Valproate (All indications) 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.
S16067
R66677		 Christensen (Valproate) (All indications) (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 1.00 [0.81;1.23] C
excluded (control group) 		120/2,669   395/8,756 515 2,669
ref
S16022
R66509		 Christensen (Valproate) (All indications) (Controls unexposed, general population), 2024 Low birth weight (<2500 g) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.00 [0.83;1.21] 120/2,669   141,442/4,467,848 141,562 2,669
ref
S9391
R32874		 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
S9392
R32892		 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
S9441
R33153		 Wen (Valproate) (Mixed indications), 2017 Low birth weight ( 1500 - 2500 g) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.65 [1.08;2.53] C 24/226   2,945/43,956 2,969 226
ref
S9424
R33070		 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
S9426
R33088		 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
S9427
R33102		 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
S9346
R32596		 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 5 studies 1.36 [0.96;1.94] 236,110 3,989
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) (All indications) (Controls unexposed, general population), 2024Christensen, 2024 1 1.00[0.83; 1.21]141,5622,66932%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]91,54399131%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Wen (Valproate) (Mixed indications), 2017Wen, 2017 3 1.65[1.08; 2.53]2,96922623%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Valproate) (Controls unexposed, sick) b, 2013Veiby, 2013 4 1.88[0.52; 6.73]19406%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Kini (Valproate) (Controls unexposed, sick), 2006Kini, 2006 5 0.86[0.30; 2.46]17639%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 75% 1.36[0.96; 1.94]236,1103,9890.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (All indications) (Controls unexposed, general population; 2: Valproate) (Controls unexposed, NOS; 3: Valproate) (Mixed indications; 4: Valproate) (Controls unexposed, sick) ; 5: Valproate) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.36[0.96; 1.94]236,1103,98975%NAChristensen (Valproate) (All indications) (Controls unexposed, general population), 2024 Coste (Valproate) (Controls unexposed, NOS), 2020 Wen (Valproate) (Mixed indications), 2017 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.40[0.93; 2.10]236,0743,88687%NAChristensen (Valproate) (All indications) (Controls unexposed, general population), 2024 Coste (Valproate) (Controls unexposed, NOS), 2020 Wen (Valproate) (Mixed indications), 2017 3 unexposed, sickunexposed, sick 1.18[0.52; 2.65]361030%NAVeiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 2 Tags Adjustment   - No  - No 1.68[1.39; 2.02]94,5481,3200%NACoste (Valproate) (Controls unexposed, NOS), 2020 Wen (Valproate) (Mixed indications), 2017 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 4   - Yes  - Yes 1.00[0.83; 1.21]141,5622,669 -NAChristensen (Valproate) (All indications) (Controls unexposed, general population), 2024 1 All studiesAll studies 1.36[0.96; 1.94]236,1103,98975%NAChristensen (Valproate) (All indications) (Controls unexposed, general population), 2024 Coste (Valproate) (Controls unexposed, NOS), 2020 Wen (Valproate) (Mixed indications), 2017 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.51.80.7830.000Christensen (Valproate) (All indications) (Controls unexposed, general population), 2024Coste (Valproate) (Controls unexposed, NOS), 2020Wen (Valproate) (Mixed indications), 2017Veiby (Valproate) (Controls unexposed, sick) b, 2013Kini (Valproate) (Controls unexposed, sick), 2006

Asymetry test p-value = 0.7806 (by Egger's regression)

slope=0.1857 (0.2808); intercept=0.5612 (1.8428); t=0.3045; p=0.7806

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9424, 9426, 9391, 16067

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.39[0.95; 2.03]241,1013,92680%NAChristensen (Valproate) (All indications) (Controls unexposed, general population), 2024 Coste (Valproate) (Controls unexposed, NOS), 2020 Wen (Valproate) (Mixed indications), 2017 Veiby (Valproate) (Controls unexposed, disease free) b, 2013 4 unexposed, sick controlsunexposed, sick controls 1.18[0.52; 2.65]361030%NAVeiby (Valproate) (Controls unexposed, sick) b, 2013 Kini (Valproate) (Controls unexposed, sick), 2006 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.21[0.86; 1.72]7403,70063%NAChristensen (Valproate) (All indications) (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