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

Caesarean

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.
S15488
R63665		 Kelty - Alprazolam (Controls unexposed, disease free), 2023 Caesarian section during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No BZD Coexposure: Not specified 2.02 [0.99;4.13] C
excluded (control group) 		23/48   30/96 53 48
ref
S15487
R63661		 Kelty - Alprazolam (Controls unexposed, sick), 2023 Caesarian section during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No BZD Coexposure: Not specified 1.76 [0.87;3.56] C 23/48   33/96 56 48
ref
S15314
R63006		 Yonkers - BZDs, 2017 Cesarean Delivery during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...) 2.45 [1.36;4.40] 36/67   -/- - 67
ref
S15518
R63751		 Salisbury - BZDs (Controls unexposed, disease free), 2016 Cesarean section delivery during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Co-administration Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.78 [0.15;4.06] C
excluded (control group) 		2/10   16/66 18 10
ref
S15519
R63769		 Salisbury - BZDs (Controls unexposed, sick), 2016 Cesarean section delivery during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Co-administration Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.53 [0.10;2.74] C 2/10   18/56 20 10
ref
S17712
R74716		 Hironaka - BZDs (Control exposed to Atypical antipsy), 2011 Emergency cesarean section during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.56 [0.02;16.77] C
excluded (control group) 		0/5   1/9 1 5
ref
S17710
R74704		 Hironaka - BZDs (Control unexposed, disease free), 2011 Emergency cesarean section during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...) 1.88 [0.10;36.55] C
excluded (control group) 		0/5   15/278 15 5
ref
S17711
R74710		 Hironaka - BZDs (Control unexposed, sick), 2011 Emergency cesarean section during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.56 [0.01;37.57] C 0/5   0/3 0 5
ref
S15524
R63786		 Oberlander - Clonazepam (Controls unexposed, disease free), 2004 Caesarean section during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Co-administration Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.46 [0.10;2.10] C
excluded (control group) 		3/18   7/23 10 18
ref
S15525
R63792		 Oberlander - Clonazepam (Controls unexposed, sick), 2004 Caesarean section during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Co-administration Indication BZD: Psychiatric diseases (depression, anxiety, ...) 0.92 [0.19;4.43] C 3/18   5/28 8 18
ref
Total 5 studies 1.78 [1.15;2.77] 84 148
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 Kelty - Alprazolam (Controls unexposed, sick), 2023Kelty - Alprazolam, 2023 1 1.76[0.87; 3.56]564835%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Yonkers - BZDs, 2017Yonkers - BZDs, 2017 2.45[1.36; 4.40]-6749%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Salisbury - BZDs (Controls unexposed, sick), 2016Salisbury - BZDs, 2016 2 0.53[0.10; 2.74]20107%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Hironaka - BZDs (Control unexposed, sick), 2011Hironaka - BZDs, 2011 3 0.56[0.01; 37.57]051%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Oberlander - Clonazepam (Controls unexposed, sick), 2004Oberlander - Clonazepam, 2004 4 0.92[0.19; 4.43]8188%ROB confusion: criticalROB selection: lowROB classification: unclearROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 5% 1.78[1.15; 2.77]841480.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Control unexposed, sick; 4: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.78[1.15; 2.77]841485%NAKelty - Alprazolam (Controls unexposed, sick), 2023 Yonkers - BZDs, 2017 Salisbury - BZDs (Controls unexposed, sick), 2016 Hironaka - BZDs (Control unexposed, sick), 2011 Oberlander - Clonazepam (Controls unexposed, sick), 2004 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.45[1.36; 4.41]-67 -NAYonkers - BZDs, 2017 1 unexposed, sickunexposed, sick 1.34[0.74; 2.43]84810%NAKelty - Alprazolam (Controls unexposed, sick), 2023 Salisbury - BZDs (Controls unexposed, sick), 2016 Hironaka - BZDs (Control unexposed, sick), 2011 Oberlander - Clonazepam (Controls unexposed, sick), 2004 4 Tags Adjustment   - No  - No 1.34[0.74; 2.43]84810%NAKelty - Alprazolam (Controls unexposed, sick), 2023 Salisbury - BZDs (Controls unexposed, sick), 2016 Hironaka - BZDs (Control unexposed, sick), 2011 Oberlander - Clonazepam (Controls unexposed, sick), 2004 4   - Yes  - Yes 2.45[1.36; 4.41]-67 -NAYonkers - BZDs, 2017 1 BZD Coexposure   - Not specified  - Not specified 2.11[1.34; 3.30]561200%NAKelty - Alprazolam (Controls unexposed, sick), 2023 Yonkers - BZDs, 2017 Hironaka - BZDs (Control unexposed, sick), 2011 3   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 0.71[0.23; 2.20]28280%NASalisbury - BZDs (Controls unexposed, sick), 2016 Oberlander - Clonazepam (Controls unexposed, sick), 2004 2 Co-administrationCo-administration 0.71[0.23; 2.20]28280%NASalisbury - BZDs (Controls unexposed, sick), 2016 Oberlander - Clonazepam (Controls unexposed, sick), 2004 2 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 1.42[0.62; 3.23]2810028%NAYonkers - BZDs, 2017 Salisbury - BZDs (Controls unexposed, sick), 2016 Hironaka - BZDs (Control unexposed, sick), 2011 Oberlander - Clonazepam (Controls unexposed, sick), 2004 4 All studiesAll studies 1.78[1.15; 2.77]841485%NAKelty - Alprazolam (Controls unexposed, sick), 2023 Yonkers - BZDs, 2017 Salisbury - BZDs (Controls unexposed, sick), 2016 Hironaka - BZDs (Control unexposed, sick), 2011 Oberlander - Clonazepam (Controls unexposed, sick), 2004 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.15.62.5800.000Kelty - Alprazolam (Controls unexposed, sick), 2023Yonkers - BZDs, 2017Salisbury - BZDs (Controls unexposed, sick), 2016Hironaka - BZDs (Control unexposed, sick), 2011Oberlander - Clonazepam (Controls unexposed, sick), 2004

Asymetry test p-value = 0.0750 (by Egger's regression)

slope=1.2116 (0.2667); intercept=-1.5012 (0.5600); t=2.6806; p=0.0750

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 15524, 17712, 17710, 15518, 15488

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.70[0.99; 2.91]12314823%NAKelty - Alprazolam (Controls unexposed, disease free), 2023 Yonkers - BZDs, 2017 Salisbury - BZDs (Controls unexposed, disease free), 2016 Hironaka - BZDs (Control unexposed, disease free), 2011 Oberlander - Clonazepam (Controls unexposed, disease free), 2004 5 unexposed, sick controlsunexposed, sick controls 1.34[0.74; 2.43]84810%NAKelty - Alprazolam (Controls unexposed, sick), 2023 Salisbury - BZDs (Controls unexposed, sick), 2016 Hironaka - BZDs (Control unexposed, sick), 2011 Oberlander - Clonazepam (Controls unexposed, sick), 2004 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.56[0.02; 16.77]15 -NAHironaka - BZDs (Control exposed to Atypical antipsy), 2011 10.510.01.0