Valproate (Epilepsy) updated on 04-22-2025

Early intrauterine deaths (< 22 weeks) / Spontaneous abortions

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.
S16702
R70280		 Alsaadi (Controls exposed to LTG), 2020 Miscarriage 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.52 [0.03;9.10] C
excluded (control group) 		1/24   1/13 2 24
ref
S16703
R70284		 Alsaadi (Controls unexposed sick), 2020 Miscarriage 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.78 [0.07;9.13] C 1/24   2/38 3 24
ref
S7419
R21845		 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
S7049
R19909		 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
S7414
R21823		 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
S6255
R16668		 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
S7814
R23205		 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
S307
R16402		 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
S318
R14445		 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 6 studies 1.04 [0.84;1.29] 369 2,499
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 Alsaadi (Controls unexposed sick), 2020Alsaadi, 2020 1 0.78[0.07; 9.13]3241%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Miškov (Valproate) (Controls unexposed, sick), 2016Miškov, 2016 2 0.64[0.01; 40.08]060%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Arkilo (Valproate), 2015Arkilo, 2015 3 2.87[0.09; 91.05]220%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Valproate), 2015Tomson, 2015 4 1.02[0.78; 1.34]2341,17162%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Babic (Valproate), 2014Babic, 2014 5 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 6 1.05[0.73; 1.50]1291,29036%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 0% 1.04[0.84; 1.29]3692,4990.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed sick; 2: Valproate) (Controls unexposed, sick; 3: Valproate; 4: Valproate; 5: Valproate; 6: Valproate) (Controls exposed to Lamotrigine, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.04[0.84; 1.29]3692,4990%NAAlsaadi (Controls unexposed sick), 2020 Miškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 6 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 0.74[0.09; 6.14]3300%NAAlsaadi (Controls unexposed sick), 2020 Miškov (Valproate) (Controls unexposed, sick), 2016 2 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]3692,4990%NAAlsaadi (Controls unexposed sick), 2020 Miškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 6 All studiesAll studies 1.04[0.84; 1.29]3692,4990%NAAlsaadi (Controls unexposed sick), 2020 Miškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.05.02.5360.000Alsaadi (Controls unexposed sick), 2020Miškov (Valproate) (Controls unexposed, sick), 2016Arkilo (Valproate), 2015Tomson (Valproate), 2015Babic (Valproate), 2014Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014

Asymetry test p-value = 0.3459 (by Egger's regression)

slope=-0.0173 (0.0744); intercept=0.2936 (0.2751); t=1.0674; p=0.3459

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 7419, 7049, 16702

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 0.74[0.09; 6.14]3300%NAAlsaadi (Controls unexposed sick), 2020 Miškov (Valproate) (Controls unexposed, sick), 2016 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.04[0.83; 1.29]3712,4990%NAAlsaadi (Controls exposed to LTG), 2020 Miškov (Valproate) (Controls exposed to Lamotrigine, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 60.510.01.0