Valproate (Epilepsy)

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.
S7663
R22687		 Tomson (Valproate), 2018 Hypospadias at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 6.77 [2.74;16.73] C 22/1,381   6/2,514 28 1,381
ref
S318
R14438		 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hypospadias and genitourinary tract defects 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.60 [1.16;5.81] 15/1,220   10/2,098 25 1,220
ref
S5940
R23798		 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Hypospadias 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 54.10 [2.98;980.87] C 5/323   0/1,562 5 323
ref
S6505
R17911		 Bànhidy (Valproate), 2011 Hypospadias throughout pregnancy case control unexposed, sick Adjustment: No Matched 2.00 [0.29;13.74] C 3/8   3/13 6 8
ref
S6687
R18646		 D'Souza (Valproate) (Controls unexposed, disease free), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 123.00 [1.00;15058.31] C
excluded (control group) 		0/1   0/62 0 1
ref
S6695
R18807		 D'Souza (Valproate) (Controls unexposed, sick), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, sick Adjustment: No 15.00 [0.12;1923.88] C 0/1   0/8 0 1
ref
Total 5 studies 4.64 [2.00;10.77] 64 2,933
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 (Valproate), 2018Tomson, 2018 1 6.77[2.74; 16.73]281,38136%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 2 2.60[1.16; 5.81]251,22039%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 3 54.10[2.98; 980.87]53237%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Valproate), 2011Bànhidy, 2011 4 2.00[0.29; 13.74]6815%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate D'Souza (Valproate) (Controls unexposed, sick), 1991D'Souza, 1991 5 15.00[0.12; 1923.88]013%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 36% 4.64[2.00; 10.77]642,9330.9500.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 5.64[2.06; 15.49]582,92547%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 D'Souza (Valproate) (Controls unexposed, sick), 1991 4 case control studiescase control studies 2.00[0.29; 13.74]68 -NABànhidy (Valproate), 2011 1 Type of controls unexposed, sickunexposed, sick 2.63[0.44; 15.78]690%NABànhidy (Valproate), 2011 D'Souza (Valproate) (Controls unexposed, sick), 1991 2 exposed to other treatment, sickexposed to other treatment, sick 5.66[1.82; 17.62]582,92463%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 3 Tags Adjustment   - No  - No 4.64[2.00; 10.77]642,93336%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Valproate), 2011 D'Souza (Valproate) (Controls unexposed, sick), 1991 5 Controls   - mixed indications  - mixed indications 54.10[2.98; 980.87]5323 -NAHernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 1 MatchedMatched 2.00[0.29; 13.74]68 -NABànhidy (Valproate), 2011 1 All studiesAll studies 4.64[2.00; 10.77]642,93336%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Valproate), 2011 D'Souza (Valproate) (Controls unexposed, sick), 1991 50.51000.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.87.42.9720.000Tomson (Valproate), 2018Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Valproate), 2011D'Souza (Valproate) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.4291 (by Egger's regression)

slope=0.8872 (0.7034); intercept=1.0045 (1.1016); t=0.9119; p=0.4291

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6687

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale123.00[1.00; 15058.31]-1 -NAD'Souza (Valproate) (Controls unexposed, disease free), 1991 1 unexposed, sick controlsunexposed, sick controls 2.63[0.44; 15.78]690%NABànhidy (Valproate), 2011 D'Souza (Valproate) (Controls unexposed, sick), 1991 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 5.66[1.82; 17.62]582,92463%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 30.510.01.0