Phenytoin (Epilepsy)

Limb defects

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.
S12848
R48436		 Thomas (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 Skeletal malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.26 [0.05;31.56] C
excluded (control group) 		1/119   0/50 1 119
ref
S12849
R48446		 Thomas (Phenytoin) (Controls unexposed, sick), 2021 Skeletal malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 1.43 [0.13;15.94] C 1/119   2/340 3 119
ref
S10299
R37738		 Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 Skeletal / Limb Malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 7.23 [0.14;369.08] C
excluded (control group) 		0/44   0/315 0 44
ref
S9842
R37742		 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Skeletal / Limb Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.11 [0.04;27.86] C 0/44   1/147 1 44
ref
S9851
R35383		 Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.82 [0.07;49.76] C
excluded (control group) 		0/7   1/37 1 7
ref
S9852
R35389		 Mawer (Phenytoin) (Controls unexposed, disease free), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 43.77 [0.80;2381.04] C
excluded (control group) 		0/7   0/285 0 7
ref
S9853
R35395		 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 6.23 [0.11;342.42] C 0/7   0/41 0 7
ref
S319
R15726		 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 Skeletal abnormalities 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.58 [0.08;33.23] C 0/82   2/647 2 82
ref
S6098
R35922		 Artama (Phenytoin), 2005 Certain musculoskeletal deformities and Other anomalies of limbs 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 3.60 [0.43;30.01] C 1/38   7/939 8 38
ref
Total 5 studies 2.20 [0.64;7.52] 14 290
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 Thomas (Phenytoin) (Controls unexposed, sick), 2021Thomas, 2021 1 1.43[0.13; 15.94]311926%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Phenytoin) (Controls unexposed, sick), 2013Vajda, 2013 2 1.11[0.04; 27.86]14415%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mawer (Phenytoin) (Controls unexposed, sick), 2010Mawer, 2010 3 6.23[0.11; 342.42]079%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006Morrow, 2006 4 1.58[0.08; 33.23]28216%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Artama (Phenytoin), 2005Artama, 2005 5 3.60[0.43; 30.01]83834%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 2.20[0.64; 7.52]142900.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.20[0.64; 7.52]142900%NAThomas (Phenytoin) (Controls unexposed, sick), 2021 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 Artama (Phenytoin), 2005 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 2.34[0.61; 8.98]122080%NAThomas (Phenytoin) (Controls unexposed, sick), 2021 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Artama (Phenytoin), 2005 4 exposed to other treatment, sickexposed to other treatment, sick 1.58[0.08; 33.23]282 -NAMorrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 1 Tags Adjustment   - No  - No 2.20[0.64; 7.52]142900%NAThomas (Phenytoin) (Controls unexposed, sick), 2021 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 Artama (Phenytoin), 2005 5 All studiesAll studies 2.20[0.64; 7.52]142900%NAThomas (Phenytoin) (Controls unexposed, sick), 2021 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 Artama (Phenytoin), 2005 50.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.62.4530.000Thomas (Phenytoin) (Controls unexposed, sick), 2021Vajda (Phenytoin) (Controls unexposed, sick), 2013Mawer (Phenytoin) (Controls unexposed, sick), 2010Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006Artama (Phenytoin), 2005

Asymetry test p-value = 0.9801 (by Egger's regression)

slope=0.8268 (1.5016); intercept=-0.0290 (1.0702); t=0.0271; p=0.9801

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9851, 9852, 10299, 12848

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale43.77[0.80; 2381.04]-7 -NAMawer (Phenytoin) (Controls unexposed, disease free), 2010 1 unexposed, sick controlsunexposed, sick controls 2.34[0.61; 8.98]122080%NAThomas (Phenytoin) (Controls unexposed, sick), 2021 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Artama (Phenytoin), 2005 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.03[0.38; 10.72]42520%NAThomas (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 40.510.01.0