Valproate (Epilepsy) updated on 04-22-2025

Oro-facial clefts

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
R73559		 Wiggs, 2024 Cleft lip and cleft palate early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes 2.65 [0.92;7.66] -/624   -/12,666 - 624
ref
S7663
R22688		 Tomson (Valproate), 2018 Cleft lip or palate at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 3.65 [0.91;14.63] C 6/1,381   3/2,514 9 1,381
ref
S318
R14440		 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Facial cleft 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 11.29 [2.54;50.12] 13/1,220   2/2,098 15 1,220
ref
S10732
R39684		 De Jonge (Valproate), 2013 Oral clefts 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.76 [0.05;12.28] C 0/65   294/29,452 294 65
ref
S5940
R23802		 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Oral clefts 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 2.79 [0.81;9.57] C 4/323   7/1,562 11 323
ref
Total 5 studies 3.44 [1.86;6.36] 329 3,613
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 2.65[0.92; 7.66]-62434%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Tomson (Valproate), 2018Tomson, 2018 1 3.65[0.91; 14.63]91,38120%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 2 11.29[2.54; 50.12]151,22017%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA De Jonge (Valproate), 2013De Jonge, 2013 3 0.76[0.05; 12.28]294655%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 4 2.79[0.81; 9.57]1132325%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 3.44[1.86; 6.36]3293,6130.250.01.0ROB: 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; 4: Valproate) (Controls exposed to Lamotrigine, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.72[1.98; 6.98]353,5480%NAWiggs, 2024 Tomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 4 case control studiescase control studies 0.76[0.05; 12.28]29465 -NADe Jonge (Valproate), 2013 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.76[0.05; 12.28]29465 -NADe Jonge (Valproate), 2013 1 unexposed, sickunexposed, sick 2.65[0.92; 7.65]-624 -NAWiggs, 2024 1 exposed to other treatment, sickexposed to other treatment, sick 4.50[2.00; 10.11]352,9246%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 3.90[1.68; 9.04]3292,98916%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 De Jonge (Valproate), 2013 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 4   - Yes  - Yes 2.65[0.92; 7.65]-624 -NAWiggs, 2024 1 Controls   - mixed indications  - mixed indications 2.79[0.81; 9.57]11323 -NAHernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 1 Monotherapy   - no or not specified  - no or not specified 0.76[0.05; 12.28]29465 -NADe Jonge (Valproate), 2013 1 All studiesAll studies 3.44[1.86; 6.36]3293,6130%NAWiggs, 2024 Tomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 De Jonge (Valproate), 2013 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 50.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.34.61.7050.000Wiggs, 2024Tomson (Valproate), 2018Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014De Jonge (Valproate), 2013Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012

Asymetry test p-value = 0.7494 (by Egger's regression)

slope=1.6792 (1.3158); intercept=-0.6566 (1.8757); t=0.3501; p=0.7494

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.76[0.05; 12.28]29465 -NADe Jonge (Valproate), 2013 1 unexposed, sick controlsunexposed, sick controls 2.65[0.92; 7.65]-624 -NAWiggs, 2024 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 4.50[2.00; 10.11]352,9246%NATomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Tanoshima (Cleft lip and/or palate)Tanoshima (Cleft lip and/or palate) 3.37[2.09; 5.42]9%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT11 metaPregmetaPreg 3.44[1.86; 6.36]0%3,613----Wiggs, 2024 Tomson (Valproate), 2018 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 De Jonge (Valproate), 2013 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 50.510.01.0