Levetiracetam (Epilepsy) updated on 04-22-2025

ASD (Autism spectrum disorder): Diagnosis/Risk

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.
S17431
R73239		 Madley-Dowd_SE (Levetiracetam) (Controls exposed to LTG), 2024 Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 0.64 [0.30;1.36] C
excluded (control group) 		8/556   53/2,383 61 556
ref
S17432
R73240		 Madley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Partial overlapping 0.94 [0.46;1.90] 8/556   425/10,769 433 556
ref
S17252
R72250		 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Autism - ICD10 codes - Median 4.19 (2.56-6.79) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.95 [0.20;4.49] -/174   78/4,075 - 174
ref
S15871
R65403		 Dreier (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Autism spectrum disorder - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 0.62 [0.30;1.30] C
excluded (control group) 		8/1,061   64/5,288 72 1,061
ref
S15872
R65411		 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Autism spectrum disorder - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: Yes 0.85 [0.37;1.94] 8/1,061   323/22,203 331 1,061
ref
S10072
R46412		 Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Diagnosis Pervasive developmental disorders (F84) (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 1.80 [0.50;6.60]
excluded (control group) 		4/621   7/2,108 11 621
ref
S7807
R46413		 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Diagnosis Pervasive developmental disorders (F84) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 2.50 [0.90;6.60] 4/621   4,280/1,710,441 4,284 621
ref
S7511
R46415		 Huber-Mollema (Levetiracetam), 2019 Diagnosis of autism spectrum disorder throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 0.72 [0.08;6.75] C 1/30   4/88 5 30
ref
S9963
R46416		 Bjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 2.42 [0.63;9.26] C
excluded (control group) 		4/12   13/76 17 12
ref
S9933
R46417		 Bjørk (Levetiracetam) (Controls unexposed, disease free), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: No 4.97 [1.49;16.49] C
excluded (control group) 		4/12   6,907/75,497 6,911 12
ref
S9961
R46418		 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 4.54 [1.28;16.06] C 4/12   27/272 31 12
ref
Total 6 studies 1.36 [0.78;2.37] 5,084 2,454
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 Madley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 1 0.94[0.46; 1.90]43355628%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024Madley-Dowd_UK, 2024 2 0.95[0.20; 4.49]-17410%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Dreier, 2023 3 0.85[0.37; 1.94]3311,06124%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 4 2.50[0.90; 6.60]4,28462119%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Huber-Mollema (Levetiracetam), 2019Huber-Mollema, 2019 5 0.72[0.08; 6.75]5305%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bjørk (Levetiracetam) (Controls unexposed, sick), 2018Bjørk, 2018 6 4.54[1.28; 16.06]311214%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 35% 1.36[0.78; 2.37]5,0842,4540.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Levetiracetam) (Controls unexposed, sick; 2: Levetiracetam) (Epilepsy; 3: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 4: Levetiracetam) (Controls unexposed, NOS; 5: Levetiracetam; 6: Levetiracetam) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.36[0.78; 2.37]5,0842,45435%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.50[0.92; 6.77]4,284621 -NACoste (Levetiracetam) (Controls unexposed, NOS), 2020 1 unexposed, sickunexposed, sick 1.24[0.63; 2.44]7951,80344%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 4 exposed to other treatment, sickexposed to other treatment, sick 0.72[0.08; 6.75]530 -NAHuber-Mollema (Levetiracetam), 2019 1 Tags Adjustment   - No  - No 2.30[0.41; 13.07]364249%NAHuber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 2   - Yes  - Yes 1.12[0.70; 1.80]5,0482,4126%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 4 Partial overlappingPartial overlapping 0.94[0.46; 1.91]433556 -NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 1 All studiesAll studies 1.36[0.78; 2.37]5,0842,45435%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.73.01.3660.000Madley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Coste (Levetiracetam) (Controls unexposed, NOS), 2020Huber-Mollema (Levetiracetam), 2019Bjørk (Levetiracetam) (Controls unexposed, sick), 2018

Asymetry test p-value = 0.6474 (by Egger's regression)

slope=-0.1459 (0.8519); intercept=0.8029 (1.6264); t=0.4937; p=0.6474

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9963, 9933, 10072, 15871, 17431

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.31[1.54; 7.12]11,1956330%NACoste (Levetiracetam) (Controls unexposed, NOS), 2020 Bjørk (Levetiracetam) (Controls unexposed, disease free), 2018 2 unexposed, sick controlsunexposed, sick controls 1.24[0.63; 2.44]8641,80344%NAMadley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.88[0.52; 1.49]1662,28018%NAMadley-Dowd_SE (Levetiracetam) (Controls exposed to LTG), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2018 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Epilepsy) (Autism/dyspraxia)Veroniki b (NMA) (Epilepsy) (Autism/dyspraxia) 3.52[0.00; 272.20]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.36[0.78; 2.37]35%2,454----Madley-Dowd_SE (Levetiracetam) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Levetiracetam) (Epilepsy), 2024 Dreier (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 60.510.01.0