Levetiracetam (All indications) updated on 04-22-2025

Psychomotor developmental disorders/delay

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.
S19390
R82365
Honybun (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Processing Speed Index (Assesses psychomotor speed across time-based tasks) - Wechsler Intelligence Scale - Children aged 3–18 years (mean age about 10 years) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 2.62 [0.86;7.92]
excluded (control group)
-/20   -/23 - 20
ref
S19386
R82325
Honybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Processing Speed Index (Assesses psychomotor speed across time-based tasks) - Wechsler Intelligence Scale - Children aged 3–18 years (mean age about 10 years) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 3.56 [1.10;11.53] -/20   -/19 - 20
ref
S19396
R82409
Li (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Manual dexterity and fine hand motor function - Grooved Pegboard Test (GPB) scores - Follow up to 6 years during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 1.12 [0.63;1.99]
excluded (control group)
-/67   -/90 - 67
ref
S19395
R82404
Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Manual dexterity and fine hand motor function - Grooved Pegboard Test (GPB) scores - Follow up to 6 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 1.09 [0.60;1.97] -/67   -/79 - 67
ref
S19378
R82261
Straub (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Coordination disorders - ICD-10 codes: F82 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.00 [0.61;1.63] C
excluded (control group)
36/3,929   30/3,273 66 3,929
ref
S19369
R82125
Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Coordination disorders - ICD-10 codes: F82 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.86 [0.57;1.31] 36/3,929   91/8,887 127 3,929
ref
S19339
R82018
Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 Gross motor disorders - Assessment offered to all children - At the 27–30 months during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick Adjustment: No 0.98 [0.56;1.72] C 20/527   36/934 56 527
ref
S15220
R62427
Bromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Motor mean score ≤ 86 (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 1.02 [0.31;3.43] C
excluded (control group)
5/51   7/73 12 51
ref
S15219
R62414
Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Motor mean score ≤ 86 (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 1.20 [0.30;4.74] C 5/51   4/48 9 51
ref
S16612
R69683
Thomas (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2022 Delayed motor development quotient (< 84, i.e one SD of the mean) - 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 0.41 [0.02;6.81] C
excluded (control group)
1/62   1/26 2 62
ref
S16613
R69684
Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 The motor development quotient (MODQ) - 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) 0.24 [0.13;0.43] -/62   -/110 - 62
ref
S9946
R35767
Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 Griffiths Mental Developmental Scale - Locomotor (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) 0.27 [0.04;1.85]
excluded (control group)
-/7   -/8 - 7
ref
S9950
R35791
Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Griffiths Mental Developmental Scale - Locomotor (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 2.78 [0.66;11.65] -/7   -/59 - 7
ref
S9028
R30773
Shallcross (Levetiracetam), 2011 Locomotor (Griffiths scale) throughout pregnancy prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 0.75 [0.41;1.39] -/51   -/97 - 51
ref
Total 8 studies 0.94 [0.57;1.53] 192 4,714
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 Honybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Honybun, 2026 1 3.56[1.10; 11.53]-209%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026Li, 2026 2 1.09[0.60; 1.97]-6715%ROB confusion: criticalROB selection: lowROB classification: unclearROB missing: moderateROB mesure: lowROB reporting: low Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Straub, 2026 3 0.86[0.57; 1.31]1273,92917%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025Moore, 2025 4 0.98[0.56; 1.72]5652715%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: low Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Bromley, 2023 5 1.20[0.30; 4.74]9518%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022Thomas, 2022 6 0.24[0.13; 0.43]-6215%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Videman (Levetiracetam) (Controls unexposed, disease free), 2016Videman, 2016 7 2.78[0.66; 11.65]-77%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Shallcross (Levetiracetam), 2011Shallcross, 2011 8 0.75[0.41; 1.39]-5115%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 74% 0.94[0.57; 1.53]1924,7140.210.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Levetiracetam) (Epilepsy; 2: Controls unexposed, disease free) (Levetiracetam) (Epilepsy; 3: Controls unexposed, sick) (Levetiracetam) (Epilepsy; 4: Controls exposed to LTG) (Levetiracetam) (Indication NOS; 5: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 6: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 7: Levetiracetam) (Controls unexposed, disease free; 8: Levetiracetam;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.94[0.57; 1.53]1924,71474%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.04[0.61; 1.75]-12531%NALi (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 3 unexposed, sickunexposed, sick 0.88[0.32; 2.41]1364,06286%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 4 exposed to other treatment, sickexposed to other treatment, sick 0.98[0.56; 1.72]56527 -NAMoore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 1 Tags Adjustment   - No  - No 0.99[0.53; 1.84]6578577%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 7   - Yes  - Yes 0.86[0.57; 1.30]1273,929 -NAStraub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.01[0.42; 2.42]-20784%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5 All studiesAll studies 0.94[0.57; 1.53]1924,71474%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 80.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.70.8790.000Honybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022Videman (Levetiracetam) (Controls unexposed, disease free), 2016Shallcross (Levetiracetam), 2011

Asymetry test p-value = 0.2890 (by Egger's regression)

slope=-0.8559 (0.6012); intercept=2.1145 (1.8180); t=1.1631; p=0.2890

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9946, 16612, 15220, 19390, 19396, 19378

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.61; 1.75]-12531%NALi (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 3 unexposed, sick controlsunexposed, sick controls 0.88[0.32; 2.41]1364,06286%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.05[0.79; 1.40]1364,6630%NAHonybun (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Li (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Straub (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 Bromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2022 Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 70.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Psychomotor developmental delay)Veroniki b (NMA) (Psychomotor developmental delay) Out of scale0.27[0.00; 4.26]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 0.94[0.57; 1.53]74%4,714----Honybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Moore (Controls exposed to LTG) (Levetiracetam) (Indication NOS), 2025 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Thomas (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2022 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 80.510.01.0