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

Eye defects

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.
S17691
R74674		 Cifuentes - Alprazolam, 2025 Congenital ocular anomalies (Anophthalmia, Microphthalmia, Congenital Glaucoma, Congenital Cataract, Colobomas, ...) 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 2.02 [0.74;5.48] 5/109   4,180/236,794 4,185 109
ref
S15381
R63374		 Noh - BZDs, 2022 Eye malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 0.99 [0.75;1.29] 57/40,846   4,044/3,053,381 4,101 40,846
ref
S15330
R63134		 Ban - Diazepam (Other indications) (Controls unexposed, disease free), 2014 Eye malformations 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...) 1.78 [0.44;7.14] C
excluded (control group) 		2/1,159   342/351,785 344 1,159
ref
S15327
R63104		 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 Eye malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...) 1.74 [0.41;7.50] C 2/1,159   19/19,193 21 1,159
ref
S15535
R63835		 Czeizel - Diazepam, 2003 Eye congenital anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Matched 0.30 [0.10;7.60] -/-   104/- - -
ref
Total 4 studies 1.11 [0.72;1.70] 8,307 42,114
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 Cifuentes - Alprazolam, 2025Cifuentes - Alprazolam, 2025 2.02[0.74; 5.48]4,18510916%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Noh - BZDs, 2022Noh - BZDs, 2022 0.99[0.75; 1.29]4,10140,84672%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014Ban - Diazepam, 2014 1 1.74[0.41; 7.50]211,1598%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: unclearROB reporting: moderate Czeizel - Diazepam, 2003Czeizel - Diazepam, 2003 0.30[0.10; 7.60]--4%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (4 studies) I2 = 16% 1.11[0.72; 1.70]8,30742,1140.25.01.0ROB: 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 1.01[0.77; 1.32]4,12242,0050%NANoh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 2 case control studiescase control studies 1.00[0.17; 6.07]4,18510959%NACifuentes - Alprazolam, 2025 Czeizel - Diazepam, 2003 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.00[0.17; 6.07]4,18510959%NACifuentes - Alprazolam, 2025 Czeizel - Diazepam, 2003 2 unexposed, sickunexposed, sick 1.01[0.77; 1.32]4,12242,0050%NANoh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 2 Tags Adjustment   - No  - No 1.74[0.41; 7.50]211,159 -NABan - Diazepam (Other indications) (Controls unexposed, sick), 2014 1   - Yes  - Yes 1.09[0.59; 2.00]8,28640,95535%NACifuentes - Alprazolam, 2025 Noh - BZDs, 2022 Czeizel - Diazepam, 2003 3 BZD Coexposure   - No (among psychiatric (ATD and/or p ...  - No (among psychiatric (ATD and/or psychotropics) medications) 1.74[0.41; 7.50]211,159 -NABan - Diazepam (Other indications) (Controls unexposed, sick), 2014 1   - Not specified  - Not specified 1.19[0.65; 2.21]8,28640,95545%NACifuentes - Alprazolam, 2025 Noh - BZDs, 2022 2   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 0.30[0.03; 2.62]-- -NACzeizel - Diazepam, 2003 1 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 1.74[0.41; 7.50]211,159 -NABan - Diazepam (Other indications) (Controls unexposed, sick), 2014 1 MatchedMatched 0.30[0.03; 2.62]-- -NACzeizel - Diazepam, 2003 1 All studiesAll studies 1.11[0.72; 1.70]8,30742,11416%NACifuentes - Alprazolam, 2025 Noh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 Czeizel - Diazepam, 2003 40.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.62.71.3260.000Cifuentes - Alprazolam, 2025Noh - BZDs, 2022Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014Czeizel - Diazepam, 2003

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) 1.45[0.59; 3.54]4,6241,26820%NACifuentes - Alprazolam, 2025 Ban - Diazepam (Other indications) (Controls unexposed, disease free), 2014 Czeizel - Diazepam, 2003 3 unexposed, sick controlsunexposed, sick controls 1.01[0.77; 1.32]4,12242,0050%NANoh - BZDs, 2022 Ban - Diazepam (Other indications) (Controls unexposed, sick), 2014 20.510.01.0