Phenytoin (Epilepsy)

Neural Tube 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.
S7661
R22671		 Tomson (Phenytoin), 2018 Neural tube defects at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 20.27 [1.26;325.93] C 1/125   1/2,514 2 125
ref
S10299
R37735		 Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 Neural Tube Malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 22.20 [0.89;553.77] C
excluded (control group) 		1/44   0/315 1 44
ref
S9842
R37739		 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Neural Tube Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 10.34 [0.41;258.52] C 1/44   0/147 1 44
ref
S5878
R23784		 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Neural tube defects 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 0.75 [0.04;15.67] C 0/416   2/1,562 2 416
ref
S6501
R17862		 Bànhidy (Phenytoin), 2011 Neural tube defects throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.53 [0.03;9.34] C 1/20   1/11 2 20
ref
S9851
R35380		 Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 Neural Tube Malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 5.62 [0.10;309.00] C
excluded (control group) 		0/7   0/37 0 7
ref
S9852
R35386		 Mawer (Phenytoin) (Controls unexposed, disease free), 2010 Neural Tube Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 14.54 [0.54;391.72] C
excluded (control group) 		0/7   1/285 1 7
ref
S9853
R35392		 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Neural Tube Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 6.23 [0.11;342.42] C 0/7   0/41 0 7
ref
S319
R15674		 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 Neural tube defect 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.64 [0.11;65.35] C 0/82   1/647 1 82
ref
Total 6 studies 3.20 [0.89;11.45] 8 694
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 Tomson (Phenytoin), 2018Tomson, 2018 1 20.27[1.26; 325.93]212521%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Phenytoin) (Controls unexposed, sick), 2013Vajda, 2013 2 10.34[0.41; 258.52]14416%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 3 0.75[0.04; 15.67]241618%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Phenytoin), 2011Bànhidy, 2011 4 0.53[0.03; 9.34]22020%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Mawer (Phenytoin) (Controls unexposed, sick), 2010Mawer, 2010 5 6.23[0.11; 342.42]0710%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006Morrow, 2006 6 2.64[0.11; 65.35]18216%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 0% 3.20[0.89; 11.45]86940.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenytoin; 2: Phenytoin) (Controls unexposed, sick; 3: Phenytoin) (Controls exposed to Lamotrigine, sick; 4: Phenytoin; 5: Phenytoin) (Controls unexposed, sick; 6: Phenytoin) (Controls exposed to Lamotrigine, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 4.98[1.20; 20.66]66740%NATomson (Phenytoin), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 5 case control studiescase control studies 0.53[0.03; 9.34]220 -NABànhidy (Phenytoin), 2011 1 Type of controls unexposed, sickunexposed, sick 2.57[0.37; 17.71]3714%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Bànhidy (Phenytoin), 2011 Mawer (Phenytoin) (Controls unexposed, sick), 2010 3 exposed to other treatment, sickexposed to other treatment, sick 3.76[0.53; 26.45]562321%NATomson (Phenytoin), 2018 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 3 Tags Adjustment   - No  - No 3.20[0.89; 11.45]86940%NATomson (Phenytoin), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Phenytoin), 2011 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 6 Controls   - mixed indications  - mixed indications 0.75[0.04; 15.67]2416 -NAHernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 1 MatchedMatched 0.53[0.03; 9.34]220 -NABànhidy (Phenytoin), 2011 1 All studiesAll studies 3.20[0.89; 11.45]86940%NATomson (Phenytoin), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2013 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Phenytoin), 2011 Mawer (Phenytoin) (Controls unexposed, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 60.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.86.02.4530.000Tomson (Phenytoin), 2018Vajda (Phenytoin) (Controls unexposed, sick), 2013Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Phenytoin), 2011Mawer (Phenytoin) (Controls unexposed, sick), 2010Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006

Asymetry test p-value = 0.8479 (by Egger's regression)

slope=-0.1267 (6.3432); intercept=0.8142 (3.9797); t=0.2046; p=0.8479

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9851, 9852, 10299

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale14.54[0.54; 391.72]17 -NAMawer (Phenytoin) (Controls unexposed, disease free), 2010 1 unexposed, sick controlsunexposed, sick controls 2.57[0.37; 17.71]3714%NAVajda (Phenytoin) (Controls unexposed, sick), 2013 Bànhidy (Phenytoin), 2011 Mawer (Phenytoin) (Controls unexposed, sick), 2010 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 5.71[1.38; 23.67]66740%NATomson (Phenytoin), 2018 Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 50.510.01.0