Phenytoin (Epilepsy) updated on 04-22-2025

ASD (Autism spectrum disorder): Diagnosis

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.
S17393
R72922		 Madley-Dowd_SE (Phenytoin) (Controls exposed to LTG), 2024 Autism - ICD-8/9/10 codes - 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 2.20 [0.98;4.92] C
excluded (control group) 		7/147   53/2,383 60 147
ref
S17394
R72926		 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 0.80 [0.38;1.70] 7/147   425/10,769 432 147
ref
S17253
R72210		 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Autism - ICD10 codes - 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 1.19 [0.17;8.52] -/45   78/4,075 - 45
ref
S6601
R18099		 Bromley (Phenytoin) (Controls exposed to Lamotrigine, sick), 2008 Autism spectrum disorder (a majority aged 6 and above) early pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No 5.38 [0.30;95.06] C
excluded (control group) 		1/9   1/44 2 9
ref
S6594
R18089		 Bromley (Phenytoin) (Controls unexposed, disease free), 2008 Autism spectrum disorder (a majority aged 6 and above) early pregnancy prospective cohort unexposed, disease free excluded Adjustment: No 13.88 [1.30;148.33] C
excluded (control group) 		1/9   3/336 4 9
ref
S6598
R18094		 Bromley (Phenytoin) (Controls unexposed, sick), 2008 Autism spectrum disorder (a majority aged 6 and above) early pregnancy prospective cohort unexposed, sick Adjustment: No 18.60 [0.69;500.42] C 1/9   0/47 1 9
ref
Total 3 studies 1.34 [0.37;4.89] 433 201
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, sick), 2024Madley-Dowd_SE, 2024 1 0.80[0.38; 1.70]43214760%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024Madley-Dowd_UK, 2024 2 1.19[0.17; 8.52]-4528%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Bromley (Phenytoin) (Controls unexposed, sick), 2008Bromley, 2008 3 18.60[0.69; 500.42]1913%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 41% 1.34[0.37; 4.89]4332010.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.34[0.37; 4.89]43320141%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Bromley (Phenytoin) (Controls unexposed, sick), 2008 3 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.34[0.37; 4.89]43320141%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Bromley (Phenytoin) (Controls unexposed, sick), 2008 3 Tags Adjustment   - No  - No 18.60[0.69; 500.42]19 -NABromley (Phenytoin) (Controls unexposed, sick), 2008 1   - Yes  - Yes 0.84[0.42; 1.69]4321920%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 2 All studiesAll studies 1.34[0.37; 4.89]43320141%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Bromley (Phenytoin) (Controls unexposed, sick), 2008 30.250.01.0

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 6601, 6594, 17393

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale13.88[1.30; 148.33]49 -NABromley (Phenytoin) (Controls unexposed, disease free), 2008 1 unexposed, sick controlsunexposed, sick controls 1.34[0.37; 4.89]50220141%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Phenytoin) (Epilepsy), 2024 Bromley (Phenytoin) (Controls unexposed, sick), 2008 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.35[1.08; 5.10]621560%NAMadley-Dowd_SE (Phenytoin) (Controls exposed to LTG), 2024 Bromley (Phenytoin) (Controls exposed to Lamotrigine, sick), 2008 20.510.01.0