Selective Serotonin Reuptake Inhibitor (SSRI) updated on 07-01-2025

Cardiac septal 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.
S18158
R76361		 Chan (Controls exposed to TCA), 2024 Cardiac septal defect 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.70 [0.33;1.50] C
excluded (control group) 		21/956   10/322 31 956
ref
S18138
R76289		 Chan (Controls unexposed, general pop), 2024 Cardiac septal defect 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: SSRI only 1.46 [0.78;2.75]
excluded (control group) 		21/956   6,299/462,377 6,320 956
ref
S18139
R76294		 Chan (Controls unexposed, sick), 2024 Cardiac septal defect 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.31 [0.75;2.30] 14/714   74/4,413 88 714
ref
S7467
R22101		 Anderson, 2020 Septal defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.08 [0.88;1.32] -/-   0/- - -
ref
S6704
R18918		 Bérard - Non Sertraline SSRI, 2015 Ventricular/atrial septal defect 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.13 [0.81;1.58] 41/1,963   272/14,868 313 1,963
ref
S516
R15352		 Furu (Controls unexposed, NOS), 2015 Atrial and ventricular septal defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.17 [1.05;1.31] 376/36,772   17,503/2,266,875 17,879 36,772
ref
S7348
R21444		 Wemakor, 2015 Septal defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.36 [0.99;1.87] 64/163   8,067/25,051 8,131 163
ref
S517
R14661		 Ban (Controls unexposed, disease free), 2014 Septal defects 1st trimester retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Monotherapy: SSRI only 0.89 [0.63;1.27] -/7,683   -/325,294 - 7,683
ref
S5386
R15151		 Margulis, 2013 Septal defects (first year of life) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Matched Monotherapy: SSRI only 1.15 [0.46;2.87] 10/3,046   26/8,991 36 3,046
ref
S6999
R76906		 Reis (Controls exposed to TCA), 2010 Ventricular septal defect and/or Atrial septal defect early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.58 [0.34;1.00] C
excluded (control group) 		61/10,170   17/1,662 78 10,170
ref
S5410
R76901		 Reis (Controls unexposed, NOS), 2010 Ventricular septal defect and/or Atrial septal defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.00 [0.77;1.29] 61/10,170   -/1,062,190 - 10,170
ref
S5394
R20643		 Davis, 2007 Bulbus cordis anomalies and anomalies of cardiac septal closure 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.93 [0.50;1.73] 10/805   672/49,031 682 805
ref
S5424
R16101		 Louik, 2007 Septal defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.20 [0.80;1.80] 32/192   1,129/6,829 1,161 192
ref
Total 10 studies 1.13 [1.05;1.22] 28,290 61,508
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, sick), 2024Chan, 2024 1 1.31[0.75; 2.30]887142%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.08[0.88; 1.32]--15%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bérard - Non Sertraline SSRI, 2015Bérard - Non Sertraline SSRI, 2015 1.13[0.81; 1.58]3131,9636%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Furu (Controls unexposed, NOS), 2015Furu, 2015 2 1.17[1.05; 1.31]17,87936,77251%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.36[0.99; 1.87]8,1311636%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, disease free), 2014Ban, 2014 3 0.89[0.63; 1.27]-7,6835%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Margulis, 2013Margulis, 2013 1.15[0.46; 2.87]363,0461%ROB confusion: moderateROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 4 1.00[0.77; 1.29]-10,1709%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Davis, 2007Davis, 2007 0.93[0.50; 1.73]6828052%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Louik, 2007Louik, 2007 1.20[0.80; 1.80]1,1611924%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (10 studies) I2 = 0% 1.13[1.05; 1.22]28,29061,5080.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, NOS; 3: Controls unexposed, disease free; 4: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.12[1.02; 1.23]18,99861,1530%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Ban (Controls unexposed, disease free), 2014 Margulis, 2013 Reis (Controls unexposed, NOS), 2010 Davis, 2007 7 case control studiescase control studies 1.16[0.99; 1.36]9,2923550%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.13[1.04; 1.22]27,88958,8310%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Margulis, 2013 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Louik, 2007 8 unexposed, sickunexposed, sick 1.17[0.88; 1.57]4012,6770%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 2 Tags Adjustment   - No  - No 0.99[0.59; 1.66]7183,8510%NAMargulis, 2013 Davis, 2007 2   - Yes  - Yes 1.13[1.05; 1.23]27,57257,6570%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Reis (Controls unexposed, NOS), 2010 Louik, 2007 8 MatchedMatched 1.15[0.46; 2.87]363,046 -NAMargulis, 2013 1 Monotherapy   - no or not specified  - no or not specified 1.11[0.79; 1.56]1,8439970%NADavis, 2007 Louik, 2007 2   - SSRI only  - SSRI only 1.13[1.04; 1.23]26,44760,5110%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Margulis, 2013 Reis (Controls unexposed, NOS), 2010 8 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.13[0.81; 1.58]3131,963 -NABérard - Non Sertraline SSRI, 2015 1   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.31[0.75; 2.29]88714 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.13[1.05; 1.22]28,29061,5080%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Margulis, 2013 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Louik, 2007 100.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.11.20.5600.000Chan (Controls unexposed, sick), 2024Anderson, 2020Bérard - Non Sertraline SSRI, 2015Furu (Controls unexposed, NOS), 2015Wemakor, 2015Ban (Controls unexposed, disease free), 2014Margulis, 2013Reis (Controls unexposed, NOS), 2010Davis, 2007Louik, 2007

Asymetry test p-value = 0.5841 (by Egger's regression)

slope=0.1515 (0.0592); intercept=-0.2654 (0.4654); t=0.5703; p=0.5841

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6999, 18158, 18138

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.13[1.04; 1.23]34,26159,7870%NAChan (Controls unexposed, general pop), 2024 Anderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Margulis, 2013 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Louik, 2007 9 unexposed, sick controlsunexposed, sick controls 1.17[0.88; 1.57]4012,6770%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.62[0.40; 0.96]10911,1260%NAChan (Controls exposed to TCA), 2024 Reis (Controls exposed to TCA), 2010 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Septal defects)Gao - SSRI (Septal defects) 1.38[1.00; 1.91]67.4%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT6 Zhang - SSRI (Ventricular septal defect and/o ...Zhang - SSRI (Ventricular septal defect and/or Atrial septal defect) 1.27[1.14; 1.42]40%-Wwhatever (meta-analysis)T11st trimesterstudies TTT18 metaPregmetaPreg 1.13[1.05; 1.22]0%61,508----Chan (Controls unexposed, sick), 2024 Anderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Margulis, 2013 Reis (Controls unexposed, NOS), 2010 Davis, 2007 Louik, 2007 100.510.01.0