Levetiracetam (All indications)

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.
S15220
R62426		 Bromley (Levetiracetam) (Epilepsy) (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
S15219
R62413		 Bromley (Levetiracetam) (Epilepsy) (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
S15224
R62809		 Meador (Controls exposed to LTG), 2023 Verbal Index score < 85 - Average scores on 2 subtests of Differential Ability Scales­II (DAS­II), Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale­5 (PLS­5), and Peabody Picture Vocabulary Test­ (PPVT­4) - At age 3 years during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.97 [0.21;4.50] C
excluded (control group) 		3/67   4/87 7 67
ref
S15276
R62811		 Meador (Controls unexposed, disease free), 2023 Verbal Index score - Average scores on 2 subtests of Differential Ability Scales­II (DAS­II), Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale­5 (PLS­5), and Peabody Picture Vocabulary Test­ (PPVT­4) - At age 3 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 0.81 [0.47;1.39] -/73   -/106 - 73
ref
S10071
R36657		 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
S9020
R30718		 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
S9023
R30763		 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
S9024
R30765		 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
S9025
R30767		 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
S9018
R30670		 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
S9946
R35769		 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
S9950
R35793		 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
S9028
R30775		 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 7 studies 0.89 [0.68;1.16] 72,083 851
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 1.63[0.37; 7.23]8513%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Meador (Controls unexposed, disease free), 2023Meador, 2023 2 0.81[0.47; 1.39]-7324%ROB confusion: seriousROB selection: moderateROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 3 0.80[0.60; 1.30]72,03462147%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Husebye (Levetiracetam) (Controls unexposed, sick), 2020Husebye, 2020 4 0.66[0.07; 5.81]3661%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Levetiracetam), 2016Bromley, 2016 5 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 6 2.61[0.62; 10.93]-73%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Shallcross (Levetiracetam), 2011Shallcross, 2011 7 1.09[0.59; 2.01]-5119%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 0% 0.89[0.68; 1.16]72,0838510.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.89[0.68; 1.16]72,0838510%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Meador (Controls unexposed, disease free), 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 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.89[0.68; 1.17]72,0347520%NAMeador (Controls unexposed, disease free), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 4 unexposed, sickunexposed, sick 0.89[0.30; 2.61]49990%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 3 Tags Adjustment   - No  - No 1.16[0.70; 1.91]491570%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5   - Yes  - Yes 0.80[0.59; 1.10]72,0346940%NAMeador (Controls unexposed, disease free), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.02[0.65; 1.59]-13116%NAMeador (Controls unexposed, disease free), 2023 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 3 All studiesAll studies 0.89[0.68; 1.16]72,0838510%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Meador (Controls unexposed, disease free), 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 70.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.72.61.3650.000Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Meador (Controls unexposed, disease free), 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 = 0.5693 (by Egger's regression)

slope=-0.2322 (0.2300); intercept=0.3895 (0.6399); t=0.6088; p=0.5693

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9946, 10071, 9023, 9024, 15220, 15224

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]80,2857580%NAMeador (Controls unexposed, disease free), 2023 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Husebye (Levetiracetam) (Controls unexposed, disease free), 2020 Videman (Levetiracetam) (Controls unexposed, disease free), 2016 Shallcross (Levetiracetam), 2011 5 unexposed, sick controlsunexposed, sick controls 0.89[0.30; 2.61]49990%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Husebye (Levetiracetam) (Controls unexposed, sick), 2020 Bromley (Levetiracetam), 2016 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.81[0.53; 1.25]1707520%NABromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Meador (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 50.510.01.0