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

Atrial septal defect

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.
S18158
R76363		 Chan (Controls exposed to TCA), 2024 Atrial septal defect (ASD) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.63 [0.28;1.43] C
excluded (control group) 		17/956   9/322 26 956
ref
S18138
R76291		 Chan (Controls unexposed, general pop), 2024 Atrial septal defect (ASD) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: SSRI only 1.38 [0.76;2.53]
excluded (control group) 		17/956   4,755/462,377 4,772 956
ref
S18139
R76296		 Chan (Controls unexposed, sick), 2024 Atrial septal defect (ASD) 1st 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 1.32 [0.68;2.54] 10/714   55/4,413 65 714
ref
S7467
R22105		 Anderson, 2020 Atrial septal defect (ASD) – secundum type 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.18 [0.92;1.52] -/-   0/- - -
ref
S7348
R21421		 Wemakor, 2015 Atrial septal defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.71 [1.09;2.68] 25/124   2,666/19,650 2,691 124
ref
S517
R14663		 Ban (Controls unexposed, disease free), 2014 Atrial septal defect 1st trimester retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Monotherapy: SSRI only 1.68 [0.98;2.91] -/7,683   -/325,294 - 7,683
ref
S11325
R41724		 Louik, 2014 Atrial septal defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.30 [0.90;1.80] 42/332   1,100/9,421 1,142 332
ref
S6013
R15465		 Jimenez-Solem (Controls unexposed, NOS), 2012 Atrial septal defects 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 2.60 [1.84;3.68]
excluded (control group) 		34/4,183   2,490/843,797 2,524 4,183
ref
S518
R15456		 Jimenez-Solem (Controls unexposed, sick), 2012 Atrial septal defects 1st trimester population based cohort retrospective unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.09 [0.46;2.61] C 34/4,183   6/806 40 4,183
ref
S493
R15251		 Colvin, 2011 Ostium secundum type atrial septal defect 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.73 [1.26;5.89] 7/2,701   90/94,561 97 2,701
ref
S497
R367		 Malm, 2011 Atrial septal defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.04 [0.64;1.69] 18/6,976   1,279/628,607 1,297 6,976
ref
S520
R17639		 Oberlander a, 2008 Atrial septal defects (ASD) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: SSRI only 3.28 [1.42;7.53] C 6/2,625   75/107,320 81 2,625
ref
Total 9 studies 1.43 [1.17;1.75] 5,413 25,338
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, sick), 2024Chan, 2024 1 1.32[0.68; 2.54]657148%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Anderson, 2020Anderson, 2020 1.18[0.92; 1.52]--24%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Wemakor, 2015Wemakor, 2015 1.71[1.09; 2.68]2,69112413%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Controls unexposed, disease free), 2014Ban, 2014 2 1.68[0.98; 2.91]-7,68310%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Louik, 2014Louik, 2014 1.30[0.90; 1.80]1,14233218%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, sick), 2012Jimenez-Solem, 2012 3 1.09[0.46; 2.61]404,1835%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 2.73[1.26; 5.89]972,7016%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 1.04[0.64; 1.69]1,2976,97612%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Oberlander a, 2008Oberlander a, 2008 3.28[1.42; 7.53]812,6255%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (9 studies) I2 = 32% 1.43[1.17; 1.75]5,41325,3380.510.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, disease free; 3: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.60[1.12; 2.29]1,58024,88242%NAChan (Controls unexposed, sick), 2024 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 6 case control studiescase control studies 1.29[1.07; 1.55]3,8334560%NAAnderson, 2020 Wemakor, 2015 Louik, 2014 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.49[1.17; 1.90]5,30820,44148%NAAnderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Louik, 2014 Colvin, 2011 Malm, 2011 Oberlander a, 2008 7 unexposed, sickunexposed, sick 1.23[0.73; 2.08]1054,8970%NAChan (Controls unexposed, sick), 2024 Jimenez-Solem (Controls unexposed, sick), 2012 2 Tags Adjustment   - No  - No 2.18[1.14; 4.14]2189,50945%NAJimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Oberlander a, 2008 3   - Yes  - Yes 1.29[1.10; 1.52]5,19515,8290%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Louik, 2014 Malm, 2011 6 Monotherapy   - no or not specified  - no or not specified 1.34[0.95; 1.88]2,57614,19234%NALouik, 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 4   - SSRI only  - SSRI only 1.53[1.15; 2.05]2,83711,14643%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Oberlander a, 2008 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.09[0.46; 2.61]404,183 -NAJimenez-Solem (Controls unexposed, sick), 2012 1   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.32[0.68; 2.55]65714 -NAChan (Controls unexposed, sick), 2024 1 All studiesAll studies 1.43[1.17; 1.75]5,41325,33832%NAChan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 90.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.41.40.5330.000Chan (Controls unexposed, sick), 2024Anderson, 2020Wemakor, 2015Ban (Controls unexposed, disease free), 2014Louik, 2014Jimenez-Solem (Controls unexposed, sick), 2012Colvin, 2011Malm, 2011Oberlander a, 2008

Asymetry test p-value = 0.0895 (by Egger's regression)

slope=-0.0533 (0.2017); intercept=1.7122 (0.8692); t=1.9699; p=0.0895

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6013, 18158, 18138

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.64[1.27; 2.11]12,60425,58064%NAChan (Controls unexposed, general pop), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 9 unexposed, sick controlsunexposed, sick controls 1.23[0.73; 2.08]1054,8970%NAChan (Controls unexposed, sick), 2024 Jimenez-Solem (Controls unexposed, sick), 2012 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.63[0.28; 1.43]26956 -NAChan (Controls exposed to TCA), 2024 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Zhang - SSRI (Atrial septal defect)Zhang - SSRI (Atrial septal defect) 2.06[1.40; 3.03]58%-Wwhatever (meta-analysis)T11st trimesterstudies TTT6 Gao - SSRI (Atrial septal defects)Gao - SSRI (Atrial septal defects) 1.83[1.22; 2.73]72%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT7 metaPregmetaPreg 1.43[1.17; 1.75]32%25,338----Chan (Controls unexposed, sick), 2024 Anderson, 2020 Wemakor, 2015 Ban (Controls unexposed, disease free), 2014 Louik, 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 Oberlander a, 2008 90.510.01.0