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
S9331
R32554
Bànhidy (Valproate), 2011 Poly/syndactyly throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.58 [0.02;16.72] C 0/5   2/12 2 5
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 5 studies 2.55 [0.48;13.67] 3,095 2,112
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]81,38123%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]3,08569735%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bànhidy (Valproate), 2011Bànhidy, 2011 3 0.58[0.02; 16.72]2518%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Viinikainen (Valproate) (Controls unexposed, sick) a, 2006Viinikainen, 2006 4 1.87[0.04; 96.99]02814%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate D'Souza (Valproate) (Controls unexposed, sick), 1991D'Souza, 1991 5 15.00[0.12; 1923.88]0110%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 30% 2.55[0.48; 13.67]3,0952,1120.2100.01.0ROB: 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; 4: Valproate) (Controls unexposed, sick) ; 5: 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 0.58[0.02; 16.72]25 -NABànhidy (Valproate), 2011 1 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 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, sickexposed to other treatment, sick 31.13[1.80; 539.82]81,381 -NATomson (Valproate), 2018 1 Tags Adjustment   - No  - No 2.55[0.48; 13.67]3,0952,11230%NATomson (Valproate), 2018 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Valproate), 2011 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 5 MatchedMatched 0.58[0.02; 16.72]25 -NABànhidy (Valproate), 2011 1 All studiesAll studies 2.55[0.48; 13.67]3,0952,11230%NATomson (Valproate), 2018 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Valproate), 2011 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 50.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.86.82.9720.000Tomson (Valproate), 2018Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013Bànhidy (Valproate), 2011Viinikainen (Valproate) (Controls unexposed, sick) a, 2006D'Souza (Valproate) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.4933 (by Egger's regression)

slope=-1.2575 (2.7477); intercept=1.4239 (1.8302); t=0.7780; p=0.4933

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