Risperidone Paliperidone 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.
S18399
R77627		 Chan (Controls exposed to FGA), 2024 Major congenital malformations at least 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.71 [0.71;4.11] C
excluded (control group) 		7/69   26/420 33 69
ref
S18342
R77628		 Chan (Controls unexposed, general pop), 2024 Major congenital malformations at least 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes 2.35 [0.61;11.91]
excluded (control group) 		7/69   22,929/464,017 22,936 69
ref
S18396
R77629		 Chan (Controls unexposed, sick), 2024 Major congenital malformations at least 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes 3.09 [0.62;27.00] 6/49   385/6,476 391 49
ref
S14306
R56439		 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 1.19 [1.00;1.41]
excluded (control group) 		134/2,798   177,165/6,455,324 177,299 2,798
ref
S14307
R56451		 Huybrechts (Controls unexposed, sick), 2023 Major congenital malformations overall (excluding chromosomal abnormality) 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 1.30 [1.08;1.55] 119/2,270   11,647/318,731 11,766 2,270
ref
S2481
R11410		 Raguideau, 2017 26 major malformations early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.90 [1.00;3.60] 10/507   18,682/1,888,130 18,692 507
ref
S3898
R11408		 Ozturk, 2016 Major birth defects during pregnancy (anytime or not specified) excluded retrospective cohort unexposed (general population or NOS) Adjustment: No 23.10 [0.79;671.66] C
excluded (exposition period) 		0/2   3/246 3 2
ref
S2700
R11409		 Peng, 2013 Major malformations throughout pregnancy prospective cohort unexposed, disease free Adjustment: No 4.87 [0.09;254.99] C 0/16   0/76 0 16
ref
S2698
R11413		 Sadowski, 2013 Major malformations during pregnancy (anytime or not specified) excluded prospective cohort unexposed, disease free Adjustment: No 1.11 [0.05;22.56] C
excluded (exposition period) 		0/15   3/116 3 15
ref
S2488
R11414		 Shechtman (Control exposed to Haloperidol), 2009 Major malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.71 [0.05;11.18]
excluded (control group) 		-/106   -/- - 106
ref
S2485
R11415		 Shechtman (Unexposed control), 2009 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 0.71 [0.09;5.73] -/106   -/- - 106
ref
S2468
R11411		 Reis (Control exposed to FGA), 2008 Relatively severe malformations early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.80 [0.18;3.54] C
excluded (control group) 		2/51   21/435 23 51
ref
S2471
R11412		 Reis (Unexposed control, NOS), 2008 Relative severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: No 1.25 [0.31;5.16] C 2/51   30,679/973,767 30,681 51
ref
Total 6 studies 1.34 [1.13;1.59] 61,530 2,999
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 3.09[0.62; 27.00]391491%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Huybrechts (Controls unexposed, sick), 2023Huybrechts, 2023 2 1.30[1.08; 1.55]11,7662,27090%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Raguideau, 2017Raguideau, 2017 1.90[1.00; 3.60]18,6925077%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Peng, 2013Peng, 2013 4.87[0.09; 254.99]0160%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Shechtman (Unexposed control), 2009Shechtman, 2009 3 0.71[0.09; 5.73]-1061%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: unclear Reis (Unexposed control, NOS), 2008Reis, 2008 4 1.25[0.31; 5.16]30,681511%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Total (6 studies) I2 = 0% 1.34[1.13; 1.59]61,5302,9990.210.01.0ROB: 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: Unexposed control; 4: Unexposed control, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.34[1.13; 1.59]61,5302,9990%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2023 Raguideau, 2017 Peng, 2013 Shechtman (Unexposed control), 2009 Reis (Unexposed control, NOS), 2008 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.69[0.97; 2.95]49,3736800%NARaguideau, 2017 Peng, 2013 Shechtman (Unexposed control), 2009 Reis (Unexposed control, NOS), 2008 4 unexposed, sickunexposed, sick 1.31[1.09; 1.57]12,1572,3190%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2023 2 Tags Adjustment   - No  - No 1.19[0.39; 3.64]30,6811730%NAPeng, 2013 Shechtman (Unexposed control), 2009 Reis (Unexposed control, NOS), 2008 3   - Yes  - Yes 1.35[1.13; 1.60]30,8492,8260%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2023 Raguideau, 2017 3 All studiesAll studies 1.34[1.13; 1.59]61,5302,9990%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2023 Raguideau, 2017 Peng, 2013 Shechtman (Unexposed control), 2009 Reis (Unexposed control, NOS), 2008 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.02.4230.000Chan (Controls unexposed, sick), 2024Huybrechts (Controls unexposed, sick), 2023Raguideau, 2017Peng, 2013Shechtman (Unexposed control), 2009Reis (Unexposed control, NOS), 2008

Asymetry test p-value = 0.3322 (by Egger's regression)

slope=0.2369 (0.0824); intercept=0.4246 (0.3851); t=1.1024; p=0.3322

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2468, 2488, 14306, 18399, 18342

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.24[1.05; 1.46]249,6083,5470%NAChan (Controls unexposed, general pop), 2024 Huybrechts (Controls unexposed, NOS), 2023 Raguideau, 2017 Peng, 2013 Shechtman (Unexposed control), 2009 Reis (Unexposed control, NOS), 2008 6 unexposed, sick controlsunexposed, sick controls 1.31[1.09; 1.57]12,1572,3190%NAChan (Controls unexposed, sick), 2024 Huybrechts (Controls unexposed, sick), 2023 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.34[0.65; 2.77]562260%NAChan (Controls exposed to FGA), 2024 Shechtman (Control exposed to Haloperidol), 2009 Reis (Control exposed to FGA), 2008 30.510.01.0