Tricyclic antidepressants

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Avalos (Controls exposed to SSRIs), 2015	USA 2010 - 2012	Women who were screened for depression in early pregnancy, had a depression diagnosis or were taking antidepressant medications during pregnancy.	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).	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 unexposed, disease free), 2015	USA 2010 - 2012	Women who were screened for depression in early pregnancy, had a depression diagnosis or were taking antidepressant medications during pregnancy.	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.	116 / 16402	Results of TCA only reported rather than 'TCA only and TCA plus other antidepressant'.
Avalos (Controls unexposed, sick), 2015	USA 2010 - 2012	Women who were screened for depression in early pregnancy, had a depression diagnosis or were taking antidepressant medications during pregnancy.	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).	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'.
Bahat, 2020	Israel 2001 - 2015	Pregnancies of women, who consulted the Israeli Teratology Information Service (TIS) during the study period.	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.	83 / 511	Major congenital anomalies excluding genetic or cytogenetic not reported because number of cases, exposures and exclusions not provided.
Ban (Controls exposed to SSRIs), 2014	United Kingdom 1990 - 2009	All singleton live births for women aged 15– 45years in which the medical records of the mothers and the children were linked to provide prospectively recorded information throughout pregnancy and in the year before pregnancy.	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).	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), 2012	The United Kingdom (UK). 1990 - 2009	All clinically recognised singleton pregnancies among women aged 15– 45 years that ended in live birth, stillbirth, termination or miscarriage.	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.	4349 / 14191	Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status.
Ban (Controls unexposed, disease free), 2014	United Kingdom 1990 - 2009	All singleton live births for women aged 15– 45 years in which the medical records of the mothers and the children were linked to provide prospectively recorded information throughout pregnancy and in the year before pregnancy.	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.	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), 2012	The United Kingdom (UK). 1990 - 2009	All clinically recognised singleton pregnancies among women aged 15– 45 years that ended in live birth, stillbirth, termination or miscarriage.	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.	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), 2014	United Kingdom 1990 - 2009	All singleton live births for women aged 15– 45years in which the medical records of the mothers and the children were linked to provide prospectively recorded information throughout pregnancy and in the year before pregnancy.	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.	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), 2012	The United Kingdom (UK). 1990 - 2009	All clinically recognised singleton pregnancies among women aged 15– 45 years that ended in live birth, stillbirth, termination or miscarriage.	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.	4349 / -9	Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status. Number of unexposed women not provided.
Bérard (Controls exposed to SSRIs), 2017	Canada 1998 - 2009	Pregnancies ending with a live-born singleton with continuous prescription drug insurance coverage of at least 12 months before the 1DLMP and during pregnancy; pregnancies with a diagnosis of depression and/or anxiety or exposed to antidepressants in the 12 months before pregnancy.	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.	382 / 2327	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Bérard (Controls unexposed, sick), 2017	Canada 1998 - 2009	Pregnancies ending with a live-born singleton with continuous prescription drug insurance coverage of at least 12 months before the 1DLMP and during pregnancy; pregnancies with a diagnosis of depression and/or anxiety or exposed to antidepressants in the 12 months before pregnancy.	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.	382 / 14847	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Bernard, 2019	Canada 2005 - 2010	Pregnant women aged 18 years or older without chronic hepatic or renal disease recruited during their first prenatal visit.	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.	8 / 6502
Boukhris (Controls exposed to SSRIs), 2016	Canada 1998 - 2009	All full-term (≥37 weeks’ gestation) singleton infants born during the study period and whose mothers were covered by the RAMQ drug plan for at least 12 months before and during pregnancy.	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).	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), 2017	Canada 1998 - 2009	All full-term (≥37 weeks of gestation) singletons born alive during the study period in the province of Quebec and whose mothers were covered by the RAMQ drug plan for at least 12 months before and during pregnancy.	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).	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 unexposed, NOS), 2016	Canada 1998 - 2009	All full-term (≥37 weeks’ gestation) singleton infants born during the study period and whose mothers were covered by the RAMQ drug plan for at least 12 months before and during pregnancy.	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.	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), 2017	Canada 1998 - 2009	All full-term (≥37 weeks of gestation) singletons born alive during the study period in the province of Quebec and whose mothers were covered by the RAMQ drug plan for at least 12 months before and during pregnancy.	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.	227 / 141905	‘Single class exposure was defined as the filling of prescriptions for only one antidepressant class in the time window of interest.'
Chan (Controls exposed to SSRIs), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	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.	322 / 956
Chan (Controls unexposed, general pop), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	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.	322 / 462377
Chan (Controls unexposed, sick), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	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.	181 / 4413
Chen, 2021	Taiwan 2000 - 2013	Pregnant women aged 18–55 years with perinatal depression (ICD-9-CM codes 296.2–296.3 and 311) who were diagnosed with depression within 90 days before the date of their pregnancy test.	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.	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.
Davis, 2007	USA 1996 - 2000	Female older than 15 years of age who were admitted to a hospital during study period for delivery of an infant and were continuously enrolled with prescription drug coverage for 1 year prior to the admission.	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.	339 / 81146	Polyhydramnios, Oligohydramnios, Poly- and/or oligo-hydramnios not reported because not sure that the 3rd trimester exposure occurred before outcome.
Hagberg (Controls exposed to SSRIs), 2018	United Kingdom 1989 - 2011	Mothers, aged 13–44 years, and their live-born, singleton infants born.	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).	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 unexposed, disease free), 2018	United Kingdom 1989 - 2011	Mothers, aged 13–44 years, and their live-born, singleton infants born.	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.	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, sick), 2018	United Kingdom 1989 - 2011	Mothers, aged 13–44 years, and their live-born, singleton infants born.	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).	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.
Heuvelman, 2023	United Kingdom 1995 - 2017	Pregnancies in Clinical Practice Research Datalink (CPRD) with a history of depressive symptoms or use of antidepressants in the preceding year before pregnancy.	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.	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.
Huybrechts (Controls unexposed, NOS), 2014	USA 2000 - 2007	All completed pregnancies and their linked liveborn infants.	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.	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, sick), 2014	USA 2000 - 2007	All completed pregnancies and their linked liveborn infants.	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.	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).
Källen, 2013	Sweden 1996 - 2011	Nearly all births in Sweden, based on standardized medical records, used in the whole country.	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.	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.
Källén (Controls exposed to SSRIs), 2004	Sweden 1995 - 2001	All singleton children born during the study period.	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).	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 unexposed, NOS), 2004	Sweden 1995 - 2001	All singleton children born during the study period.	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.	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.
Kjaersgaard (Controls unexposed, NOS), 2013	Denmark 1997 - 2008	All clinically recognized pregnancies in Denmark with an estimated conception and an observed pregnancy outcome during the study period.	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.	-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, sick), 2013	Denmark 1997 - 2008	All clinically recognized pregnancies in Denmark with an estimated conception and an observed pregnancy outcome during the study period.	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.	-9 / -9	Molar or ectopic pregnancies (ICD-10: O00.0– O01.9) were excluded from the main analyses.
Kolding (Controls unexposed, disease free), 2021	Denmark 2007 - 2014	All clinically recognized singleton pregnancies with fetuses alive at the nuchal scan from 11 completed gestational weeks.	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.	254 / 353581	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Kolding (Controls unexposed, sick), 2021	Denmark 2007 - 2014	All clinically recognized singleton pregnancies with fetuses alive at the nuchal scan from 11 completed gestational weeks.	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).	254 / 6326	'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.'
Laugesen, 2013	Denmark 1996 - 2009	All Danish singletons born alive during the study period	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.	716 / 816792
Lee (Controls exposed to SSRI), 2025	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003 and December 31, 2018.	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.	613 / 1465
Lee (Controls unexposed, general pop), 2025	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003 and December 31, 2018.	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.	613 / 463440
Liu, 2015	Denmark 1996 - 2007	All live singletons born in Denmark during the study period.	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.	409 / 12476	Number of women exposed to Tricyclic antidepressants (TCAs) based on % provided by authors (81%*505).
Lupattelli (Controls exposed to SSRIs), 2017	Norway 1999 - 2008	Depressed pregnant women recruited from all over Norway through a postal invitation in connection with a routine ultrasound at gestational weeks (GWs) 17 and 18.	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.	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 unexposed, sick), 2017	Norway 1999 - 2008	Depressed pregnant women recruited from all over Norway through a postal invitation in connection with a routine ultrasound at gestational weeks (GWs) 17 and 18.	Depressed pregnant women that reported use of Tricyclic antidepressants (TCAs) monotherapy during pregnancy.	unexposed, sick Depressed pregnant women nonmedicated.	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'
Martin - Amitriptyline, 2024	Norway, Sweden and United Kingdom. 1996 - 2020	Singleton deliveries 22 weeks’ completed gestational weeks registered in the different databases during the study periods (UK: 1996-2018, Norway: 2009-2020, Sweden: 2006-2020).	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.	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.
Nijenhuis (Controls exposed to SSRIs), 2012	The Netherlands 1995 - 2009	Children selected by date of birth (between 1995 - 2009) and the female person (15–50 years) with the same address code (considered to be the mother).	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.	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 unexposed, NOS), 2012	The Netherlands 1995 - 2009	Children selected by date of birth (between 1995 - 2009) and the female person (15–50 years) with the same address code (considered to be the mother).	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.	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).
Nulman (Controls exposed to Fluoxetine), 1997	Canada Since 1985	Pregnant women counseled by the program.	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).	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 unexposed, disease free), 2002	Canada Until 1985	Mothers were approached during the first trimester of pregnancy when contact was made with Motherisk to provide information and consultation on the risk/safety of drug.	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.	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, NOS), 1997	Canada Since 1985	Pregnant women counseled by the program.	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.	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 - Fluoxetine (Controls exposed to Fluoxetine), 2002	Canada Until 1985	Mothers were approached during the first trimester of pregnancy when contact was made with Motherisk to provide information and consultation on the risk/safety of drug.	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.	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.'
Ozturk - Amitriptyline, 2016	Turkey 2007 - 2012	Pregnant women referred to the prenatal consultation service for psychotropic drug exposure.	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.	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.
Palmsten (Controls exposed to SSRIs), 2012	Canada 1997 - 2006	Pregnancies that ended in a livebirth in women with at least 1 inpatient or outpatient code for depression during the year prior to the last menstrual period until 20 completed gestational weeks.	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).	146 / 3169	'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	Pregnancies that ended in a livebirth in women with at least 1 inpatient or outpatient code for depression during the year prior to the last menstrual period until 20 completed gestational weeks.	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.	146 / 65392	'Exposure was classified as monotherapy if dispensings for only 1 antidepressant class were present during pregnancy and as polytherapy otherwise.'
Palmsten a (control exposed to SSRIs), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	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.	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 (Controls unexposed, sick), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	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.	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 b, 2013	USA 2000 - 2007	Subcohort of pregnancies in women with diagnoses for mood or anxiety disorders (between one and five months before delivery), ending in live birth among women aged 12-55.	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.	175 / 69044	Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Pastuszak (Controls exposed to Fluoxetine), 1993	USA and Canada Not specified	All cases of women contacting one of the above Teratogen Information Services (TIS) during pregnancy.	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.	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	All cases of women contacting one of the above Teratogen Information Services (TIS) during pregnancy.	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.	74 / 74	The matched data were taken into consideration. Authors made comparison TCAs versus Fluoxetine, thus considered as mono-exposure.
Pearson (Controls exposed to SSRIs), 2007	USA 1996 - 2000	Infants whose mothers Massachusetts General Hospital (MGH).	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).	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 unexposed, NOS), 2007	USA 1996 - 2000	Infants whose mothers Massachusetts General Hospital (MGH).	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.	37 / 168	TCA: nortriptyline (N = 13), imipramine (N = 11), desipramine (N = 7), clomipramine (N = 4), amitriptyline (N = 2).
Pedersen, 2010	Denmark 1996 - 2002	Recruitment among danish pregnant women by about 50% of general practitioners nationwide.	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).	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.
Rai - Clomipramine only (Controls exposed to SSRIs), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	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).	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 unexposed, disease free), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	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	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.
Rai - Clomipramine only (Controls unexposed, sick), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	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.	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.
Reis (Controls exposed to SSRIs), 2010	Sweden 1995 - 2007	Almost all deliveries in Sweden (1–2% missing).	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.	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 unexposed, NOS), 2010	Sweden 1995 - 2007	Almost all deliveries in Sweden (1–2% missing).	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).	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).
Simon (Controls exposed to SSRIs), 2002	USA 1986 - 1998	All live births of mothers continuously enrolled in Group Health Cooperative for 360 days before delivery.	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).	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 unexposed, NOS), 2002	USA 1986 - 1998	All live births of mothers continuously enrolled in Group Health Cooperative for 360 days before delivery.	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.	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.
Suarez (Controls unexposed, discontinuers), 2022	USA 2000 - 2015	Individuals aged 12 to 55 years with live-birth deliveries linked to infants that have insurance coverage from 3 months before the date of the estimated last menstrual period (LMP) to 1 month after delivery.	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.	4307 / 5710	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	Individuals aged 12 to 55 years with live-birth deliveries linked to infants that have insurance coverage from 3 months before the date of the estimated last menstrual period (LMP) to 1 month after delivery.	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.	4357 / 2965988	The Medicaid Analytic eXtract (MAX): 2000 to 2014 and the MarketScan Commercial Claims Database (MarketScan): 2003 to 2015.
Sørensen (Controls exposed to SSRIs), 2013	Denmark 1996 - 2006	All children born alive in Denmark during the study period.	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).	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 unexposed, NOS), 2013	Denmark 1996 - 2006	All children born alive in Denmark during the study period.	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.	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.
Ter Host (Controls exposed to SSRIs), 2013	The Netherlands 1995 - 2009	Children selected by date of birth (between 1995 - 2009) and the female person (15–50 years) with the same address code (considered to be the mother).	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.	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 unexposed, NOS), 2013	The Netherlands 1995 - 2009	Children selected by date of birth (between 1995 - 2009) and the female person (15–50 years) with the same address code (considered to be the mother).	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.	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).
Tran (Controls exposed to SSRI), 2022	The Netherlands 2000 - 2010	Pregnant women who had her first pregnancy (primigravida) with a singleton during the study period.	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).	214 / 1488
Tran (Controls unexposed, NOS), 2022	The Netherlands 2000 - 2010	Pregnant women who had her first pregnancy (primigravida) with a singleton during the study period.	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.	214 / 95376
Vasilakis-Scaramozza (Controls exposed to SSRIs), 2013	United Kingdom 1991 - 2002	Offspring of singleton pregnancies among women aged 15–45 years that occurred during the study period.	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.	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 unexposed, NOS), 2013	United Kingdom 1991 - 2002	Offspring of singleton pregnancies among women aged 15–45 years that occurred during the study period.	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.	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.
Wall-Wieler, 2020	USA 2008 - 2015	Pregnant women with have a prepregnancy depression diagnosis, among women aged 15 to 44.	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).	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.
Yang, 2021	Taiwan 2010 - 2016	First recorded singleton pregnancies in women aged 18 to 49 years who gave birth during the study period with at least 1 outpatient or 1 inpatient diagnosis of depression between 12 months before the start of pregnancy and the start of the 20 weeks’ gestation.	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.	105 / 2832	'In addition, we restricted the cohort of antidepressant users to patients who were only prescribed 1 consistent antidepressant during the exposure period.'
Yaris, 2005	Turkey 1999 - 2004	Pregnant women calling for a counseling about the teratogenic risks of drugs, chemicals, and X-ray.	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.	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.
Zakiyah, 2018	The Netherlands 1994 - 2015	Singleton pregnant women who were registered in the IADB.nl pregnancy database during the study period.	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.	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.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Abadie, 2015	France 1984 - 2010	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'.	838 / 4508
Anderson, 2020	USA 1997 - 2011	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.	30630 / 11478	'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.'
Croen, 2011	USA 1995 - 1999	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.	298 / 1507
Dandjinou, 2019	Canada 1998 - 2015	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.	20905 / 209050	The 10 categories of exposure were mutually exclusive.
De Vera, 2012	Canada 1997 - 2003	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.	1216 / 12160	Tricyclic antidepressants (amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline and trimipramine).
Greenberg, 1977	United Kingdom (England and Wales). 1969 - 1974	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.	836 / 836
Hartwig, 2022	The Netherlands 1995 - 2016	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.	1304 / 1529
Kieler, 2015	Denmark, Finland, and Norway 1996 - 2007	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.	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.
Kitchin, 2022	Spain 2002 - 2015	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.	18070 / 54209
Kullander - Imipramine, 1976	Sweden 1963 - 1965	Infants with different kinds of malformations.	Infants without malformations.	751 / 5002
Louik, 2014	USA and Canada 1992 - 2011	Infants with any of a wide range of malformations (infants with isolated minor defects are excluded)..	Infants without malformations.	2734 / 8611
Nakhai-Pour, 2010	Canada 1998 - 2003	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.	5124 / 51240
Solé, 2020	Spain 2005 - 2017	Pregnant women who had a C-Section (C-Section group).	Pregnant women who had a vaginal delivery (non-C-Section group).	40 / 60
Song, 2023	South Korea Jan-Dec 2017	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.	7285 / 117321

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