Levetiracetam (Epilepsy) updated on 04-22-2025

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.
S16807
R70522		 Ertürk Çetin (Epilepsy) (Levetiracetam), 2024 Developmental delay in one domain - The Denver Developmental Screening Test (DDST) - At 18 month of age throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 0.43 [0.01;23.69] C 0/18   0/8 0 18
ref
S15842
R65223		 Bromley (Levetiracetam) (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
S15843
R65236		 Bromley (Levetiracetam) (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
S16783
R70456		 Thomas (Controls exposed to LTG), 2022 The mental development quotient (MEDQ) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 0.43 [0.19;1.00]
excluded (control group) 		-/62   -/26 - 62
ref
S16784
R70459		 Thomas (Controls unexposed, sick), 2022 The mental development quotient (MEDQ) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 0.49 [0.28;0.87] -/62   -/110 - 62
ref
S9949
R53773		 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
S9951
R53774		 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
S6762
R53772		 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 5 studies 0.97 [0.41;2.30] 23 189
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 Ertürk Çetin (Epilepsy) (Levetiracetam), 2024Ertürk Çetin, 2024 1 0.43[0.01; 23.69]0184%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bromley (Levetiracetam) (Controls unexposed, sick), 2023Bromley, 2023 2 2.50[0.46; 13.55]75116%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Thomas (Controls unexposed, sick), 2022Thomas, 2022 3 0.49[0.28; 0.87]-6236%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Videman (Levetiracetam) (Controls unexposed, disease free), 2016Videman, 2016 4 3.30[0.79; 13.90]-720%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Shallcross (Levetiracetam), 2011Shallcross, 2011 5 0.60[0.18; 1.97]165124%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 52% 0.97[0.41; 2.30]231890.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Epilepsy) (Levetiracetam; 2: Levetiracetam) (Controls unexposed, sick; 3: Controls unexposed, sick; 4: Levetiracetam) (Controls unexposed, disease free; 5: Levetiracetam;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.97[0.41; 2.30]2318952%NAErtürk Çetin (Epilepsy) (Levetiracetam), 2024 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Thomas (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5 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 0.90[0.19; 4.25]711369%NABromley (Levetiracetam) (Controls unexposed, sick), 2023 Thomas (Controls unexposed, sick), 2022 2 exposed to other treatment, sickexposed to other treatment, sick 0.43[0.01; 23.69]-18 -NAErtürk Çetin (Epilepsy) (Levetiracetam), 2024 1 Tags Adjustment   - No  - No 0.97[0.41; 2.30]2318952%NAErtürk Çetin (Epilepsy) (Levetiracetam), 2024 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Thomas (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.13[0.18; 7.22]-6983%NAThomas (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 2 All studiesAll studies 0.97[0.41; 2.30]2318952%NAErtürk Çetin (Epilepsy) (Levetiracetam), 2024 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Thomas (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.82.4560.000Ertürk Çetin (Epilepsy) (Levetiracetam), 2024Bromley (Levetiracetam) (Controls unexposed, sick), 2023Thomas (Controls unexposed, sick), 2022Videman (Levetiracetam) (Controls unexposed, disease free), 2016Shallcross (Levetiracetam), 2011

Asymetry test p-value = 0.3033 (by Egger's regression)

slope=-1.0109 (0.6093); intercept=1.4384 (1.1605); t=1.2395; p=0.3033

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9949, 16783, 15842

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 0.90[0.19; 4.25]711369%NABromley (Levetiracetam) (Controls unexposed, sick), 2023 Thomas (Controls unexposed, sick), 2022 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.85[0.28; 2.60]713844%NAErtürk Çetin (Epilepsy) (Levetiracetam), 2024 Bromley (Levetiracetam) (Controls exposed to LTG), 2023 Thomas (Controls exposed to LTG), 2022 Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 40.510.01.0