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

Cleft palate

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.
S19424
R82742		 Kim (Controls exposed to LTG) (Valproate) (Indications NOS), 2026 Cleft palate without cleft lip 1st trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 4.33 [0.48;38.80] C
excluded (control group) 		4/667   1/718 5 667
ref
S19425
R82753		 Kim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026 Cleft palate without cleft lip 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 5.55 [1.93;15.92] 4/667   3,086/2,489,078 3,090 667
ref
S10174
R37214		 Blotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Cleft palate 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 4.94 [0.82;29.59] C
excluded (control group) 		3/913   2/2,997 5 913
ref
S10051
R36488		 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Cleft palate 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 5.40 [1.10;15.80] 3/913   1,178/1,875,733 1,181 913
ref
S9329
R32530		 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Cleft palate throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.87 [0.04;96.99] C 0/28   0/52 0 28
ref
Total 3 studies 5.25 [2.34;11.79] 4,271 1,608
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 Kim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026Kim, 2026 1 5.55[1.93; 15.92]3,09066759%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 2 5.40[1.10; 15.80]1,18191337%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Viinikainen (Valproate) (Controls unexposed, sick) a, 2006Viinikainen, 2006 3 1.87[0.04; 96.99]0284%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 0% 5.25[2.34; 11.79]4,2711,6080.520.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS) (Valproate) (Indications NOS; 2: Valproate) (Controls unexposed NOS) (Mixed indications; 3: Valproate) (Controls unexposed, sick) ;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 5.25[2.34; 11.79]4,2711,6080%NAKim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 5.49[2.40; 12.56]4,2711,5800%NAKim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 2 unexposed, sickunexposed, sick 1.87[0.04; 96.99]-28 -NAViinikainen (Valproate) (Controls unexposed, sick) a, 2006 1 Tags Adjustment   - No  - No 4.85[1.37; 17.12]1,1819410%NABlotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 2   - Yes  - Yes 5.55[1.93; 15.94]3,090667 -NAKim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026 1 All studiesAll studies 5.25[2.34; 11.79]4,2711,6080%NAKim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 30.520.01.0

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 10174, 19424

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 5.49[2.40; 12.56]4,2711,5800%NAKim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 2 unexposed, sick controlsunexposed, sick controls 1.87[0.04; 96.99]-28 -NAViinikainen (Valproate) (Controls unexposed, sick) a, 2006 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 4.68[1.17; 18.75]101,5800%NAKim (Controls exposed to LTG) (Valproate) (Indications NOS), 2026 Blotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 20.510.01.0