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

Cognitive developmental disorders/delay (< 3 years old)

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.
S7492
R53812
Van der Veere, 2020 Cognition (Bayley Scales of Infant and Toddler Development (BSID)) - At 2.5 years during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Monotherapy: SSRI only 2.89 [1.39;6.01] -/61   -/41 - 61
ref
S8046
R53807
Batton, 2013 Moderate-risk range of neurodevelopmental delay with the Bayley Infant Neuro-developmental Screener (BINS) at 24 months during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free Adjustment: No Monotherapy: SSRI only 0.61 [0.15;2.44] C 5/19   7/19 12 19
ref
S7969
R53811
Oberlander, 2004 Mental developmental index from Bayley scales of infant development - At 8 months during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Monotherapy: SSRI only 0.68 [0.25;1.86] -/28   -/23 - 28
ref
S510
R53808
Casper, 2003 Mental Development Index (Bayley Scales of Infant Development tested by a clinical child psychologist) at age from 6 months to 40 months during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.64 [0.50;5.32] -/31   -/13 - 31
ref
S8013
R53809
Nulman - Fluoxetine (Controls exposed to TCA), 2002 Mental development IQ with Bayley Scales of Infant Development-II at 15 and 30 months of age throughout pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) Monotherapy: SSRI only 2.01 [0.80;5.05]
excluded (control group)
-/33   -/28 - 33
ref
S8014
R53810
Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Mental development IQ with Bayley Scales of Infant Development-II at 15 and 30 months of age throughout pregnancy prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Monotherapy: SSRI only 0.96 [0.34;2.73] -/33   -/18 - 33
ref
Total 5 studies 1.24 [0.65;2.36] 12 172
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 Van der Veere, 2020Van der Veere, 2020 2.89[1.39; 6.01]-6127%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: lowROB reporting: low Batton, 2013Batton, 2013 0.61[0.15; 2.44]121914%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Oberlander, 2004Oberlander, 2004 0.68[0.25; 1.86]-2821%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Casper, 2003Casper, 2003 1.64[0.50; 5.32]-3117%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Nulman - Fluoxetine (Controls unexposed, disease free), 2002Nulman - Fluoxetine, 2002 1 0.96[0.34; 2.73]-3320%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: lowROB reporting: moderate Total (5 studies) I2 = 48% 1.24[0.65; 2.36]121720.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.24[0.65; 2.36]1217248%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.14[0.51; 2.55]1214161%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 4 unexposed, sickunexposed, sick 1.64[0.50; 5.35]-31 -NACasper, 2003 1 Tags Adjustment   - No  - No 1.24[0.65; 2.36]1217248%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 5 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.40[0.70; 2.81]-15352%NAVan der Veere, 2020 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 4 Monotherapy   - no or not specified  - no or not specified 1.64[0.50; 5.35]-31 -NACasper, 2003 1   - SSRI only  - SSRI only 1.14[0.51; 2.55]1214161%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 4 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.64[0.50; 5.35]-31 -NACasper, 2003 1 All studiesAll studies 1.24[0.65; 2.36]1217248%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.90.8470.000Van der Veere, 2020Batton, 2013Oberlander, 2004Casper, 2003Nulman - Fluoxetine (Controls unexposed, disease free), 2002

Asymetry test p-value = 0.1288 (by Egger's regression)

slope=2.5291 (1.0819); intercept=-4.4225 (2.1247); t=2.0815; p=0.1288

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8013

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.14[0.51; 2.55]1214161%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 4 unexposed, sick controlsunexposed, sick controls 1.64[0.50; 5.35]-31 -NACasper, 2003 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.01[0.80; 5.05]-33 -NANulman - Fluoxetine (Controls exposed to TCA), 2002 10.510.01.0