Valproate (All indications)

Perinatal death

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.
S9364
R32753		 Tomson (Valproate), 2015 Perinatal death (during the first week after delivery from gestational week 24) at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 3.82 [0.98;14.79] C 7/1,083   3/1,763 10 1,083
ref
S9283
R32208		 Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013 Perinatal death (stillbirth or early neonatal death (0–6 days of age)) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 3.70 [0.21;65.18] C
excluded (control group) 		7/706   0/173 7 706
ref
S9284
R32220		 Artama (Valproate) (Controls unexposed, disease free), 2013 Perinatal death (stillbirth or early neonatal death (0–6 days of age)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 1.49 [0.70;3.18]
excluded (control group) 		7/706   3,543/721,948 3,550 706
ref
S9285
R32232		 Artama (Valproate) (Controls unexposed, sick), 2013 Perinatal death (stillbirth or early neonatal death (0–6 days of age)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.68 [0.58;4.84] 7/706   10/1,800 17 706
ref
S9335
R32577		 Canger (Valproate), 1999 Perinatal deaths (NOS) 1st trimester prospective cohort unexposed, sick Adjustment: No 0.56 [0.01;29.28] C 0/44   0/25 0 44
ref
Total 3 studies 2.16 [0.95;4.89] 27 1,833
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), 2015Tomson, 2015 1 3.82[0.98; 14.79]101,08336%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Artama (Valproate) (Controls unexposed, sick), 2013Artama, 2013 2 1.68[0.58; 4.84]1770659%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Canger (Valproate), 1999Canger, 1999 3 0.56[0.01; 29.28]0444%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 0% 2.16[0.95; 4.89]271,8330.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.16[0.95; 4.89]271,8330%NATomson (Valproate), 2015 Artama (Valproate) (Controls unexposed, sick), 2013 Canger (Valproate), 1999 3 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.56[0.56; 4.35]177500%NAArtama (Valproate) (Controls unexposed, sick), 2013 Canger (Valproate), 1999 2 exposed to other treatment, sickexposed to other treatment, sick 3.82[0.98; 14.79]101,083 -NATomson (Valproate), 2015 1 Tags Adjustment   - No  - No 3.12[0.87; 11.24]101,1270%NATomson (Valproate), 2015 Canger (Valproate), 1999 2   - Yes  - Yes 1.68[0.58; 4.85]17706 -NAArtama (Valproate) (Controls unexposed, sick), 2013 1 All studiesAll studies 2.16[0.95; 4.89]271,8330%NATomson (Valproate), 2015 Artama (Valproate) (Controls unexposed, sick), 2013 Canger (Valproate), 1999 30.210.01.0

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 9283, 9284

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.49[0.70; 3.18]3,550706 -NAArtama (Valproate) (Controls unexposed, disease free), 2013 1 unexposed, sick controlsunexposed, sick controls 1.56[0.56; 4.35]177500%NAArtama (Valproate) (Controls unexposed, sick), 2013 Canger (Valproate), 1999 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.80[1.12; 12.92]171,7890%NATomson (Valproate), 2015 Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013 20.510.01.0