Diazepam updated on 02-10-2025

Cleft lip with or without 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.
S17689
R74658		 Laspro, 2024 Any cleft lip (ICD 10 codes Q36 or Q37) during pregnancy (anytime or not specified) excluded nested case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 1.25 [0.90;1.73]
excluded (exposition period) 		36/-   6,203/- 6,239 -
ref
S15602
R64327		 Tinker, 2019 Cleft lip with or without cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) 1.10 [0.40;2.90] 5/23   3,081/14,596 3,086 23
ref
S15661
R64650		 Czeizel, 2003 Cleft lip /- palate 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Matched 1.60 [0.90;2.70] -/-   1,378/- - -
ref
S15660
R64644		 Czeizel, 1987 Isolated cleft lip and/or cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified Matched 0.94 [0.47;1.88] C 16/33   614/1,227 630 33
ref
S15663
R64678		 Rosenberg, 1983 Cleft lip with or without cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: Yes BZD Coexposure: Not specified 0.80 [0.40;1.70] 10/64   435/2,879 445 64
ref
S15648
R64574		 Aarskog, 1975 Cleft lip with or without cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 5.77 [1.60;20.88] C 6/10   93/451 99 10
ref
S15665
R64681		 Safra, 1975 Cleft lip with or without cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: No BZD Coexposure: Not specified 4.10 [1.50;11.50] 7/16   42/262 49 16
ref
Total 6 studies 1.58 [0.92;2.71] 4,309 146
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 Tinker, 2019Tinker, 2019 1.10[0.40; 2.90]3,0862315%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Czeizel, 2003Czeizel, 2003 1.60[0.90; 2.70]--22%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Czeizel, 1987Czeizel, 1987 0.94[0.47; 1.88]6303319%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: moderateROB mesure: unclearROB reporting: moderate Rosenberg, 1983Rosenberg, 1983 0.80[0.40; 1.70]4456419%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Aarskog, 1975Aarskog, 1975 5.77[1.60; 20.88]991011%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Safra, 1975Safra, 1975 4.10[1.50; 11.50]491614%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Total (6 studies) I2 = 61% 1.58[0.92; 2.71]4,3091460.220.01.0ROB: 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 0 case control studiescase control studies 1.58[0.92; 2.71]4,30914661%NATinker, 2019 Czeizel, 2003 Czeizel, 1987 Rosenberg, 1983 Aarskog, 1975 Safra, 1975 6 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.58[0.92; 2.71]4,30914661%NATinker, 2019 Czeizel, 2003 Czeizel, 1987 Rosenberg, 1983 Aarskog, 1975 Safra, 1975 6 Tags Adjustment   - No  - No 2.59[0.78; 8.62]7785978%NACzeizel, 1987 Aarskog, 1975 Safra, 1975 3   - Yes  - Yes 1.20[0.78; 1.86]3,5318712%NATinker, 2019 Czeizel, 2003 Rosenberg, 1983 3 BZD Coexposure   - Not specified  - Not specified 1.84[0.74; 4.56]1,22312376%NACzeizel, 1987 Rosenberg, 1983 Aarskog, 1975 Safra, 1975 4   - Yes (with psychiatric (ATD and/or p ...  - Yes (with psychiatric (ATD and/or psychotropics) medications) 1.47[0.91; 2.37]3,086230%NATinker, 2019 Czeizel, 2003 2 MatchedMatched 1.28[0.77; 2.14]6303328%NACzeizel, 2003 Czeizel, 1987 2 All studiesAll studies 1.58[0.92; 2.71]4,30914661%NATinker, 2019 Czeizel, 2003 Czeizel, 1987 Rosenberg, 1983 Aarskog, 1975 Safra, 1975 60.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.12.10.7870.000Tinker, 2019Czeizel, 2003Czeizel, 1987Rosenberg, 1983Aarskog, 1975Safra, 1975

Asymetry test p-value = 0.2639 (by Egger's regression)

slope=-0.7690 (0.8999); intercept=2.9424 (2.2659); t=1.2986; p=0.2639

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) 1.58[0.92; 2.71]5,67814661%NATinker, 2019 Czeizel, 2003 Czeizel, 1987 Rosenberg, 1983 Aarskog, 1975 Safra, 1975 60.510.01.0