Aripiprazole 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.
S14302
R56391		 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 0.95 [0.83;1.10]
excluded (control group) 		188/4,523   177,165/6,455,324 177,353 4,523
ref
S14303
R56403		 Huybrechts (Controls unexposed, sick), 2023 Major congenital malformations overall (excluding chromosomal abnormality) 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 0.96 [0.83;1.12] 161/3,861   11,647/318,731 11,808 3,861
ref
S12444
R46709		 Freeman, 2021 Major malformations 1st trimester prospective cohort unexposed, sick Adjustment: Yes 1.35 [0.43;4.20] 7/163   14/704 21 163
ref
S2479
R11402		 Raguideau, 2017 26 major malformations early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.70 [1.00;2.90] 14/790   18,682/1,888,130 18,696 790
ref
S2399
R3015		 Bellet, 2015 All malformations (minor and major) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 2.03 [0.66;6.28] 6/71   7/161 13 71
ref
S2444
R11399		 Habermann (Control exposed to FGA), 2013 Major malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.66 [0.43;6.39] C
excluded (control group) 		3/44   9/213 12 44
ref
S2443
R11400		 Habermann (Control unexposed, disease free), 2013 Major malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 2.89 [0.84;9.98] C 3/44   25/1,014 28 44
ref
S2695
R11403		 Sadowski, 2013 Major malformations during pregnancy (anytime or not specified) excluded prospective cohort unexposed, disease free Adjustment: No 10.71 [0.37;312.44] C
excluded (exposition period) 		0/2   3/116 3 2
ref
Total 5 studies 1.40 [0.91;2.17] 30,566 4,929
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 0.96[0.83; 1.12]11,8083,86142%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Freeman, 2021Freeman, 2021 1.35[0.43; 4.20]2116311%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: lowROB reporting: low Raguideau, 2017Raguideau, 2017 1.70[1.00; 2.90]18,69679027%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bellet, 2015Bellet, 2015 2.03[0.66; 6.28]137111%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: unclearROB reporting: moderate Habermann (Control unexposed, disease free), 2013Habermann, 2013 2 2.89[0.84; 9.98]284410%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 53% 1.40[0.91; 2.17]30,5664,9290.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Control unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.40[0.91; 2.17]30,5664,92953%NAHuybrechts (Controls unexposed, sick), 2023 Freeman, 2021 Raguideau, 2017 Bellet, 2015 Habermann (Control unexposed, disease free), 2013 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.88[1.20; 2.94]18,7379050%NARaguideau, 2017 Bellet, 2015 Habermann (Control unexposed, disease free), 2013 3 unexposed, sickunexposed, sick 0.97[0.83; 1.12]11,8294,0240%NAHuybrechts (Controls unexposed, sick), 2023 Freeman, 2021 2 Tags Adjustment   - No  - No 2.38[1.04; 5.48]411150%NABellet, 2015 Habermann (Control unexposed, disease free), 2013 2   - Yes  - Yes 1.19[0.78; 1.83]30,5254,81454%NAHuybrechts (Controls unexposed, sick), 2023 Freeman, 2021 Raguideau, 2017 3 All studiesAll studies 1.40[0.91; 2.17]30,5664,92953%NAHuybrechts (Controls unexposed, sick), 2023 Freeman, 2021 Raguideau, 2017 Bellet, 2015 Habermann (Control unexposed, disease free), 2013 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.51.80.7580.000Huybrechts (Controls unexposed, sick), 2023Freeman, 2021Raguideau, 2017Bellet, 2015Habermann (Control unexposed, disease free), 2013

Asymetry test p-value = 0.0380 (by Egger's regression)

slope=-0.1555 (0.0747); intercept=1.6485 (0.4641); t=3.5518; p=0.0380

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2444, 14302

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.45[0.86; 2.45]196,0905,42865%NAHuybrechts (Controls unexposed, NOS), 2023 Raguideau, 2017 Bellet, 2015 Habermann (Control unexposed, disease free), 2013 4 unexposed, sick controlsunexposed, sick controls 0.97[0.83; 1.12]11,8294,0240%NAHuybrechts (Controls unexposed, sick), 2023 Freeman, 2021 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.66[0.43; 6.39]1244 -NAHabermann (Control exposed to FGA), 2013 10.510.01.0