Clozapine updated on 06-10-2025

All congenital malformations (majors, minors, majors and minors, or unspecified)

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.
S14327
R56691		 Huybrechts (Controls unexposed, NOS), 2023 Major congenital malformations overall (excluding chromosomal abnormality) 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes 0.91 [0.34;2.44]
excluded (control group) 		-/-   177,165/6,455,324 - -
ref
S14326
R56679		 Huybrechts (Controls unexposed, sick), 2023 Major congenital malformations overall (excluding chromosomal abnormality) 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 1.54 [0.50;4.78] -/-   11,647/318,731 - -
ref
S2699
R11439		 Peng, 2013 Major malformations throughout pregnancy prospective cohort unexposed, disease free Adjustment: No 2.32 [0.05;119.63] C 0/33   0/76 0 33
ref
S2465
R11440		 Reis (Control exposed to FGA), 2008 Relatively severe malformations early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.16 [0.15;9.13] C
excluded (control group) 		1/18   21/435 22 18
ref
S2464
R11441		 Reis (Unexposed control, NOS), 2008 Relative severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: No 1.81 [0.24;13.59] C 1/18   30,679/973,767 30,680 18
ref
S2706
R11438		 McKenna, 2005 Major malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 4.82 [0.21;112.88] C 0/6   2/135 2 6
ref
Total 4 studies 1.79 [0.72;4.47] 30,682 57
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 Huybrechts (Controls unexposed, sick), 2023Huybrechts, 2023 1 1.54[0.50; 4.78]--66%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Peng, 2013Peng, 2013 2.32[0.05; 119.63]0335%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Reis (Unexposed control, NOS), 2008Reis, 2008 2 1.81[0.24; 13.59]30,6801821%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate McKenna, 2005McKenna, 2005 4.82[0.21; 112.88]268%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 1.79[0.72; 4.47]30,682570.510.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Unexposed control, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.79[0.72; 4.47]30,682570%NAHuybrechts (Controls unexposed, sick), 2023 Peng, 2013 Reis (Unexposed control, NOS), 2008 McKenna, 2005 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.39[0.50; 11.38]30,682570%NAPeng, 2013 Reis (Unexposed control, NOS), 2008 McKenna, 2005 3 unexposed, sickunexposed, sick 1.54[0.50; 4.76]-- -NAHuybrechts (Controls unexposed, sick), 2023 1 Tags Adjustment   - No  - No 2.39[0.50; 11.38]30,682570%NAPeng, 2013 Reis (Unexposed control, NOS), 2008 McKenna, 2005 3   - Yes  - Yes 1.54[0.50; 4.76]-- -NAHuybrechts (Controls unexposed, sick), 2023 1 All studiesAll studies 1.79[0.72; 4.47]30,682570%NAHuybrechts (Controls unexposed, sick), 2023 Peng, 2013 Reis (Unexposed control, NOS), 2008 McKenna, 2005 40.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.32.4130.000Huybrechts (Controls unexposed, sick), 2023Peng, 2013Reis (Unexposed control, NOS), 2008McKenna, 2005

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2465, 14327

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.20[0.52; 2.76]207,838570%NAHuybrechts (Controls unexposed, NOS), 2023 Peng, 2013 Reis (Unexposed control, NOS), 2008 McKenna, 2005 4 unexposed, sick controlsunexposed, sick controls 1.54[0.50; 4.76]11,638- -NAHuybrechts (Controls unexposed, sick), 2023 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.16[0.15; 9.13]2218 -NAReis (Control exposed to FGA), 2008 10.510.01.0