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

Late intrauterine deaths (> 22 weeks) / Stillbirths

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.
S7479
R22386		 Richardson, 2019 Intrauterine fetal death or stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.03 [0.40;2.63] C 7/658   12/1,162 19 658
ref
S5430
R21324		 Norby, 2016 Stillbirth (NOS) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.20 [1.00;1.50] -/17,736   -/718,533 - 17,736
ref
S7572
R23845		 Stephansson, 2013 Stillbirth (after 22 weeks of gestation) throughout pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.94 [0.53;1.65] 14/-   5,919/1,604,649 5,933 -
ref
S5428
R20502		 Colvin, 2012 Stillbirths during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.07 [0.72;1.59] 26/3,764   612/94,561 638 3,764
ref
S5395
R16286		 Klieger-Grossmann - Escitalopram, 2012 Stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: SSRI only 1.50 [0.25;9.07] C 3/213   2/212 5 213
ref
S7579
R23158		 Manakova, 2011 Stillbirth (NOS) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 5.02 [0.20;125.59] C 1/52   0/85 1 52
ref
S5958
R15302		 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.13 [0.37;3.48] C 5/809   8/1,467 13 809
ref
S5405
R16049		 Wen, 2006 Fetal death (stillbirth with a birth weight of R500 g or a gestational age of >20 weeks) 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: no or not specified 2.23 [1.01;4.93]
excluded (exposition period) 		11/972   17/3,878 28 972
ref
S508
R17589		 Sivojelezova - Citalopram, 2005 Stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 2.02 [0.18;22.50] C 2/132   1/132 3 132
ref
S510
R15164		 Casper, 2003 Stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.41 [0.01;21.82] C 0/31   0/13 0 31
ref
S513
R16331		 Kulin, 1998 Stillbirths 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.20 [0.01;4.15] C 0/267   2/267 2 267
ref
S490
R15187		 Chambers - Fluoxetine, 1996 Stillbirth late pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.73 [0.15;19.31] C 1/74   2/254 3 74
ref
Total 11 studies 1.15 [0.97;1.35] 6,617 23,736
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 Richardson, 2019Richardson, 2019 1.03[0.40; 2.63]196583%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Norby, 2016Norby, 2016 1.20[1.00; 1.50]-17,73666%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Stephansson, 2013Stephansson, 2013 0.94[0.53; 1.65]5,933-8%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Colvin, 2012Colvin, 2012 1.07[0.72; 1.59]6383,76417%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Klieger-Grossmann - Escitalopram, 2012Klieger-Grossmann - Escitalopram, 2012 1.50[0.25; 9.07]52131%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Manakova, 2011Manakova, 2011 5.02[0.20; 125.59]1520%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Diav-Citrin - Fluoxetine or Paroxetine, 2008Diav-Citrin - Fluoxetine or Paroxetine, 2008 1.13[0.37; 3.48]138092%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Sivojelezova - Citalopram, 2005Sivojelezova - Citalopram, 2005 2.02[0.18; 22.50]31320%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Casper, 2003Casper, 2003 0.41[0.01; 21.82]0310%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kulin, 1998Kulin, 1998 0.20[0.01; 4.15]22670%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Chambers - Fluoxetine, 1996Chambers - Fluoxetine, 1996 1.73[0.15; 19.31]3740%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (11 studies) I2 = 0% 1.15[0.97; 1.35]6,61723,7360.020.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.15[0.97; 1.35]6,61723,7360%NARichardson, 2019 Norby, 2016 Stephansson, 2013 Colvin, 2012 Klieger-Grossmann - Escitalopram, 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Sivojelezova - Citalopram, 2005 Casper, 2003 Kulin, 1998 Chambers - Fluoxetine, 1996 11 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.15[0.98; 1.36]6,61723,7050%NARichardson, 2019 Norby, 2016 Stephansson, 2013 Colvin, 2012 Klieger-Grossmann - Escitalopram, 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Sivojelezova - Citalopram, 2005 Kulin, 1998 Chambers - Fluoxetine, 1996 10 unexposed, sickunexposed, sick 0.41[0.01; 21.82]-31 -NACasper, 2003 1 Tags Adjustment   - No  - No 1.09[0.79; 1.52]6846,0000%NARichardson, 2019 Colvin, 2012 Klieger-Grossmann - Escitalopram, 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Sivojelezova - Citalopram, 2005 Casper, 2003 Kulin, 1998 Chambers - Fluoxetine, 1996 9   - Yes  - Yes 1.17[0.96; 1.41]5,93317,7360%NANorby, 2016 Stephansson, 2013 2 MatchedMatched 1.67[0.39; 7.05]83450%NAKlieger-Grossmann - Escitalopram, 2012 Sivojelezova - Citalopram, 2005 2 Monotherapy   - no or not specified  - no or not specified 1.15[0.97; 1.35]6,61223,5230%NARichardson, 2019 Norby, 2016 Stephansson, 2013 Colvin, 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Sivojelezova - Citalopram, 2005 Casper, 2003 Kulin, 1998 Chambers - Fluoxetine, 1996 10   - SSRI only  - SSRI only 1.50[0.25; 9.07]5213 -NAKlieger-Grossmann - Escitalopram, 2012 1 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.41[0.01; 21.82]-31 -NACasper, 2003 1 All studiesAll studies 1.15[0.97; 1.35]6,61723,7360%NARichardson, 2019 Norby, 2016 Stephansson, 2013 Colvin, 2012 Klieger-Grossmann - Escitalopram, 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Sivojelezova - Citalopram, 2005 Casper, 2003 Kulin, 1998 Chambers - Fluoxetine, 1996 110.020.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.92.4340.000Richardson, 2019Norby, 2016Stephansson, 2013Colvin, 2012Klieger-Grossmann - Escitalopram, 2012Manakova, 2011Diav-Citrin - Fluoxetine or Paroxetine, 2008Sivojelezova - Citalopram, 2005Casper, 2003Kulin, 1998Chambers - Fluoxetine, 1996

Asymetry test p-value = 0.7401 (by Egger's regression)

slope=0.1547 (0.0711); intercept=-0.0871 (0.2545); t=0.3421; p=0.7401

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.15[0.98; 1.36]6,61723,7050%NARichardson, 2019 Norby, 2016 Stephansson, 2013 Colvin, 2012 Klieger-Grossmann - Escitalopram, 2012 Manakova, 2011 Diav-Citrin - Fluoxetine or Paroxetine, 2008 Sivojelezova - Citalopram, 2005 Kulin, 1998 Chambers - Fluoxetine, 1996 10 unexposed, sick controlsunexposed, sick controls Out of scale0.41[0.01; 21.82]-31 -NACasper, 2003 10.510.01.0