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

Psychomotor developmental 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
R82285		 Straub (Controls exposed to LTG) (Phenytoin) (Epilepsy), 2026 Coordination disorders - ICD-10 codes: F82 - 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 1.26 [0.68;2.32] C
excluded (control group) 		16/1,390   30/3,273 46 1,390
ref
S19370
R82141		 Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Coordination disorders - ICD-10 codes: F82 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 1.02 [0.57;1.84] 16/1,390   91/8,887 107 1,390
ref
S16619
R69700		 Thomas b (Phenytoin) (Epilepsy) (Controls exposed to LTG), 2022 Delayed motor development quotient (< 84, i.e one SD of the mean) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 5.68 [0.71;45.30] C
excluded (control group) 		15/81   1/26 16 81
ref
S16620
R69701		 Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 The motor development quotient (MODQ) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 1.09 [0.65;1.83] -/81   -/110 - 81
ref
S9259
R32101		 Cohen (Phenytoin), 2011 Motor Index score (the Bayley Scales of Infant Development (BSID-II)) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes extrapolated (cont. endpoint) 0.60 [0.28;1.31] -/32   -/62 - 32
ref
S9263
R32123		 Koch (Phenytoin), 1996 Minor neurological dysfunction (at age 6) (Touwen) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched 0.83 [0.08;8.43] C 1/10   4/34 5 10
ref
Total 4 studies 0.94 [0.67;1.33] 112 1,513
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 1.02[0.57; 1.84]1071,39034%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022Thomas b, 2022 2 1.09[0.65; 1.83]-8144%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Cohen (Phenytoin), 2011Cohen, 2011 3 0.60[0.28; 1.31]-3220%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Koch (Phenytoin), 1996Koch, 1996 4 0.83[0.08; 8.43]5102%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 0% 0.94[0.67; 1.33]1121,5130.25.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.94[0.67; 1.33]1121,5130%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 Cohen (Phenytoin), 2011 Koch (Phenytoin), 1996 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.83[0.08; 8.43]510 -NAKoch (Phenytoin), 1996 1 unexposed, sickunexposed, sick 1.06[0.72; 1.56]1071,4710%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 2 exposed to other treatment, sickexposed to other treatment, sick 0.60[0.28; 1.30]-32 -NACohen (Phenytoin), 2011 1 Tags Adjustment   - No  - No 1.08[0.65; 1.78]5910%NAThomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 Koch (Phenytoin), 1996 2   - Yes  - Yes 0.83[0.50; 1.38]1071,42213%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Cohen (Phenytoin), 2011 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 0.87[0.49; 1.53]-11337%NAThomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 Cohen (Phenytoin), 2011 2 MatchedMatched 0.83[0.08; 8.43]510 -NAKoch (Phenytoin), 1996 1 All studiesAll studies 0.94[0.67; 1.33]1121,5130%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 Cohen (Phenytoin), 2011 Koch (Phenytoin), 1996 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.82.71.4170.000Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022Cohen (Phenytoin), 2011Koch (Phenytoin), 1996

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 16619, 19381

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.83[0.08; 8.43]510 -NAKoch (Phenytoin), 1996 1 unexposed, sick controlsunexposed, sick controls 1.06[0.72; 1.56]1071,4710%NAStraub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.14[0.48; 2.67]621,50359%NAStraub (Controls exposed to LTG) (Phenytoin) (Epilepsy), 2026 Thomas b (Phenytoin) (Epilepsy) (Controls exposed to LTG), 2022 Cohen (Phenytoin), 2011 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Psychomotor developmental delay)Veroniki b (NMA) (Psychomotor developmental delay) 2.84[0.97; 7.93]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 0.94[0.67; 1.33]0%1,513----Straub (Controls unexposed, sick) (Phenytoin) (Epilepsy), 2026 Thomas b (Phenytoin) (Epilepsy) (Controls unexposed, sick), 2022 Cohen (Phenytoin), 2011 Koch (Phenytoin), 1996 40.510.01.0