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

Caesarean

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.
S18442
R78268		 Lee (Controls exposed to TCAs), 2025 Cesarean delivery during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.03 [0.84;1.26] C
excluded (control group) 		472/1,465   194/613 666 1,465
ref
S18408
R77690		 Lee (Controls unexposed, general pop), 2025 Cesarean delivery during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.93 [0.76;1.15] 472/1,465   111,640/463,440 112,112 1,465
ref
S18131
R76222		 Raviv, 2025 Cesarean sections (elective and emergent) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.65 [1.51;1.81] C 668/2,321   20,375/103,607 21,043 2,321
ref
S14988
R61337		 Gover, 2023 Cesarean section throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.25 [0.34;4.64] C 15/21   14/21 29 21
ref
S5461
R24123		 Levy, 2020 Cesarean section throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.00 [0.47;2.13] C 17/82   17/82 34 82
ref
S11332
R41737		 Solé, 2020 C-section during pregnancy (anytime or not specified) nested case control exposed to other treatment, sick Adjustment: No Monotherapy: no or not specified 0.84 [0.23;3.08] C 4/11   36/89 40 11
ref
S7917
R24137		 Corti, 2019 Cesarean section throughout pregnancy prospective cohort unexposed, disease free Adjustment: No Monotherapy: SSRI only 1.85 [0.87;3.94] C 20/42   28/85 48 42
ref
S12918
R48999		 Gungor (Controls exposed to Mirtazapine), 2019 Surgical delivery during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.00 [0.30;3.31] C
excluded (control group) 		25/40   10/16 35 40
ref
S8158
R25125		 Gungor (Controls unexposed, disease free), 2019 Surgical delivery during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Monotherapy: SSRI only 0.89 [0.30;2.59] C
excluded (control group) 		25/40   15/23 40 40
ref
S8159
R25132		 Gungor (Controls unexposed, sick), 2019 Surgical delivery during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 0.73 [0.24;2.18] C 25/40   16/23 41 40
ref
S7921
R23964		 Giardinelli (Controls unexposed, disease free), 2018 Cesarean delivery during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Monotherapy: no or not specified 3.00 [0.84;10.67] C
excluded (control group) 		10/24   5/26 15 24
ref
S7916
R23955		 Giardinelli (Controls unexposed, sick), 2018 Cesarean delivery 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) 2.02 [0.59;6.96] C 10/24   6/23 16 24
ref
S7570
R22763		 Kivistö, 2016 Caesarean during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.15 [0.88;1.51] 73/358   4,216/24,402 4,289 358
ref
S5430
R21316		 Norby, 2016 Cesarean delivery during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.50 [1.40;1.50] -/17,736   -/718,533 - 17,736
ref
S8053
R24536		 Salisbury (Controls unexposed, disease free), 2016 Cesarean section delivery during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Monotherapy: no or not specified 1.65 [0.74;3.69] C
excluded (control group) 		18/52   16/66 34 52
ref
S8071
R24579		 Salisbury (Controls unexposed, sick), 2016 Cesarean section delivery during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.12 [0.50;2.49] C 18/52   18/56 36 52
ref
S6107
R15963		 Malm (Controls unexposed, disease free), 2015 Cesarean section during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes Monotherapy: no or not specified 1.18 [1.11;1.25]
excluded (control group) 		3,004/15,729   4,984/31,394 7,988 15,729
ref
S5374
R15947		 Malm (Controls unexposed, sick), 2015 Cesarean section 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) 0.70 [0.66;0.75] 3,004/15,729   2,387/9,652 5,391 15,729
ref
S7980
R24299		 de Vries, 2013 Caesarean section during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 1.05 [0.28;3.97] C 6/63   4/44 10 63
ref
S493
R15219		 Colvin, 2011 Caesarean (emergency and elective) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.09 [1.02;1.17] C 1,258/3,703   29,801/92,995 31,059 3,703
ref
S10064
R36608		 Mulder, 2011 Cesarean section throughout pregnancy prospective cohort unexposed, disease free Adjustment: No Monotherapy: SSRI only 2.22 [0.95;5.19] C 15/96   10/130 25 96
ref
S5379
R17686		 Roca, 2011 Cesarean section during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Matched Monotherapy: no or not specified 1.56 [0.82;2.98] C 20/84   28/168 48 84
ref
S10040
R36266		 Davidson, 2009 Caesarean section throughout pregnancy retrospective cohort unexposed, disease free Adjustment: No Matched Monotherapy: no or not specified 0.95 [0.02;50.34] C 0/21   0/20 0 21
ref
S7969
R24461		 Oberlander, 2004 Caesarean section during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Monotherapy: SSRI only 0.50 [0.13;1.85] C 5/28   7/23 12 28
ref
S510
R15163		 Casper, 2003 Cesarean delivery 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) 0.78 [0.19;3.26] C 8/31   4/13 12 31
ref
S10192
R37356		 Heikkinen - Fluoxetine only, 2003 Cesarean during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.50 [0.20;11.54] C 3/11   2/10 5 11
ref
S18242
R76540		 Heikkinen - Citalopram only, 2002 Cesarean during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 0.90 [0.05;16.60] C 1/11   1/10 2 11
ref
S490
R15185		 Chambers - Fluoxetine, 1996 Cesarean section late pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.61 [1.47;4.62] C 29/73   45/223 74 73
ref
S6197
R16355		 Pastuszak - Fluoxetine (Controls exposed to TCA), 1993 Caesarean section 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched Monotherapy: SSRI only 0.91 [0.34;2.44] C
excluded (control group) 		10/42   11/43 21 42
ref
S515
R16345		 Pastuszak - Fluoxetine (Controls unexposed, NOS), 1993 Caesarean section 1st trimester excluded prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: SSRI only 1.02 [0.50;2.05] C
excluded (exposition period) 		21/82   21/83 42 82
ref
Total 22 studies 1.22 [0.98;1.53] 174,326 42,002
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 Lee (Controls unexposed, general pop), 2025Lee, 2025 1 0.93[0.76; 1.15]112,1121,4659%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Raviv, 2025Raviv, 2025 1.65[1.51; 1.81]21,0432,3219%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Gover, 2023Gover, 2023 1.25[0.34; 4.64]29212%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Levy, 2020Levy, 2020 1.00[0.47; 2.13]34824%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Solé, 2020Solé, 2020 0.84[0.23; 3.08]40112%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Corti, 2019Corti, 2019 1.85[0.87; 3.94]48424%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Gungor (Controls unexposed, sick), 2019Gungor, 2019 2 0.73[0.24; 2.18]41403%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Giardinelli (Controls unexposed, sick), 2018Giardinelli, 2018 3 2.02[0.59; 6.96]16242%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kivistö, 2016Kivistö, 2016 1.15[0.88; 1.51]4,2893588%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Norby, 2016Norby, 2016 1.50[1.40; 1.50]-17,7369%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Salisbury (Controls unexposed, sick), 2016Salisbury, 2016 4 1.12[0.50; 2.49]36524%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Malm (Controls unexposed, sick), 2015Malm, 2015 5 0.70[0.66; 0.75]5,39115,7299%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate de Vries, 2013de Vries, 2013 1.05[0.28; 3.97]10632%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: low Colvin, 2011Colvin, 2011 1.09[1.02; 1.17]31,0593,7039%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Mulder, 2011Mulder, 2011 2.22[0.95; 5.19]25964%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Roca, 2011Roca, 2011 1.56[0.82; 2.98]48845%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Davidson, 2009Davidson, 2009 0.95[0.02; 50.34]0210%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Oberlander, 2004Oberlander, 2004 0.50[0.13; 1.85]12282%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Casper, 2003Casper, 2003 0.78[0.19; 3.26]12312%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Heikkinen - Fluoxetine only, 2003Heikkinen - Fluoxetine only, 2003 1.50[0.20; 11.54]5111%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Heikkinen - Citalopram only, 2002Heikkinen - Citalopram only, 2002 0.90[0.05; 16.60]2111%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Chambers - Fluoxetine, 1996Chambers - Fluoxetine, 1996 2.61[1.47; 4.62]74736%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (22 studies) I2 = 96% 1.22[0.98; 1.53]174,32642,0020.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, general pop; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick; 5: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.23[0.98; 1.54]174,28641,99196%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Levy, 2020 Corti, 2019 Gungor (Controls unexposed, sick), 2019 Giardinelli (Controls unexposed, sick), 2018 Kivistö, 2016 Norby, 2016 Salisbury (Controls unexposed, sick), 2016 Malm (Controls unexposed, sick), 2015 de Vries, 2013 Colvin, 2011 Mulder, 2011 Roca, 2011 Davidson, 2009 Oberlander, 2004 Casper, 2003 Heikkinen - Fluoxetine only, 2003 Heikkinen - Citalopram only, 2002 Chambers - Fluoxetine, 1996 21 case control studiescase control studies 0.84[0.23; 3.08]4011 -NASolé, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.33[1.13; 1.56]168,79026,11586%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Levy, 2020 Corti, 2019 Kivistö, 2016 Norby, 2016 de Vries, 2013 Colvin, 2011 Mulder, 2011 Roca, 2011 Davidson, 2009 Oberlander, 2004 Heikkinen - Fluoxetine only, 2003 Heikkinen - Citalopram only, 2002 Chambers - Fluoxetine, 1996 16 unexposed, sickunexposed, sick 0.72[0.62; 0.84]5,49615,8764%NAGungor (Controls unexposed, sick), 2019 Giardinelli (Controls unexposed, sick), 2018 Salisbury (Controls unexposed, sick), 2016 Malm (Controls unexposed, sick), 2015 Casper, 2003 5 exposed to other treatment, sickexposed to other treatment, sick 0.84[0.23; 3.08]4011 -NASolé, 2020 1 Tags Adjustment   - No  - No 1.40[1.18; 1.65]52,53424,45080%NARaviv, 2025 Gover, 2023 Levy, 2020 Solé, 2020 Corti, 2019 Gungor (Controls unexposed, sick), 2019 Giardinelli (Controls unexposed, sick), 2018 Norby, 2016 Salisbury (Controls unexposed, sick), 2016 de Vries, 2013 Colvin, 2011 Mulder, 2011 Roca, 2011 Davidson, 2009 Oberlander, 2004 Casper, 2003 Heikkinen - Fluoxetine only, 2003 Heikkinen - Citalopram only, 2002 Chambers - Fluoxetine, 1996 19   - Yes  - Yes 0.89[0.66; 1.20]121,79217,55289%NALee (Controls unexposed, general pop), 2025 Kivistö, 2016 Malm (Controls unexposed, sick), 2015 3 MatchedMatched 1.27[0.81; 2.00]1132190%NAGover, 2023 Levy, 2020 Roca, 2011 Davidson, 2009 Heikkinen - Citalopram only, 2002 5 Monotherapy   - no or not specified  - no or not specified 1.27[0.96; 1.67]57,78939,91097%NARaviv, 2025 Gover, 2023 Levy, 2020 Solé, 2020 Giardinelli (Controls unexposed, sick), 2018 Norby, 2016 Salisbury (Controls unexposed, sick), 2016 Malm (Controls unexposed, sick), 2015 Colvin, 2011 Roca, 2011 Davidson, 2009 Casper, 2003 Heikkinen - Fluoxetine only, 2003 Heikkinen - Citalopram only, 2002 Chambers - Fluoxetine, 1996 15   - SSRI only  - SSRI only 1.10[0.86; 1.40]116,5372,09230%NALee (Controls unexposed, general pop), 2025 Corti, 2019 Gungor (Controls unexposed, sick), 2019 Kivistö, 2016 de Vries, 2013 Mulder, 2011 Oberlander, 2004 7 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.70[0.66; 0.75]5,39115,729 -NAMalm (Controls unexposed, sick), 2015 1   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 0.96[0.50; 1.84]77920%NAGungor (Controls unexposed, sick), 2019 Salisbury (Controls unexposed, sick), 2016 2   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.35[0.53; 3.43]28550%NAGiardinelli (Controls unexposed, sick), 2018 Casper, 2003 2 All studiesAll studies 1.22[0.98; 1.53]174,32642,00296%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Levy, 2020 Solé, 2020 Corti, 2019 Gungor (Controls unexposed, sick), 2019 Giardinelli (Controls unexposed, sick), 2018 Kivistö, 2016 Norby, 2016 Salisbury (Controls unexposed, sick), 2016 Malm (Controls unexposed, sick), 2015 de Vries, 2013 Colvin, 2011 Mulder, 2011 Roca, 2011 Davidson, 2009 Oberlander, 2004 Casper, 2003 Heikkinen - Fluoxetine only, 2003 Heikkinen - Citalopram only, 2002 Chambers - Fluoxetine, 1996 220.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.02.4300.000Lee (Controls unexposed, general pop), 2025Raviv, 2025Gover, 2023Levy, 2020Solé, 2020Corti, 2019Gungor (Controls unexposed, sick), 2019Giardinelli (Controls unexposed, sick), 2018Kivistö, 2016Norby, 2016Salisbury (Controls unexposed, sick), 2016Malm (Controls unexposed, sick), 2015de Vries, 2013Colvin, 2011Mulder, 2011Roca, 2011Davidson, 2009Oberlander, 2004Casper, 2003Heikkinen - Fluoxetine only, 2003Heikkinen - Citalopram only, 2002Chambers - Fluoxetine, 1996

Asymetry test p-value = 0.8527 (by Egger's regression)

slope=0.2481 (0.0773); intercept=-0.5368 (1.2378); t=0.4337; p=0.8527

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6197, 6107, 8053, 7921, 12918, 8158, 18442

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.32[1.15; 1.51]176,86741,96086%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Levy, 2020 Corti, 2019 Gungor (Controls unexposed, disease free), 2019 Giardinelli (Controls unexposed, disease free), 2018 Kivistö, 2016 Norby, 2016 Salisbury (Controls unexposed, disease free), 2016 Malm (Controls unexposed, disease free), 2015 de Vries, 2013 Colvin, 2011 Mulder, 2011 Roca, 2011 Davidson, 2009 Oberlander, 2004 Heikkinen - Fluoxetine only, 2003 Heikkinen - Citalopram only, 2002 Chambers - Fluoxetine, 1996 20 unexposed, sick controlsunexposed, sick controls 0.72[0.62; 0.84]5,49615,8764%NAGungor (Controls unexposed, sick), 2019 Giardinelli (Controls unexposed, sick), 2018 Salisbury (Controls unexposed, sick), 2016 Malm (Controls unexposed, sick), 2015 Casper, 2003 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.02[0.84; 1.24]7411,5160%NALee (Controls exposed to TCAs), 2025 Solé, 2020 Gungor (Controls exposed to Mirtazapine), 2019 30.510.01.0