Phenytoin (All indications)

Neuro-developmental disorders (as a whole)

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.
S9186
R31768		 Arkilo (Phenytoin), 2015 Abnormal development (At 2 years of age, assessed by developmental specialists) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 0.96 [0.04;23.49] C 0/5   2/24 2 5
ref
S9229
R32031		 Dean (Phenytoin) (Controls exposed to Lamotrigine, sick), 2007 Neurodevelopmental disorder (mean age in years: m1=11.6 and m0=1.5) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No 3.84 [0.18;83.45] C
excluded (control group) 		8/24   0/4 8 24
ref
S9230
R32033		 Dean (Phenytoin) (Controls unexposed, sick), 2007 Neurodevelopmental disorder (mean age in years: m1=11.6 and m0=15.25) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 7.17 [1.69;30.42] C 8/24   3/46 11 24
ref
S9184
R31759		 Adab (Phenytoin), 2004 Any additional educational needs during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.98 [0.36;2.68] 7/22   28/87 35 22
ref
S9208
R31952		 Katz (Phenytoin), 2001 Developmental delay (Based on the DSM-IV-TR criteria) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 7.00 [0.22;218.96] C 3/6   0/3 3 6
ref
Total 4 studies 2.37 [0.65;8.62] 51 57
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 Arkilo (Phenytoin), 2015Arkilo, 2015 1 0.96[0.04; 23.49]2513%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Dean (Phenytoin) (Controls unexposed, sick), 2007Dean, 2007 2 7.17[1.69; 30.42]112433%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: criticalROB reporting: moderate Adab (Phenytoin), 2004Adab, 2004 3 0.98[0.36; 2.68]352243%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Katz (Phenytoin), 2001Katz, 2001 4 7.00[0.22; 218.96]3611%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 47% 2.37[0.65; 8.62]51570.220.01.0ROB: 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; 4: Phenytoin;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.37[0.65; 8.62]515747%NAArkilo (Phenytoin), 2015 Dean (Phenytoin) (Controls unexposed, sick), 2007 Adab (Phenytoin), 2004 Katz (Phenytoin), 2001 4 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 2.47[0.35; 17.27]464680%NADean (Phenytoin) (Controls unexposed, sick), 2007 Adab (Phenytoin), 2004 2 exposed to other treatment, sickexposed to other treatment, sick 2.41[0.23; 25.10]5110%NAArkilo (Phenytoin), 2015 Katz (Phenytoin), 2001 2 Tags Adjustment   - No  - No 2.37[0.65; 8.62]515747%NAArkilo (Phenytoin), 2015 Dean (Phenytoin) (Controls unexposed, sick), 2007 Adab (Phenytoin), 2004 Katz (Phenytoin), 2001 4 All studiesAll studies 2.37[0.65; 8.62]515747%NAArkilo (Phenytoin), 2015 Dean (Phenytoin) (Controls unexposed, sick), 2007 Adab (Phenytoin), 2004 Katz (Phenytoin), 2001 40.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.15.02.1080.000Arkilo (Phenytoin), 2015Dean (Phenytoin) (Controls unexposed, sick), 2007Adab (Phenytoin), 2004Katz (Phenytoin), 2001

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9229

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 2.47[0.35; 17.27]464680%NADean (Phenytoin) (Controls unexposed, sick), 2007 Adab (Phenytoin), 2004 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.86[0.44; 18.45]13350%NAArkilo (Phenytoin), 2015 Dean (Phenytoin) (Controls exposed to Lamotrigine, sick), 2007 Katz (Phenytoin), 2001 30.510.01.0