Phenytoin (All indications) updated on 04-22-2025

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.
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

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (MA) (All indications) (Cleft Lip/ ...Veroniki a (MA) (All indications) (Cleft Lip/Palate) 4.88[1.55; 18.46]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT10 Veroniki a (NMA) (All indications) (Cleft lip ...Veroniki a (NMA) (All indications) (Cleft lip/palate) 3.11[1.30; 7.72]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT-9 metaPregmetaPreg 5.07[0.94; 27.30]0%113----Vajda (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