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

Neural Tube 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.
S7467
R22109		 Anderson, 2020 Any neural tube defect 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.99 [0.74;1.33] -/-   0/- - -
ref
S7348
R21447		 Wemakor, 2015 Neural tube defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.90 [0.43;1.88] 8/107   1,314/18,298 1,322 107
ref
S6013
R15471		 Jimenez-Solem (Controls unexposed, NOS), 2012 Neural Tube Defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.73 [0.10;5.21] 1/4,183   -/843,797 - 4,183
ref
S497
R16468		 Malm, 2011 Neural tube defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.85 [1.07;3.20] -/6,976   -/628,607 - 6,976
ref
S495
R76910		 Källén, 2007 Neural tube defects early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.49 [0.06;1.78] 2/6,555   707/873,876 709 6,555
ref
S5424
R16109		 Louik, 2007 Neural-tube defects 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.60 [0.20;1.40] 5/165   315/6,015 320 165
ref
Total 6 studies 1.04 [0.75;1.45] 2,351 17,986
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 0.99[0.74; 1.33]--45%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Wemakor, 2015Wemakor, 2015 0.90[0.43; 1.88]1,32210715%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Jimenez-Solem (Controls unexposed, NOS), 2012Jimenez-Solem, 2012 1 0.73[0.10; 5.21]-4,1833%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Malm, 2011Malm, 2011 1.85[1.07; 3.20]-6,97624%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Källén, 2007Källén, 2007 0.49[0.06; 1.78]7096,5554%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Louik, 2007Louik, 2007 0.60[0.20; 1.40]32016510%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 24% 1.04[0.75; 1.45]2,35117,9860.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.26[0.56; 2.85]70917,71427%NAJimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Källén, 2007 3 case control studiescase control studies 0.94[0.73; 1.23]1,6422720%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.04[0.75; 1.45]2,35117,98624%NAAnderson, 2020 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Källén, 2007 Louik, 2007 6 Tags Adjustment   - Yes  - Yes 1.04[0.75; 1.45]2,35117,98624%NAAnderson, 2020 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Källén, 2007 Louik, 2007 6 Monotherapy   - no or not specified  - no or not specified 1.09[0.46; 2.57]32011,32454%NAJimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Louik, 2007 3   - SSRI only  - SSRI only 0.96[0.73; 1.26]2,0316,6620%NAAnderson, 2020 Wemakor, 2015 Källén, 2007 3 All studiesAll studies 1.04[0.75; 1.45]2,35117,98624%NAAnderson, 2020 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Källén, 2007 Louik, 2007 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.41.2100.000Anderson, 2020Wemakor, 2015Jimenez-Solem (Controls unexposed, NOS), 2012Malm, 2011Källén, 2007Louik, 2007

Asymetry test p-value = 0.5409 (by Egger's regression)

slope=0.1899 (0.2581); intercept=-0.5927 (0.8877); t=0.6677; p=0.5409

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.75; 1.45]2,35117,98624%NAAnderson, 2020 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Källén, 2007 Louik, 2007 60.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Neural tube defects)Gao - SSRI (Neural tube defects) 1.49[1.05; 2.10]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT4 metaPregmetaPreg 1.04[0.75; 1.45]24%17,986----Anderson, 2020 Wemakor, 2015 Jimenez-Solem (Controls unexposed, NOS), 2012 Malm, 2011 Källén, 2007 Louik, 2007 60.510.01.0