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

Digestive 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.
S12482
R47062		 Benevent, 2023 Digestive system anomalites 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 0.57 [0.08;4.04] C 1/1,653   157/146,855 158 1,653
ref
S6704
R18913		 Bérard - Non Sertraline SSRI, 2015 Digestive 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) 0.98 [0.63;1.52] 23/1,963   176/14,868 199 1,963
ref
S7348
R21449		 Wemakor, 2015 Digestive system anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.13 [0.69;1.87] 19/118   2,720/19,704 2,739 118
ref
S5881
R14677		 Ban (Controls exposed to TCA), 2014 Digestive system malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.16 [0.32;4.16] C
excluded (control group) 		11/7,683   3/2,428 14 7,683
ref
S517
R14655		 Ban (Controls unexposed, disease free), 2014 Digestive system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 1.43 [0.79;2.61]
excluded (control group) 		11/7,683   313/325,294 324 7,683
ref
S6700
R18882		 Ban (Controls unexposed, sick), 2014 Digestive 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) 1.75 [0.76;4.04] C 11/7,683   11/13,432 22 7,683
ref
S6013
R15466		 Jimenez-Solem (Controls unexposed, NOS), 2012 Congenital malformations of the digestive system 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.80 [1.04;3.12]
excluded (control group) 		13/4,183   1,545/843,797 1,558 4,183
ref
S518
R15457		 Jimenez-Solem (Controls unexposed, sick), 2012 Congenital malformations of the digestive system 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) 2.51 [0.33;19.21] C 13/4,183   1/806 14 4,183
ref
S493
R15240		 Colvin, 2011 Gastrointestinal defects (ICD 749–751) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.98 [0.59;1.65] 15/2,701   534/94,561 549 2,701
ref
S497
R16472		 Malm, 2011 Digestive system 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.87 [0.54;1.38] -/6,976   -/628,607 - 6,976
ref
S5394
R20649		 Davis, 2007 Other congenital anomalies of digestive system 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.37 [0.44;4.27] 3/805   136/49,031 139 805
ref
Total 8 studies 1.04 [0.83;1.30] 3,820 26,082
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 0.57[0.08; 4.04]1581,6531%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard - Non Sertraline SSRI, 2015Bérard - Non Sertraline SSRI, 2015 0.98[0.63; 1.52]1991,96326%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.13[0.69; 1.87]2,73911820%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 1.75[0.76; 4.04]227,6837%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, sick), 2012Jimenez-Solem, 2012 2 2.51[0.33; 19.21]144,1831%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.98[0.59; 1.65]5492,70119%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 0.87[0.54; 1.38]-6,97622%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Davis, 2007Davis, 2007 1.37[0.44; 4.27]1398054%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 0% 1.04[0.83; 1.30]3,82026,0820.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.79; 1.31]1,08125,9640%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 7 case control studiescase control studies 1.13[0.69; 1.86]2,739118 -NAWemakor, 2015 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.99[0.75; 1.30]3,58512,2530%NABenevent, 2023 Wemakor, 2015 Colvin, 2011 Malm, 2011 Davis, 2007 5 unexposed, sickunexposed, sick 1.15[0.78; 1.71]23513,8292%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 1.17[0.79; 1.74]88217,0250%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Davis, 2007 5   - Yes  - Yes 0.98[0.75; 1.29]2,9389,0570%NABérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Malm, 2011 3 Monotherapy   - no or not specified  - no or not specified 0.97[0.70; 1.35]70214,6650%NAJimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 4   - SSRI only  - SSRI only 1.10[0.81; 1.49]3,11811,4170%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.15[0.78; 1.71]23513,8292%NABérard - Non Sertraline SSRI, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 All studiesAll studies 1.04[0.83; 1.30]3,82026,0820%NABenevent, 2023 Bérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 80.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.51.2460.000Benevent, 2023Bérard - Non Sertraline SSRI, 2015Wemakor, 2015Ban (Controls unexposed, sick), 2014Jimenez-Solem (Controls unexposed, sick), 2012Colvin, 2011Malm, 2011Davis, 2007

Asymetry test p-value = 0.2816 (by Egger's regression)

slope=-0.1521 (0.1802); intercept=0.6639 (0.5613); t=1.1828; p=0.2816

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6013, 5881, 517

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.16[0.92; 1.45]5,46724,1190%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 7 unexposed, sick controlsunexposed, sick controls 1.15[0.78; 1.71]23513,8292%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 1.16[0.32; 4.16]147,683 -NABan (Controls exposed to TCA), 2014 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Huang - SSRIs (Abdominal birth defects)Huang - SSRIs (Abdominal birth defects) 1.33[1.16; 1.53]18%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Huang - SSRIs (Congenital anomalies of the di ...Huang - SSRIs (Congenital anomalies of the digestive system) 1.11[1.01; 1.21]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT-9 Gao - SSRI (Digestive system malformations)Gao - SSRI (Digestive system malformations) 1.23[0.94; 1.60]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 1.04[0.83; 1.30]0%26,082----Benevent, 2023 Bérard - Non Sertraline SSRI, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Davis, 2007 80.510.01.0