Valproate (Epilepsy)

Low birth weight (< 2500g)

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.
S10070
R36642		 Coste (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Weight at birth <2500 g during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.51 [1.14;2.00] C
excluded (control group) 		88/991   128/2,108 216 991
ref
S7799
R23025		 Coste (Valproate) (Controls unexposed, NOS), 2020 Weight at birth <2500 g during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.73 [1.39;2.15] C 88/991   91,455/1,710,441 91,543 991
ref
S5931
R15132		 Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013 Low birth weight (< 2500g) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.15 [0.47;2.83] C
excluded (control group) 		28/703   6/173 34 703
ref
S5911
R14911		 Artama (Valproate) (Controls unexposed, disease free), 2013 Low birth weight (< 2500g) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 1.14 [0.78;1.67]
excluded (control group) 		28/703   21,546/719,509 21,574 703
ref
S5919
R15007		 Artama (Valproate) (Controls unexposed, sick), 2013 Low birth weight (< 2500g) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.00 [0.63;1.61] 28/703   65/1,793 93 703
ref
S6353
R17322		 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013 Low birth weight (< 2500 grams) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.31 [0.31;5.51] C
excluded (control group) 		3/40   6/103 9 40
ref
S5506
R17326		 Veiby (Valproate) (Controls unexposed, disease free) b, 2013 Low birth weight (< 2500 grams) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: Yes 1.30 [0.30;5.30]
excluded (control group) 		3/40   5,024/106,899 5,027 40
ref
S6350
R17330		 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Low birth weight (< 2500 grams) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.88 [0.52;6.73] C 3/40   16/386 19 40
ref
S371
R18041		 Kini (Valproate) (Controls unexposed, sick), 2006 Birth weight <2500 g during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.86 [0.30;2.46] C 6/63   11/101 17 63
ref
Total 4 studies 1.35 [0.92;2.00] 91,672 1,797
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 Coste (Valproate) (Controls unexposed, NOS), 2020Coste, 2020 1 1.73[1.39; 2.15]91,54399149%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Artama (Valproate) (Controls unexposed, sick), 2013Artama, 2013 2 1.00[0.63; 1.61]9370332%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Veiby (Valproate) (Controls unexposed, sick) b, 2013Veiby, 2013 3 1.88[0.52; 6.73]19408%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Kini (Valproate) (Controls unexposed, sick), 2006Kini, 2006 4 0.86[0.30; 2.46]176311%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 46% 1.35[0.92; 2.00]91,6721,7970.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (Controls unexposed, NOS; 2: Valproate) (Controls unexposed, sick; 3: Valproate) (Controls unexposed, sick) ; 4: Valproate) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.35[0.92; 2.00]91,6721,79746%NACoste (Valproate) (Controls unexposed, NOS), 2020 Artama (Valproate) (Controls unexposed, sick), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.73[1.39; 2.15]91,543991 -NACoste (Valproate) (Controls unexposed, NOS), 2020 1 unexposed, sickunexposed, sick 1.04[0.69; 1.56]1298060%NAArtama (Valproate) (Controls unexposed, sick), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 3 Tags Adjustment   - No  - No 1.68[1.36; 2.08]91,5791,0940%NACoste (Valproate) (Controls unexposed, NOS), 2020 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 3   - Yes  - Yes 1.00[0.63; 1.60]93703 -NAArtama (Valproate) (Controls unexposed, sick), 2013 1 All studiesAll studies 1.35[0.92; 2.00]91,6721,79746%NACoste (Valproate) (Controls unexposed, NOS), 2020 Artama (Valproate) (Controls unexposed, sick), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.51.80.7830.000Coste (Valproate) (Controls unexposed, NOS), 2020Artama (Valproate) (Controls unexposed, sick), 2013Veiby (Valproate) (Controls unexposed, sick) b, 2013Kini (Valproate) (Controls unexposed, sick), 2006

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 5931, 5911, 6353, 5506, 10070

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.46[1.05; 2.01]118,1441,73443%NACoste (Valproate) (Controls unexposed, NOS), 2020 Artama (Valproate) (Controls unexposed, disease free), 2013 Veiby (Valproate) (Controls unexposed, disease free) b, 2013 3 unexposed, sick controlsunexposed, sick controls 1.04[0.69; 1.56]1298060%NAArtama (Valproate) (Controls unexposed, sick), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.47[1.12; 1.91]2591,7340%NACoste (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013 30.510.01.0