Chlordiazepoxide 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.
S15393
R64467		 Noh, 2022 Overall major congenital malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes BZD Coexposure: Not specified 1.50 [1.06;2.11] 30/381   156,896/3,053,381 156,926 381
ref
S15450
R64455		 Czeizel, 2004 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 1.50 [1.00;2.30] -/-   22,874/- - -
ref
S15425
R64453		 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, ...) 1.81 [0.55;5.94] C 5/11   1,365/4,327 1,370 11
ref
S15662
R64677		 Kullander, 1976 Minor and major malformations 1st trimester nested case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 0.56 [0.26;1.23] C 7/89   744/5,664 751 89
ref
S15639
R64545		 Hartz, 1975 Malformed child (with uniform rates, thus excluding inguinal hernia, clubfoot, pectus excavatum, cleft gum and abnormal hand or fingers other tha polydactyly or syndactyly) early pregnancy prospective cohort unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 0.80 [0.40;1.60] 11/257   2,179/48,412 2,190 257
ref
Total 5 studies 1.18 [0.82;1.70] 161,237 738
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 1.50[1.06; 2.11]156,92638132%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Czeizel, 2004Czeizel, 2004 1.50[1.00; 2.30]--28%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: moderateROB mesure: criticalROB reporting: moderate Bracken, 1981Bracken, 1981 1.81[0.55; 5.94]1,370118%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Kullander, 1976Kullander, 1976 0.56[0.26; 1.23]7518915%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Hartz, 1975Hartz, 1975 0.80[0.40; 1.60]2,19025717%ROB confusion: seriousROB selection: unclearROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 48% 1.18[0.82; 1.70]161,2377380.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.18[0.65; 2.15]159,11663861%NANoh, 2022 Hartz, 1975 2 case control studiescase control studies 1.13[0.57; 2.26]2,12110061%NACzeizel, 2004 Bracken, 1981 Kullander, 1976 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.04[0.62; 1.75]4,31135753%NACzeizel, 2004 Bracken, 1981 Kullander, 1976 Hartz, 1975 4 unexposed, sickunexposed, sick 1.50[1.06; 2.12]156,926381 -NANoh, 2022 1 Tags Adjustment   - No  - No 0.92[0.30; 2.85]2,12110061%NABracken, 1981 Kullander, 1976 2   - Yes  - Yes 1.35[1.00; 1.83]159,11663827%NANoh, 2022 Czeizel, 2004 Hartz, 1975 3 BZD Coexposure   - Not specified  - Not specified 1.05[0.62; 1.77]161,23773857%NANoh, 2022 Bracken, 1981 Kullander, 1976 Hartz, 1975 4   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.50[0.99; 2.27]-- -NACzeizel, 2004 1 Indication BZD   - Psychiatric diseases (depression, a ...  - Psychiatric diseases (depression, anxiety, ...) 1.81[0.55; 5.94]1,37011 -NABracken, 1981 1 MatchedMatched 1.50[0.99; 2.27]-- -NACzeizel, 2004 1 All studiesAll studies 1.18[0.82; 1.70]161,23773848%NANoh, 2022 Czeizel, 2004 Bracken, 1981 Kullander, 1976 Hartz, 1975 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.41.60.7280.000Noh, 2022Czeizel, 2004Bracken, 1981Kullander, 1976Hartz, 1975

Asymetry test p-value = 0.3453 (by Egger's regression)

slope=0.6716 (0.4052); intercept=-1.7141 (1.5343); t=1.1172; p=0.3453

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.62; 1.75]27,17635753%NACzeizel, 2004 Bracken, 1981 Kullander, 1976 Hartz, 1975 4 unexposed, sick controlsunexposed, sick controls 1.50[1.06; 2.12]156,926381 -NANoh, 2022 10.510.01.0