Valproate (Epilepsy)

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.
S8087
R24749		 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
S7922
R24636		 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
S8143
R25025		 Cohen (Valproate) (Controls exposed to Lamotrigine, sick), 2019 Preeclampsia early pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 1.25 [0.61;2.56]
excluded (control group) 		-/-   -/- - -
ref
S8139
R24997		 Cohen (Valproate) (Controls unexposed NOS), 2019 Preeclampsia early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.53 [0.83;2.81] -/-   53,634/1,440,631 - -
ref
S6416
R17613		 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
S6281
R16912		 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
S6277
R16896		 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
S6280
R16908		 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 1.41 [0.84;2.37] 22 91
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]0112%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Cohen (Valproate) (Controls unexposed NOS), 2019Cohen, 2019 2 1.53[0.83; 2.81]--73%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Pennell (Valproate), 2012Pennell, 2012 3 1.29[0.33; 5.01]96115%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]131911%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 1.41[0.84; 2.37]22910.25.01.0ROB: 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; 3: Valproate; 4: Valproate) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.41[0.84; 2.37]22910%NAAydin (Valproate) (Controls unexposed, sick), 2020 Cohen (Valproate) (Controls unexposed NOS), 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) 1.53[0.83; 2.82]-- -NACohen (Valproate) (Controls unexposed NOS), 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 1.53[0.83; 2.82]-- -NACohen (Valproate) (Controls unexposed NOS), 2019 1 All studiesAll studies 1.41[0.84; 2.37]22910%NAAydin (Valproate) (Controls unexposed, sick), 2020 Cohen (Valproate) (Controls unexposed NOS), 2019 Pennell (Valproate), 2012 Borthen (Valproate) (Controls unexposed, sick), 2011 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.12.4420.000Aydin (Valproate) (Controls unexposed, sick), 2020Cohen (Valproate) (Controls unexposed NOS), 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 6281, 6277, 8143, 8087

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.59[0.90; 2.82]53,638190%NACohen (Valproate) (Controls unexposed NOS), 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 1.10[0.61; 1.99]17910%NAAydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Cohen (Valproate) (Controls exposed to Lamotrigine, sick), 2019 Pennell (Valproate), 2012 Borthen (Valproate) (Controls exposed to Lamotrigine, sick), 2011 40.510.01.0