Valproate (All indications)

Intrauterine deaths (as a whole or unspecified)

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.
S9365
R32754		 Trivedi (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.85 [0.28;2.56] C
excluded (control group) 		23/322   4/48 27 322
ref
S9366
R32755		 Trivedi (Valproate) (Controls unexposed, sick), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort unexposed, sick Adjustment: Yes 6.92 [1.70;28.18] 23/322   5/178 28 322
ref
S9367
R32756		 Vajda (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Intrauterine foetal death throughout pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.86 [0.37;2.02] C
excluded (control group) 		9/284   14/382 23 284
ref
S9368
R32757		 Vajda (Valproate) (Controls unexposed, sick), 2018 Intrauterine foetal death throughout pregnancy prospective cohort unexposed, sick Adjustment: No 5.39 [0.65;42.15] 9/284   1/170 10 284
ref
S9320
R32474		 Miškov (Valproate) (Controls exposed to Lamotrigine, sick), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.66 [0.03;13.98] C
excluded (control group) 		0/6   4/37 4 6
ref
S9321
R32478		 Miškov (Valproate) (Controls unexposed, disease free), 2016 Fetal loss 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
R32482		 Miškov (Valproate) (Controls unexposed, sick), 2016 Fetal loss 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
R32197		 Arkilo (Valproate), 2015 Unsuccessful pregnancies (miscarriages/stillbirths) 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
R32752		 Tomson (Valproate), 2015 Intrauterine death at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: Yes 1.18 [0.91;1.52] 95/1,171   150/1,910 245 1,171
ref
S9333
R32563		 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Intrauterine death 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.25 [0.92;1.69] C 76/1,290   105/2,198 181 1,290
ref
S9319
R32471		 Meador (Valproate), 2006 Fetal death (early and late intrauterine deaths) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 7.33 [0.35;155.16] C 2/69   0/98 2 69
ref
Total 7 studies 1.46 [1.01;2.11] 468 3,144
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 Trivedi (Valproate) (Controls unexposed, sick), 2018Trivedi, 2018 1 6.92[1.70; 28.18]283226%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Valproate) (Controls unexposed, sick), 2018Vajda, 2018 2 5.39[0.65; 42.15]102843%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Miškov (Valproate) (Controls unexposed, sick), 2016Miškov, 2016 3 0.64[0.01; 40.08]061%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Arkilo (Valproate), 2015Arkilo, 2015 4 2.87[0.09; 91.05]221%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Valproate), 2015Tomson, 2015 5 1.18[0.91; 1.52]2451,17145%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 6 1.25[0.92; 1.69]1811,29042%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Meador (Valproate), 2006Meador, 2006 7 7.33[0.35; 155.16]2691%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 36% 1.46[1.01; 2.11]4683,1440.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (Controls unexposed, sick; 2: Valproate) (Controls unexposed, sick; 3: Valproate) (Controls unexposed, sick; 4: Valproate; 5: Valproate; 6: Valproate) (Controls exposed to Lamotrigine, sick; 7: Valproate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.46[1.01; 2.11]4683,14436%NATrivedi (Valproate) (Controls unexposed, sick), 2018 Vajda (Valproate) (Controls unexposed, sick), 2018 Miškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Meador (Valproate), 2006 7 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 5.41[1.76; 16.59]386120%NATrivedi (Valproate) (Controls unexposed, sick), 2018 Vajda (Valproate) (Controls unexposed, sick), 2018 Miškov (Valproate) (Controls unexposed, sick), 2016 3 exposed to other treatment, sickexposed to other treatment, sick 1.22[1.00; 1.48]4302,5320%NAArkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Meador (Valproate), 2006 4 Tags Adjustment   - No  - No 1.31[0.97; 1.76]1951,6510%NAVajda (Valproate) (Controls unexposed, sick), 2018 Miškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Meador (Valproate), 2006 5   - Yes  - Yes 2.48[0.45; 13.75]2731,49383%NATrivedi (Valproate) (Controls unexposed, sick), 2018 Tomson (Valproate), 2015 2 All studiesAll studies 1.46[1.01; 2.11]4683,14436%NATrivedi (Valproate) (Controls unexposed, sick), 2018 Vajda (Valproate) (Controls unexposed, sick), 2018 Miškov (Valproate) (Controls unexposed, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Meador (Valproate), 2006 70.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.05.32.5360.000Trivedi (Valproate) (Controls unexposed, sick), 2018Vajda (Valproate) (Controls unexposed, sick), 2018Miškov (Valproate) (Controls unexposed, sick), 2016Arkilo (Valproate), 2015Tomson (Valproate), 2015Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Meador (Valproate), 2006

Asymetry test p-value = 0.0753 (by Egger's regression)

slope=0.0501 (0.1281); intercept=1.1048 (0.4933); t=2.2395; p=0.0753

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9320, 9321, 9365, 9367

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 5.41[1.76; 16.59]386120%NATrivedi (Valproate) (Controls unexposed, sick), 2018 Vajda (Valproate) (Controls unexposed, sick), 2018 Miškov (Valproate) (Controls unexposed, sick), 2016 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.18[0.98; 1.43]4843,1440%NATrivedi (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Vajda (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Miškov (Valproate) (Controls exposed to Lamotrigine, sick), 2016 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Meador (Valproate), 2006 70.510.01.0