Phenytoin (All indications)

Hypospadias

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.
S9246
R32079		 Tomson (Phenytoin), 2018 Hypospadias at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.55 [0.09;27.66] C 0/125   6/2,514 6 125
ref
S10229
R37471		 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Hypospadias 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 3.76 [0.07;189.69] C 0/416   0/1,562 0 416
ref
S9225
R32019		 Bànhidy (Phenytoin), 2011 Hypospadias throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.35 [0.05;2.46] C 2/21   3/13 5 21
ref
S9238
R32060		 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 Hypospadias/genitourinary tract defects 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 0.60 [0.03;10.83] C 0/82   6/647 6 82
ref
S9194
R31848		 D'Souza (Phenytoin) (Controls unexposed, disease free), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 9.00 [0.35;229.68] C
excluded (control group) 		1/22   0/62 1 22
ref
S9195
R31877		 D'Souza (Phenytoin) (Controls unexposed, sick), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.10 [0.04;30.00] C 1/22   0/8 1 22
ref
Total 5 studies 0.75 [0.22;2.57] 18 666
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 Tomson (Phenytoin), 2018Tomson, 2018 1 1.55[0.09; 27.66]612518%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 2 3.76[0.07; 189.69]041610%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Phenytoin), 2011Bànhidy, 2011 3 0.35[0.05; 2.46]52140%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006Morrow, 2006 4 0.60[0.03; 10.83]68218%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA D'Souza (Phenytoin) (Controls unexposed, sick), 1991D'Souza, 1991 5 1.10[0.04; 30.00]12214%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 0.75[0.22; 2.57]186660.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenytoin; 2: Phenytoin) (Controls exposed to Lamotrigine, sick; 3: Phenytoin; 4: Phenytoin) (Controls exposed to Lamotrigine, sick; 5: Phenytoin) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.24[0.25; 6.09]136450%NATomson (Phenytoin), 2018 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 D'Souza (Phenytoin) (Controls unexposed, sick), 1991 4 case control studiescase control studies 0.35[0.05; 2.46]521 -NABànhidy (Phenytoin), 2011 1 Type of controls unexposed, sickunexposed, sick 0.47[0.09; 2.52]6430%NABànhidy (Phenytoin), 2011 D'Souza (Phenytoin) (Controls unexposed, sick), 1991 2 exposed to other treatment, sickexposed to other treatment, sick 1.29[0.21; 7.89]126230%NATomson (Phenytoin), 2018 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 3 Tags Adjustment   - No  - No 0.75[0.22; 2.57]186660%NATomson (Phenytoin), 2018 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Phenytoin), 2011 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 D'Souza (Phenytoin) (Controls unexposed, sick), 1991 5 Controls   - mixed indications  - mixed indications 3.76[0.07; 189.69]-416 -NAHernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 1 MatchedMatched 0.35[0.05; 2.46]521 -NABànhidy (Phenytoin), 2011 1 All studiesAll studies 0.75[0.22; 2.57]186660%NATomson (Phenytoin), 2018 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Phenytoin), 2011 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 D'Souza (Phenytoin) (Controls unexposed, sick), 1991 50.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.42.4010.000Tomson (Phenytoin), 2018Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Phenytoin), 2011Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006D'Souza (Phenytoin) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.0303 (by Egger's regression)

slope=-3.1707 (0.7657); intercept=2.1169 (0.5456); t=3.8797; p=0.0303

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9194

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 9.00[0.35; 229.68]122 -NAD'Souza (Phenytoin) (Controls unexposed, disease free), 1991 1 unexposed, sick controlsunexposed, sick controls Out of scale0.47[0.09; 2.52]6430%NABànhidy (Phenytoin), 2011 D'Souza (Phenytoin) (Controls unexposed, sick), 1991 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.29[0.21; 7.89]126230%NATomson (Phenytoin), 2018 Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 30.510.01.0