Phenytoin (All indications)

Cognitive developmental disorders/delay (< 3 years old)

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.
S9266
R53614		 Meador (Phenytoin), 2013 the Bayley Scales of Infant Development (BSID) <85 (at 2 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes 3.52 [1.44;8.60] C 17/42   11/68 28 42
ref
S9268
R53615		 Thomas b (Phenytoin), 2008 Impaired Mental Development Quotient < 84 (The Developmental Assessment Scale (DAS II)) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.34 [0.47;3.88] C 11/29   10/32 21 29
ref
S9223
R53616		 Wide (Phenytoin), 2000 Griffiths test total score (SD estimated) throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Matched 0.82 [0.26;2.52] -/21   -/21 - 21
ref
S9233
R53613		 Kelly (Phenytoin), 1984 Delayed development during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.06 [0.00;1.26] C 0/41   3/21 3 41
ref
Total 4 studies 1.17 [0.40;3.49] 52 133
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 Meador (Phenytoin), 2013Meador, 2013 1 3.52[1.44; 8.60]284232%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Thomas b (Phenytoin), 2008Thomas b, 2008 2 1.34[0.47; 3.88]212930%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Wide (Phenytoin), 2000Wide, 2000 3 0.82[0.26; 2.52]-2128%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: moderate Kelly (Phenytoin), 1984Kelly, 1984 4 0.06[0.00; 1.26]34110%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 66% 1.17[0.40; 3.49]521330.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenytoin; 2: Phenytoin; 3: Phenytoin; 4: Phenytoin;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.17[0.40; 3.49]5213366%NAMeador (Phenytoin), 2013 Thomas b (Phenytoin), 2008 Wide (Phenytoin), 2000 Kelly (Phenytoin), 1984 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.82[0.26; 2.55]-21 -NAWide (Phenytoin), 2000 1 unexposed, sickunexposed, sick 0.40[0.02; 7.68]247072%NAThomas b (Phenytoin), 2008 Kelly (Phenytoin), 1984 2 exposed to other treatment, sickexposed to other treatment, sick 3.52[1.44; 8.60]2842 -NAMeador (Phenytoin), 2013 1 Tags Adjustment   - No  - No 0.76[0.25; 2.33]249145%NAThomas b (Phenytoin), 2008 Wide (Phenytoin), 2000 Kelly (Phenytoin), 1984 3   - Yes  - Yes 3.52[1.44; 8.60]2842 -NAMeador (Phenytoin), 2013 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 0.82[0.26; 2.55]-21 -NAWide (Phenytoin), 2000 1 MatchedMatched 0.82[0.26; 2.55]-21 -NAWide (Phenytoin), 2000 1 All studiesAll studies 1.17[0.40; 3.49]5213366%NAMeador (Phenytoin), 2013 Thomas b (Phenytoin), 2008 Wide (Phenytoin), 2000 Kelly (Phenytoin), 1984 40.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.81.8460.000Meador (Phenytoin), 2013Thomas b (Phenytoin), 2008Wide (Phenytoin), 2000Kelly (Phenytoin), 1984

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

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.82[0.26; 2.55]-21 -NAWide (Phenytoin), 2000 1 unexposed, sick controlsunexposed, sick controls Out of scale0.40[0.02; 7.68]247072%NAThomas b (Phenytoin), 2008 Kelly (Phenytoin), 1984 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.52[1.44; 8.60]2842 -NAMeador (Phenytoin), 2013 10.510.01.0