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

Persistent pulmonary hypertension

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.
S18258
R76647		 Cornet - SSRIs, 2024 Persistent pulmonary hypertension of the newborn (ICD-9 747.83; ICD-10 P29.3 or treatment with nitric oxide) late pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.21 [0.66;2.22] 10/7,573   298/272,517 308 7,573
ref
S14988
R61343		 Gover, 2023 Persistant pulmonary hypertension throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.00 [0.02;52.85] C 0/21   0/21 0 21
ref
S13112
R49969		 Marks - Sertraline (Controls exposed to Bupropion), 2021 Pulmonary Hypertension during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 1.72 [0.09;33.38] C 3/1,653   0/406 3 1,653
ref
S5461
R24132		 Levy, 2020 Neonatal Persistent pulmonary hypertension throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 11.72 [0.64;215.53] C 5/82   0/82 5 82
ref
S5427
R14811		 Bérard a, 2017 Persistent pulmonary hypertension of the newborn (PPHN) 2nd and/or 3rd trimester population based cohort propective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 4.29 [1.34;13.77] -/1,537   258/141,097 - 1,537
ref
S5430
R76975		 Norby, 2016 Persistent pulmonary hypertension in the newborn (PPHN) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.30 [1.00;1.70] 89/17,736   2,051/718,533 2,140 17,736
ref
S5432
R15849		 Huybrechts (Controls unexposed, NOS), 2015 Persistent Pulmonary Hypertension of the Newborn 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: No Monotherapy: SSRI only 1.51 [1.35;1.69]
excluded (control group) 		322/102,179   7,630/3,660,380 7,952 102,179
ref
S6094
R15851		 Huybrechts (Controls unexposed, sick), 2015 Persistent Pulmonary Hypertension of the Newborn 3rd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.10 [0.94;1.29] 221/65,316   1,635/657,515 1,856 65,316
ref
S5373
R15781		 Kieler, 2012 Persistent pulmonary hypertension of the newborn 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 2.10 [1.50;3.00] 33/11,014   1,935/1,588,140 1,968 11,014
ref
S5431
R17527		 Wilson, 2011 Persistent pulmonary hyper- tension of the newborn (PPHN) 2nd and/or 3rd trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.45 [0.02;8.27] C 0/6   20/134 20 6
ref
S5410
R76982		 Reis (Controls unexposed, NOS), 2010 Persistent pulmonary hypertension of the newborn (PPHN) 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 2.56 [1.17;4.85] 9/4,759   572/1,019,514 581 4,759
ref
S5426
R14619		 Andrade, 2009 Persistent pulmonary hypertension of the newborn 3rd trimester retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: SSRI only 0.79 [0.07;6.89] -/933   -/- - 933
ref
S5403
R16616		 Wichman, 2009 Pulmonary hypertension of the newborn (PPHN) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.92 [0.05;15.27] C 0/808   16/24,406 16 808
ref
S5366
R15192		 Chambers, 2006 Persistent pulmonary hypertension of the newborn (PPHN) 2nd and/or 3rd trimester nested case control unexposed (general population or NOS) Adjustment: Yes Matched Monotherapy: SSRI only 6.10 [2.20;16.80] 14/20   363/1,193 377 20
ref
Total 13 studies 1.73 [1.26;2.37] 7,274 111,458
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 Cornet - SSRIs, 2024Cornet - SSRIs, 2024 1.21[0.66; 2.22]3087,57312%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Gover, 2023Gover, 2023 1.00[0.02; 52.85]0211%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Marks - Sertraline (Controls exposed to Bupropion), 2021Marks - Sertraline, 2021 1 1.72[0.09; 33.38]31,6531%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Levy, 2020Levy, 2020 11.72[0.64; 215.53]5821%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard a, 2017Bérard a, 2017 4.29[1.34; 13.77]-1,5376%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Norby, 2016Norby, 2016 1.30[1.00; 1.70]2,14017,73619%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Huybrechts (Controls unexposed, sick), 2015Huybrechts, 2015 2 1.10[0.94; 1.29]1,85665,31621%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kieler, 2012Kieler, 2012 2.10[1.50; 3.00]1,96811,01418%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Wilson, 2011Wilson, 2011 0.45[0.02; 8.27]2061%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 3 2.56[1.17; 4.85]5814,75910%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Andrade, 2009Andrade, 2009 0.79[0.07; 6.89]-9332%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Wichman, 2009Wichman, 2009 0.92[0.05; 15.27]168081%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Chambers, 2006Chambers, 2006 6.10[2.20; 16.80]377207%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (13 studies) I2 = 61% 1.73[1.26; 2.37]7,274111,4580.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.56[1.17; 2.06]6,877111,43254%NACornet - SSRIs, 2024 Gover, 2023 Marks - Sertraline (Controls exposed to Bupropion), 2021 Levy, 2020 Bérard a, 2017 Norby, 2016 Huybrechts (Controls unexposed, sick), 2015 Kieler, 2012 Reis (Controls unexposed, NOS), 2010 Andrade, 2009 Wichman, 2009 11 case control studiescase control studies 2.40[0.21; 27.88]3972664%NAWilson, 2011 Chambers, 2006 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.96[1.36; 2.82]5,41544,48949%NACornet - SSRIs, 2024 Gover, 2023 Levy, 2020 Bérard a, 2017 Norby, 2016 Kieler, 2012 Wilson, 2011 Reis (Controls unexposed, NOS), 2010 Andrade, 2009 Wichman, 2009 Chambers, 2006 11 unexposed, sickunexposed, sick 1.10[0.94; 1.29]1,85665,316 -NAHuybrechts (Controls unexposed, sick), 2015 1 exposed to other treatment, sickexposed to other treatment, sick 1.72[0.09; 33.38]31,653 -NAMarks - Sertraline (Controls exposed to Bupropion), 2021 1 Tags Adjustment   - No  - No 1.32[0.41; 4.25]443,5030%NAGover, 2023 Marks - Sertraline (Controls exposed to Bupropion), 2021 Levy, 2020 Wilson, 2011 Andrade, 2009 Wichman, 2009 6   - Yes  - Yes 1.79[1.26; 2.53]7,230107,95579%NACornet - SSRIs, 2024 Bérard a, 2017 Norby, 2016 Huybrechts (Controls unexposed, sick), 2015 Kieler, 2012 Reis (Controls unexposed, NOS), 2010 Chambers, 2006 7 MatchedMatched 3.95[1.34; 11.63]3821,05615%NAGover, 2023 Levy, 2020 Andrade, 2009 Chambers, 2006 4 Monotherapy   - no or not specified  - no or not specified 1.53[1.14; 2.06]4,45737,24025%NACornet - SSRIs, 2024 Gover, 2023 Levy, 2020 Norby, 2016 Kieler, 2012 Wilson, 2011 Wichman, 2009 7   - SSRI only  - SSRI only 2.36[1.06; 5.29]2,81472,56580%NABérard a, 2017 Huybrechts (Controls unexposed, sick), 2015 Reis (Controls unexposed, NOS), 2010 Andrade, 2009 Chambers, 2006 5   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 1.72[0.09; 33.38]31,653 -NAMarks - Sertraline (Controls exposed to Bupropion), 2021 1 Unexposed sick   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.10[0.94; 1.29]1,85665,316 -NAHuybrechts (Controls unexposed, sick), 2015 1 All studiesAll studies 1.73[1.26; 2.37]7,274111,45861%NACornet - SSRIs, 2024 Gover, 2023 Marks - Sertraline (Controls exposed to Bupropion), 2021 Levy, 2020 Bérard a, 2017 Norby, 2016 Huybrechts (Controls unexposed, sick), 2015 Kieler, 2012 Wilson, 2011 Reis (Controls unexposed, NOS), 2010 Andrade, 2009 Wichman, 2009 Chambers, 2006 130.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.32.4290.000Cornet - SSRIs, 2024Gover, 2023Marks - Sertraline (Controls exposed to Bupropion), 2021Levy, 2020Bérard a, 2017Norby, 2016Huybrechts (Controls unexposed, sick), 2015Kieler, 2012Wilson, 2011Reis (Controls unexposed, NOS), 2010Andrade, 2009Wichman, 2009Chambers, 2006

Asymetry test p-value = 0.1126 (by Egger's regression)

slope=0.1355 (0.1218); intercept=0.9521 (0.5523); t=1.7241; p=0.1126

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5432

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.75[1.38; 2.23]13,616146,66846%NACornet - SSRIs, 2024 Gover, 2023 Levy, 2020 Bérard a, 2017 Norby, 2016 Huybrechts (Controls unexposed, NOS), 2015 Kieler, 2012 Wilson, 2011 Reis (Controls unexposed, NOS), 2010 Andrade, 2009 Wichman, 2009 Chambers, 2006 12 unexposed, sick controlsunexposed, sick controls 1.10[0.94; 1.29]1,85665,316 -NAHuybrechts (Controls unexposed, sick), 2015 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.72[0.09; 33.38]31,653 -NAMarks - Sertraline (Controls exposed to Bupropion), 2021 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 McDonagh - SSRI (Persistent pulmonary hyperte ...McDonagh - SSRI (Persistent pulmonary hypertension) 2.72[1.63; 4.54]NA-U,GPunexposed (general population or NOS)Latelate pregnancystudies TTT3 Ng - SSRI (Persistent pulmonary hypertension ...Ng - SSRI (Persistent pulmonary hypertension of newborn) 1.52[1.04; 2.00]84%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT8 Grigoriadis - SSRI (Persistent pulmonary hype ...Grigoriadis - SSRI (Persistent pulmonary hypertension of the newborn) 1.55[0.79; 3.04]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT2 Grigoriadis - SSRI (Persistent pulmonary hype ...Grigoriadis - SSRI (Persistent pulmonary hypertension of the newborn) 3.33[1.58; 7.02]0%-Wwhatever (meta-analysis)Allthroughout pregnancystudies TTT2 Grigoriadis - SSRI (Persistent pulmonary hype ...Grigoriadis - SSRI (Persistent pulmonary hypertension of the newborn) 2.50[1.32; 4.73]51.9%-Wwhatever (meta-analysis)Latelate pregnancystudies TTT5 Grigoriadis - SSRI (Persistent pulmonary hype ...Grigoriadis - SSRI (Persistent pulmonary hypertension of the newborn) 1.23[0.58; 2.60]77.8%-Wwhatever (meta-analysis)Earlyearly pregnancystudies TTT3 metaPregmetaPreg 1.73[1.26; 2.37]61%111,458----Cornet - SSRIs, 2024 Gover, 2023 Marks - Sertraline (Controls exposed to Bupropion), 2021 Levy, 2020 Bérard a, 2017 Norby, 2016 Huybrechts (Controls unexposed, sick), 2015 Kieler, 2012 Wilson, 2011 Reis (Controls unexposed, NOS), 2010 Andrade, 2009 Wichman, 2009 Chambers, 2006 130.510.01.0