Valproate (Epilepsy) updated on 04-22-2025

Nervous system anomalies

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.
S17504
R73555		 Wiggs, 2024 Nervous system malformations early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes 3.80 [1.39;10.39] -/624   -/12,666 - 624
ref
S12860
R48518		 Thomas (Valproate) (Controls exposed to Lamotrigine, sick), 2021 Neural malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.03 [0.05;20.18] C
excluded (control group) 		3/341   0/50 3 341
ref
S12861
R48528		 Thomas (Valproate) (Controls unexposed, sick), 2021 Neural malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 7.04 [0.36;136.85] C 3/341   0/340 3 341
ref
S10732
R39683		 De Jonge (Valproate), 2013 Central nervous system anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: No 15.05 [5.09;44.51] 3/31   205/29,400 208 31
ref
Total 3 studies 7.35 [2.65;20.39] 211 996
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, 2024Wiggs, 2024 3.80[1.39; 10.39]-62446%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Thomas (Valproate) (Controls unexposed, sick), 2021Thomas, 2021 1 7.04[0.36; 136.85]334110%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate De Jonge (Valproate), 2013De Jonge, 2013 2 15.05[5.09; 44.51]2083143%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 40% 7.35[2.65; 20.39]2119960.950.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (Controls unexposed, sick; 2: Valproate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 4.05[1.56; 10.50]39650%NAWiggs, 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 2 case control studiescase control studies 15.05[5.09; 44.50]20831 -NADe Jonge (Valproate), 2013 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 15.05[5.09; 44.50]20831 -NADe Jonge (Valproate), 2013 1 unexposed, sickunexposed, sick 4.05[1.56; 10.50]39650%NAWiggs, 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 2 Tags Adjustment   - No  - No 13.76[4.97; 38.10]2113720%NAThomas (Valproate) (Controls unexposed, sick), 2021 De Jonge (Valproate), 2013 2   - Yes  - Yes 3.80[1.39; 10.39]-624 -NAWiggs, 2024 1 All studiesAll studies 7.35[2.65; 20.39]21199640%NAWiggs, 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 De Jonge (Valproate), 2013 30.550.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 12860

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale15.05[5.09; 44.50]20831 -NADe Jonge (Valproate), 2013 1 unexposed, sick controlsunexposed, sick controls 4.05[1.56; 10.50]39650%NAWiggs, 2024 Thomas (Valproate) (Controls unexposed, sick), 2021 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.03[0.05; 20.18]3341 -NAThomas (Valproate) (Controls exposed to Lamotrigine, sick), 2021 10.510.01.0