Diazepam updated on 02-10-2025

Congenital heart 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.
S15390
R63453		 Noh, 2022 Heart malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 1.12 [1.04;1.21] 641/17,923   83,584/3,053,381 84,225 17,923
ref
S15602
R64305		 Tinker, 2019 Heart defect (any) 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) 0.80 [0.40;1.60] 17/35   12,181/23,696 12,198 35
ref
S15649
R64576		 Ban (Other indications) (Controls unexposed, disease free), 2014 Heart 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, ...) 1.34 [0.63;2.86]
excluded (control group) 		12/1,159   2,642/351,785 2,654 1,159
ref
S15650
R64592		 Ban (Other indications) (Controls unexposed, sick), 2014 Heart 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, ...) 1.29 [0.60;2.80] 12/1,159   149/19,193 161 1,159
ref
S15588
R64150		 Källén, 2013 Any cardiac defects early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 1.03 [0.57;1.85] 11/865   -/1,575,847 - 865
ref
S15661
R64658		 Czeizel, 2003 Cardiovascular congenital anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Matched 1.30 [1.00;1.80] -/-   4,476/- - -
ref
S15667
R64692		 Tikkanen, 1992 Cardiovascular malformations 1st trimester nested case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 0.50 [0.02;10.00] 2/10   404/1,152 406 10
ref
S15664
R64680		 Rothman, 1979 Congenital heart disease (defects) early pregnancy case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 2.24 [1.15;4.36] C 15/37   375/1,607 390 37
ref
Total 7 studies 1.15 [1.03;1.29] 97,380 20,029
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 1.12[1.04; 1.21]84,22517,92377%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Tinker, 2019Tinker, 2019 0.80[0.40; 1.60]12,198352%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Ban (Other indications) (Controls unexposed, sick), 2014Ban, 2014 1 1.29[0.60; 2.80]1611,1592%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: unclearROB reporting: moderate Källén, 2013Källén, 2013 1.03[0.57; 1.85]-8653%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Czeizel, 2003Czeizel, 2003 1.30[1.00; 1.80]--13%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Tikkanen, 1992Tikkanen, 1992 0.50[0.02; 10.00]406100%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Rothman, 1979Rothman, 1979 2.24[1.15; 4.36]390373%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Total (7 studies) I2 = 6% 1.15[1.03; 1.29]97,38020,0290.25.01.0ROB: 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 1.12[1.04; 1.21]84,38619,9470%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 Källén, 2013 3 case control studiescase control studies 1.30[0.86; 1.98]12,9948238%NATinker, 2019 Czeizel, 2003 Tikkanen, 1992 Rothman, 1979 4 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.25[0.91; 1.70]12,99494725%NATinker, 2019 Källén, 2013 Czeizel, 2003 Tikkanen, 1992 Rothman, 1979 5 unexposed, sickunexposed, sick 1.12[1.04; 1.21]84,38619,0820%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 2 Tags Adjustment   - No  - No 2.24[1.15; 4.36]39037 -NARothman, 1979 1   - Yes  - Yes 1.13[1.05; 1.21]96,99019,9920%NANoh, 2022 Tinker, 2019 Ban (Other indications) (Controls unexposed, sick), 2014 Källén, 2013 Czeizel, 2003 Tikkanen, 1992 6 BZD Coexposure   - No (among psychiatric (ATD and/or p ...  - No (among psychiatric (ATD and/or psychotropics) medications) 1.29[0.60; 2.79]1611,159 -NABan (Other indications) (Controls unexposed, sick), 2014 1   - Not specified  - Not specified 1.22[0.90; 1.66]85,02118,83533%NANoh, 2022 Källén, 2013 Tikkanen, 1992 Rothman, 1979 4   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.13[0.74; 1.74]12,1983537%NATinker, 2019 Czeizel, 2003 2 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 1.29[0.60; 2.79]1611,159 -NABan (Other indications) (Controls unexposed, sick), 2014 1 MatchedMatched 1.30[0.97; 1.74]-- -NACzeizel, 2003 1 All studiesAll studies 1.15[1.03; 1.29]97,38020,0296%NANoh, 2022 Tinker, 2019 Ban (Other indications) (Controls unexposed, sick), 2014 Källén, 2013 Czeizel, 2003 Tikkanen, 1992 Rothman, 1979 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.73.91.9020.000Noh, 2022Tinker, 2019Ban (Other indications) (Controls unexposed, sick), 2014Källén, 2013Czeizel, 2003Tikkanen, 1992Rothman, 1979

Asymetry test p-value = 0.6587 (by Egger's regression)

slope=0.1112 (0.0515); intercept=0.2499 (0.5325); t=0.4692; p=0.6587

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) 1.26[0.99; 1.61]20,1172,1067%NATinker, 2019 Ban (Other indications) (Controls unexposed, disease free), 2014 Källén, 2013 Czeizel, 2003 Tikkanen, 1992 Rothman, 1979 6 unexposed, sick controlsunexposed, sick controls 1.12[1.04; 1.21]84,38619,0820%NANoh, 2022 Ban (Other indications) (Controls unexposed, sick), 2014 20.510.01.0