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

Late intrauterine deaths (> 22 weeks) / Stillbirths

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.
S17848
R75323		 Meng a - BZDs (Controls unexposed, sibling), 2023 Stillbirth (fetal death at or after 20 weeks’ gestation) early pregnancy population based cohort retrospective sibling excluded Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) 1.07 [0.91;1.26]
excluded (control group) 		-/-   -/- - -
ref
S15409
R63479		 Meng a - BZDs (Controls unexposed, sick), 2023 Stillbirth (fetal death at or after 20 weeks’ gestation) early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) 1.16 [1.07;1.26] 755/61,975   29,056/2,772,076 29,811 61,975
ref
S15405
R63472		 Lee - Alprazolam, 2022 Stillbirth 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 3.30 [0.30;36.75] C 1/96   2/629 3 96
ref
S15449
R63540		 Milkovich - Chlordiazepoxide, 1974 Fetal deaths at or after 20 weeks of gestation during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...) 1.45 [0.57;3.64] C 7/186   14/532 21 186
ref
Total 3 studies 1.16 [1.07;1.26] 29,835 62,257
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 Meng a - BZDs (Controls unexposed, sick), 2023Meng a - BZDs, 2023 1 1.16[1.07; 1.26]29,81161,97599%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Lee - Alprazolam, 2022Lee - Alprazolam, 2022 3.30[0.30; 36.75]3960%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: unclearROB reporting: moderate Milkovich - Chlordiazepoxide, 1974Milkovich - Chlordiazepoxide, 1974 1.45[0.57; 3.64]211861%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Total (3 studies) I2 = 0% 1.16[1.07; 1.26]29,83562,2570.510.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.16[1.07; 1.26]29,83562,2570%NAMeng a - BZDs (Controls unexposed, sick), 2023 Lee - Alprazolam, 2022 Milkovich - Chlordiazepoxide, 1974 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.30[0.30; 36.75]396 -NALee - Alprazolam, 2022 1 unexposed, sickunexposed, sick 1.16[1.07; 1.26]29,83262,1610%NAMeng a - BZDs (Controls unexposed, sick), 2023 Milkovich - Chlordiazepoxide, 1974 2 Tags Adjustment   - No  - No 1.61[0.68; 3.81]242820%NALee - Alprazolam, 2022 Milkovich - Chlordiazepoxide, 1974 2   - Yes  - Yes 1.16[1.07; 1.26]29,81161,975 -NAMeng a - BZDs (Controls unexposed, sick), 2023 1 BZD Coexposure   - Not specified  - Not specified 1.61[0.68; 3.81]242820%NALee - Alprazolam, 2022 Milkovich - Chlordiazepoxide, 1974 2   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.16[1.07; 1.26]29,81161,975 -NAMeng a - BZDs (Controls unexposed, sick), 2023 1 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 1.45[0.57; 3.64]21186 -NAMilkovich - Chlordiazepoxide, 1974 1 All studiesAll studies 1.16[1.07; 1.26]29,83562,2570%NAMeng a - BZDs (Controls unexposed, sick), 2023 Lee - Alprazolam, 2022 Milkovich - Chlordiazepoxide, 1974 30.510.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 17848

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.30[0.30; 36.75]396 -NALee - Alprazolam, 2022 1 unexposed, sick controlsunexposed, sick controls 1.16[1.07; 1.26]29,83262,1610%NAMeng a - BZDs (Controls unexposed, sick), 2023 Milkovich - Chlordiazepoxide, 1974 2 siblingssiblings 1.07[0.91; 1.26]-- -NAMeng a - BZDs (Controls unexposed, sibling), 2023 10.510.01.0