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

Hypospadias

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.
S7467
R22129		 Anderson, 2020 Hypospadias, 2nd or 3rd degree 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.02 [0.78;1.32] -/-   0/- - -
ref
S516
R15357		 Furu (Controls unexposed, NOS), 2015 Hypospadias 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.99 [0.79;1.25] 79/36,772   4,526/2,266,875 4,605 36,772
ref
S7348
R21407		 Wemakor, 2015 Hypospadias 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.34 [0.86;2.09] 25/124   3,016/20,000 3,041 124
ref
S493
R15255		 Colvin, 2011 Hypospadias and epispadias 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.00 [0.53;1.88] 10/2,701   349/94,561 359 2,701
ref
S6999
R76907		 Reis (Controls exposed to TCA), 2010 Hypospadias early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.69 [0.33;1.43] C
excluded (control group) 		38/10,170   9/1,662 47 10,170
ref
S5410
R76902		 Reis (Controls unexposed, NOS), 2010 Hypospadias early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.30 [0.94;1.80] 38/10,170   -/1,062,190 - 10,170
ref
S5424
R16105		 Louik, 2007 Hypospadias 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.20 [0.60;2.20] 14/174   483/6,183 497 174
ref
Total 6 studies 1.09 [0.95;1.25] 8,502 49,941
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 Anderson, 2020Anderson, 2020 1.02[0.78; 1.32]--27%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Furu (Controls unexposed, NOS), 2015Furu, 2015 1 0.99[0.79; 1.25]4,60536,77236%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.34[0.86; 2.09]3,04112410%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Colvin, 2011Colvin, 2011 1.00[0.53; 1.88]3592,7015%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 2 1.30[0.94; 1.80]-10,17018%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Louik, 2007Louik, 2007 1.20[0.60; 2.20]4971744%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 0% 1.09[0.95; 1.25]8,50249,9410.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.08[0.90; 1.29]4,96449,6430%NAFuru (Controls unexposed, NOS), 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 3 case control studiescase control studies 1.11[0.89; 1.37]3,5382980%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.09[0.95; 1.25]8,50249,9410%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Louik, 2007 6 Tags Adjustment   - No  - No 1.00[0.53; 1.88]3592,701 -NAColvin, 2011 1   - Yes  - Yes 1.09[0.95; 1.26]8,14347,2400%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Reis (Controls unexposed, NOS), 2010 Louik, 2007 5 Monotherapy   - no or not specified  - no or not specified 1.09[0.69; 1.72]8562,8750%NAColvin, 2011 Louik, 2007 2   - SSRI only  - SSRI only 1.09[0.94; 1.26]7,64647,0660%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Reis (Controls unexposed, NOS), 2010 4 All studiesAll studies 1.09[0.95; 1.25]8,50249,9410%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Louik, 2007 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-0.80.90.3980.000Anderson, 2020Furu (Controls unexposed, NOS), 2015Wemakor, 2015Colvin, 2011Reis (Controls unexposed, NOS), 2010Louik, 2007

Asymetry test p-value = 0.3525 (by Egger's regression)

slope=-0.0620 (0.1500); intercept=0.9173 (0.8726); t=1.0512; p=0.3525

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6999

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.09[0.95; 1.25]8,53149,9410%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Louik, 2007 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.69[0.33; 1.43]4710,170 -NAReis (Controls exposed to TCA), 2010 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Hypospadias)Gao - SSRI (Hypospadias) 1.19[0.93; 1.51]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT3 metaPregmetaPreg 1.09[0.95; 1.25]0%49,941----Anderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Louik, 2007 60.510.01.0