Valproate (All indications)

Late intrauterine deaths (> 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.
S9280
R32190		 AlSheikh (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Stillbirth during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 39.00 [0.31;4841.77] C
excluded (control group) 		0/1   0/20 0 1
ref
S9281
R32193		 AlSheikh (Valproate) (Controls unexposed, sick), 2020 Stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 15.00 [0.12;1923.88] C 0/1   0/8 0 1
ref
S9287
R32244		 Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Intrauterine fetal demise 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
R32254		 Aydin (Valproate) (Controls unexposed, sick), 2020 Intrauterine fetal demise throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 2.05 [0.04;110.56] C 0/11   0/22 0 11
ref
S9282
R32199		 Arkilo (Valproate), 2015 Stillbirth during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 15.67 [0.22;1102.00] C 0/2   0/24 0 2
ref
S9364
R32751		 Tomson (Valproate), 2015 Stillbirths at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.36 [0.41;4.47] C 5/1,171   6/1,910 11 1,171
ref
S9333
R32565		 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Stillbirths 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.83 [0.90;3.71] C 16/1,290   15/2,198 31 1,290
ref
Total 5 studies 1.83 [1.01;3.31] 42 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 AlSheikh (Valproate) (Controls unexposed, sick), 2020AlSheikh, 2020 1 15.00[0.12; 1923.88]011%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: moderate Aydin (Valproate) (Controls unexposed, sick), 2020Aydin, 2020 2 2.05[0.04; 110.56]0112%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Arkilo (Valproate), 2015Arkilo, 2015 3 15.67[0.22; 1102.00]022%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Valproate), 2015Tomson, 2015 4 1.36[0.41; 4.47]111,17125%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 5 1.83[0.90; 3.71]311,29070%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.83[1.01; 3.31]422,4750.550.01.0ROB: 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; 4: Valproate; 5: Valproate) (Controls exposed to Lamotrigine, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.83[1.01; 3.31]422,4750%NAAlSheikh (Valproate) (Controls unexposed, sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 4.57[0.21; 99.60]-120%NAAlSheikh (Valproate) (Controls unexposed, sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 2 exposed to other treatment, sickexposed to other treatment, sick 1.77[0.97; 3.23]422,4630%NAArkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 3 Tags Adjustment   - No  - No 1.83[1.01; 3.31]422,4750%NAAlSheikh (Valproate) (Controls unexposed, sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 5 All studiesAll studies 1.83[1.01; 3.31]422,4750%NAAlSheikh (Valproate) (Controls unexposed, sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 50.550.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.86.42.9720.000AlSheikh (Valproate) (Controls unexposed, sick), 2020Aydin (Valproate) (Controls unexposed, sick), 2020Arkilo (Valproate), 2015Tomson (Valproate), 2015Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014

Asymetry test p-value = 0.1757 (by Egger's regression)

slope=0.2335 (0.2706); intercept=0.7087 (0.4015); t=1.7652; p=0.1757

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9280, 9287

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 4.57[0.21; 99.60]-120%NAAlSheikh (Valproate) (Controls unexposed, sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.81[1.00; 3.27]422,4750%NAAlSheikh (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 50.510.01.0