Valproate (All indications)

Early intrauterine death (< 22 weeks)

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.
S9320
R32475		 Miškov (Valproate) (Controls exposed to Lamotrigine, sick), 2016 Spontaneous abortion during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.87 [0.04;19.27] C
excluded (control group) 		0/6   3/37 3 6
ref
S9321
R32479		 Miškov (Valproate) (Controls unexposed, disease free), 2016 Spontaneous abortion during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 23.18 [0.42;1280.78] C
excluded (control group) 		0/6   0/128 0 6
ref
S9322
R32483		 Miškov (Valproate) (Controls unexposed, sick), 2016 Spontaneous abortion during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.64 [0.01;40.08] C 0/6   0/4 0 6
ref
S9282
R32198		 Arkilo (Valproate), 2015 Spontaneous miscarriages during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 2.87 [0.09;91.05] C 0/2   2/24 2 2
ref
S9364
R32750		 Tomson (Valproate), 2015 Spontaneous abortions at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.02 [0.78;1.34] C 90/1,171   144/1,910 234 1,171
ref
S9289
R32260		 Babic (Valproate), 2014 Miscarriage (8–10 gestational week) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 5.00 [0.17;150.93] C 1/6   0/8 1 6
ref
S9333
R32564		 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Spontaneous abortions 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.05 [0.73;1.50] C 49/1,290   80/2,198 129 1,290
ref
Total 5 studies 1.04 [0.84;1.29] 366 2,475
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 Miškov (Valproate) (Controls unexposed, sick), 2016Miškov, 2016 1 0.64[0.01; 40.08]060%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Arkilo (Valproate), 2015Arkilo, 2015 2 2.87[0.09; 91.05]220%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Valproate), 2015Tomson, 2015 3 1.02[0.78; 1.34]2341,17163%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Babic (Valproate), 2014Babic, 2014 4 5.00[0.17; 150.93]160%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 5 1.05[0.73; 1.50]1291,29036%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.04[0.84; 1.29]3662,4750.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (Controls unexposed, sick; 2: Valproate; 3: Valproate; 4: Valproate; 5: Valproate) (Controls exposed to Lamotrigine, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.04[0.84; 1.29]3662,4750%NAMiškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 0.64[0.01; 40.08]-6 -NAMiškov (Valproate) (Controls unexposed, sick), 2016 1 exposed to other treatment, sickexposed to other treatment, sick 1.04[0.84; 1.29]3662,4690%NAArkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 4 Tags Adjustment   - No  - No 1.04[0.84; 1.29]3662,4750%NAMiškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 5 All studiesAll studies 1.04[0.84; 1.29]3662,4750%NAMiškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.05.02.5360.000Miškov (Valproate) (Controls unexposed, sick), 2016Arkilo (Valproate), 2015Tomson (Valproate), 2015Babic (Valproate), 2014Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014

Asymetry test p-value = 0.2291 (by Egger's regression)

slope=-0.0409 (0.0750); intercept=0.4555 (0.3024); t=1.5061; p=0.2291

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9320, 9321

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale23.18[0.42; 1280.78]-6 -NAMiškov (Valproate) (Controls unexposed, disease free), 2016 1 unexposed, sick controlsunexposed, sick controls 0.64[0.01; 40.08]-6 -NAMiškov (Valproate) (Controls unexposed, sick), 2016 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.04[0.84; 1.29]3692,4750%NAMiškov (Valproate) (Controls exposed to Lamotrigine, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 50.510.01.0