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

Oro-facial clefts

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.
S18236
R76486		 Laspro - Sertraline, 2024 Oral clefts (ICD 10 codes Q35 or Q36 or Q37) during pregnancy (anytime or not specified) excluded nested case control unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.25 [1.16;1.34]
excluded (exposition period) 		751/-   11,347/- 12,098 -
ref
S12482
R47061		 Benevent, 2023 Orofacial clefts 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 0.59 [0.08;4.23] C 1/1,653   150/146,855 151 1,653
ref
S7467
R22121		 Anderson, 2020 Any oral cleft 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.95 [0.77;1.16] -/-   0/- - -
ref
S5372
R18256		 Jordan, 2016 Oro‐facial clefts 3 months or more before pregnancy or1st trimester excluded retrospective cohort (registry) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.05 [0.68;1.60]
excluded (exposition period) 		22/12,962   861/506,155 883 12,962
ref
S5881
R14674		 Ban (Controls exposed to TCA), 2014 Orofacialcleft 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.74 [0.39;7.85] C
excluded (control group) 		11/7,683   2/2,428 13 7,683
ref
S517
R14652		 Ban (Controls unexposed, disease free), 2014 Orofacialcleft 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: SSRI only 1.06 [0.58;1.93]
excluded (control group) 		11/7,683   438/325,294 449 7,683
ref
S6700
R18879		 Ban (Controls unexposed, sick), 2014 Orofacialcleft 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) 0.92 [0.44;1.90] C 11/7,683   21/13,432 32 7,683
ref
S6013
R15475		 Jimenez-Solem (Controls unexposed, NOS), 2012 Oro-facial clefts 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.02 [0.46;2.27] 6/4,183   -/843,797 - 4,183
ref
S5394
R20647		 Davis, 2007 Cleft palate and cleft lip 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.22 [0.69;7.08] 3/805   90/49,031 93 805
ref
S495
R76913		 Källén, 2007 Orofacial cleft early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.80 [0.46;1.39] 13/6,555   2,373/873,876 2,386 6,555
ref
Total 6 studies 0.95 [0.79;1.13] 2,662 20,879
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 0.59[0.08; 4.23]1511,6531%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 0.95[0.77; 1.16]--76%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 0.92[0.44; 1.90]327,6836%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 2 1.02[0.46; 2.27]-4,1835%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Davis, 2007Davis, 2007 2.22[0.69; 7.08]938052%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Källén, 2007Källén, 2007 0.80[0.46; 1.39]2,3866,55510%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Total (6 studies) I2 = 0% 0.95[0.79; 1.13]2,66220,8790.25.01.0ROB: 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 0.95[0.66; 1.36]2,66220,8790%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Davis, 2007 Källén, 2007 5 case control studiescase control studies 0.95[0.77; 1.17]-- -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.95[0.79; 1.14]2,63013,1960%NABenevent, 2023 Anderson, 2020 Jimenez-Solem (Controls unexposed, NOS), 2012 Davis, 2007 Källén, 2007 5 unexposed, sickunexposed, sick 0.92[0.44; 1.90]327,683 -NABan (Controls unexposed, sick), 2014 1 Tags Adjustment   - No  - No 1.11[0.61; 2.01]27610,1411%NABenevent, 2023 Ban (Controls unexposed, sick), 2014 Davis, 2007 3   - Yes  - Yes 0.94[0.78; 1.13]2,38610,7380%NAAnderson, 2020 Jimenez-Solem (Controls unexposed, NOS), 2012 Källén, 2007 3 Monotherapy   - no or not specified  - no or not specified 1.33[0.65; 2.75]934,98814%NAJimenez-Solem (Controls unexposed, NOS), 2012 Davis, 2007 2   - SSRI only  - SSRI only 0.93[0.77; 1.11]2,56915,8910%NABenevent, 2023 Anderson, 2020 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) 0.92[0.44; 1.90]327,683 -NABan (Controls unexposed, sick), 2014 1 All studiesAll studies 0.95[0.79; 1.13]2,66220,8790%NABenevent, 2023 Anderson, 2020 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Davis, 2007 Källén, 2007 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.31.2040.000Benevent, 2023Anderson, 2020Ban (Controls unexposed, sick), 2014Jimenez-Solem (Controls unexposed, NOS), 2012Davis, 2007Källén, 2007

Asymetry test p-value = 0.7443 (by Egger's regression)

slope=-0.0833 (0.1161); intercept=0.1824 (0.5219); t=0.3495; p=0.7443

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) 0.96[0.81; 1.14]3,07920,8790%NABenevent, 2023 Anderson, 2020 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Davis, 2007 Källén, 2007 6 unexposed, sick controlsunexposed, sick controls 0.92[0.44; 1.90]327,683 -NABan (Controls unexposed, sick), 2014 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.74[0.39; 7.85]137,683 -NABan (Controls exposed to TCA), 2014 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Orofacial cleft)Gao - SSRI (Orofacial cleft) 1.02[0.78; 1.34]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 0.95[0.79; 1.13]0%20,879----Benevent, 2023 Anderson, 2020 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Davis, 2007 Källén, 2007 60.510.01.0