Phenytoin (All indications)

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.
S10301
R37748		 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Palate/lip malformation at least 1st trimester prospective cohort unexposed, sick Adjustment: No 3.37 [0.07;172.23] C 0/44   0/147 0 44
ref
S9225
R32016		 Bànhidy (Phenytoin), 2011 Cleft lip with or without cleft palate throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.57 [0.01;30.76] C 1/20   0/10 1 20
ref
S9220
R31994		 Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 Cleft lip throughout pregnancy prospective cohort unexposed, sick Adjustment: No 34.33 [0.49;2389.88] C 0/2   0/52 0 2
ref
S9224
R32006		 Artama (Phenytoin), 2005 Cleft lip/ cleft palate 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 4.99 [0.24;105.88] C 0/38   2/939 2 38
ref
S9236
R32053		 Lowe (Phenytoin) (Controls unexposed, disease free), 1973 Cleft lip and/or cleft palate 1st trimester population based cohort retrospective unexposed, disease free excluded Adjustment: No 37.53 [2.14;659.17] C
excluded (control group) 		0/9   49/31,632 49 9
ref
S9237
R32055		 Lowe (Phenytoin) (Controls unexposed, sick), 1973 Cleft lip and/or cleft palate 1st trimester population based cohort retrospective unexposed, sick Adjustment: No 13.00 [0.24;696.83] C 0/9   0/111 0 9
ref
Total 5 studies 5.07 [0.94;27.30] 3 113
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 Vajda (Phenytoin) (Controls unexposed, sick), 2013Vajda, 2013 1 3.37[0.07; 172.23]04418%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Bànhidy (Phenytoin), 2011Bànhidy, 2011 2 0.57[0.01; 30.76]12018%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006Viinikainen, 2006 3 34.33[0.49; 2389.88]0216%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Artama (Phenytoin), 2005Artama, 2005 4 4.99[0.24; 105.88]23830%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lowe (Phenytoin) (Controls unexposed, sick), 1973Lowe, 1973 5 13.00[0.24; 696.83]0918%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 5.07[0.94; 27.30]31130.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenytoin) (Controls unexposed, sick; 2: Phenytoin; 3: Phenytoin) (Controls unexposed, sick) ; 4: Phenytoin; 5: Phenytoin) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 8.14[1.27; 52.08]2930%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 Artama (Phenytoin), 2005 Lowe (Phenytoin) (Controls unexposed, sick), 1973 4 case control studiescase control studies 0.57[0.01; 30.76]120 -NABànhidy (Phenytoin), 2011 1 Type of controls unexposed, sickunexposed, sick 5.07[0.94; 27.30]31130%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Bànhidy (Phenytoin), 2011 Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 Artama (Phenytoin), 2005 Lowe (Phenytoin) (Controls unexposed, sick), 1973 5 Tags Adjustment   - No  - No 5.07[0.94; 27.30]31130%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Bànhidy (Phenytoin), 2011 Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 Artama (Phenytoin), 2005 Lowe (Phenytoin) (Controls unexposed, sick), 1973 5 MatchedMatched 0.57[0.01; 30.76]120 -NABànhidy (Phenytoin), 2011 1 All studiesAll studies 5.07[0.94; 27.30]31130%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Bànhidy (Phenytoin), 2011 Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 Artama (Phenytoin), 2005 Lowe (Phenytoin) (Controls unexposed, sick), 1973 50.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.16.72.5980.000Vajda (Phenytoin) (Controls unexposed, sick), 2013Bànhidy (Phenytoin), 2011Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006Artama (Phenytoin), 2005Lowe (Phenytoin) (Controls unexposed, sick), 1973

Asymetry test p-value = 0.8213 (by Egger's regression)

slope=0.1701 (5.9478); intercept=0.7631 (3.0983); t=0.2463; p=0.8213

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9236

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale37.53[2.14; 659.17]499 -NALowe (Phenytoin) (Controls unexposed, disease free), 1973 1 unexposed, sick controlsunexposed, sick controls 5.07[0.94; 27.30]31130%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Bànhidy (Phenytoin), 2011 Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 Artama (Phenytoin), 2005 Lowe (Phenytoin) (Controls unexposed, sick), 1973 50.510.01.0