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

Cleft palate

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.
S16123
R66892		 Laspro - BZDs, 2024 Isolated Cleft Palate (ICD-10 code Q35 excluding Q36 or Q37) during pregnancy (anytime or not specified) excluded nested case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 1.40 [1.29;1.53]
excluded (exposition period) 		616/-   5,243/- 5,859 -
ref
S15464
R63596		 Blotière - Clonazepam (Other indications), 2019 Cleft palate 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No BZD Coexposure: No (among antiseizure medications) 1.63 [0.23;11.56] C 1/980   1,178/1,875,733 1,179 980
ref
S15593
R64211		 Tinker - BZDs, 2019 Cleft palate alone 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) 1.20 [0.70;2.10] 15/96   1,563/13,015 1,578 96
ref
S15535
R63821		 Czeizel - Diazepam, 2003 Cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Matched 1.00 [0.30;2.90] -/-   606/- - -
ref
S17769
R75085		 Robert - BZDs, 1994 Cleft palate (ICD-9 749.0) 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 0.97 [0.02;5.49] 1/-   39/- 40 -
ref
S15357
R63172		 Czeizel - Diazepam, 1987 Isolated posterior cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified Matched 0.75 [0.16;3.38] C 3/7   176/351 179 7
ref
S15361
R63194		 Rosenberg - Diazepam, 1983 Cleft palate alone 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 0.80 [0.20;2.50] 3/57   163/2,607 166 57
ref
S15497
R63693		 Aarskog - Diazepam, 1975 Clef palate 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 8.14 [0.84;78.91] C 1/5   11/369 12 5
ref
S15363
R63201		 Safra - Diazepam, 1975 Cleft palate alone 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 0.85 [0.11;6.81] C 1/16   19/262 20 16
ref
S15362
R63196		 Saxen - BZDs, 1975 Isolated cleft palate only 1st trimester nested case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified Matched 2.84 [1.01;8.02] C 14/19   218/439 232 19
ref
Total 9 studies 1.30 [0.89;1.90] 3,406 1,180
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 Blotière - Clonazepam (Other indications), 2019Blotière - Clonazepam, 2019 1 1.63[0.23; 11.56]1,1799804%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tinker - BZDs, 2019Tinker - BZDs, 2019 1.20[0.70; 2.10]1,5789648%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Czeizel - Diazepam, 2003Czeizel - Diazepam, 2003 1.00[0.30; 2.90]--11%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Robert - BZDs, 1994Robert - BZDs, 1994 0.97[0.02; 5.49]40-2%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Czeizel - Diazepam, 1987Czeizel - Diazepam, 1987 0.75[0.16; 3.38]17976%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: moderateROB mesure: unclearROB reporting: moderate Rosenberg - Diazepam, 1983Rosenberg - Diazepam, 1983 0.80[0.20; 2.50]166579%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Aarskog - Diazepam, 1975Aarskog - Diazepam, 1975 8.14[0.84; 78.91]1253%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Safra - Diazepam, 1975Safra - Diazepam, 1975 0.85[0.11; 6.81]20163%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Saxen - BZDs, 1975Saxen - BZDs, 1975 2.84[1.01; 8.02]2321913%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (9 studies) I2 = 0% 1.30[0.89; 1.90]3,4061,1800.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Other indications;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.63[0.23; 11.56]1,179980 -NABlotière - Clonazepam (Other indications), 2019 1 case control studiescase control studies 1.29[0.87; 1.90]2,2272000%NATinker - BZDs, 2019 Czeizel - Diazepam, 2003 Robert - BZDs, 1994 Czeizel - Diazepam, 1987 Rosenberg - Diazepam, 1983 Aarskog - Diazepam, 1975 Safra - Diazepam, 1975 Saxen - BZDs, 1975 8 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.30[0.89; 1.90]3,4061,1800%NABlotière - Clonazepam (Other indications), 2019 Tinker - BZDs, 2019 Czeizel - Diazepam, 2003 Robert - BZDs, 1994 Czeizel - Diazepam, 1987 Rosenberg - Diazepam, 1983 Aarskog - Diazepam, 1975 Safra - Diazepam, 1975 Saxen - BZDs, 1975 9 Tags Adjustment   - No  - No 1.84[0.94; 3.63]1,6621,0270%NABlotière - Clonazepam (Other indications), 2019 Robert - BZDs, 1994 Czeizel - Diazepam, 1987 Aarskog - Diazepam, 1975 Safra - Diazepam, 1975 Saxen - BZDs, 1975 6   - Yes  - Yes 1.10[0.70; 1.75]1,7441530%NATinker - BZDs, 2019 Czeizel - Diazepam, 2003 Rosenberg - Diazepam, 1983 3 BZD Coexposure   - No (among antiseizure medications)  - No (among antiseizure medications) 1.63[0.23; 11.56]1,179980 -NABlotière - Clonazepam (Other indications), 2019 1   - Not specified  - Not specified 1.49[0.75; 2.98]64910413%NARobert - BZDs, 1994 Czeizel - Diazepam, 1987 Rosenberg - Diazepam, 1983 Aarskog - Diazepam, 1975 Safra - Diazepam, 1975 Saxen - BZDs, 1975 6   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.16[0.71; 1.90]1,578960%NATinker - BZDs, 2019 Czeizel - Diazepam, 2003 2 MatchedMatched 1.43[0.63; 3.22]4112628%NACzeizel - Diazepam, 2003 Czeizel - Diazepam, 1987 Saxen - BZDs, 1975 3 All studiesAll studies 1.30[0.89; 1.90]3,4061,1800%NABlotière - Clonazepam (Other indications), 2019 Tinker - BZDs, 2019 Czeizel - Diazepam, 2003 Robert - BZDs, 1994 Czeizel - Diazepam, 1987 Rosenberg - Diazepam, 1983 Aarskog - Diazepam, 1975 Safra - Diazepam, 1975 Saxen - BZDs, 1975 90.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.43.61.7190.000Blotière - Clonazepam (Other indications), 2019Tinker - BZDs, 2019Czeizel - Diazepam, 2003Robert - BZDs, 1994Czeizel - Diazepam, 1987Rosenberg - Diazepam, 1983Aarskog - Diazepam, 1975Safra - Diazepam, 1975Saxen - BZDs, 1975

Asymetry test p-value = 0.7280 (by Egger's regression)

slope=0.1399 (0.3796); intercept=0.2358 (0.6512); t=0.3621; p=0.7280

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) 1.30[0.89; 1.90]4,0031,1800%NABlotière - Clonazepam (Other indications), 2019 Tinker - BZDs, 2019 Czeizel - Diazepam, 2003 Robert - BZDs, 1994 Czeizel - Diazepam, 1987 Rosenberg - Diazepam, 1983 Aarskog - Diazepam, 1975 Safra - Diazepam, 1975 Saxen - BZDs, 1975 90.510.01.0