Phenytoin (All indications) updated on 04-22-2025

Language disorders/delay

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.
S19381
R82282		 Straub (Controls exposed to LTG) (Phenytoin) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - 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 1.01 [0.76;1.33] C
excluded (control group) 		75/1,390   175/3,273 250 1,390
ref
S19370
R82138		 Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.76 [0.59;0.99] 75/1,390   456/8,887 531 1,390
ref
S12898
R48734		 Adams (Phenytoin), 2022 Verbal IQ - The Wechsler Intelligence Scale for Children, 3rd Edition (WISC-III) (mean >6 years old) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) Matched 1.11 [0.50;2.45] -/40   -/40 - 40
ref
S15272
R62773		 Thomas a (Phenytoin), 2022 Verbal IQ/Verbal comprehension index (VCI) - Wechsler Intelligence Scale for Children or Adult - Ages 13 to 21 years (mean of 16.5 ± 2.2 years) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 2.05 [0.43;9.86] -/10   -/11 - 10
ref
S9266
R32139		 Meador (Phenytoin), 2013 Verbal index score (at age 6 years old) (Created by averaging standard scores) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes extrapolated (cont. endpoint) 0.85 [0.42;1.71] -/40   -/74 - 40
ref
S9271
R32149		 Vinten (Phenytoin), 2005 Verbal IQ score <69 (Wechsler Intelligence Scale for Children (WISC III)) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.28 [0.01;5.10] C 0/21   6/80 6 21
ref
Total 5 studies 0.81 [0.64;1.01] 537 1,501
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 0.76[0.59; 0.99]5311,39078%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Adams (Phenytoin), 2022Adams, 2022 2 1.11[0.50; 2.45]-408%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: lowROB reporting: moderate Thomas a (Phenytoin), 2022Thomas a, 2022 3 2.05[0.43; 9.86]-102%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Meador (Phenytoin), 2013Meador, 2013 4 0.85[0.42; 1.71]-4011%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Vinten (Phenytoin), 2005Vinten, 2005 5 0.28[0.01; 5.10]6211%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Total (5 studies) I2 = 0% 0.81[0.64; 1.01]5371,5010.25.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Phenytoin) (Epilepsy; 2: Phenytoin; 3: Phenytoin; 4: Phenytoin; 5: Phenytoin;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.81[0.64; 1.01]5371,5010%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Adams (Phenytoin), 2022 Thomas a (Phenytoin), 2022 Meador (Phenytoin), 2013 Vinten (Phenytoin), 2005 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 0.80[0.63; 1.02]5371,4610%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Adams (Phenytoin), 2022 Thomas a (Phenytoin), 2022 Vinten (Phenytoin), 2005 4 exposed to other treatment, sickexposed to other treatment, sick 0.85[0.42; 1.72]-40 -NAMeador (Phenytoin), 2013 1 Tags Adjustment   - No  - No 1.16[0.58; 2.30]6710%NAAdams (Phenytoin), 2022 Thomas a (Phenytoin), 2022 Vinten (Phenytoin), 2005 3   - Yes  - Yes 0.77[0.60; 0.98]5311,4300%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Meador (Phenytoin), 2013 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.03[0.63; 1.70]-900%NAAdams (Phenytoin), 2022 Thomas a (Phenytoin), 2022 Meador (Phenytoin), 2013 3 MatchedMatched 1.11[0.50; 2.46]-40 -NAAdams (Phenytoin), 2022 1 All studiesAll studies 0.81[0.64; 1.01]5371,5010%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Adams (Phenytoin), 2022 Thomas a (Phenytoin), 2022 Meador (Phenytoin), 2013 Vinten (Phenytoin), 2005 50.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.31.7860.000Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026Adams (Phenytoin), 2022Thomas a (Phenytoin), 2022Meador (Phenytoin), 2013Vinten (Phenytoin), 2005

Asymetry test p-value = 0.5015 (by Egger's regression)

slope=-0.3101 (0.1601); intercept=0.4669 (0.6128); t=0.7619; p=0.5015

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 19381

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 0.80[0.63; 1.02]5371,4610%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Adams (Phenytoin), 2022 Thomas a (Phenytoin), 2022 Vinten (Phenytoin), 2005 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.99[0.76; 1.28]2501,4300%NAStraub (Controls exposed to LTG) (Phenytoin) (Epilepsy), 2026 Meador (Phenytoin), 2013 20.510.01.0