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

Urinary malformations

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.
S17499
R73525		 Wiggs (Epilepsy) (Valproate), 2024 Urinary system malformations early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes 1.83 [0.59;5.64] -/624   -/12,666 - 624
ref
S12862
R48541		 Thomas (Valproate) (Controls exposed to Lamotrigine, sick), 2021 Urinary malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.43 [0.04;4.26] C
excluded (control group) 		3/341   1/50 4 341
ref
S12864
R48553		 Thomas (Valproate) (Controls unexposed, sick), 2021 Urinary malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.49 [0.12;1.99] C 3/341   6/340 9 341
ref
S9359
R32740		 Tomson (Valproate), 2018 Renal malformations at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.60 [0.58;4.41] C 7/1,381   8/2,514 15 1,381
ref
S9325
R32511		 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Urinary throughout pregnancy population based cohort retrospective exposed to other treatment, sick Adjustment: No 1.25 [0.11;13.85] C 1/333   2/833 3 333
ref
S9330
R32544		 Artama (Valproate), 2005 Urinary system 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 3.58 [0.22;57.43] C 1/263   1/939 2 263
ref
Total 5 studies 1.35 [0.72;2.52] 29 2,942
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 Wiggs (Epilepsy) (Valproate), 2024Wiggs, 2024 1 1.83[0.59; 5.64]-62431%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Thomas (Valproate) (Controls unexposed, sick), 2021Thomas, 2021 2 0.49[0.12; 1.99]934120%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Valproate), 2018Tomson, 2018 3 1.60[0.58; 4.41]151,38138%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Veiby, 2014 4 1.25[0.11; 13.85]33337%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Artama (Valproate), 2005Artama, 2005 5 3.58[0.22; 57.43]22635%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 1.35[0.72; 2.52]292,9420.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.35[0.72; 2.52]292,9420%NAWiggs (Epilepsy) (Valproate), 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 Tomson (Valproate), 2018 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Valproate), 2005 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.21[0.43; 3.39]111,22826%NAWiggs (Epilepsy) (Valproate), 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 Artama (Valproate), 2005 3 exposed to other treatment, sickexposed to other treatment, sick 1.54[0.60; 3.92]181,7140%NATomson (Valproate), 2018 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 2 Tags Adjustment   - No  - No 1.18[0.56; 2.49]292,3180%NAThomas (Valproate) (Controls unexposed, sick), 2021 Tomson (Valproate), 2018 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Valproate), 2005 4   - Yes  - Yes 1.83[0.59; 5.66]-624 -NAWiggs (Epilepsy) (Valproate), 2024 1 All studiesAll studies 1.35[0.72; 2.52]292,9420%NAWiggs (Epilepsy) (Valproate), 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 Tomson (Valproate), 2018 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Valproate), 2005 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.33.61.6990.000Wiggs (Epilepsy) (Valproate), 2024Thomas (Valproate) (Controls unexposed, sick), 2021Tomson (Valproate), 2018Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Artama (Valproate), 2005

Asymetry test p-value = 0.9297 (by Egger's regression)

slope=0.2183 (0.8965); intercept=0.1208 (1.2597); t=0.0959; p=0.9297

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 12862

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 1.21[0.43; 3.39]111,22826%NAWiggs (Epilepsy) (Valproate), 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 Artama (Valproate), 2005 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.28[0.54; 3.05]222,0550%NAThomas (Valproate) (Controls exposed to Lamotrigine, sick), 2021 Tomson (Valproate), 2018 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 30.510.01.0