Valproate (All indications)

Polydactyly

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.
S9359
R32739		 Tomson (Valproate), 2018 Polydactyly at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 31.13 [1.80;539.82] C 8/1,381   0/2,514 8 1,381
ref
S9309
R32430		 Källén (Valproate) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Poly/syndactyly early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.52 [0.05;4.99] C
excluded (control group) 		1/697   3/1,084 4 697
ref
S9310
R32438		 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Poly/syndactyly early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: No 0.73 [0.10;5.21] C 1/697   3,084/1,575,847 3,085 697
ref
S9329
R32531		 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Polydactyly throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.87 [0.04;96.99] C 0/28   0/52 0 28
ref
S9297
R32300		 D'Souza (Valproate) (Controls unexposed, disease free), 1991 Extra digits throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 123.00 [1.00;15058.31] C
excluded (control group) 		0/1   0/62 0 1
ref
S9298
R32329		 D'Souza (Valproate) (Controls unexposed, sick), 1991 Extra digits throughout pregnancy prospective cohort unexposed, sick Adjustment: No 15.00 [0.12;1923.88] C 0/1   0/8 0 1
ref
Total 4 studies 3.78 [0.50;28.86] 3,093 2,107
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 Tomson (Valproate), 2018Tomson, 2018 1 31.13[1.80; 539.82]81,38128%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 2 0.73[0.10; 5.21]3,08569740%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Viinikainen (Valproate) (Controls unexposed, sick) a, 2006Viinikainen, 2006 3 1.87[0.04; 96.99]02819%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate D'Souza (Valproate) (Controls unexposed, sick), 1991D'Souza, 1991 4 15.00[0.12; 1923.88]0114%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 40% 3.78[0.50; 28.86]3,0932,1070.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate; 2: Valproate) (Controls unexposed, NOS) (Indications NOS; 3: Valproate) (Controls unexposed, sick) ; 4: Valproate) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.78[0.50; 28.86]3,0932,10740%NATomson (Valproate), 2018 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.73[0.10; 5.21]3,085697 -NAKällén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 1 unexposed, sickunexposed, sick 4.29[0.20; 91.66]-290%NAViinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 2 exposed to other treatment, sickexposed to other treatment, sick 31.13[1.80; 539.82]81,381 -NATomson (Valproate), 2018 1 Tags Adjustment   - No  - No 3.78[0.50; 28.86]3,0932,10740%NATomson (Valproate), 2018 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 4 All studiesAll studies 3.78[0.50; 28.86]3,0932,10740%NATomson (Valproate), 2018 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 40.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.87.22.9720.000Tomson (Valproate), 2018Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013Viinikainen (Valproate) (Controls unexposed, sick) a, 2006D'Souza (Valproate) (Controls unexposed, sick), 1991

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 9297, 9309

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 5.82[0.04; 803.87]3,08569873%NAKällén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 D'Souza (Valproate) (Controls unexposed, disease free), 1991 2 unexposed, sick controlsunexposed, sick controls 1.73[0.18; 16.66]2340%NABànhidy (Valproate), 2011 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.65[0.07; 201.27]122,07879%NATomson (Valproate), 2018 Källén (Valproate) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 20.510.01.0