Sertraline updated on 07-01-2025

Limb 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.
S7468
R22189		 Anderson, 2020 Any limb deficiency 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.85 [0.46;1.58] -/-   0/- - -
ref
S5398
R14859		 Bérard (Controls exposed to non-Sertraline SSRI), 2015 Musculoskeletal system 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.82 [0.48;1.40] C
excluded (control group) 		16/366   104/1,963 120 366
ref
S6705
R18931		 Bérard (Controls unexposed, sick), 2015 Musculoskeletal 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) 1.04 [0.63;1.72] 16/366   619/14,868 635 366
ref
S5888
R14765		 Ban (Controls unexposed, disease free), 2014 Limb malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.36 [0.57;3.28]
excluded (control group) 		-/757   1,750/325,294 - 757
ref
S5889
R14780		 Ban (Controls unexposed, sick), 2014 Limb 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) 1.29 [0.52;3.20] -/757   71/13,432 - 757
ref
S6018
R15579		 Jimenez-Solem (Controls unexposed, NOS), 2012 Congenital malformations of the limbs 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 1.00 [0.55;1.81]
excluded (control group) 		11/817   11,785/843,797 11,796 817
ref
S6023
R15632		 Jimenez-Solem (Controls unexposed, sick), 2012 Congenital malformations of the limbs 1st trimester population based cohort retrospective unexposed, sick Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 0.77 [0.35;1.71] C 11/817   14/806 25 817
ref
S7178
R20172		 Colvin, 2011 Musculoskeletal defects (ICD 754–756) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.69 [0.33;1.46] 7/908   1,052/94,561 1,059 908
ref
S6244
R16526		 Malm, 2011 Musculoskeletal malformations (including limb defects) 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.97 [0.50;1.88] -/869   -/628,607 - 869
ref
Total 6 studies 0.92 [0.70;1.21] 1,719 3,717
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 Anderson, 2020Anderson, 2020 0.85[0.46; 1.58]--19%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Bérard (Controls unexposed, sick), 2015Bérard, 2015 1 1.04[0.63; 1.72]63536629%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ban (Controls unexposed, sick), 2014Ban, 2014 2 1.29[0.52; 3.20]-7579%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Jimenez-Solem (Controls unexposed, sick), 2012Jimenez-Solem, 2012 3 0.77[0.35; 1.71]2581712%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Colvin, 2011Colvin, 2011 0.69[0.33; 1.46]1,05990813%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 0.97[0.50; 1.88]-86917%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 0% 0.92[0.70; 1.21]1,7193,7170.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.94[0.69; 1.27]1,7193,7170%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 5 case control studiescase control studies 0.85[0.46; 1.58]-- -NAAnderson, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.84[0.57; 1.24]1,0591,7770%NAAnderson, 2020 Colvin, 2011 Malm, 2011 3 unexposed, sickunexposed, sick 1.01[0.69; 1.48]6601,9400%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 Tags Adjustment   - No  - No 0.73[0.42; 1.25]1,0841,7250%NAJimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 2   - Yes  - Yes 1.00[0.73; 1.37]6351,9920%NAAnderson, 2020 Bérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Malm, 2011 4 Monotherapy   - no or not specified  - no or not specified 0.97[0.50; 1.88]-869 -NAMalm, 2011 1   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 0.96[0.65; 1.42]6353660%NAAnderson, 2020 Bérard (Controls unexposed, sick), 2015 2   - substance alone among the specific ...  - substance alone among the specific class of antidep (SSRI, SNRI, ...) 0.85[0.53; 1.35]1,0842,4820%NABan (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 3 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.01[0.69; 1.48]6601,9400%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 All studiesAll studies 0.92[0.70; 1.21]1,7193,7170%NAAnderson, 2020 Bérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.11.00.5560.000Anderson, 2020Bérard (Controls unexposed, sick), 2015Ban (Controls unexposed, sick), 2014Jimenez-Solem (Controls unexposed, sick), 2012Colvin, 2011Malm, 2011

Asymetry test p-value = 0.7709 (by Egger's regression)

slope=0.0567 (0.4552); intercept=-0.4167 (1.3368); t=0.3117; p=0.7709

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6018, 5888, 5398

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.93[0.69; 1.26]14,5963,3510%NAAnderson, 2020 Ban (Controls unexposed, disease free), 2014 Jimenez-Solem (Controls unexposed, NOS), 2012 Colvin, 2011 Malm, 2011 5 unexposed, sick controlsunexposed, sick controls 1.01[0.69; 1.48]7221,9400%NABérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.82[0.48; 1.40]120366 -NABérard (Controls exposed to non-Sertraline SSRI), 2015 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Shen (Musculoskeletal system malformations)Shen (Musculoskeletal system malformations) 0.97[0.69; 1.36]0%-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 0.92[0.70; 1.21]0%3,717----Anderson, 2020 Bérard (Controls unexposed, sick), 2015 Ban (Controls unexposed, sick), 2014 Jimenez-Solem (Controls unexposed, sick), 2012 Colvin, 2011 Malm, 2011 60.510.01.0