Benzodiazepines (Psy and mixed indications) updated on 02-10-2025

Genital anomalies

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.
S17044
R75080		 Chuang - BZDs, 2024 Genital system malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 1.13 [0.84;1.52] 56/50,272   2,385/2,632,733 2,441 50,272
ref
S15381
R63382		 Noh - BZDs, 2022 Genital organ malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 1.11 [0.97;1.27] 227/40,846   13,514/3,053,381 13,741 40,846
ref
S15330
R63127		 Ban - Diazepam (Other indications) (Controls unexposed, disease free), 2014 Genital system malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.69 [0.16;3.09]
excluded (control group) 		3/1,159   1,361/351,785 1,364 1,159
ref
S15327
R63097		 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 Genital system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.57 [0.12;2.60] 3/1,159   85/19,193 88 1,159
ref
S17769
R75090		 Robert - BZDs, 1994 Congenital anomalies of genital organs 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 0.55 [0.10;1.70] 3/-   157/- 160 -
ref
Total 4 studies 1.10 [0.98;1.25] 16,430 92,277
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 Chuang - BZDs, 2024Chuang - BZDs, 2024 1.13[0.84; 1.52]2,44150,27217%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Noh - BZDs, 2022Noh - BZDs, 2022 1.11[0.97; 1.27]13,74140,84682%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014Ban - Diazepam, 2014 1 0.57[0.12; 2.60]881,1591%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: unclearROB reporting: moderate Robert - BZDs, 1994Robert - BZDs, 1994 0.55[0.10; 1.70]160-1%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Total (4 studies) I2 = 0% 1.10[0.98; 1.25]16,43092,2770.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Other indications) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.11[0.98; 1.25]16,27092,2770%NAChuang - BZDs, 2024 Noh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 3 case control studiescase control studies 0.55[0.13; 2.27]160- -NARobert - BZDs, 1994 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.55[0.13; 2.27]160- -NARobert - BZDs, 1994 1 unexposed, sickunexposed, sick 1.11[0.98; 1.25]16,27092,2770%NAChuang - BZDs, 2024 Noh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 3 Tags Adjustment   - No  - No 0.55[0.13; 2.27]160- -NARobert - BZDs, 1994 1   - Yes  - Yes 1.11[0.98; 1.25]16,27092,2770%NAChuang - BZDs, 2024 Noh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 3 BZD Coexposure   - No (among psychiatric (ATD and/or p ...  - No (among psychiatric (ATD and/or psychotropics) medications) 0.57[0.12; 2.65]881,159 -NABan - Diazepam (Other indications) (Controls unexposed, sick), 2014 1   - Not specified  - Not specified 1.11[0.98; 1.25]16,34291,1180%NAChuang - BZDs, 2024 Noh - BZDs, 2022 Robert - BZDs, 1994 3 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 0.57[0.12; 2.65]881,159 -NABan - Diazepam (Other indications) (Controls unexposed, sick), 2014 1 All studiesAll studies 1.10[0.98; 1.25]16,43092,2770%NAChuang - BZDs, 2024 Noh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 Robert - BZDs, 1994 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.81.90.9420.000Chuang - BZDs, 2024Noh - BZDs, 2022Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014Robert - BZDs, 1994

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 15330

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.61[0.22; 1.71]1,5241,1590%NABan - Diazepam (Other indications) (Controls unexposed, disease free), 2014 Robert - BZDs, 1994 2 unexposed, sick controlsunexposed, sick controls 1.11[0.98; 1.25]16,27092,2770%NAChuang - BZDs, 2024 Noh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 30.510.01.0