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

Preterm (< 37 weeks)

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.
S18401
R77647
Kernizan (Controls exposed to LTG), 2024 Preterm delivery during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.99 [0.18;5.45] C
excluded (control group)
7/46   2/13 9 46
ref
S18348
R77393
Kernizan (Controls unexposed, sick), 2024 Preterm delivery during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.41 [0.17;1.00] C 7/46   42/139 49 46
ref
S18385
R77520
Kananen - Quetiapine, 2023 Preterm birth (delivery before the 37th gestational week) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes 1.30 [0.80;2.12] 20/152   2,151/35,133 2,171 152
ref
S14268
R56085
Viguera b, 2023 Preterm birth during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 0.99 [0.52;1.88] C 21/193   21/191 42 193
ref
S12454
R46735
Wang a (Controls exposed to FGA), 2021 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.96 [0.59;1.56] C
excluded (control group)
28/199   59/405 87 199
ref
S12453
R46731
Wang a (Controls unexposed, NOS), 2021 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.83 [1.22;2.72] C 28/199   33,799/410,545 33,827 199
ref
S3851
R8196
Ellfolk (Control exposed to FGA), 2019 Preterm birth 32–36 weeks during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: Yes 0.87 [0.63;1.20]
excluded (control group)
295/4,225   97/1,576 392 4,225
ref
S3818
R8133
Ellfolk (Control unexposed), 2019 Preterm birth 32–36 weeks during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.29 [1.03;1.62] 295/4,225   794/21,125 1,089 4,225
ref
S3905
R8276
Schaffer (Controls unexposed, NOS), 2019 Preterm (20–36weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: No 1.97 [1.66;2.34] C
excluded (control group)
154/1,063   7,571/95,523 7,725 1,063
ref
S3907
R8285
Schaffer (Controls unexposed, sick), 2019 Preterm (20–36weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No 1.09 [0.86;1.40] C 154/1,063   148/1,104 302 1,063
ref
S3876
R8233
Ozturk, 2016 Preterm birth (<37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No 1.21 [0.07;22.37] C 0/12   8/246 8 12
ref
S2329
R2696
Bellet - Aripiprazole, 2015 Preterm (< 37 weeks) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 2.57 [1.06;6.27] 11/67   11/155 22 67
ref
S2294
R3114
Vigod, 2015 Preterm birth <37 weeks gestation during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes Matched 0.99 [0.78;1.26] 136/923   146/1,021 282 923
ref
S2341
R2766
Habermann (Control exposed to FGA), 2013 Preterm (less than 37 gestational weeks) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.54 [0.33;0.87]
excluded (control group)
41/453   36/238 77 453
ref
S2385
R2948
Habermann (Control unexposed, disease free), 2013 Preterm (less than 37 gestational weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No 1.06 [0.72;1.56] 41/453   88/1,014 129 453
ref
S2343
R2769
Källen, 2013 Preterm (< 37 weeks) 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.31 [0.73;1.99] -/258   -/- - 258
ref
S2286
R2657
Sadowski, 2013 Preterm (gestational age <37weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Matched 2.64 [0.90;7.75] C 12/113   5/116 17 113
ref
S3842
R8162
Hironaka (Control exposed to BZD), 2011 Preterm labor during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No 1.80 [0.06;54.33] C
excluded (control group)
1/9   0/5 1 9
ref
S2334
R2736
Hironaka (Control unexposed, disease free), 2011 Preterm birth (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No 6.48 [0.29;145.66] C
excluded (control group)
0/9   2/278 2 9
ref
S14447
R57307
Hironaka (Control unexposed, sick), 2011 Preterm birth (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.29 [0.00;18.96] C 0/9   0/3 0 9
ref
S3849
R8180
Lin (Control exposed to FGA), 2010 Preterm birth during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.65 [0.26;1.65] C
excluded (control group)
6/48   35/194 41 48
ref
S3848
R8176
Lin (Control unexposed, disease free), 2010 Preterm birth during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: No 1.81 [0.76;4.29] C
excluded (control group)
6/48   255/3,480 261 48
ref
S2331
R2710
Lin (Control unexposed, sick), 2010 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.61 [0.63;4.12] 6/48   37/454 43 48
ref
S2391
R3363
Vial (Control exposed to FGA), 2009 Preterm (NOS) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched 0.45 [0.14;1.43] C
excluded (control group)
4/59   14/100 18 59
ref
S2390
R3362
Vial (Control unexposed, NOS), 2009 Preterm (NOS) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No 3.71 [0.80;17.10] C 4/59   3/156 7 59
ref
S2339
R2743
Newport, 2007 Preterm (<37 weeks estimated gestational age) late pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 3.08 [0.15;61.39] C 4/41   0/13 4 41
ref
S2305
R3066
McKenna, 2005 Preterm (NOS) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Matched 1.73 [0.62;4.78] C 10/77   7/88 17 77
ref
Total 17 studies 1.24 [1.06;1.45] 38,009 7,938
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 Kernizan (Controls unexposed, sick), 2024Kernizan, 2024 1 0.41[0.17; 1.00]49463%ROB confusion: unclearROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Kananen - Quetiapine, 2023Kananen - Quetiapine, 2023 1.30[0.80; 2.12]2,1711527%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Viguera b, 2023Viguera b, 2023 0.99[0.52; 1.88]421935%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: low Wang a (Controls unexposed, NOS), 2021Wang a, 2021 2 1.83[1.22; 2.72]33,8271999%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ellfolk (Control unexposed), 2019Ellfolk, 2019 3 1.29[1.03; 1.62]1,0894,22516%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: low Schaffer (Controls unexposed, sick), 2019Schaffer, 2019 4 1.09[0.86; 1.40]3021,06316%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Ozturk, 2016Ozturk, 2016 1.21[0.07; 22.37]8120%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bellet - Aripiprazole, 2015Bellet - Aripiprazole, 2015 2.57[1.06; 6.27]22673%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: unclearROB reporting: moderate Vigod, 2015Vigod, 2015 0.99[0.78; 1.26]28292316%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Habermann (Control unexposed, disease free), 2013Habermann, 2013 5 1.06[0.72; 1.56]12945310%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Källen, 2013Källen, 2013 1.31[0.73; 1.99]-2587%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: critical Sadowski, 2013Sadowski, 2013 2.64[0.90; 7.75]171132%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Hironaka (Control unexposed, sick), 2011Hironaka, 2011 6 0.29[0.00; 18.96]090%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Lin (Control unexposed, sick), 2010Lin, 2010 7 1.61[0.63; 4.12]43482%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Vial (Control unexposed, NOS), 2009Vial, 2009 8 3.71[0.80; 17.10]7591%ROB confusion: unclearROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: unclear Newport, 2007Newport, 2007 3.08[0.15; 61.39]4410%ROB confusion: criticalROB selection: unclearROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate McKenna, 2005McKenna, 2005 1.73[0.62; 4.78]17772%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (17 studies) I2 = 30% 1.24[1.06; 1.45]38,0097,9380.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, NOS; 3: Control unexposed; 4: Controls unexposed, sick; 5: Control unexposed, disease free; 6: Control unexposed, sick; 7: Control unexposed, sick; 8: Control unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.24[1.06; 1.45]38,0097,93830%NAKernizan (Controls unexposed, sick), 2024 Kananen - Quetiapine, 2023 Viguera b, 2023 Wang a (Controls unexposed, NOS), 2021 Ellfolk (Control unexposed), 2019 Schaffer (Controls unexposed, sick), 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Vigod, 2015 Habermann (Control unexposed, disease free), 2013 Källen, 2013 Sadowski, 2013 Hironaka (Control unexposed, sick), 2011 Lin (Control unexposed, sick), 2010 Vial (Control unexposed, NOS), 2009 Newport, 2007 McKenna, 2005 17 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.39[1.19; 1.62]37,2875,6152%NAKananen - Quetiapine, 2023 Wang a (Controls unexposed, NOS), 2021 Ellfolk (Control unexposed), 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Habermann (Control unexposed, disease free), 2013 Källen, 2013 Sadowski, 2013 Vial (Control unexposed, NOS), 2009 McKenna, 2005 10 unexposed, sickunexposed, sick 1.00[0.78; 1.27]6762,08929%NAKernizan (Controls unexposed, sick), 2024 Schaffer (Controls unexposed, sick), 2019 Vigod, 2015 Hironaka (Control unexposed, sick), 2011 Lin (Control unexposed, sick), 2010 5 exposed to other treatment, sickexposed to other treatment, sick 1.04[0.56; 1.94]462340%NAViguera b, 2023 Newport, 2007 2 Tags Adjustment   - No  - No 1.31[0.99; 1.74]34,4242,33243%NAKernizan (Controls unexposed, sick), 2024 Viguera b, 2023 Wang a (Controls unexposed, NOS), 2021 Schaffer (Controls unexposed, sick), 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Habermann (Control unexposed, disease free), 2013 Sadowski, 2013 Hironaka (Control unexposed, sick), 2011 Vial (Control unexposed, NOS), 2009 Newport, 2007 McKenna, 2005 12   - Yes  - Yes 1.18[1.02; 1.36]3,5855,6060%NAKananen - Quetiapine, 2023 Ellfolk (Control unexposed), 2019 Vigod, 2015 Källen, 2013 Lin (Control unexposed, sick), 2010 5 MatchedMatched 1.37[0.75; 2.50]3161,11349%NAVigod, 2015 Sadowski, 2013 McKenna, 2005 3 All studiesAll studies 1.24[1.06; 1.45]38,0097,93830%NAKernizan (Controls unexposed, sick), 2024 Kananen - Quetiapine, 2023 Viguera b, 2023 Wang a (Controls unexposed, NOS), 2021 Ellfolk (Control unexposed), 2019 Schaffer (Controls unexposed, sick), 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Vigod, 2015 Habermann (Control unexposed, disease free), 2013 Källen, 2013 Sadowski, 2013 Hironaka (Control unexposed, sick), 2011 Lin (Control unexposed, sick), 2010 Vial (Control unexposed, NOS), 2009 Newport, 2007 McKenna, 2005 170.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.05.22.5510.000Kernizan (Controls unexposed, sick), 2024Kananen - Quetiapine, 2023Viguera b, 2023Wang a (Controls unexposed, NOS), 2021Ellfolk (Control unexposed), 2019Schaffer (Controls unexposed, sick), 2019Ozturk, 2016Bellet - Aripiprazole, 2015Vigod, 2015Habermann (Control unexposed, disease free), 2013Källen, 2013Sadowski, 2013Hironaka (Control unexposed, sick), 2011Lin (Control unexposed, sick), 2010Vial (Control unexposed, NOS), 2009Newport, 2007McKenna, 2005

Asymetry test p-value = 0.2773 (by Egger's regression)

slope=0.0824 (0.1105); intercept=0.5413 (0.4801); t=1.1275; p=0.2773

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2391, 3849, 3848, 3842, 2334, 2341, 3851, 3905, 12454, 18401

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.57[1.31; 1.89]45,2756,73537%NAKananen - Quetiapine, 2023 Wang a (Controls unexposed, NOS), 2021 Ellfolk (Control unexposed), 2019 Schaffer (Controls unexposed, NOS), 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Habermann (Control unexposed, disease free), 2013 Källen, 2013 Sadowski, 2013 Hironaka (Control unexposed, disease free), 2011 Lin (Control unexposed, disease free), 2010 Vial (Control unexposed, NOS), 2009 McKenna, 2005 13 unexposed, sick controlsunexposed, sick controls 1.00[0.78; 1.27]6762,08929%NAKernizan (Controls unexposed, sick), 2024 Schaffer (Controls unexposed, sick), 2019 Vigod, 2015 Hironaka (Control unexposed, sick), 2011 Lin (Control unexposed, sick), 2010 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.80[0.65; 0.99]6715,2730%NAKernizan (Controls exposed to LTG), 2024 Viguera b, 2023 Wang a (Controls exposed to FGA), 2021 Ellfolk (Control exposed to FGA), 2019 Habermann (Control exposed to FGA), 2013 Hironaka (Control exposed to BZD), 2011 Lin (Control exposed to FGA), 2010 Vial (Control exposed to FGA), 2009 Newport, 2007 90.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Terrana (Preterm (births occurring <37 weeks ...Terrana (Preterm (births occurring <37 weeks of gestation)) 1.85[1.20; 2.86]43%-U,DFunexposed, disease freeAnyduring pregnancy (anytime or not specified)studies TTT7 Coughlin (Preterm (compared to unexposed))Coughlin (Preterm (compared to unexposed)) 1.61[1.15; 2.25]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.24[1.06; 1.45]30%7,938----Kernizan (Controls unexposed, sick), 2024 Kananen - Quetiapine, 2023 Viguera b, 2023 Wang a (Controls unexposed, NOS), 2021 Ellfolk (Control unexposed), 2019 Schaffer (Controls unexposed, sick), 2019 Ozturk, 2016 Bellet - Aripiprazole, 2015 Vigod, 2015 Habermann (Control unexposed, disease free), 2013 Källen, 2013 Sadowski, 2013 Hironaka (Control unexposed, sick), 2011 Lin (Control unexposed, sick), 2010 Vial (Control unexposed, NOS), 2009 Newport, 2007 McKenna, 2005 170.510.01.0