectively collected data on filled prescriptions.	during pregnancy (anytime or not specified)	5124 / 51240
Nakhai-Pour 2010	Canada 1998 - 2003 nested case control		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).			during pregnancy (anytime or not specified)	5124 / 51240
Solé 2020	Spain 2005 - 2017 nested case control	The Perinatal Mental Health Unit in a general university hospital (Hospital Clinic of Barcelona)	Pregnant women who had a C-Section (C-Section group).	Pregnant women who had a vaginal delivery (non-C-Section group).	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.	during pregnancy (anytime or not specified)	40 / 60
Solé 2020	Spain 2005 - 2017 nested case control		Obstetric and medical histories were obtained for all women by systematic review of obstetric records and prenatal care.			during pregnancy (anytime or not specified)	40 / 60
Song 2023	South Korea Jan-Dec 2017 nested case control	Korea National Health Insurance claims.	Preterm labour or birth (birth before 37 weeks of gestation) with or without premature rupture of membranes (PROM) or other indicated preterm birth.	Term birth.	The data on medication history were screened from ATC codes in the Korea National Health Insurance claims.	3 months (or more) before pregnancy or during pregnancy	7285 / 117321
Song 2023	South Korea Jan-Dec 2017 nested case control	Korea National Health Insurance claims.	The data on disease were screened from ICD-10 in the Korea National Health Insurance claims.			3 months (or more) before pregnancy or during pregnancy	7285 / 117321

Risk of bias: : NA; : low; : moderate; : serious; : critical; : unclear;

master protocol