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

Eye defects

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
R47057		 Benevent, 2023 Eye malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 0.94 [0.13;6.71] C 1/1,653   95/146,855 96 1,653
ref
S7348
R21416		 Wemakor, 2015 Eye malformations 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.13 [0.52;2.47] 7/106   821/17,805 828 106
ref
S5881
R14678		 Ban (Controls exposed to TCA), 2014 Eye malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.47 [0.13;1.68] C
excluded (control group) 		6/7,683   4/2,428 10 7,683
ref
S517
R14656		 Ban (Controls unexposed, disease free), 2014 Eye malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 0.82 [0.36;1.86]
excluded (control group) 		6/7,683   313/325,294 319 7,683
ref
S6700
R18883		 Ban (Controls unexposed, sick), 2014 Eye 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) 1.17 [0.41;3.28] C 6/7,683   9/13,432 15 7,683
ref
S6013
R15472		 Jimenez-Solem (Controls unexposed, NOS), 2012 Malformations of the eye 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.43 [0.68;3.01] 7/4,183   -/843,797 - 4,183
ref
S493
R15236		 Colvin, 2011 Congenital abnormalities of eye 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.95 [0.23;3.86] -/2,701   74/94,561 - 2,701
ref
S5394
R20640		 Davis, 2007 Congenital anomalies of eye 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.33 [0.82;2.17] 16/805   633/49,031 649 805
ref
S495
R76911		 Källén, 2007 Eye malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.93 [0.82;2.07] 6/6,555   1,088/873,876 1,094 6,555
ref
Total 7 studies 1.14 [0.87;1.49] 2,682 23,686
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 0.94[0.13; 6.71]961,6532%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.13[0.52; 2.47]82810612%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 1.17[0.41; 3.28]157,6837%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 2 1.43[0.68; 3.01]-4,18313%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.95[0.23; 3.86]-2,7014%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Davis, 2007Davis, 2007 1.33[0.82; 2.17]64980530%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Källén, 2007Källén, 2007 0.93[0.82; 2.07]1,0946,55533%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Total (7 studies) I2 = 0% 1.14[0.87; 1.49]2,68223,6860.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.14[0.86; 1.51]1,85423,5800%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Källén, 2007 6 case control studiescase control studies 1.13[0.52; 2.46]828106 -NAWemakor, 2015 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.14[0.86; 1.50]2,66716,0030%NABenevent, 2023 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Källén, 2007 6 unexposed, sickunexposed, sick 1.17[0.41; 3.28]157,683 -NABan (Controls unexposed, sick), 2014 1 Tags Adjustment   - No  - No 1.25[0.83; 1.88]76012,8420%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Colvin, 2011 Davis, 2007 4   - Yes  - Yes 1.06[0.75; 1.51]1,92210,8440%NAWemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Källén, 2007 3 Monotherapy   - no or not specified  - no or not specified 1.32[0.89; 1.96]6497,6890%NAJimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 3   - SSRI only  - SSRI only 1.00[0.69; 1.44]2,03315,9970%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Källén, 2007 4 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.17[0.41; 3.28]157,683 -NABan (Controls unexposed, sick), 2014 1 All studiesAll studies 1.14[0.87; 1.49]2,68223,6860%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Källén, 2007 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.51.2070.000Benevent, 2023Wemakor, 2015Ban (Controls unexposed, sick), 2014Jimenez-Solem (Controls unexposed, NOS), 2012Colvin, 2011Davis, 2007Källén, 2007

Asymetry test p-value = 0.9482 (by Egger's regression)

slope=0.1408 (0.1857); intercept=-0.0352 (0.5154); t=0.0683; p=0.9482

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) 1.10[0.85; 1.43]3,05123,6860%NABenevent, 2023 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Källén, 2007 7 unexposed, sick controlsunexposed, sick controls 1.17[0.41; 3.28]157,683 -NABan (Controls unexposed, sick), 2014 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls Out of scale0.47[0.13; 1.68]107,683 -NABan (Controls exposed to TCA), 2014 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Eye malformations)Gao - SSRI (Eye malformations) 1.09[0.85; 1.40]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT6 metaPregmetaPreg 1.14[0.87; 1.49]0%23,686----Benevent, 2023 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Davis, 2007 Källén, 2007 70.510.01.0