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

Ventricular septal defect

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
R76362		 Chan (Controls exposed to TCA), 2024 Ventral septal defect (VSD) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.12 [0.31;4.11] C
excluded (control group) 		10/956   3/322 13 956
ref
S18138
R76290		 Chan (Controls unexposed, general pop), 2024 Ventral septal defect (VSD) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: SSRI only 1.28 [0.46;3.62]
excluded (control group) 		10/956   2,586/462,377 2,596 956
ref
S18139
R76295		 Chan (Controls unexposed, sick), 2024 Ventral septal defect (VSD) 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 1.58 [0.72;3.45] 7/714   32/4,413 39 714
ref
S7467
R22102		 Anderson, 2020 Ventricular septal defect (VSD) – perimembranous type 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.96 [0.70;1.32] -/-   0/- - -
ref
S7348
R21420		 Wemakor, 2015 Ventricular septal defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.12 [0.77;1.61] 41/140   6,126/23,110 6,167 140
ref
S517
R14664		 Ban (Controls unexposed, disease free), 2014 Ventricular septal defect 1st trimester retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Monotherapy: SSRI only 0.63 [0.38;1.03] -/7,683   -/325,294 - 7,683
ref
S494
R15880		 Huybrechts (Controls unexposed, NOS), 2014 Ventricular Septal Defect 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.20 [1.04;1.39]
excluded (control group) 		201/46,144   3,212/885,115 3,413 46,144
ref
S6097
R15884		 Huybrechts (Controls unexposed, sick), 2014 Ventricular Septal Defect 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 0.99 [0.81;1.21] 155/36,783   751/180,564 906 36,783
ref
S11325
R41719		 Louik, 2014 Ventricular septal defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.30 [1.00;1.60] 102/392   2,602/10,923 2,704 392
ref
S6013
R15464		 Jimenez-Solem (Controls unexposed, NOS), 2012 Ventricular septal defects 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.62 [1.05;2.50]
excluded (control group) 		21/4,183   2,803/843,797 2,824 4,183
ref
S518
R15455		 Jimenez-Solem (Controls unexposed, sick), 2012 Ventricular septal defects 1st trimester population based cohort retrospective unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.45 [0.20;0.98] C 21/4,183   9/806 30 4,183
ref
S493
R15250		 Colvin, 2011 Ventricular septal defect 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.99 [0.44;2.23] 6/2,701   212/94,561 218 2,701
ref
S497
R16465		 Malm, 2011 Ventricular septal defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.20 [0.96;1.50] 85/6,976   5,465/628,607 5,550 6,976
ref
S5403
R16617		 Wichman, 2009 Ventricular septal defect during pregnancy (anytime or not specified) excluded retrospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.62 [0.04;10.14] C
excluded (exposition period) 		0/808   24/24,406 24 808
ref
S520
R17638		 Oberlander a, 2008 Ventricular septal defects (VSD) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 1.12 [0.50;2.52] C 6/2,625   219/107,320 225 2,625
ref
Total 10 studies 1.04 [0.90;1.22] 15,839 62,197
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 1.58[0.72; 3.45]397143%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 0.96[0.70; 1.32]--13%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.12[0.77; 1.61]6,16714011%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, disease free), 2014Ban, 2014 2 0.63[0.38; 1.03]-7,6837%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Huybrechts (Controls unexposed, sick), 2014Huybrechts, 2014 3 0.99[0.81; 1.21]90636,78320%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Louik, 2014Louik, 2014 1.30[1.00; 1.60]2,70439218%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, sick), 2012Jimenez-Solem, 2012 4 0.45[0.20; 0.98]304,1833%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.99[0.44; 2.23]2182,7013%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 1.20[0.96; 1.50]5,5506,97618%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Oberlander a, 2008Oberlander a, 2008 1.12[0.50; 2.52]2252,6253%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (10 studies) I2 = 39% 1.04[0.90; 1.22]15,83962,1970.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.97[0.77; 1.22]6,96861,66547%NAChan (Controls unexposed, sick), 2024 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 7 case control studiescase control studies 1.15[0.96; 1.38]8,87153213%NAAnderson, 2020 Wemakor, 2015 Louik, 2014 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.09[0.93; 1.28]14,86420,51725%NAAnderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Louik, 2014 Colvin, 2011 Malm, 2011 Oberlander a, 2008 7 unexposed, sickunexposed, sick 0.91[0.53; 1.57]97541,68062%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 0.78[0.44; 1.39]4739,50934%NAJimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Oberlander a, 2008 3   - Yes  - Yes 1.08[0.93; 1.25]15,36652,68839%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, sick), 2014 Louik, 2014 Malm, 2011 7 Monotherapy   - no or not specified  - no or not specified 1.08[0.87; 1.33]9,40851,03554%NAHuybrechts (Controls unexposed, sick), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 5   - SSRI only  - SSRI only 0.98[0.77; 1.25]6,43111,16221%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Oberlander a, 2008 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.45[0.20; 0.98]304,183 -NAJimenez-Solem (Controls unexposed, sick), 2012 1   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.07[0.76; 1.49]94537,49722%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2014 2 All studiesAll studies 1.04[0.90; 1.22]15,83962,19739%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, sick), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 100.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.01.00.4970.000Chan (Controls unexposed, sick), 2024Anderson, 2020Wemakor, 2015Ban (Controls unexposed, disease free), 2014Huybrechts (Controls unexposed, sick), 2014Louik, 2014Jimenez-Solem (Controls unexposed, sick), 2012Colvin, 2011Malm, 2011Oberlander a, 2008

Asymetry test p-value = 0.3118 (by Egger's regression)

slope=0.2088 (0.1457); intercept=-0.9280 (0.8595); t=1.0797; p=0.3118

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6013, 494, 18158, 18138

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.16[1.04; 1.30]23,69771,80016%NAChan (Controls unexposed, general pop), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, NOS), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 10 unexposed, sick controlsunexposed, sick controls 0.91[0.53; 1.57]97541,68062%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.12[0.31; 4.11]13956 -NAChan (Controls exposed to TCA), 2024 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Zhang - SSRI (Ventricular septal defect)Zhang - SSRI (Ventricular septal defect) 1.15[0.97; 1.36]30%-Wwhatever (meta-analysis)T11st trimesterstudies TTT7 Gao - SSRI (Ventricular septal defects)Gao - SSRI (Ventricular septal defects) 1.10[0.94; 1.29]36.2%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT8 metaPregmetaPreg 1.04[0.90; 1.22]39%62,197----Chan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, sick), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 100.510.01.0