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

Craniosynostosis

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
R22134		 Anderson, 2020 Craniosynostosis 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.77 [1.39;2.26] -/-   0/- - -
ref
S6704
R18920		 Bérard - Non Sertraline SSRI, 2015 Craniosynostosis 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 2.43 [1.44;4.11] 19/1,963   63/14,868 82 1,963
ref
S516
R15360		 Furu (Controls unexposed, NOS), 2015 Craniosynostosis 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.92 [0.58;1.44] 23/36,772   1,210/2,266,875 1,233 36,772
ref
S7348
R21411		 Wemakor, 2015 Craniosynostosis 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 2.48 [0.99;6.22] 5/104   302/17,286 307 104
ref
S497
R16476		 Malm, 2011 Craniocynostosis 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 1.53 [0.61;3.87] -/6,976   -/628,607 - 6,976
ref
S495
R76923		 Källén, 2007 Craniostenosis early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.53 [0.56;3.33] 6/6,555   612/873,876 618 6,555
ref
S5424
R16093		 Louik, 2007 Craniosynostosis 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 0.80 [0.20;3.50] 2/162   113/5,813 115 162
ref
Total 7 studies 1.59 [1.17;2.16] 2,355 52,532
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 1.77[1.39; 2.26]--31%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bérard - Non Sertraline SSRI, 2015Bérard - Non Sertraline SSRI, 2015 2.43[1.44; 4.11]821,96318%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Furu (Controls unexposed, NOS), 2015Furu, 2015 1 0.92[0.58; 1.44]1,23336,77221%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Wemakor, 2015Wemakor, 2015 2.48[0.99; 6.22]3071049%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Malm, 2011Malm, 2011 1.53[0.61; 3.87]-6,9769%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Källén, 2007Källén, 2007 1.53[0.56; 3.33]6186,5559%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Louik, 2007Louik, 2007 0.80[0.20; 3.50]1151624%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (7 studies) I2 = 43% 1.59[1.17; 2.16]2,35552,5320.25.01.0ROB: 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 1.49[0.88; 2.51]1,93352,26660%NABérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Malm, 2011 Källén, 2007 4 case control studiescase control studies 1.77[1.40; 2.23]4222660%NAAnderson, 2020 Wemakor, 2015 Louik, 2007 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.45[1.04; 2.01]2,27350,56938%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Malm, 2011 Källén, 2007 Louik, 2007 6 unexposed, sickunexposed, sick 2.43[1.44; 4.11]821,963 -NABérard - Non Sertraline SSRI, 2015 1 Tags Adjustment   - Yes  - Yes 1.59[1.17; 2.16]2,35552,53243%NAAnderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Malm, 2011 Källén, 2007 Louik, 2007 7 Monotherapy   - no or not specified  - no or not specified 1.26[0.58; 2.75]1157,1380%NAMalm, 2011 Louik, 2007 2   - SSRI only  - SSRI only 1.65[1.15; 2.37]2,24045,39458%NAAnderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Källén, 2007 5 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 2.43[1.44; 4.11]821,963 -NABérard - Non Sertraline SSRI, 2015 1 All studiesAll studies 1.59[1.17; 2.16]2,35552,53243%NAAnderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Malm, 2011 Källén, 2007 Louik, 2007 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.72.20.8760.000Anderson, 2020Bérard - Non Sertraline SSRI, 2015Furu (Controls unexposed, NOS), 2015Wemakor, 2015Malm, 2011Källén, 2007Louik, 2007

Asymetry test p-value = 0.7322 (by Egger's regression)

slope=0.5697 (0.2553); intercept=-0.3719 (1.0273); t=0.3620; p=0.7322

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) 1.45[1.04; 2.01]2,27350,56938%NAAnderson, 2020 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Malm, 2011 Källén, 2007 Louik, 2007 6 unexposed, sick controlsunexposed, sick controls 2.43[1.44; 4.11]821,963 -NABérard - Non Sertraline SSRI, 2015 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Gao - SSRI (Craniosynostosis)Gao - SSRI (Craniosynostosis) Out of scale1.05[-9.00; -9.00]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT5 metaPregmetaPreg 1.59[1.17; 2.16]43%52,532----Anderson, 2020 Bérard - Non Sertraline SSRI, 2015 Furu (Controls unexposed, NOS), 2015 Wemakor, 2015 Malm, 2011 Källén, 2007 Louik, 2007 70.510.01.0