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

Small for gestational age (weight)

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.
S16075
R66710
Christensen (Phenytoin) (All indications) (Controls exposed to LTG), 2024 Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations)) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.81 [0.37;1.75] C
excluded (control group)
7/81   920/8,756 927 81
ref
S16049
R66611
Christensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 0.79 [0.36;1.73] 7/81   446,267/4,467,848 446,274 81
ref
S9192
R31821
Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020 Small for gestational age (birth weight) throughout pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 13.00 [0.10;1680.94] C
excluded (control group)
0/1   0/7 0 1
ref
S9193
R31831
Aydin (Phenytoin) (Controls unexposed, sick), 2020 Small for gestational age (birth weight) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 43.00 [0.35;5328.22] C 0/1   0/22 0 1
ref
S9272
R32151
Bank (Phenytoin) (Mixed indications), 2017 Small for Gestational Age birthweight (<10th percentile) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.86 [0.07;46.97] C 0/3   3/36 3 3
ref
S9216
R31975
Pennell (Phenytoin), 2012 Small for gestational age (SGA) (at birth) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes 0.56 [0.09;3.46] 2/55   4/98 6 55
ref
S9223
R31998
Wide (Phenytoin), 2000 Small for gestationnal age throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Matched 0.86 [0.02;45.54] C 0/22   0/19 0 22
ref
Total 5 studies 0.85 [0.43;1.69] 446,283 162
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 Christensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024Christensen, 2024 1 0.79[0.36; 1.73]446,2748176%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Aydin (Phenytoin) (Controls unexposed, sick), 2020Aydin, 2020 2 43.00[0.35; 5328.22]012%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bank (Phenytoin) (Mixed indications), 2017Bank, 2017 3 1.86[0.07; 46.97]335%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Pennell (Phenytoin), 2012Pennell, 2012 4 0.56[0.09; 3.46]65514%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Wide (Phenytoin), 2000Wide, 2000 5 0.86[0.02; 45.54]0223%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 0.85[0.43; 1.69]446,2831620.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenytoin) (All indications) (Controls unexposed, general population; 2: Phenytoin) (Controls unexposed, sick; 3: Phenytoin) (Mixed indications; 4: Phenytoin; 5: Phenytoin;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.85[0.43; 1.69]446,2831620%NAChristensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Aydin (Phenytoin) (Controls unexposed, sick), 2020 Bank (Phenytoin) (Mixed indications), 2017 Pennell (Phenytoin), 2012 Wide (Phenytoin), 2000 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.79[0.37; 1.71]446,2741030%NAChristensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Wide (Phenytoin), 2000 2 unexposed, sickunexposed, sick 43.00[0.35; 5328.22]-1 -NAAydin (Phenytoin) (Controls unexposed, sick), 2020 1 exposed to other treatment, sickexposed to other treatment, sick 0.75[0.15; 3.67]9580%NABank (Phenytoin) (Mixed indications), 2017 Pennell (Phenytoin), 2012 2 Tags Adjustment   - No  - No 2.85[0.31; 26.29]3260%NAAydin (Phenytoin) (Controls unexposed, sick), 2020 Bank (Phenytoin) (Mixed indications), 2017 Wide (Phenytoin), 2000 3   - Yes  - Yes 0.75[0.36; 1.54]446,2801360%NAChristensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Pennell (Phenytoin), 2012 2 MatchedMatched 0.86[0.02; 45.54]-22 -NAWide (Phenytoin), 2000 1 All studiesAll studies 0.85[0.43; 1.69]446,2831620%NAChristensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Aydin (Phenytoin) (Controls unexposed, sick), 2020 Bank (Phenytoin) (Mixed indications), 2017 Pennell (Phenytoin), 2012 Wide (Phenytoin), 2000 50.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.85.62.9510.000Christensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024Aydin (Phenytoin) (Controls unexposed, sick), 2020Bank (Phenytoin) (Mixed indications), 2017Pennell (Phenytoin), 2012Wide (Phenytoin), 2000

Asymetry test p-value = 0.2709 (by Egger's regression)

slope=-0.6498 (0.4556); intercept=0.7839 (0.5823); t=1.3462; p=0.2709

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9192, 16075

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.79[0.37; 1.71]446,2741030%NAChristensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Wide (Phenytoin), 2000 2 unexposed, sick controlsunexposed, sick controls Out of scale43.00[0.35; 5328.22]-1 -NAAydin (Phenytoin) (Controls unexposed, sick), 2020 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.84[0.42; 1.68]9361400%NAChristensen (Phenytoin) (All indications) (Controls exposed to LTG), 2024 Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020 Bank (Phenytoin) (Mixed indications), 2017 Pennell (Phenytoin), 2012 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (NMA) (All indications) (Prenatal ...Veroniki a (NMA) (All indications) (Prenatal growth restriction) 0.68[0.37; 1.21]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 0.85[0.43; 1.69]0%162----Christensen (Phenytoin) (All indications) (Controls unexposed, general population), 2024 Aydin (Phenytoin) (Controls unexposed, sick), 2020 Bank (Phenytoin) (Mixed indications), 2017 Pennell (Phenytoin), 2012 Wide (Phenytoin), 2000 50.510.01.0