Valproate (Epilepsy) updated on 04-22-2025

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.
S16079
R66725		 Christensen (Valproate) (Epilepsy) (Controls exposed to LTG), 2024 Low birth weight (<2500 g) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.09 [0.85;1.40] C
excluded (control group) 		92/1,953   230/5,299 322 1,953
ref
S16023
R66513		 Christensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 Low birth weight (<2500 g) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.10 [0.85;1.41] 92/1,953   1,006/22,227 1,098 1,953
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
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 [0.95;1.93] 92,677 3,047
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 Christensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024Christensen, 2024 1 1.10[0.85; 1.41]1,0981,95341%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Coste (Valproate) (Controls unexposed, NOS), 2020Coste, 2020 2 1.73[1.39; 2.15]91,54399143%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Veiby (Valproate) (Controls unexposed, sick) b, 2013Veiby, 2013 3 1.88[0.52; 6.73]19407%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]17639%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 62% 1.35[0.95; 1.93]92,6773,0470.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.35[0.95; 1.93]92,6773,04762%NAChristensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 Coste (Valproate) (Controls unexposed, NOS), 2020 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 1.11[0.87; 1.41]1,1342,0560%NAChristensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 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 1.10[0.85; 1.42]1,0981,953 -NAChristensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 1 All studiesAll studies 1.35[0.95; 1.93]92,6773,04762%NAChristensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 Coste (Valproate) (Controls unexposed, NOS), 2020 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
0.0-1.51.80.7830.000Christensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024Coste (Valproate) (Controls unexposed, NOS), 2020Veiby (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 6353, 5506, 10070, 16079

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.71[1.38; 2.13]96,5701,0310%NACoste (Valproate) (Controls unexposed, NOS), 2020 Veiby (Valproate) (Controls unexposed, disease free) b, 2013 2 unexposed, sick controlsunexposed, sick controls 1.11[0.87; 1.41]1,1342,0560%NAChristensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 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 1.27[0.99; 1.63]5472,98430%NAChristensen (Valproate) (Epilepsy) (Controls exposed to LTG), 2024 Coste (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013 30.510.01.0