Sertraline updated on 07-01-2025

Congenital heart defects

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S18170
R76407		 Chan (Controls exposed to TCA), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.84 [0.33;2.12] C
excluded (control group) 		8/277   11/322 19 277
ref
S18148
R76300		 Chan (Controls unexposed, pop general), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 2.24 [0.60;8.39] 8/277   8,107/462,377 8,115 277
ref
S13130
R50074		 Marks (Controls exposed to Bupropion), 2021 Cardiac Malformations during pregnancy (anytime or not specified) excluded retrospective cohort exposed to other treatment, sick Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.22 [0.66;2.23] C
excluded (exposition period) 		64/1,653   13/406 77 1,653
ref
S7468
R22139		 Anderson, 2020 Any heart defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.16 [0.92;1.48] -/-   0/- - -
ref
S5398
R14842		 Bérard (Controls exposed to non-Sertraline SSRI), 2015 Circulatory system 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.09 [0.60;2.01] C
excluded (control group) 		13/366   64/1,963 77 366
ref
S6705
R18926		 Bérard (Controls unexposed, sick), 2015 Circulatory system 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.28 [0.73;2.23] 13/366   408/14,868 421 366
ref
S6008
R15423		 Furu, 2015 Any cardiac defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.13 [0.93;1.38] 109/7,245   26,745/2,266,875 26,854 7,245
ref
S7352
R21529		 Wemakor, 2015 Congenital heart defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.51 [0.73;3.12] 16/30   12,860/29,929 12,876 30
ref
S5888
R14764		 Ban (Controls unexposed, disease free), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.52 [0.78;2.96]
excluded (control group) 		-/757   2,444/325,294 - 757
ref
S5889
R14779		 Ban (Controls unexposed, sick), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.39 [0.70;2.74] -/757   112/13,432 - 757
ref
S6104
R15932		 Huybrechts (Controls unexposed, NOS), 2014 Any cardiac malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.27 [1.07;1.52]
excluded (control group) 		129/14,040   6,403/885,115 6,532 14,040
ref
S6105
R15936		 Huybrechts (Controls unexposed, sick), 2014 Any cardiac malformations 1st trimester cohort unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.06 [0.86;1.32] 106/11,045   1,497/180,564 1,603 11,045
ref
S6390
R61465		 Nordeng (Controls unexposed, NOS), 2012 Cardiovascular malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.15 [0.16;8.28] C
excluded (control group) 		1/99   541/61,648 542 99
ref
S7833
R61479		 Nordeng (Controls unexposed, sick), 2012 Cardiovascular malformations 1st trimester cohort unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.52 [0.18;12.46] C 1/99   7/1,048 8 99
ref
S7178
R20168		 Colvin, 2011 Cardiovascular defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.74 [0.96;3.17] 11/908   661/94,561 672 908
ref
S18287
R76958		 Reis (Controls exposed to TCA), 2010 Any cardiovascular defect early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.43 [0.25;0.73] C
excluded (control group) 		26/3,297   30/1,662 56 3,297
ref
S18288
R76962		 Reis (Controls unexposed, NOS), 2010 Any cardiovascular defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.74 [0.50;1.09] 26/3,297   -/1,062,190 - 3,297
ref
S7004
R19863		 Merlob, 2009 Nonsyndromic congenital heart malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 8.78 [1.08;71.42] C 1/8   1,083/67,636 1,084 8
ref
S6429
R17651		 Oberlander, 2008 Cardiovascular congenital defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.03 [0.33;3.23] C 3/608   512/107,320 515 608
ref
S6159
R16151		 Louik, 2007 Any cardiac defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.50 [0.90;2.60] 32/78   3,692/9,506 3,724 78
ref
Total 13 studies 1.15 [1.01;1.31] 55,872 24,718
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Chan (Controls unexposed, pop general), 2024Chan, 2024 1 2.24[0.60; 8.39]8,1152771%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.16[0.92; 1.48]--20%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Bérard (Controls unexposed, sick), 2015Bérard, 2015 2 1.28[0.73; 2.23]4213665%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Furu, 2015Furu, 2015 1.13[0.93; 1.38]26,8547,24525%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.51[0.73; 3.12]12,876303%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 3 1.39[0.70; 2.74]-7573%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Huybrechts (Controls unexposed, sick), 2014Huybrechts, 2014 4 1.06[0.86; 1.32]1,60311,04522%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Nordeng (Controls unexposed, sick), 2012Nordeng, 2012 5 1.52[0.18; 12.46]8990%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.74[0.96; 3.17]6729084%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 6 0.74[0.50; 1.09]-3,2979%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Merlob, 2009Merlob, 2009 8.78[1.08; 71.42]1,08480%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Oberlander, 2008Oberlander, 2008 1.03[0.33; 3.23]5156081%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Louik, 2007Louik, 2007 1.50[0.90; 2.60]3,724785%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (13 studies) I2 = 14% 1.15[1.01; 1.31]55,87224,7180.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, pop general; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick; 5: Controls unexposed, sick; 6: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.13[0.95; 1.36]39,27224,61026%NAChan (Controls unexposed, pop general), 2024 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander, 2008 10 case control studiescase control studies 1.23[1.00; 1.52]16,6001080%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.20[0.98; 1.47]53,84012,45138%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander, 2008 Louik, 2007 9 unexposed, sickunexposed, sick 1.11[0.92; 1.34]2,03212,2670%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 4 Tags Adjustment   - No  - No 1.72[1.01; 2.90]2,2791,6233%NANordeng (Controls unexposed, sick), 2012 Colvin, 2011 Merlob, 2009 Oberlander, 2008 4   - Yes  - Yes 1.12[1.00; 1.25]53,59323,0952%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 Louik, 2007 9 Monotherapy   - no or not specified  - no or not specified 1.75[0.55; 5.56]2,69511,15250%NAHuybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Merlob, 2009 3   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.17[1.02; 1.35]48,2667,9180%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Wemakor, 2015 5   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.20[0.82; 1.76]4,9115,64850%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander, 2008 Louik, 2007 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.33[0.87; 2.03]4291,2220%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.06[0.86; 1.31]1,60311,045 -NAHuybrechts (Controls unexposed, sick), 2014 1 All studiesAll studies 1.15[1.01; 1.31]55,87224,71814%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander, 2008 Louik, 2007 130.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.62.71.2890.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Bérard (Controls unexposed, sick), 2015Furu, 2015Wemakor, 2015Ban (Controls unexposed, sick), 2014Huybrechts (Controls unexposed, sick), 2014Nordeng (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Merlob, 2009Oberlander, 2008Louik, 2007

Asymetry test p-value = 0.0492 (by Egger's regression)

slope=-0.0260 (0.0875); intercept=0.9819 (0.4442); t=2.2105; p=0.0492

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18287, 6390, 5888, 6104, 5398, 18170

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.21[1.05; 1.39]63,36627,34722%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, NOS), 2014 Nordeng (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander, 2008 Louik, 2007 12 unexposed, sick controlsunexposed, sick controls 1.11[0.92; 1.34]2,13512,2670%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.71[0.38; 1.34]1523,94063%NAChan (Controls exposed to TCA), 2024 Bérard (Controls exposed to non-Sertraline SSRI), 2015 Reis (Controls exposed to TCA), 2010 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Viswanathan (Cardiac anomalies)Viswanathan (Cardiac anomalies) 1.08[0.91; 1.28]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 Myles (Cardiac malformations)Myles (Cardiac malformations) 0.93[0.70; 1.24]63%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT5 Shen (Cardiovascular-related malformations)Shen (Cardiovascular-related malformations) 1.36[1.06; 1.74]64.4%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT12 De Vries (Congenital Heart Defects)De Vries (Congenital Heart Defects) 1.29[1.14; 1.45]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT7 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.42[1.13; 1.80]63.9%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT13 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.12[0.92; 1.35]0%-U,Sunexposed, sickT11st trimesterstudies TTT3 metaPregmetaPreg 1.15[1.01; 1.31]14%24,718----Chan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Oberlander, 2008 Louik, 2007 130.510.01.0