Diazepam updated on 02-10-2025

All congenital malformations (majors, minors, majors and minors, or unspecified)

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.
S15390
R64470		 Noh, 2022 Overall major congenital malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 1.08 [1.01;1.14] 1,110/17,923   156,896/3,053,381 158,006 17,923
ref
S15649
R64590		 Ban (Other indications) (Controls unexposed, disease free), 2014 Any major congenital anomalies (excluding genetic anomalies and anomalies attributed to known teratogens, e.g. anomalies due to maternal infections and fetal alcohol syndrome) 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, ...) 1.02 [0.63;1.64]
excluded (control group) 		31/1,159   9,368/351,785 9,399 1,159
ref
S15650
R64606		 Ban (Other indications) (Controls unexposed, sick), 2014 Any major congenital anomalies (excluding genetic anomalies and anomalies attributed to known teratogens, e.g. anomalies due to maternal infections and fetal alcohol syndrome) 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, ...) 0.99 [0.61;1.61] 31/1,159   518/19,193 549 1,159
ref
S15588
R64460		 Källén, 2013 Relatively severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 0.94 [0.67;1.33] 32/865   49,499/1,575,847 49,531 865
ref
S15661
R64672		 Czeizel, 2003 Major congenital anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Matched 1.20 [1.10;1.40] -/-   22,874/- - -
ref
S15658
R64639		 Bracken, 1981 Major congenital malformations 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...) 2.77 [1.67;4.61] C 34/61   1,336/4,277 1,370 61
ref
Total 5 studies 1.18 [0.99;1.41] 209,456 20,008
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 Noh, 2022Noh, 2022 1.08[1.01; 1.14]158,00617,92335%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Ban (Other indications) (Controls unexposed, sick), 2014Ban, 2014 1 0.99[0.61; 1.61]5491,15910%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: unclearROB reporting: moderate Källén, 2013Källén, 2013 0.94[0.67; 1.33]49,53186515%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Czeizel, 2003Czeizel, 2003 1.20[1.10; 1.40]--31%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Bracken, 1981Bracken, 1981 2.77[1.67; 4.61]1,370619%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 75% 1.18[0.99; 1.41]209,45620,0080.210.01.0ROB: 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 1.07[1.01; 1.14]208,08619,9470%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 Källén, 2013 3 case control studiescase control studies 1.76[0.78; 3.97]1,3706190%NACzeizel, 2003 Bracken, 1981 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.38[0.89; 2.15]50,90192684%NAKällén, 2013 Czeizel, 2003 Bracken, 1981 3 unexposed, sickunexposed, sick 1.08[1.02; 1.15]158,55519,0820%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 2 Tags Adjustment   - No  - No 2.77[1.67; 4.61]1,37061 -NABracken, 1981 1   - Yes  - Yes 1.10[1.03; 1.18]208,08619,94710%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 Källén, 2013 Czeizel, 2003 4 BZD Coexposure   - No (among psychiatric (ATD and/or p ...  - No (among psychiatric (ATD and/or psychotropics) medications) 0.99[0.61; 1.61]5491,159 -NABan (Other indications) (Controls unexposed, sick), 2014 1   - Not specified  - Not specified 1.33[0.85; 2.07]208,90718,84985%NANoh, 2022 Källén, 2013 Bracken, 1981 3   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.20[1.06; 1.35]-- -NACzeizel, 2003 1 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 1.65[0.60; 4.53]1,9191,22088%NABan (Other indications) (Controls unexposed, sick), 2014 Bracken, 1981 2 MatchedMatched 1.20[1.06; 1.35]-- -NACzeizel, 2003 1 All studiesAll studies 1.18[0.99; 1.41]209,45620,00875%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 Källén, 2013 Czeizel, 2003 Bracken, 1981 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.21.20.3120.000Noh, 2022Ban (Other indications) (Controls unexposed, sick), 2014Källén, 2013Czeizel, 2003Bracken, 1981

Asymetry test p-value = 0.4624 (by Egger's regression)

slope=0.0497 (0.0845); intercept=1.1777 (1.4015); t=0.8403; p=0.4624

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 15649

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.28[0.91; 1.81]83,1652,08576%NABan (Other indications) (Controls unexposed, disease free), 2014 Källén, 2013 Czeizel, 2003 Bracken, 1981 4 unexposed, sick controlsunexposed, sick controls 1.08[1.02; 1.15]158,55519,0820%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 20.510.01.0