Levetiracetam (Epilepsy) updated on 04-22-2025

Language 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.
S19435
R82822
Honybun (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Verbal Comprehension Index - 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) 2.43 [0.81;7.33]
excluded (control group)
-/20   -/23 - 20
ref
S19439
R82862
Honybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Verbal Comprehension Index - 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) 5.97 [1.77;20.09] -/20   -/19 - 20
ref
S19454
R82924
Li (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Verbal domain - The Differential Ability Scales–2nd Edition (DAS-II) - At 6 years old during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: Yes extrapolated (cont. endpoint) 1.44 [0.82;2.52]
excluded (control group)
-/73   -/90 - 73
ref
S19455
R82929
Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Verbal domain - The Differential Ability Scales–2nd Edition (DAS-II) - At 6 years old during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 0.80 [0.45;1.42] -/73   -/79 - 73
ref
S19458
R82948
Straub (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - 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 0.82 [0.66;1.02] C
excluded (control group)
174/3,929   175/3,273 349 3,929
ref
S19468
R83034
Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.96 [0.79;1.16] 174/3,929   456/8,887 630 3,929
ref
S18100
R76171
Bhaskaran, 2025 Speech delay - Expressive language age on Receptive–Expressive Emergent Language Scale (REELS) < 70 - Infants ages of 1.5 to 2.5 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No 1.14 [0.21;6.29] 2/10   9/50 11 10
ref
S16766
R70401
Stjerna (Levetiracetam) (Epilepsy), 2024 Verbal intelligence quotient (VIQ continuous) - The Wechsler Intelligence Scale for Children (WISC-III) - At 6-7 years old throughout pregnancy retrospective cohort exposed to other treatment, sick Adjustment: Yes extrapolated (cont. endpoint) 0.88 [0.33;2.34] -/16   -/74 - 16
ref
S15842
R65224
Bromley (Levetiracetam) (Controls exposed to LTG), 2023 Language 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 1.88 [0.48;7.35] C
excluded (control group)
5/51   4/73 9 51
ref
S15843
R65237
Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Language 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 1.63 [0.37;7.23] C 5/51   3/48 8 51
ref
S10072
R36667
Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Visits to a speech therapist (mean age of 3.7 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 0.70 [0.40;1.10]
excluded (control group)
22/621   122/2,108 144 621
ref
S7807
R23119
Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Health care utilization: Speech therapy (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.80 [0.60;1.30] 22/621   72,012/1,710,441 72,034 621
ref
S7712
R22901
Husebye (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 0.71 [0.07;6.89] C
excluded (control group)
1/6   9/41 10 6
ref
S7702
R22881
Husebye (Levetiracetam) (Controls unexposed, disease free), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: Yes 0.70 [0.10;6.00]
excluded (control group)
1/6   8,250/42,550 8,251 6
ref
S7707
R22891
Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 0.66 [0.07;5.81] C 1/6   35/150 36 6
ref
S7308
R21193
Bromley (Levetiracetam), 2016 Verbal abilities <85 (Wechsler Preschool and Primary Scale of Intelligence (WPPSI) / Wechsler Intelligence Scale for Children (WISC)) (5-9 years old) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, sick Adjustment: No 0.31 [0.03;2.89] C 1/42   4/55 5 42
ref
S9949
R35787
Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 Griffiths Mental Developmental Scale - Hearing and speech (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) 1.00 [0.16;6.30]
excluded (control group)
-/7   -/8 - 7
ref
S9951
R35799
Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Griffiths Mental Developmental Scale - Hearing and speech (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 2.61 [0.62;10.93] -/7   -/59 - 7
ref
S6762
R19108
Shallcross (Levetiracetam), 2011 Hearing and language (Griffiths scale) throughout pregnancy prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 1.09 [0.59;2.01] -/51   -/97 - 51
ref
Total 11 studies 1.01 [0.78;1.29] 72,724 4,826
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 5.97[1.77; 20.09]-204%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026Li, 2026 2 0.80[0.45; 1.42]-7313%ROB confusion: criticalROB selection: lowROB classification: unclearROB missing: moderateROB mesure: lowROB reporting: low Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Straub, 2026 3 0.96[0.79; 1.16]6303,92934%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Bhaskaran, 2025Bhaskaran, 2025 1.14[0.21; 6.29]11102%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: lowROB mesure: lowROB reporting: moderate Stjerna (Levetiracetam) (Epilepsy), 2024Stjerna, 2024 4 0.88[0.33; 2.34]-166%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: lowROB mesure: lowROB reporting: moderate Bromley (Levetiracetam) (Controls unexposed, sick), 2023Bromley, 2023 5 1.63[0.37; 7.23]8513%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 6 0.80[0.60; 1.30]72,03462121%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Husebye (Levetiracetam) (Controls unexposed, sick), 2020Husebye, 2020 7 0.66[0.07; 5.81]3661%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Levetiracetam), 2016Bromley, 2016 8 0.31[0.03; 2.89]5421%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Videman (Levetiracetam) (Controls unexposed, disease free), 2016Videman, 2016 9 2.61[0.62; 10.93]-73%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Shallcross (Levetiracetam), 2011Shallcross, 2011 10 1.09[0.59; 2.01]-5112%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (11 studies) I2 = 27% 1.01[0.78; 1.29]72,7244,8260.220.01.0ROB: 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: Levetiracetam) (Epilepsy; 5: Levetiracetam) (Controls unexposed, sick; 6: Levetiracetam) (Controls unexposed, NOS; 7: Levetiracetam) (Controls unexposed, sick; 8: Levetiracetam; 9: Levetiracetam) (Controls unexposed, disease free; 10: Levetiracetam;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.01[0.78; 1.29]72,7244,82627%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bhaskaran, 2025 Stjerna (Levetiracetam) (Epilepsy), 2024 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 11 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.90[0.68; 1.18]72,0457620%NALi (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Bhaskaran, 2025 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5 unexposed, sickunexposed, sick 1.34[0.55; 3.23]6794,04860%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 5 exposed to other treatment, sickexposed to other treatment, sick 0.88[0.33; 2.34]-16 -NAStjerna (Levetiracetam) (Epilepsy), 2024 1 Tags Adjustment   - No  - No 1.54[0.81; 2.91]6018734%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bhaskaran, 2025 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 7   - Yes  - Yes 0.91[0.78; 1.08]72,6644,6390%NALi (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Stjerna (Levetiracetam) (Epilepsy), 2024 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 4 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.39[0.74; 2.59]-16761%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Stjerna (Levetiracetam) (Epilepsy), 2024 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5 All studiesAll studies 1.01[0.78; 1.29]72,7244,82627%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bhaskaran, 2025 Stjerna (Levetiracetam) (Epilepsy), 2024 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 110.120.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.72.71.3650.000Honybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Li (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026Bhaskaran, 2025Stjerna (Levetiracetam) (Epilepsy), 2024Bromley (Levetiracetam) (Controls unexposed, sick), 2023Coste (Levetiracetam) (Controls unexposed, NOS), 2020Husebye (Levetiracetam) (Controls unexposed, sick), 2020Bromley (Levetiracetam), 2016Videman (Levetiracetam) (Controls unexposed, disease free), 2016Shallcross (Levetiracetam), 2011

Asymetry test p-value = 0.3865 (by Egger's regression)

slope=-0.1257 (0.1343); intercept=0.4731 (0.5199); t=0.9100; p=0.3865

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9949, 10072, 7712, 7702, 15842, 19435, 19454, 19458

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.89[0.68; 1.17]80,2967680%NALi (Controls unexposed, disease free) (Levetiracetam) (Epilepsy), 2026 Bhaskaran, 2025 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Husebye (Levetiracetam) (Controls unexposed, disease free), 2020 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 6 unexposed, sick controlsunexposed, sick controls 1.34[0.55; 3.23]6794,04860%NAHonybun (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Straub (Controls unexposed, sick) (Levetiracetam) (Epilepsy), 2026 Bromley (Levetiracetam) (Controls unexposed, sick), 2023 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.96[0.74; 1.24]5124,72319%NAHonybun (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Li (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Straub (Controls exposed to LTG) (Levetiracetam) (Epilepsy), 2026 Stjerna (Levetiracetam) (Epilepsy), 2024 Bromley (Levetiracetam) (Controls exposed to LTG), 2023 Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Husebye (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Videman (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2016 80.510.01.0