Atypical antipsychotics (Second generation) updated on 06-10-2025

Early intrauterine deaths (< 22 weeks) / Spontaneous abortions

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.
S17709
R74699		 Ishikawa, 2024 Miscarriage (4 - 22 weeks of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes 0.97 [0.80;1.17] 213/811   43,905/175,624 44,118 811
ref
S12447
R46712		 Yakuwa, 2019 Spontaneous abortions NOS) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.18 [0.82;1.71] C 34/404   312/4,330 346 404
ref
S3876
R8235		 Ozturk, 2016 Miscarriage during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No 0.69 [0.04;12.24] C 0/12   15/261 15 12
ref
S2329
R2700		 Bellet - Aripiprazole, 2015 Miscarriage (spontaneous abortion before 22 GW) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.66 [0.63;4.38] 8/86   10/172 18 86
ref
S2340
R2751		 Sorensen - Olanzapine, 2015 Spontaneous abortion (< 22 weeks) early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.10 [0.83;1.46] 39/223   114,314/841,183 114,353 223
ref
S2341
R8718		 Habermann (Control exposed to FGA), 2013 Spontaneous abortion during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.12 [0.65;1.91] C
excluded (control group) 		46/561   21/284 67 561
ref
S2385
R8719		 Habermann (Control unexposed, disease free), 2013 Spontaneous abortion during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No 0.84 [0.58;1.20] C 46/561   108/1,122 154 561
ref
S2389
R8155		 Paulus - Aripiprazole only, 2013 Spontaneous abortions 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.12 [0.39;3.21] C 5/57   15/189 20 57
ref
S2391
R2955		 Vial (Control exposed to FGA), 2009 Spontaneous abortion (NOS) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched 1.31 [0.50;3.46] C
excluded (control group) 		8/89   10/143 18 89
ref
S2390
R2956		 Vial (Control unexposed, NOS), 2009 Spontaneous abortion (NOS) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.37 [0.54;3.47] C 8/89   12/178 20 89
ref
S2305
R2679		 McKenna, 2005 Spontaneous abortion during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Matched 1.81 [0.88;3.74] C 22/151   13/151 35 151
ref
S2346
R2805		 Paulus, 2005 Spontaneous abortion 1st trimester prospective cohort unexposed, disease free Adjustment: No 0.55 [0.21;1.41] C 5/75   65/565 70 75
ref
S3899
R8268		 Yaris, 2005 Spontaneous abortions during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No 3.59 [0.17;74.48] C 0/4   9/248 9 4
ref
Total 11 studies 1.03 [0.91;1.17] 159,158 2,473
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 Ishikawa, 2024Ishikawa, 2024 0.97[0.80; 1.17]44,11881145%ROB confusion: moderateROB selection: moderateROB classification: criticalROB missing: criticalROB mesure: criticalROB reporting: moderate Yakuwa, 2019Yakuwa, 2019 1.18[0.82; 1.71]34640412%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Ozturk, 2016Ozturk, 2016 0.69[0.04; 12.24]15120%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Bellet - Aripiprazole, 2015Bellet - Aripiprazole, 2015 1.66[0.63; 4.38]18862%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: unclearROB reporting: moderate Sorensen - Olanzapine, 2015Sorensen - Olanzapine, 2015 1.10[0.83; 1.46]114,35322320%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Habermann (Control unexposed, disease free), 2013Habermann, 2013 1 0.84[0.58; 1.20]15456112%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: low Paulus - Aripiprazole only, 2013Paulus - Aripiprazole only, 2013 1.12[0.39; 3.21]20571%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: unclear Vial (Control unexposed, NOS), 2009Vial, 2009 2 1.37[0.54; 3.47]20892%ROB confusion: unclearROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: unclear McKenna, 2005McKenna, 2005 1.81[0.88; 3.74]351513%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Paulus, 2005Paulus, 2005 0.55[0.21; 1.41]70752%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: unclear Yaris, 2005Yaris, 2005 3.59[0.17; 74.48]940%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (11 studies) I2 = 0% 1.03[0.91; 1.17]159,1582,4730.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Control unexposed, disease free; 2: Control unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.08[0.91; 1.28]115,0401,6620%NAYakuwa, 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Sorensen - Olanzapine, 2015 Habermann (Control unexposed, disease free), 2013 Paulus - Aripiprazole only, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 Paulus, 2005 Yaris, 2005 10 case control studiescase control studies 0.97[0.80; 1.17]44,118811 -NAIshikawa, 2024 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.03[0.91; 1.17]159,1582,4730%NAIshikawa, 2024 Yakuwa, 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Sorensen - Olanzapine, 2015 Habermann (Control unexposed, disease free), 2013 Paulus - Aripiprazole only, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 Paulus, 2005 Yaris, 2005 11 Tags Adjustment   - No  - No 1.07[0.86; 1.33]6871,4390%NAYakuwa, 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Habermann (Control unexposed, disease free), 2013 Paulus - Aripiprazole only, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 Paulus, 2005 Yaris, 2005 9   - Yes  - Yes 1.01[0.86; 1.18]158,4711,0340%NAIshikawa, 2024 Sorensen - Olanzapine, 2015 2 MatchedMatched 1.81[0.88; 3.74]35151 -NAMcKenna, 2005 1 All studiesAll studies 1.03[0.91; 1.17]159,1582,4730%NAIshikawa, 2024 Yakuwa, 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Sorensen - Olanzapine, 2015 Habermann (Control unexposed, disease free), 2013 Paulus - Aripiprazole only, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 Paulus, 2005 Yaris, 2005 110.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.71.8570.000Ishikawa, 2024Yakuwa, 2019Ozturk, 2016Bellet - Aripiprazole, 2015Sorensen - Olanzapine, 2015Habermann (Control unexposed, disease free), 2013Paulus - Aripiprazole only, 2013Vial (Control unexposed, NOS), 2009McKenna, 2005Paulus, 2005Yaris, 2005

Asymetry test p-value = 0.3285 (by Egger's regression)

slope=-0.0492 (0.0961); intercept=0.4605 (0.4457); t=1.0332; p=0.3285

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2391, 2341

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.03[0.91; 1.17]159,1582,4730%NAIshikawa, 2024 Yakuwa, 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Sorensen - Olanzapine, 2015 Habermann (Control unexposed, disease free), 2013 Paulus - Aripiprazole only, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 Paulus, 2005 Yaris, 2005 11 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.16[0.73; 1.86]856500%NAHabermann (Control exposed to FGA), 2013 Vial (Control exposed to FGA), 2009 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Terrana (Miscarriage (fetal death occurring < ...Terrana (Miscarriage (fetal death occurring <20 weeks of gestation)) 1.10[0.74; 1.64]38%-U,DFunexposed, disease freeAnyduring pregnancy (anytime or not specified)studies TTT6 metaPregmetaPreg 1.03[0.91; 1.17]0%2,473----Ishikawa, 2024 Yakuwa, 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Sorensen - Olanzapine, 2015 Habermann (Control unexposed, disease free), 2013 Paulus - Aripiprazole only, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 Paulus, 2005 Yaris, 2005 110.510.01.0