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

Urinary 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.
S18158
R76359		 Chan (Controls exposed to TCA), 2024 Urinary system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 2.21 [0.50;9.83] C
excluded (control group) 		13/956   2/322 15 956
ref
S18138
R76245		 Chan (Controls unexposed, general pop), 2024 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: SSRI only 1.55 [0.45;5.34]
excluded (control group) 		13/956   3,740/462,377 3,753 956
ref
S18139
R76251		 Chan (Controls unexposed, sick), 2024 Urinary system malformations 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 1.08 [0.39;3.03] 10/714   51/4,413 61 714
ref
S12482
R47064		 Benevent, 2023 Urinary system anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 1.16 [0.62;2.17] C 10/1,653   767/146,855 777 1,653
ref
S5372
R18264		 Jordan, 2016 Urinary 3 months or more before pregnancy or1st trimester excluded retrospective cohort (registry) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.31 [0.98;1.73] C
excluded (exposition period) 		50/12,962   1,496/506,155 1,546 12,962
ref
S6704
R18915		 Bérard - Non Sertraline SSRI, 2015 Urinary 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) 0.37 [0.18;0.79] 7/1,963   141/14,868 148 1,963
ref
S5881
R14672		 Ban (Controls exposed to TCA), 2014 Urinary system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.81 [0.37;1.75] C
excluded (control group) 		23/7,683   9/2,428 32 7,683
ref
S517
R14650		 Ban (Controls unexposed, disease free), 2014 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 1.20 [0.79;1.82]
excluded (control group) 		23/7,683   815/325,294 838 7,683
ref
S6700
R18877		 Ban (Controls unexposed, sick), 2014 Urinary system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Monotherapy: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.09 [0.65;1.83] C 23/7,683   37/13,432 60 7,683
ref
S6989
R19779		 Vasilakis-Scaramozza (Controls exposed to TCA), 2013 Urinary anomalies 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.88 [0.12;6.26] C
excluded (control group) 		2/1,825   2/1,608 4 1,825
ref
S5362
R16698		 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Urinary anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SSRI only 1.10 [0.30;4.90] 2/1,825   5/6,617 7 1,825
ref
S6013
R15467		 Jimenez-Solem (Controls unexposed, NOS), 2012 Congenital malformations of the internal urinary system 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.84 [0.45;1.57] 11/4,183   2,333/843,797 2,344 4,183
ref
S493
R15256		 Colvin, 2011 Congenital anomaly of urinary system 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.09 [0.66;1.79] 16/2,701   515/94,561 531 2,701
ref
S5394
R20651		 Davis, 2007 Congenital anomalies of urinary system 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.93 [0.44;1.96] 7/805   463/49,031 470 805
ref
S5424
R16104		 Louik, 2007 Renal-collecting-system defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.10 [0.70;1.90] 17/177   627/6,327 644 177
ref
Total 9 studies 0.96 [0.78;1.19] 5,042 21,704
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 1.08[0.39; 3.03]617144%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Benevent, 2023Benevent, 2023 1.16[0.62; 2.17]7771,65312%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard - Non Sertraline SSRI, 2015Bérard - Non Sertraline SSRI, 2015 0.37[0.18; 0.79]1481,9638%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 1.09[0.65; 1.83]607,68317%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Vasilakis-Scaramozza, 2013 3 1.10[0.30; 4.90]71,8252%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 4 0.84[0.45; 1.57]2,3444,18312%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 1.09[0.66; 1.79]5312,70118%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 0.93[0.44; 1.96]4708058%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Louik, 2007Louik, 2007 1.10[0.70; 1.90]64417718%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (9 studies) I2 = 0% 0.96[0.78; 1.19]5,04221,7040.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.93[0.73; 1.19]4,39821,5276%NAChan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 8 case control studiescase control studies 1.10[0.67; 1.81]644177 -NALouik, 2007 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.04[0.80; 1.34]4,77311,3440%NABenevent, 2023 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Louik, 2007 6 unexposed, sickunexposed, sick 0.75[0.36; 1.57]26910,36066%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 3 Tags Adjustment   - No  - No 1.08[0.81; 1.44]1,83812,8420%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Colvin, 2011 Davis, 2007 4   - Yes  - Yes 0.81[0.53; 1.25]3,2048,86236%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Louik, 2007 5 MatchedMatched 1.10[0.27; 4.45]71,825 -NAVasilakis-Scaramozza (Controls unexposed, NOS), 2013 1 Monotherapy   - no or not specified  - no or not specified 1.01[0.76; 1.35]3,9897,8660%NAJimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Louik, 2007 4   - SSRI only  - SSRI only 0.88[0.56; 1.38]1,05313,83842%NAChan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.66[0.23; 1.88]2089,64682%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 2   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.08[0.39; 3.01]61714 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 0.96[0.78; 1.19]5,04221,7040%NAChan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Louik, 2007 90.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.60.8550.000Chan (Controls unexposed, sick), 2024Benevent, 2023Bérard - Non Sertraline SSRI, 2015Ban (Controls unexposed, sick), 2014Vasilakis-Scaramozza (Controls unexposed, NOS), 2013Jimenez-Solem (Controls unexposed, NOS), 2012Colvin, 2011Davis, 2007Louik, 2007

Asymetry test p-value = 0.5222 (by Egger's regression)

slope=0.2241 (0.4064); intercept=-0.8371 (1.2429); t=0.6735; p=0.5222

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6989, 5881, 517, 18158, 18138

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.09[0.88; 1.35]9,36419,9830%NAChan (Controls unexposed, general pop), 2024 Benevent, 2023 Ban (Controls unexposed, disease free), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Louik, 2007 8 unexposed, sick controlsunexposed, sick controls 0.75[0.36; 1.57]26910,36066%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.98[0.52; 1.88]5110,4640%NAChan (Controls exposed to TCA), 2024 Ban (Controls exposed to TCA), 2014 Vasilakis-Scaramozza (Controls exposed to TCA), 2013 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SSRIs (Congenital anomalies of the ki ...Huang - SSRIs (Congenital anomalies of the kidney and urinary tract) 1.14[1.02; 1.27]17%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Gao - SSRI (Urinary malformations)Gao - SSRI (Urinary malformations) 1.17[0.97; 1.42]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT6 metaPregmetaPreg 0.96[0.78; 1.19]0%21,704----Chan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Vasilakis-Scaramozza (Controls unexposed, NOS), 2013 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Louik, 2007 90.510.01.0