Phenytoin (All indications) 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.
S17390
R72904		 Madley-Dowd_SE (Phenytoin) (Controls exposed to LTG) (Mixed indications), 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: Yes 1.18 [0.62;2.24]
excluded (control group) 		10/194   134/5,035 144 194
ref
S17391
R72910		 Madley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 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 (general population or NOS) Adjustment: Yes 0.97 [0.52;1.82] 10/194   68,788/2,651,210 68,798 194
ref
S17392
R72916		 Madley-Dowd_SE (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 2024 Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective sibling excluded Adjustment: Yes 5.34 [0.70;40.88]
excluded (control group) 		-/-   -/- - -
ref
S17283
R72333		 Madley-Dowd_UK (Phenytoin) (Controls exposed to LTG) (Mixed indications), 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) exposed to other treatment, sick excluded Adjustment: Yes 1.09 [0.15;7.66]
excluded (control group) 		-/46   20/939 - 46
ref
S17268
R72288		 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 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 (general population or NOS) Adjustment: Yes 1.19 [0.18;8.05] -/46   7,657/514,066 - 46
ref
S17276
R72312		 Madley-Dowd_UK (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 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) sibling excluded Adjustment: Yes 15.33 [4.45;52.85]
excluded (control group) 		-/-   -/- - -
ref
S9256
R32098		 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
S9257
R32099		 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
S9258
R32100		 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 1.37 [0.45;4.18] 68,799 249
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 0.97[0.52; 1.82]68,79819466%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024Madley-Dowd_UK, 2024 2 1.19[0.18; 8.05]-4624%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Bromley (Phenytoin) (Controls unexposed, sick), 2008Bromley, 2008 3 18.60[0.69; 500.42]1910%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 33% 1.37[0.45; 4.18]68,7992490.250.01.0ROB: 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) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.37[0.45; 4.18]68,79924933%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Bromley (Phenytoin) (Controls unexposed, sick), 2008 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.99[0.55; 1.79]68,7982400%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 2 unexposed, sickunexposed, sick 18.60[0.69; 500.42]19 -NABromley (Phenytoin) (Controls unexposed, sick), 2008 1 Tags Adjustment   - No  - No 18.60[0.69; 500.42]19 -NABromley (Phenytoin) (Controls unexposed, sick), 2008 1   - Yes  - Yes 0.99[0.55; 1.79]68,7982400%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 1.37[0.45; 4.18]68,79924933%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 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 9256, 9257, 17390, 17392, 17283, 17276

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.79[0.46; 6.93]76,45024956%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, general pop) (Mixed indications), 2024 Bromley (Phenytoin) (Controls unexposed, disease free), 2008 3 unexposed, sick controlsunexposed, sick controls Out of scale18.60[0.69; 500.42]19 -NABromley (Phenytoin) (Controls unexposed, sick), 2008 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.25[0.69; 2.27]1572490%NAMadley-Dowd_SE (Phenytoin) (Controls exposed to LTG) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls exposed to LTG) (Mixed indications), 2024 Bromley (Phenytoin) (Controls exposed to Lamotrigine, sick), 2008 3 siblingssiblings Out of scale11.53[4.01; 33.18]--0%NAMadley-Dowd_SE (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 2024 Madley-Dowd_UK (Phenytoin) (Controls unexposed, sibling) (Mixed indications), 2024 20.510.01.0