Fluoxetine updated on 07-01-2025

Congenital heart defects

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.
S18167
R76401		 Chan (Controls exposed to TCA), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.56 [0.23;1.36] C
excluded (control group) 		9/467   11/322 20 467
ref
S18146
R76286		 Chan (Controls unexposed, pop general), 2024 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.11 [0.69;1.79] 9/467   8,107/462,377 8,116 467
ref
S13124
R50038		 Marks (Controls exposed to Bupropion), 2021 Cardiac Malformations during pregnancy (anytime or not specified) excluded retrospective cohort exposed to other treatment, sick Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.42 [0.72;2.80] C
excluded (exposition period) 		26/579   13/406 39 579
ref
S7469
R22197		 Anderson, 2020 Any heart defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.52 [1.14;2.02] -/-   0/- - -
ref
S7438
R21941		 Bérard, 2017 Circulatory system 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.52 [0.16;1.65] -/191   -/14,847 - 191
ref
S6004
R15365		 Furu, 2015 Any cardiac defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.34 [1.10;1.63] 106/6,250   26,745/2,266,875 26,851 6,250
ref
S7349
R21450		 Wemakor, 2015 Congenital heart defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.43 [0.85;2.40] 31/58   12,845/29,901 12,876 58
ref
S5882
R14690		 Ban (Controls unexposed, disease free), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.84 [0.55;1.30]
excluded (control group) 		-/3,189   2,444/325,294 - 3,189
ref
S5883
R14711		 Ban (Controls unexposed, sick), 2014 Heart congenital malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.79 [0.49;1.26] -/3,189   112/13,432 - 3,189
ref
S6102
R15924		 Huybrechts (Controls unexposed, NOS), 2014 Any cardiac malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 1.24 [1.02;1.52]
excluded (control group) 		99/11,048   6,403/885,115 6,502 11,048
ref
S6103
R15928		 Huybrechts (Controls unexposed, sick), 2014 Any cardiac malformations 1st trimester cohort unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.10 [0.87;1.40] 84/8,676   1,497/180,563 1,581 8,676
ref
S6388
R61461		 Nordeng (Controls unexposed, NOS), 2012 Cardiovascular malformations 1st trimester cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 2.26 [0.31;16.38] C
excluded (control group) 		1/51   541/61,648 542 51
ref
S7831
R61475		 Nordeng (Controls unexposed, sick), 2012 Cardiovascular malformations 1st trimester cohort unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 2.97 [0.36;24.64] C 1/51   7/1,048 8 51
ref
S7194
R20422		 Colvin, 2011 Cardiovascular defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.98 [0.74;5.33] -/291   661/94,561 - 291
ref
S18282
R76938		 Reis (Controls exposed to TCA), 2010 Any cardiovascular defect early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.76 [0.43;1.34] C
excluded (control group) 		21/1,522   30/1,662 51 1,522
ref
S18281
R76931		 Reis (Controls unexposed, NOS), 2010 Any cardiovascular defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.31 [0.85;2.02] 21/1,522   -/1,062,190 - 1,522
ref
S6419
R17630		 Merlob, 2009 Nonsyndromic congenital heart malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.92 [0.47;7.86] C 2/66   1,083/67,636 1,085 66
ref
S6733
R19036		 Diav-Citrin, 2008 Major cardiovascular anomalies 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 4.47 [1.31;15.27] 7/253   8/1,359 15 253
ref
S6426
R17645		 Oberlander, 2008 Cardiovascular congenital defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.65 [0.68;3.99] C 5/638   512/107,320 517 638
ref
S6157
R16115		 Louik, 2007 Any cardiac defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.90 [0.60;1.50] 31/92   3,693/9,492 3,724 92
ref
Total 14 studies 1.24 [1.07;1.44] 54,773 21,744
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 Chan (Controls unexposed, pop general), 2024Chan, 2024 1 1.11[0.69; 1.79]8,1164678%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.52[1.14; 2.02]--15%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Bérard, 2017Bérard, 2017 0.52[0.16; 1.65]-1912%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Furu, 2015Furu, 2015 1.34[1.10; 1.63]26,8516,25020%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.43[0.85; 2.40]12,876587%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 2 0.79[0.49; 1.26]-3,1898%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Huybrechts (Controls unexposed, sick), 2014Huybrechts, 2014 3 1.10[0.87; 1.40]1,5818,67617%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Nordeng (Controls unexposed, sick), 2012Nordeng, 2012 4 2.97[0.36; 24.64]8511%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Colvin, 2011Colvin, 2011 1.98[0.74; 5.33]-2912%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 5 1.31[0.85; 2.02]-1,5229%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Merlob, 2009Merlob, 2009 1.92[0.47; 7.86]1,085661%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Diav-Citrin, 2008Diav-Citrin, 2008 4.47[1.31; 15.27]152531%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Oberlander, 2008Oberlander, 2008 1.65[0.68; 3.99]5176383%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Louik, 2007Louik, 2007 0.90[0.60; 1.50]3,724928%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (14 studies) I2 = 28% 1.24[1.07; 1.44]54,77321,7440.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.22[1.01; 1.47]38,17321,59428%NAChan (Controls unexposed, pop general), 2024 Bérard, 2017 Furu, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Oberlander, 2008 11 case control studiescase control studies 1.28[0.93; 1.77]16,60015046%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.35[1.19; 1.54]53,1849,6371%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Oberlander, 2008 Louik, 2007 10 unexposed, sickunexposed, sick 0.97[0.72; 1.31]1,58912,10721%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 4 Tags Adjustment   - No  - No 1.88[1.06; 3.34]1,6101,0460%NANordeng (Controls unexposed, sick), 2012 Colvin, 2011 Merlob, 2009 Oberlander, 2008 4   - Yes  - Yes 1.20[1.02; 1.42]53,16320,69843%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Reis (Controls unexposed, NOS), 2010 Diav-Citrin, 2008 Louik, 2007 10 Monotherapy   - no or not specified  - no or not specified 1.85[0.86; 3.98]2,6899,04650%NAHuybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Merlob, 2009 Diav-Citrin, 2008 4   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.35[1.16; 1.56]47,8436,9660%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 5   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.10[0.82; 1.47]4,2415,73226%NABan (Controls unexposed, sick), 2014 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Oberlander, 2008 Louik, 2007 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 0.79[0.51; 1.21]83,4310%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 3   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.10[0.87; 1.40]1,5818,676 -NAHuybrechts (Controls unexposed, sick), 2014 1 All studiesAll studies 1.24[1.07; 1.44]54,77321,74428%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Oberlander, 2008 Louik, 2007 140.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.52.81.2950.000Chan (Controls unexposed, pop general), 2024Anderson, 2020Bérard, 2017Furu, 2015Wemakor, 2015Ban (Controls unexposed, sick), 2014Huybrechts (Controls unexposed, sick), 2014Nordeng (Controls unexposed, sick), 2012Colvin, 2011Reis (Controls unexposed, NOS), 2010Merlob, 2009Diav-Citrin, 2008Oberlander, 2008Louik, 2007

Asymetry test p-value = 0.5829 (by Egger's regression)

slope=0.1649 (0.1230); intercept=0.3311 (0.5867); t=0.5643; p=0.5829

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18282, 6388, 5882, 6102, 18167

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.28[1.13; 1.45]63,32723,92513%NAChan (Controls unexposed, pop general), 2024 Anderson, 2020 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Huybrechts (Controls unexposed, NOS), 2014 Nordeng (Controls unexposed, NOS), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Oberlander, 2008 Louik, 2007 13 unexposed, sick controlsunexposed, sick controls 0.97[0.72; 1.31]1,69212,10721%NABérard, 2017 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.70[0.43; 1.12]711,9890%NAChan (Controls exposed to TCA), 2024 Reis (Controls exposed to TCA), 2010 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Viswanathan (Cardiac anomalies)Viswanathan (Cardiac anomalies) 1.06[0.81; 1.39]36%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 Myles (Cardiac malformations)Myles (Cardiac malformations) 1.25[0.98; 1.60]33%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT6 Riggin (Cardiac malformations _ Case control ...Riggin (Cardiac malformations _ Case control studies) 0.63[0.39; 1.03]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT2 Riggin (Cardiac malformations _ Cohort studies)Riggin (Cardiac malformations _ Cohort studies) 1.60[1.31; 1.95]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT14 Gao (Cardiovascular malformations)Gao (Cardiovascular malformations) 1.36[1.17; 1.59]23.4%-Wwhatever (meta-analysis)T11st trimesterstudies TTT12 Grigoriadis (Cardiovascular malformations (st ...Grigoriadis (Cardiovascular malformations (studies above quality threshold)) 1.17[0.89; 1.55]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 De Vries (Congenital Heart Defects)De Vries (Congenital Heart Defects) 1.36[1.08; 1.72]40%-Wwhatever (meta-analysis)T11st trimesterstudies TTT8 Gao (Congenital heart defects)Gao (Congenital heart defects) 1.30[1.11; 1.53]29.3%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT14 Gao (Congenital heart defects)Gao (Congenital heart defects) 0.94[0.65; 1.37]41.9%-U,Sunexposed, sickT11st trimesterstudies TTT3 metaPregmetaPreg 1.24[1.07; 1.44]28%21,744----Chan (Controls unexposed, pop general), 2024 Anderson, 2020 Bérard, 2017 Furu, 2015 Wemakor, 2015 Ban (Controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2014 Nordeng (Controls unexposed, sick), 2012 Colvin, 2011 Reis (Controls unexposed, NOS), 2010 Merlob, 2009 Diav-Citrin, 2008 Oberlander, 2008 Louik, 2007 140.510.01.0