Valproate (All indications)

Cleft lip with or without 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.
S10174
R37213		 Blotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Cleft lip with or without 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
R36487		 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Cleft lip with or without cleft palate 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 3.90 [0.80;11.40] 3/913   1,637/1,875,733 1,640 913
ref
S9329
R32532		 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Cleft lip throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.87 [0.04;96.99] C 0/28   0/52 0 28
ref
S9330
R32541		 Artama (Valproate), 2005 Cleft lip/ cleft palate 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 9.08 [1.75;47.07] C 5/263   2/939 7 263
ref
Total 3 studies 5.08 [1.87;13.82] 1,647 1,204
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 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 1 3.90[0.80; 11.40]1,64091357%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Viinikainen (Valproate) (Controls unexposed, sick) a, 2006Viinikainen, 2006 2 1.87[0.04; 96.99]0286%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Artama (Valproate), 2005Artama, 2005 3 9.08[1.75; 47.07]726337%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 0% 5.08[1.87; 13.82]1,6471,2040.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 5.08[1.87; 13.82]1,6471,2040%NABlotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Artama (Valproate), 2005 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.90[1.03; 14.72]1,640913 -NABlotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 1 unexposed, sickunexposed, sick 7.19[1.57; 32.82]72910%NAViinikainen (Valproate) (Controls unexposed, sick) a, 2006 Artama (Valproate), 2005 2 Tags Adjustment   - No  - No 5.08[1.87; 13.82]1,6471,2040%NABlotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Artama (Valproate), 2005 3 All studiesAll studies 5.08[1.87; 13.82]1,6471,2040%NABlotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Artama (Valproate), 2005 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

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.90[1.03; 14.72]1,640913 -NABlotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 1 unexposed, sick controlsunexposed, sick controls 7.19[1.57; 32.82]72910%NAViinikainen (Valproate) (Controls unexposed, sick) a, 2006 Artama (Valproate), 2005 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 4.94[0.82; 29.59]5913 -NABlotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 10.510.01.0