Phenytoin (All indications) 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.
S17390
R72907
Madley-Dowd_SE (Phenytoin) (Controls exposed to LTG) (Mixed indications), 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: Yes 1.32 [0.88;1.97]
excluded (control group)
26/194   243/5,035 269 194
ref
S17391
R72913
Madley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 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 (general population or NOS) Adjustment: Yes 1.13 [0.77;1.67] 26/194   147,608/2,651,210 147,634 194
ref
S17392
R72919
Madley-Dowd_SE (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 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 sibling excluded Adjustment: Yes 2.98 [0.81;11.01]
excluded (control group)
-/-   -/- - -
ref
S17283
R72369
Madley-Dowd_UK (Phenytoin) (Controls exposed to LTG) (Mixed indications), 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) exposed to other treatment, sick excluded Adjustment: Yes 1.31 [0.17;9.91]
excluded (control group)
-/46   14/939 - 46
ref
S17268
R72370
Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 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 (general population or NOS) Adjustment: Yes 2.15 [0.30;15.39] -/46   4,794/514,066 - 46
ref
S17276
R72371
Madley-Dowd_UK (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 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) sibling excluded Adjustment: Yes 38.49 [9.14;162.11]
excluded (control group)
-/-   -/- - -
ref
S9260
R48803
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 3 studies 1.13 [0.77;1.64] 147,639 257
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 Madley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_SE, 2024 1 1.13[0.77; 1.67]147,63419494%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK, 2024 2 2.15[0.30; 15.39]-464%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Cohen (Phenytoin), 2013Cohen, 2013 3 0.42[0.04; 4.11]5173%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: criticalROB mesure: lowROB reporting: low Total (3 studies) I2 = 0% 1.13[0.77; 1.64]147,6392570.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenytoin) (Controls unexposed, general pop) (Mixed indications; 2: Phenytoin) (Controls unexposed, general pop) (Mixed indications; 3: Phenytoin;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.13[0.77; 1.64]147,6392570%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Cohen (Phenytoin), 2013 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.16[0.79; 1.69]147,6342400%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 2 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 1.16[0.79; 1.69]147,6342400%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 2 All studiesAll studies 1.13[0.77; 1.64]147,6392570%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Cohen (Phenytoin), 2013 30.25.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 17390, 17392, 17283, 17276

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.16[0.79; 1.69]152,4192400%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.28[0.86; 1.88]2792570%NAMadley-Dowd_SE (Phenytoin) (Controls exposed to LTG) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls exposed to LTG) (Mixed indications), 2024 Cohen (Phenytoin), 2013 3 siblingssiblings Out of scale10.51[0.86; 128.98]--85%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 2024 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Attention deficit hyperacti ...Veroniki b (NMA) (Attention deficit hyperactivity disorder) 0.63[0.07; 4.07]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.13[0.77; 1.64]0%257----Madley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Cohen (Phenytoin), 2013 30.510.01.0