Levetiracetam (All indications)

Cognitive developmental disorders/delay (< 3 years old)

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.
S15220
R62425		 Bromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Cognitive mean score ≤ 88 (below average performance of the cohort mean) - Bayley Scales of Infant and Toddler Development - At 24 months of age during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 3.86 [0.72;20.73] C
excluded (control group) 		5/51   2/73 7 51
ref
S15219
R62412		 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Cognitive mean score ≤ 88 (below average performance of the cohort mean) - Bayley Scales of Infant and Toddler Development - At 24 months of age during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 2.50 [0.46;13.55] C 5/51   2/48 7 51
ref
S9946
R53769		 Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 Griffiths Mental Developmental Scale - General quotient (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 0.73 [0.12;4.63]
excluded (control group) 		-/7   -/8 - 7
ref
S9950
R53770		 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Griffiths Mental Developmental Scale - General quotient (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 3.30 [0.79;13.90] -/7   -/59 - 7
ref
S9028
R53768		 Shallcross (Levetiracetam), 2011 Overall development quotient (Griffiths scale) <84 throughout pregnancy prospective cohort unexposed, disease free Adjustment: No 0.60 [0.18;1.97] C 4/51   12/97 16 51
ref
Total 3 studies 1.56 [0.51;4.80] 23 109
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 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Bromley, 2023 1 2.50[0.46; 13.55]75127%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Videman (Levetiracetam) (Controls unexposed, disease free), 2016Videman, 2016 2 3.30[0.79; 13.90]-733%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Shallcross (Levetiracetam), 2011Shallcross, 2011 3 0.60[0.18; 1.97]165140%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 47% 1.56[0.51; 4.80]231090.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 2: Levetiracetam) (Controls unexposed, disease free; 3: Levetiracetam;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.56[0.51; 4.80]2310947%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.34[0.25; 7.08]165869%NAVideman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 2 unexposed, sickunexposed, sick 2.50[0.46; 13.55]751 -NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 1 Tags Adjustment   - No  - No 1.56[0.51; 4.80]2310947%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 3.30[0.79; 13.84]-7 -NAVideman (Levetiracetam) (Controls unexposed, disease free), 2016 1 All studiesAll studies 1.56[0.51; 4.80]2310947%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 30.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 9946, 15220

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.34[0.25; 7.08]165869%NAVideman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 2 unexposed, sick controlsunexposed, sick controls 2.50[0.46; 13.55]751 -NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.75[0.34; 8.91]75842%NABromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 20.510.01.0