Sertraline updated on 07-01-2025

Major congenital malformations

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
R76406		 Chan (Controls exposed to TCA), 2024 Any major malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.23 [0.69;2.19] C
excluded (control group) 		26/277   25/322 51 277
ref
S18148
R76299		 Chan (Controls unexposed, pop general), 2024 Any major malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.61 [0.89;2.75] 26/277   22,628/462,377 22,654 277
ref
S7468
R41453		 Anderson, 2020 Major birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.13 [0.93;1.39] C 390/519   30,240/41,589 30,630 519
ref
S8217
R25619		 Jordan, 2016 All major congenital anomalies 3 months or more before pregnancy or1st trimester excluded retrospective cohort (registry) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.27 [0.95;1.70]
excluded (exposition period) 		47/1,374   13,536/506,155 13,583 1,374
ref
S7522
R22548		 Ozturk (Sertraline), 2016 Major congenital defects at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.10 [0.10;42.38] C 0/17   3/246 3 17
ref
S5398
R14838		 Bérard (Controls exposed to non-Sertraline SSRI), 2015 Major congenital malformations overall 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.03 [0.73;1.44] C
excluded (control group) 		45/366   236/1,963 281 366
ref
S6705
R18923		 Bérard (Controls unexposed, sick), 2015 Major congenital malformations overall 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) 1.11 [0.81;1.52] 45/366   1,651/14,868 1,696 366
ref
S6008
R15422		 Furu, 2015 Major birth defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.06 [0.93;1.22] 248/7,245   71,374/2,266,875 71,622 7,245
ref
S5888
R14763		 Ban (Controls unexposed, disease free), 2014 Major congenital anomalies 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.27 [0.85;1.89]
excluded (control group) 		-/757   8,731/325,294 - 757
ref
S5889
R14778		 Ban (Controls unexposed, sick), 2014 Major congenital anomalies 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) 1.17 [0.78;1.77] -/757   380/13,432 - 757
ref
S6390
R61464		 Nordeng (Controls unexposed, NOS), 2012 Major malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 0.80 [0.20;3.25] C
excluded (control group) 		2/99   1,550/61,648 1,552 99
ref
S7833
R61478		 Nordeng (Controls unexposed, sick), 2012 Major 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) 0.70 [0.16;2.97] C 2/99   30/1,048 32 99
ref
S7178
R20164		 Colvin, 2011 Any major birth 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, ...) 1.01 [0.72;1.40] 37/908   3,834/94,561 3,871 908
ref
S18287
R76957		 Reis (Controls exposed to TCA), 2010 Relatively severe malformation 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, ...) 0.64 [0.48;0.87] C
excluded (control group) 		100/3,297   77/1,662 177 3,297
ref
S18288
R76961		 Reis (Controls unexposed, NOS), 2010 Relatively severe malformation early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.99 [0.81;1.21] 100/3,297   -/1,062,190 - 3,297
ref
S5966
R15342		 Einarson, 2009 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.60 [0.08;4.52] C 1/61   25/928 26 61
ref
S6429
R17650		 Oberlander, 2008 Major congenital anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.00 [0.63;1.57] C 19/608   3,369/107,320 3,388 608
ref
Total 11 studies 1.07 [0.98;1.17] 133,922 14,154
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 1.61[0.89; 2.75]22,6542772%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.13[0.93; 1.39]30,63051918%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Ozturk (Sertraline), 2016Ozturk, 2016 2 2.10[0.10; 42.38]3170%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bérard (Controls unexposed, sick), 2015Bérard, 2015 3 1.11[0.81; 1.52]1,6963667%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Furu, 2015Furu, 2015 1.06[0.93; 1.22]71,6227,24539%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 4 1.17[0.78; 1.77]-7574%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Nordeng (Controls unexposed, sick), 2012Nordeng, 2012 5 0.70[0.16; 2.97]32990%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.01[0.72; 1.40]3,8719087%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 6 0.99[0.81; 1.21]-3,29718%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Einarson, 2009Einarson, 2009 0.60[0.08; 4.52]26610%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Oberlander, 2008Oberlander, 2008 1.00[0.63; 1.57]3,3886083%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (11 studies) I2 = 0% 1.07[0.98; 1.17]133,92214,1540.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, pop general; 2: Sertraline; 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 1.06[0.96; 1.16]103,29213,6350%NAChan (Controls unexposed, pop general), 2024 Ozturk (Sertraline), 2016 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander, 2008 10 case control studiescase control studies 1.13[0.93; 1.39]30,630519 -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.06[0.97; 1.17]132,19412,9320%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk (Sertraline), 2016 Furu, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander, 2008 8 unexposed, sickunexposed, sick 1.12[0.87; 1.43]1,7281,2220%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 1.08[0.92; 1.26]37,9502,2120%NAAnderson, 2020 Ozturk (Sertraline), 2016 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Einarson, 2009 Oberlander, 2008 6   - Yes  - Yes 1.07[0.96; 1.18]95,97211,9420%NAChan (Controls unexposed, pop general), 2024 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Ban (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 5 Monotherapy   - no or not specified  - no or not specified 0.77[0.26; 2.31]611770%NAOzturk (Sertraline), 2016 Nordeng (Controls unexposed, sick), 2012 Einarson, 2009 3   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.10[0.99; 1.22]126,6028,4070%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard (Controls unexposed, sick), 2015 Furu, 2015 4   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.02[0.88; 1.18]7,2595,5700%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander, 2008 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.12[0.87; 1.43]1,7281,2220%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3 All studiesAll studies 1.07[0.98; 1.17]133,92214,1540%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk (Sertraline), 2016 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander, 2008 110.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.71.8400.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Ozturk (Sertraline), 2016Bérard (Controls unexposed, sick), 2015Furu, 2015Ban (Controls unexposed, sick), 2014Nordeng (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Einarson, 2009Oberlander, 2008

Asymetry test p-value = 0.7837 (by Egger's regression)

slope=0.0567 (0.0502); intercept=0.0986 (0.3485); t=0.2828; p=0.7837

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18287, 6390, 5888, 5398, 18170

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.07[0.98; 1.17]142,55913,7880%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk (Sertraline), 2016 Furu, 2015 Ban (Controls unexposed, disease free), 2014 Nordeng (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander, 2008 10 unexposed, sick controlsunexposed, sick controls 1.12[0.87; 1.43]2,0991,2220%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.89[0.61; 1.32]5093,94067%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 Myles (Major congenital malformation)Myles (Major congenital malformation) 1.01[0.88; 1.17]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT6 Gao (Major congenital malformations)Gao (Major congenital malformations) 1.12[0.87; 1.44]0%-U,Sunexposed, sickT11st trimesterstudies TTT2 Gao (Major congenital malformations)Gao (Major congenital malformations) 1.10[0.99; 1.22]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT9 metaPregmetaPreg 1.07[0.98; 1.17]0%14,154----Chan (Controls unexposed, pop general), 2024 Anderson, 2020 Ozturk (Sertraline), 2016 Bérard (Controls unexposed, sick), 2015 Furu, 2015 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Einarson, 2009 Oberlander, 2008 110.510.01.0