Fluoxetine updated on 07-01-2025

Preterm (< 37 weeks)

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.
S18436
R78148		 Lee (Controls exposed to TCAs), 2025 Preterm birth (infant born at gestational age <37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.86 [0.59;1.25] C
excluded (control group) 		59/719   58/613 117 719
ref
S18415
R77843		 Lee (Controls unexposed, general pop), 2025 Preterm birth (infant born at gestational age <37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.87 [0.66;1.14] 59/719   28,543/463,440 28,602 719
ref
S18218
R76438		 Martin, 2024 Preterm delivery (delivery at <259 days (37 weeks’)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.17 [1.09;1.26] 1,004/12,978   119,950/2,408,707 120,954 12,978
ref
S13124
R50040		 Marks (Controls exposed to Bupropion), 2021 Preterm Birth during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.18 [0.83;1.67] C 100/579   61/406 161 579
ref
S7693
R22819		 Kivistö, 2016 Preterm delivery (birth before 37 completed weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.27 [0.48;3.32] -/51   1,909/24,402 - 51
ref
S7525
R22563		 Ozturk, 2016 Preterm Births (<37 weeks) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.64 [0.09;30.88] C 0/9   8/246 8 9
ref
S7194
R20400		 Colvin, 2011 Preterm birth (<37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.31 [0.84;2.05] 45/364   7,480/92,995 7,525 364
ref
S5930
R15118		 Calderon-Margalit, 2009 Preterm delivery (before 37 weeks of gestation) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.29 [0.44;3.79] 4/36   234/2,493 238 36
ref
S6733
R19038		 Diav-Citrin, 2008 Preterm delivery (<= 36 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.44 [0.90;2.32] C 24/266   84/1,306 108 266
ref
S15005
R61432		 Chambers, 1996 Preterm (< 37 weeks’ gestation) late pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.65 [1.11;6.35] C 10/70   13/220 23 70
ref
S6952
R19651		 Pastuszak (Controls unexposed, NOS), 1993 Preterm birth (< 37 weeks of gestation) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.85 [0.27;2.63] C 6/85   7/85 13 85
ref
Total 10 studies 1.16 [1.06;1.26] 157,632 15,157
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 0.87[0.66; 1.14]28,6027199%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Martin, 2024Martin, 2024 1.17[1.09; 1.26]120,95412,97875%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Marks (Controls exposed to Bupropion), 2021Marks, 2021 2 1.18[0.83; 1.67]1615796%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kivistö, 2016Kivistö, 2016 1.27[0.48; 3.32]-511%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Ozturk, 2016Ozturk, 2016 1.64[0.09; 30.88]890%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Colvin, 2011Colvin, 2011 1.31[0.84; 2.05]7,5253644%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Calderon-Margalit, 2009Calderon-Margalit, 2009 1.29[0.44; 3.79]238361%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Diav-Citrin, 2008Diav-Citrin, 2008 1.44[0.90; 2.32]1082663%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Chambers, 1996Chambers, 1996 2.65[1.11; 6.35]23701%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Pastuszak (Controls unexposed, NOS), 1993Pastuszak, 1993 3 0.85[0.27; 2.63]13851%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Total (10 studies) I2 = 3% 1.16[1.06; 1.26]157,63215,1570.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, general pop; 2: Controls exposed to Bupropion; 3: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.16[1.06; 1.26]157,63215,1573%NALee (Controls unexposed, general pop), 2025 Martin, 2024 Marks (Controls exposed to Bupropion), 2021 Kivistö, 2016 Ozturk, 2016 Colvin, 2011 Calderon-Margalit, 2009 Diav-Citrin, 2008 Chambers, 1996 Pastuszak (Controls unexposed, NOS), 1993 10 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.16[1.01; 1.32]157,47114,57814%NALee (Controls unexposed, general pop), 2025 Martin, 2024 Kivistö, 2016 Ozturk, 2016 Colvin, 2011 Calderon-Margalit, 2009 Diav-Citrin, 2008 Chambers, 1996 Pastuszak (Controls unexposed, NOS), 1993 9 exposed to other treatment, sickexposed to other treatment, sick 1.18[0.83; 1.67]161579 -NAMarks (Controls exposed to Bupropion), 2021 1 Tags Adjustment   - No  - No 1.33[1.02; 1.72]3131,0090%NAMarks (Controls exposed to Bupropion), 2021 Ozturk, 2016 Diav-Citrin, 2008 Chambers, 1996 Pastuszak (Controls unexposed, NOS), 1993 5   - Yes  - Yes 1.12[0.99; 1.27]157,31914,14814%NALee (Controls unexposed, general pop), 2025 Martin, 2024 Kivistö, 2016 Colvin, 2011 Calderon-Margalit, 2009 5 MatchedMatched 0.85[0.27; 2.63]1385 -NAPastuszak (Controls unexposed, NOS), 1993 1 Monotherapy   - no or not specified  - no or not specified 1.60[1.09; 2.36]3773810%NAOzturk, 2016 Calderon-Margalit, 2009 Diav-Citrin, 2008 Chambers, 1996 4   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.12[1.00; 1.25]149,73014,41212%NALee (Controls unexposed, general pop), 2025 Martin, 2024 Marks (Controls exposed to Bupropion), 2021 Kivistö, 2016 Pastuszak (Controls unexposed, NOS), 1993 5   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.31[0.84; 2.05]7,525364 -NAColvin, 2011 1 All studiesAll studies 1.16[1.06; 1.26]157,63215,1573%NALee (Controls unexposed, general pop), 2025 Martin, 2024 Marks (Controls exposed to Bupropion), 2021 Kivistö, 2016 Ozturk, 2016 Colvin, 2011 Calderon-Margalit, 2009 Diav-Citrin, 2008 Chambers, 1996 Pastuszak (Controls unexposed, NOS), 1993 100.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.71.7960.000Lee (Controls unexposed, general pop), 2025Martin, 2024Marks (Controls exposed to Bupropion), 2021Kivistö, 2016Ozturk, 2016Colvin, 2011Calderon-Margalit, 2009Diav-Citrin, 2008Chambers, 1996Pastuszak (Controls unexposed, NOS), 1993

Asymetry test p-value = 0.5909 (by Egger's regression)

slope=0.1355 (0.0453); intercept=0.2363 (0.4222); t=0.5598; p=0.5909

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18436

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.16[1.01; 1.32]159,37114,57814%NALee (Controls unexposed, general pop), 2025 Martin, 2024 Kivistö, 2016 Ozturk, 2016 Colvin, 2011 Calderon-Margalit, 2009 Diav-Citrin, 2008 Chambers, 1996 Pastuszak (Controls unexposed, NOS), 1993 9 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.01[0.74; 1.39]2781,29834%NALee (Controls exposed to TCAs), 2025 Marks (Controls exposed to Bupropion), 2021 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Xing (Preterm birth)Xing (Preterm birth) 1.31[0.84; 2.06]51%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 Vlenterie (Preterm birth (delivery before 37 ...Vlenterie (Preterm birth (delivery before 37 weeks of gestation)) 1.90[1.10; 3.30]-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT8 Vlenterie (Preterm birth (delivery before 37 ...Vlenterie (Preterm birth (delivery before 37 weeks of gestation)) 1.60[1.00; 2.70]-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT8 metaPregmetaPreg 1.16[1.06; 1.26]3%15,157----Lee (Controls unexposed, general pop), 2025 Martin, 2024 Marks (Controls exposed to Bupropion), 2021 Kivistö, 2016 Ozturk, 2016 Colvin, 2011 Calderon-Margalit, 2009 Diav-Citrin, 2008 Chambers, 1996 Pastuszak (Controls unexposed, NOS), 1993 100.510.01.0