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

Ear, face and neck 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
R47058		 Benevent, 2023 Ear, face and neck anomalies 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 0.46 [0.03;7.49] C 0/1,653   95/146,855 95 1,653
ref
S7348
R21418		 Wemakor, 2015 Ear, face and neck 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.71 [0.22;2.25] 3/102   743/17,727 746 102
ref
S5881
R14681		 Ban (Controls exposed to TCA), 2014 Ear, face, and neck malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.32 [0.01;15.93] C
excluded (control group) 		0/7,683   0/2,428 0 7,683
ref
S517
R14659		 Ban (Controls unexposed, disease free), 2014 Ear, face, and neck malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No Monotherapy: SSRI only 0.25 [0.02;4.09] C
excluded (control group) 		0/7,683   83/325,294 83 7,683
ref
S6700
R18886		 Ban (Controls unexposed, sick), 2014 Ear, face, and neck 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) 0.12 [0.01;2.04] C 0/7,683   7/13,432 7 7,683
ref
S6013
R15473		 Jimenez-Solem (Controls unexposed, NOS), 2012 Malformations of the ear, face and neck 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 2.36 [0.58;9.61] 2/4,183   -/843,797 - 4,183
ref
S493
R15237		 Colvin, 2011 Congenital anomalies of ear, face, and neck 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.25 [0.62;2.54] 8/2,701   224/94,561 232 2,701
ref
S5394
R20642		 Davis, 2007 Congenital anomalies of ear, face, and neck 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.83 [0.27;2.60] 3/805   208/49,031 211 805
ref
Total 6 studies 1.03 [0.64;1.67] 1,291 17,127
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 0.46[0.03; 7.49]951,6533%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 0.71[0.22; 2.25]74610217%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 0.12[0.01; 2.04]77,6833%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 2 2.36[0.58; 9.61]-4,18312%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 1.25[0.62; 2.54]2322,70147%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 0.83[0.27; 2.60]21180518%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 1.03[0.64; 1.67]1,29117,1270.05.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.10[0.62; 1.94]54517,0255%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 5 case control studiescase control studies 0.71[0.22; 2.27]746102 -NAWemakor, 2015 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.10[0.67; 1.79]1,2849,4440%NABenevent, 2023 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 5 unexposed, sickunexposed, sick 0.12[0.01; 2.04]77,683 -NABan (Controls unexposed, sick), 2014 1 Tags Adjustment   - No  - No 0.98[0.55; 1.74]54512,8420%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Colvin, 2011 Davis, 2007 4   - Yes  - Yes 1.21[0.38; 3.90]7464,28540%NAWemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 2 Monotherapy   - no or not specified  - no or not specified 1.25[0.72; 2.17]4437,6890%NAJimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 3   - SSRI only  - SSRI only 0.54[0.20; 1.47]8489,4380%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 3 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.12[0.01; 2.04]77,683 -NABan (Controls unexposed, sick), 2014 1 All studiesAll studies 1.03[0.64; 1.67]1,29117,1270%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 60.05.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.43.51.7530.000Benevent, 2023Wemakor, 2015Ban (Controls unexposed, sick), 2014Jimenez-Solem (Controls unexposed, NOS), 2012Colvin, 2011Davis, 2007

Asymetry test p-value = 0.2140 (by Egger's regression)

slope=0.6969 (0.5010); intercept=-1.2255 (0.8304); t=1.4758; p=0.2140

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5881, 517

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.05[0.65; 1.70]1,36717,1270%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 6 unexposed, sick controlsunexposed, sick controls Out of scale0.12[0.01; 2.04]77,683 -NABan (Controls unexposed, sick), 2014 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls Out of scale0.32[0.01; 15.93]-7,683 -NABan (Controls exposed to TCA), 2014 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Ear, face and neck malformations)Gao - SSRI (Ear, face and neck malformations) 1.06[0.64; 1.76]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 1.03[0.64; 1.67]0%17,127----Benevent, 2023 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 60.510.01.0