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

Psychomotor developmental disorders/delay

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.
S17049
R71332		 Suarez (Controls unexposed, discontinuers), 2022 Developmental Coordination Disorder - ≥ 2 dates with ICD-9 Dx 315.4 - At any age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.32 [1.04;1.67] 602/115,060   136/38,038 738 115,060
ref
S17050
R71340		 Suarez (Controls unexposed, general pop), 2022 Developmental Coordination Disorder - ≥ 2 dates with ICD-9 Dx 315.4 - At any age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.16 [1.04;1.28]
excluded (control group) 		602/115,110   10,471/3,000,907 11,073 115,110
ref
S7492
R22507		 Van der Veere, 2020 Gross motor (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 2.34 [1.13;4.85] -/61   -/41 - 61
ref
S7330
R21581		 Hutchison a, 2019 Gross motor scaled scores (Bayley Scales of Infant Development) at 10 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) 1.14 [0.38;3.39] -/16   -/32 - 16
ref
S7441
R21978		 Brown (Controls unexposed, disease free), 2016 Specific developmental disorder of motor function (Finnish Hospital Discharge Register - F82) (mean: 7.73 years) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes Monotherapy: no or not specified 1.26 [0.90;1.77]
excluded (control group) 		103/15,596   99/31,207 202 15,596
ref
S7442
R21981		 Brown (Controls unexposed, sick), 2016 Specific developmental disorder of motor function (Finnish Hospital Discharge Register - F82) (mean: 7.73 years) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.18 [0.81;1.72] 103/15,596   55/9,537 158 15,596
ref
S8046
R24485		 Batton, 2013 Psychomotor Developmental Index/ Motor Composite score on the Bayley Scales of Infant Development (BSID) at 36 months during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Monotherapy: SSRI only 0.71 [0.19;2.60] -/15   -/15 - 15
ref
S7965
R24154		 Pedersen, 2010 Unable to sit without support at 6 months (interviews with the mothers) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.10 [0.76;1.64] -/-   258/362 - -
ref
S7969
R24467		 Oberlander, 2004 Psychomotor 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 2.85 [1.03;7.92] -/28   -/23 - 28
ref
S510
R18938		 Casper, 2003 Psychomotor 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) 3.87 [1.15;13.00] -/31   -/13 - 31
ref
S8013
R24392		 Nulman - Fluoxetine (Controls exposed to TCA), 2002 Psychomotor 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 1.44 [0.58;3.61]
excluded (control group) 		-/33   -/28 - 33
ref
S8014
R24397		 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Psychomotor 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 1.11 [0.39;3.14] -/33   -/18 - 33
ref
S6994
R19841		 Simon (Controls exposed to TCA), 2002 Motor delay (infants’ medical records) - unspecified age during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 3.47 [0.69;17.40] C
excluded (control group) 		6/185   2/209 8 185
ref
S492
R17429		 Simon (Controls unexposed, NOS), 2002 Motor delay (infants’ medical records) - unspecified age during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SSRI only 3.07 [0.61;15.40] 6/185   2/185 8 185
ref
Total 10 studies 1.36 [1.10;1.67] 904 131,025
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 Suarez (Controls unexposed, discontinuers), 2022Suarez, 2022 1 1.32[1.04; 1.67]738115,06034%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Van der Veere, 2020Van der Veere, 2020 2.34[1.13; 4.85]-617%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: lowROB reporting: low Hutchison a, 2019Hutchison a, 2019 1.14[0.38; 3.39]-163%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: criticalROB mesure: moderateROB reporting: moderate Brown (Controls unexposed, sick), 2016Brown, 2016 2 1.18[0.81; 1.72]15815,59620%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Batton, 2013Batton, 2013 0.71[0.19; 2.60]-152%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Pedersen, 2010Pedersen, 2010 1.10[0.76; 1.64]--20%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Oberlander, 2004Oberlander, 2004 2.85[1.03; 7.92]-284%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Casper, 2003Casper, 2003 3.87[1.15; 13.00]-313%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Nulman - Fluoxetine (Controls unexposed, disease free), 2002Nulman - Fluoxetine, 2002 3 1.11[0.39; 3.14]-334%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: lowROB reporting: moderate Simon (Controls unexposed, NOS), 2002Simon, 2002 4 3.07[0.61; 15.40]81852%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (10 studies) I2 = 17% 1.36[1.10; 1.67]904131,0250.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, discontinuers; 2: Controls unexposed, sick; 3: Controls unexposed, disease free; 4: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.36[1.10; 1.67]904131,02517%NASuarez (Controls unexposed, discontinuers), 2022 Van der Veere, 2020 Hutchison a, 2019 Brown (Controls unexposed, sick), 2016 Batton, 2013 Pedersen, 2010 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 10 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.84[1.12; 3.01]832210%NAVan der Veere, 2020 Batton, 2013 Oberlander, 2004 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 5 unexposed, sickunexposed, sick 1.26[1.06; 1.51]896130,7032%NASuarez (Controls unexposed, discontinuers), 2022 Hutchison a, 2019 Brown (Controls unexposed, sick), 2016 Pedersen, 2010 Casper, 2003 5 Tags Adjustment   - No  - No 1.79[1.12; 2.87]-18420%NAVan der Veere, 2020 Hutchison a, 2019 Batton, 2013 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 6   - Yes  - Yes 1.25[1.05; 1.49]904130,8410%NASuarez (Controls unexposed, discontinuers), 2022 Brown (Controls unexposed, sick), 2016 Pedersen, 2010 Simon (Controls unexposed, NOS), 2002 4 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.79[1.12; 2.87]-18420%NAVan der Veere, 2020 Hutchison a, 2019 Batton, 2013 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 6 MatchedMatched 3.07[0.61; 15.43]8185 -NASimon (Controls unexposed, NOS), 2002 1 Monotherapy   - no or not specified  - no or not specified 1.32[1.04; 1.66]896130,70312%NASuarez (Controls unexposed, discontinuers), 2022 Hutchison a, 2019 Brown (Controls unexposed, sick), 2016 Casper, 2003 4   - SSRI only  - SSRI only 1.50[0.98; 2.31]832232%NAVan der Veere, 2020 Batton, 2013 Pedersen, 2010 Oberlander, 2004 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 6 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.18[0.81; 1.72]15815,596 -NABrown (Controls unexposed, sick), 2016 1   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.30[0.99; 1.70]738115,10723%NASuarez (Controls unexposed, discontinuers), 2022 Hutchison a, 2019 Pedersen, 2010 Casper, 2003 4 All studiesAll studies 1.36[1.10; 1.67]904131,02517%NASuarez (Controls unexposed, discontinuers), 2022 Van der Veere, 2020 Hutchison a, 2019 Brown (Controls unexposed, sick), 2016 Batton, 2013 Pedersen, 2010 Oberlander, 2004 Casper, 2003 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 100.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.92.20.9880.000Suarez (Controls unexposed, discontinuers), 2022Van der Veere, 2020Hutchison a, 2019Brown (Controls unexposed, sick), 2016Batton, 2013Pedersen, 2010Oberlander, 2004Casper, 2003Nulman - Fluoxetine (Controls unexposed, disease free), 2002Simon (Controls unexposed, NOS), 2002

Asymetry test p-value = 0.2148 (by Egger's regression)

slope=0.1163 (0.1514); intercept=0.7785 (0.5778); t=1.3473; p=0.2148

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8013, 6994, 7441, 17050

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.32[1.04; 1.67]11,283131,02829%NASuarez (Controls unexposed, general pop), 2022 Van der Veere, 2020 Brown (Controls unexposed, disease free), 2016 Batton, 2013 Oberlander, 2004 Nulman - Fluoxetine (Controls unexposed, disease free), 2002 Simon (Controls unexposed, NOS), 2002 7 unexposed, sick controlsunexposed, sick controls 1.26[1.06; 1.51]1,145130,7032%NASuarez (Controls unexposed, discontinuers), 2022 Hutchison a, 2019 Brown (Controls unexposed, sick), 2016 Pedersen, 2010 Casper, 2003 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.78[0.81; 3.95]82180%NANulman - Fluoxetine (Controls exposed to TCA), 2002 Simon (Controls exposed to TCA), 2002 20.510.01.0