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

Respiratory system 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.
S18158
R76358		 Chan (Controls exposed to TCA), 2024 Respiratory system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.18 [0.24;5.71] C
excluded (control group) 		7/956   2/322 9 956
ref
S18138
R76244		 Chan (Controls unexposed, general pop), 2024 Respiratory system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: SSRI only 7.39 [2.38;22.99]
excluded (control group) 		7/956   1,205/462,377 1,212 956
ref
S18139
R76250		 Chan (Controls unexposed, sick), 2024 Respiratory 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 2.00 [0.35;11.31] 3/714   15/4,413 18 714
ref
S12482
R47060		 Benevent, 2023 Respiratory system anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 1.18 [0.07;19.30] C 0/1,653   37/146,855 37 1,653
ref
S6704
R18912		 Bérard - Non Sertraline SSRI, 2015 Respiratory 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) 0.75 [0.36;1.55] C 8/1,963   81/14,868 89 1,963
ref
S7348
R21448		 Wemakor, 2015 Respiratory system anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.08 [0.50;2.35] 7/106   976/17,960 983 106
ref
S5881
R14680		 Ban (Controls exposed to TCA), 2014 Respiratory system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.63 [0.19;2.10] C
excluded (control group) 		8/7,683   4/2,428 12 7,683
ref
S517
R14658		 Ban (Controls unexposed, disease free), 2014 Respiratory system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 1.56 [0.77;3.15]
excluded (control group) 		8/7,683   205/325,294 213 7,683
ref
S6700
R18885		 Ban (Controls unexposed, sick), 2014 Respiratory 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) 2.80 [0.92;8.56] C 8/7,683   5/13,432 13 7,683
ref
S6013
R15474		 Jimenez-Solem (Controls unexposed, NOS), 2012 Malformations of the respiratory system 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.41 [0.67;2.98] 7/4,183   -/843,797 - 4,183
ref
S493
R15239		 Colvin, 2011 Respiratory system defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.09 [0.85;5.15] 5/2,701   84/94,561 89 2,701
ref
S497
R16469		 Malm, 2011 Respiratory tract 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.61 [0.28;1.30] -/6,976   -/628,607 - 6,976
ref
S5394
R20646		 Davis, 2007 Congenital anomalies of respiratory system 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.23 [0.03;1.68] 1/805   256/49,031 257 805
ref
Total 9 studies 1.13 [0.76;1.68] 1,486 26,784
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 2.00[0.35; 11.31]187145%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Benevent, 2023Benevent, 2023 1.18[0.07; 19.30]371,6532%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard - Non Sertraline SSRI, 2015Bérard - Non Sertraline SSRI, 2015 0.75[0.36; 1.55]891,96317%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.08[0.50; 2.35]98310616%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 2.80[0.92; 8.56]137,68310%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 3 1.41[0.67; 2.98]-4,18317%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 2.09[0.85; 5.15]892,70113%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 0.61[0.28; 1.30]-6,97616%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Davis, 2007Davis, 2007 0.23[0.03; 1.68]2578054%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (9 studies) I2 = 29% 1.13[0.76; 1.68]1,48626,7840.210.01.0ROB: 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;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.14[0.71; 1.85]50326,67837%NAChan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 8 case control studiescase control studies 1.08[0.50; 2.34]983106 -NAWemakor, 2015 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.06[0.65; 1.71]1,36616,42428%NABenevent, 2023 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 6 unexposed, sickunexposed, sick 1.42[0.56; 3.62]12010,36052%NAChan (Controls unexposed, sick), 2024 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 3 Tags Adjustment   - No  - No 1.22[0.57; 2.62]48514,80549%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Colvin, 2011 Davis, 2007 5   - Yes  - Yes 1.03[0.67; 1.58]1,00111,9791%NAChan (Controls unexposed, sick), 2024 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 4 Monotherapy   - no or not specified  - no or not specified 1.01[0.48; 2.09]34614,66557%NAJimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 4   - SSRI only  - SSRI only 1.16[0.72; 1.86]1,14012,1195%NAChan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.35[0.37; 4.88]1029,64673%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 2.00[0.35; 11.37]18714 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.13[0.76; 1.68]1,48626,78429%NAChan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 90.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.33.51.7090.000Chan (Controls unexposed, sick), 2024Benevent, 2023Bérard - Non Sertraline SSRI, 2015Wemakor, 2015Ban (Controls unexposed, sick), 2014Jimenez-Solem (Controls unexposed, NOS), 2012Colvin, 2011Malm, 2011Davis, 2007

Asymetry test p-value = 0.8788 (by Egger's regression)

slope=0.0164 (0.5662); intercept=0.1830 (1.1574); t=0.1581; p=0.8788

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5881, 517, 18158, 18138

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.39[0.80; 2.39]2,79125,06359%NAChan (Controls unexposed, general pop), 2024 Benevent, 2023 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 8 unexposed, sick controlsunexposed, sick controls 1.42[0.56; 3.62]12010,36052%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 0.79[0.31; 2.07]218,6390%NAChan (Controls exposed to TCA), 2024 Ban (Controls exposed to TCA), 2014 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SSRIs (Congenital malformations of th ...Huang - SSRIs (Congenital malformations of the respiratory system) 1.22[0.80; 1.84]42%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Gao - SSRI (Respiratory system malformations)Gao - SSRI (Respiratory system malformations) 1.14[0.66; 1.99]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 1.13[0.76; 1.68]29%26,784----Chan (Controls unexposed, sick), 2024 Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 90.510.01.0