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

Genital anomalies

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.
S12482
R47065		 Benevent, 2023 Genital anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 1.67 [0.79;3.54] C 7/1,653   372/146,855 379 1,653
ref
S6704
R18914		 Bérard - Non Sertraline SSRI, 2015 Genital organs malformations 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) 0.86 [0.53;1.41] 18/1,963   160/14,868 178 1,963
ref
S5881
R14671		 Ban (Controls exposed to TCA), 2014 Genital system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.87 [0.39;1.95] C
excluded (control group) 		22/7,683   8/2,428 30 7,683
ref
S517
R14649		 Ban (Controls unexposed, disease free), 2014 Genital system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 0.71 [0.46;1.08]
excluded (control group) 		22/7,683   1,292/325,294 1,314 7,683
ref
S6700
R18876		 Ban (Controls unexposed, sick), 2014 Genital system malformations 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) 0.57 [0.35;0.92] 22/7,683   67/13,432 89 7,683
ref
S6989
R19778		 Vasilakis-Scaramozza (Controls exposed to TCA), 2013 Genital anomalies 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.32 [0.54;3.25] C
excluded (control group) 		12/1,825   8/1,608 20 1,825
ref
S5362
R16697		 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Genital anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SSRI only 0.70 [0.40;1.30] 12/1,825   60/6,617 72 1,825
ref
S6013
R15468		 Jimenez-Solem (Controls unexposed, NOS), 2012 Congenital malformations of the external genital organs 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.55 [0.99;2.44]
excluded (control group) 		19/4,183   2,504/843,797 2,523 4,183
ref
S518
R15459		 Jimenez-Solem (Controls unexposed, sick), 2012 Congenital malformations of the external genital organs 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) 1.83 [0.43;7.89] C 19/4,183   2/806 21 4,183
ref
S493
R15254		 Colvin, 2011 Congenital anomaly of genital organs 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.88 [0.57;1.37] 21/2,701   830/94,561 851 2,701
ref
S5394
R20650		 Davis, 2007 Congenital anomalies of genital organs 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.82 [0.50;1.34] 16/805   1,152/49,031 1,168 805
ref
Total 7 studies 0.84 [0.66;1.06] 2,758 20,813
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 Benevent, 2023Benevent, 2023 1.67[0.79; 3.54]3791,6539%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard - Non Sertraline SSRI, 2015Bérard - Non Sertraline SSRI, 2015 0.86[0.53; 1.41]1781,96318%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 0.57[0.35; 0.92]897,68318%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Vasilakis-Scaramozza, 2013 2 0.70[0.40; 1.30]721,82513%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Jimenez-Solem (Controls unexposed, sick), 2012Jimenez-Solem, 2012 3 1.83[0.43; 7.89]214,1833%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.88[0.57; 1.37]8512,70121%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 0.82[0.50; 1.34]1,16880518%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 17% 0.84[0.66; 1.06]2,75820,8130.25.01.0ROB: 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, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.84[0.66; 1.06]2,75820,81317%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Davis, 2007 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.90[0.67; 1.20]2,4706,98414%NABenevent, 2023 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Colvin, 2011 Davis, 2007 4 unexposed, sickunexposed, sick 0.76[0.49; 1.19]28813,82933%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 0.99[0.72; 1.37]2,4199,34212%NABenevent, 2023 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Davis, 2007 4   - Yes  - Yes 0.70[0.52; 0.94]33911,4710%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 3 MatchedMatched 0.70[0.39; 1.26]721,825 -NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 1 Monotherapy   - no or not specified  - no or not specified 0.88[0.64; 1.22]2,0407,6890%NAJimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Davis, 2007 3   - SSRI only  - SSRI only 0.82[0.55; 1.22]71813,12449%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.76[0.49; 1.19]28813,82933%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 All studiesAll studies 0.84[0.66; 1.06]2,75820,81317%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Davis, 2007 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.81.60.8930.000Benevent, 2023Bérard - Non Sertraline SSRI, 2015Ban (Controls unexposed, sick), 2014Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Jimenez-Solem (Controls unexposed, sick), 2012Colvin, 2011Davis, 2007

Asymetry test p-value = 0.1426 (by Egger's regression)

slope=-0.7827 (0.3559); intercept=2.1937 (1.2618); t=1.7385; p=0.1426

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6013, 6989, 5881, 517

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.96[0.72; 1.29]6,30718,85050%NABenevent, 2023 Ban (Controls unexposed, disease free), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 6 unexposed, sick controlsunexposed, sick controls 0.76[0.49; 1.19]28813,82933%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.05[0.58; 1.92]509,5080%NABan (Controls exposed to TCA), 2014 Vasilakis-Scaramozza (Controls exposed to TCA), 2013 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SSRIs (Congenital malformations of ge ...Huang - SSRIs (Congenital malformations of genital organs) 0.84[0.65; 1.07]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Gao - SSRI (Genital system malformations)Gao - SSRI (Genital system malformations) 0.90[0.67; 1.21]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 0.84[0.66; 1.06]17%20,813----Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Davis, 2007 70.510.01.0