Valproate (All indications)

Preeclampsia

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.
S9287
R32247		 Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Preeclampsia/ eclampsia throughout pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.62 [0.01;35.19] C
excluded (control group) 		0/11   0/7 0 11
ref
S9288
R32257		 Aydin (Valproate) (Controls unexposed, sick), 2020 Preeclampsia/ eclampsia throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 2.05 [0.04;110.56] C 0/11   0/22 0 11
ref
S9315
R32453		 Cohen (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Preeclampsia early pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 0.69 [0.44;1.09]
excluded (control group) 		104/2,398   129/2,682 233 2,398
ref
S9316
R32460		 Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Preeclampsia early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.94 [0.77;1.15] 104/2,398   53,634/1,440,631 53,738 2,398
ref
S9323
R32488		 Pennell (Valproate), 2012 Gestational hypertension during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.29 [0.33;5.01] C 4/61   5/97 9 61
ref
S9433
R33129		 Borthen (Valproate) (Controls exposed to Lamotrigine, sick), 2011 Pre-eclampsia during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.47 [0.08;2.62] C
excluded (control group) 		2/19   6/30 8 19
ref
S9435
R33137		 Borthen (Valproate) (Controls unexposed, disease free), 2011 Pre-eclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No Matched 2.10 [0.40;10.10]
excluded (control group) 		2/19   11/205 13 19
ref
S9437
R33145		 Borthen (Valproate) (Controls unexposed, sick), 2011 Pre-eclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.83 [0.17;4.11] C 2/19   11/89 13 19
ref
Total 4 studies 0.95 [0.78;1.15] 53,760 2,489
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 Aydin (Valproate) (Controls unexposed, sick), 2020Aydin, 2020 1 2.05[0.04; 110.56]0110%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019Cohen, 2019 2 0.94[0.77; 1.15]53,7382,39896%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Pennell (Valproate), 2012Pennell, 2012 3 1.29[0.33; 5.01]9612%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Borthen (Valproate) (Controls unexposed, sick), 2011Borthen, 2011 4 0.83[0.17; 4.11]13192%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 0.95[0.78; 1.15]53,7602,4890.25.01.0ROB: 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 NOS) (Mixed indications; 3: Valproate; 4: Valproate) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.95[0.78; 1.15]53,7602,4890%NAAydin (Valproate) (Controls unexposed, sick), 2020 Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Pennell (Valproate), 2012 Borthen (Valproate) (Controls unexposed, sick), 2011 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.94[0.77; 1.15]53,7382,398 -NACohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 1 unexposed, sickunexposed, sick 0.94[0.21; 4.15]13300%NAAydin (Valproate) (Controls unexposed, sick), 2020 Borthen (Valproate) (Controls unexposed, sick), 2011 2 exposed to other treatment, sickexposed to other treatment, sick 1.29[0.33; 5.01]961 -NAPennell (Valproate), 2012 1 Tags Adjustment   - No  - No 1.12[0.41; 3.04]22910%NAAydin (Valproate) (Controls unexposed, sick), 2020 Pennell (Valproate), 2012 Borthen (Valproate) (Controls unexposed, sick), 2011 3   - Yes  - Yes 0.94[0.77; 1.15]53,7382,398 -NACohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 1 All studiesAll studies 0.95[0.78; 1.15]53,7602,4890%NAAydin (Valproate) (Controls unexposed, sick), 2020 Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Pennell (Valproate), 2012 Borthen (Valproate) (Controls unexposed, sick), 2011 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.72.4420.000Aydin (Valproate) (Controls unexposed, sick), 2020Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019Pennell (Valproate), 2012Borthen (Valproate) (Controls unexposed, sick), 2011

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9433, 9435, 9315, 9287

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.95[0.78; 1.16]53,7512,4170%NACohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Borthen (Valproate) (Controls unexposed, disease free), 2011 2 unexposed, sick controlsunexposed, sick controls 0.94[0.21; 4.15]13300%NAAydin (Valproate) (Controls unexposed, sick), 2020 Borthen (Valproate) (Controls unexposed, sick), 2011 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.71[0.47; 1.08]2502,4890%NAAydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Cohen (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Pennell (Valproate), 2012 Borthen (Valproate) (Controls exposed to Lamotrigine, sick), 2011 40.510.01.0