Phenytoin (Epilepsy) updated on 04-22-2025

ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk

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.
S19463
R82986
Straub (Controls exposed to LTG) (Phenytoin) (Epilepsy), 2026 Attention deficit hyperactivity disorder (ADHD) - ICD-10 codes: F90.x - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 2.96 [2.26;3.89] C
excluded (control group)
121/1,390   102/3,273 223 1,390
ref
S19473
R83110
Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Attention deficit hyperactivity disorder (ADHD) - ICD-10 codes: F90.x - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.97 [0.78;1.21] 121/1,390   366/8,887 487 1,390
ref
S17393
R72932
Madley-Dowd_SE (Phenytoin) (Controls exposed to LTG), 2024 Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 3.87 [2.38;6.28] C
excluded (control group)
23/147   109/2,383 132 147
ref
S17394
R72933
Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.14 [0.75;1.73] 23/147   929/10,769 952 147
ref
S17253
R72262
Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median follow up 10.75 (7.82-13.62) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 3.23 [0.40;26.19] -/45   38/4,075 - 45
ref
S7292
R48810
Cohen (Phenytoin), 2013 Children with either ADHD inattentive OR combined types > 1 SD (from the Attention Problems and Hyperactivity scales of the BASC) (Both Parent and Teacher) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 0.42 [0.04;4.11] C 1/17   4/31 5 17
ref
Total 4 studies 1.01 [0.83;1.22] 1,444 1,599
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 Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026Straub, 2026 1 0.97[0.78; 1.21]4871,39077%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 2 1.14[0.75; 1.73]95214721%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024Madley-Dowd_UK, 2024 3 3.23[0.40; 26.19]-451%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Cohen (Phenytoin), 2013Cohen, 2013 4 0.42[0.04; 4.11]5171%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: criticalROB mesure: lowROB reporting: low Total (4 studies) I2 = 0% 1.01[0.83; 1.22]1,4441,5990.210.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.01[0.83; 1.22]1,4441,5990%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Cohen (Phenytoin), 2013 4 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.01[0.84; 1.23]1,4391,5820%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 3 exposed to other treatment, sickexposed to other treatment, sick 0.42[0.04; 4.11]517 -NACohen (Phenytoin), 2013 1 Tags Adjustment   - No  - No 0.42[0.04; 4.11]517 -NACohen (Phenytoin), 2013 1   - Yes  - Yes 1.01[0.84; 1.23]1,4391,5820%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 3 All studiesAll studies 1.01[0.83; 1.22]1,4441,5990%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Cohen (Phenytoin), 2013 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.72.71.3940.000Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024Cohen (Phenytoin), 2013

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 17393, 19463

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 1.01[0.84; 1.23]1,4681,5820%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.06[1.96; 4.79]3601,55448%NAStraub (Controls exposed to LTG) (Phenytoin) (Epilepsy), 2026 Madley-Dowd_SE (Phenytoin) (Controls exposed to LTG), 2024 Cohen (Phenytoin), 2013 30.510.01.0