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

Genital 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.
S17499
R73524		 Wiggs (Epilepsy) (Valproate), 2024 Genital organ malformations early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes 5.29 [3.42;8.19] -/624   -/12,666 - 624
ref
S9442
R33159		 Ban (Valproate) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2015 Genital system anomaly 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 2.57 [0.23;28.49] C
excluded (control group) 		2/214   1/273 3 214
ref
S9443
R33164		 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Genital system anomaly 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 2.36 [0.59;9.52] C 2/214   1,023/257,153 1,025 214
ref
S9325
R32510		 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Genital throughout pregnancy population based cohort retrospective exposed to other treatment, sick Adjustment: No 3.80 [1.07;13.56] C 6/333   4/833 10 333
ref
S9330
R32543		 Artama (Valproate), 2005 Genital organs 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 3.62 [1.04;12.60] C 5/263   5/939 10 263
ref
Total 4 studies 4.68 [3.21;6.82] 1,045 1,434
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 5.29[3.42; 8.19]-62475%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015Ban, 2015 2 2.36[0.59; 9.52]1,0252147%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Veiby, 2014 3 3.80[1.07; 13.56]103339%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Artama (Valproate), 2005Artama, 2005 4 3.62[1.04; 12.60]102639%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 0% 4.68[3.21; 6.82]1,0451,4340.920.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 4.68[3.21; 6.82]1,0451,4340%NAWiggs (Epilepsy) (Valproate), 2024 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Valproate), 2005 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.36[0.59; 9.52]1,025214 -NABan (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 1 unexposed, sickunexposed, sick 5.08[3.36; 7.66]108870%NAWiggs (Epilepsy) (Valproate), 2024 Artama (Valproate), 2005 2 exposed to other treatment, sickexposed to other treatment, sick 3.80[1.07; 13.56]10333 -NAVeiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 1 Tags Adjustment   - No  - No 3.25[1.54; 6.89]1,0458100%NABan (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Valproate), 2005 3   - Yes  - Yes 5.29[3.42; 8.19]-624 -NAWiggs (Epilepsy) (Valproate), 2024 1 All studiesAll studies 4.68[3.21; 6.82]1,0451,4340%NAWiggs (Epilepsy) (Valproate), 2024 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Valproate), 2005 40.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.03.20.8530.000Wiggs (Epilepsy) (Valproate), 2024Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Artama (Valproate), 2005

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 9442

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.36[0.59; 9.52]1,025214 -NABan (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 1 unexposed, sick controlsunexposed, sick controls 5.08[3.36; 7.66]108870%NAWiggs (Epilepsy) (Valproate), 2024 Artama (Valproate), 2005 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.49[1.13; 10.74]135470%NABan (Valproate) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2015 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 20.510.01.0