Levetiracetam (Epilepsy)

Neuro-developmental disorders (as a whole)

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.
S12772
R48172
Bjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2022 Neurodevelopmental Disorder (ND): any diagnoses of autism spectrum disorder (F84.0, F84.1, F84.5) or intellectual disability (F70, F71, F72, F73) plus F84.3, F84.4, F84.8, F84.9, F79 (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.61 [0.32;1.18] C
excluded (control group)
10/1,017   81/5,073 91 1,017
ref
S12773
R48176
Bjørk (Levetiracetam) (Controls unexposed NOS), 2022 Neurodevelopmental Disorder (ND): any diagnoses of autism spectrum disorder (F84.0, F84.1, F84.5) or intellectual disability (F70, F71, F72, F73) plus F84.3, F84.4, F84.8, F84.9, F79 (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes 1.58 [0.85;2.94]
excluded (control group)
10/1,017   68,295/4,463,879 68,305 1,017
ref
S12774
R48180
Bjørk (Levetiracetam) (Controls unexposed, sick), 2022 Neurodevelopmental Disorder (ND): any diagnoses of autism spectrum disorder (F84.0, F84.1, F84.5) or intellectual disability (F70, F71, F72, F73) plus F84.3, F84.4, F84.8, F84.9, F79 (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.06 [0.56;2.02] 10/1,004   443/21,634 453 1,004
ref
S7807
R23117
Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Diagnosis Disorders of psychological development (F80–F89) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.20 [0.50;2.90] 5/621   10,010/1,710,441 10,015 621
ref
S301
R24952
Arkilo (Levetiracetam), 2015 Abnormal development (At 2 years of age, assessed by developmental specialists) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 0.41 [0.02;9.32] C 0/11   2/24 2 11
ref
Total 3 studies 1.08 [0.65;1.80] 10,470 1,636
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 Bjørk (Levetiracetam) (Controls unexposed, sick), 2022Bjørk, 2022 1 1.06[0.56; 2.02]4531,00464%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 2 1.20[0.50; 2.90]10,01562134%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Arkilo (Levetiracetam), 2015Arkilo, 2015 3 0.41[0.02; 9.32]2113%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 0% 1.08[0.65; 1.80]10,4701,6360.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Levetiracetam) (Controls unexposed, sick; 2: Levetiracetam) (Controls unexposed, NOS; 3: Levetiracetam;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.08[0.65; 1.80]10,4701,6360%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Arkilo (Levetiracetam), 2015 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.20[0.50; 2.89]10,015621 -NACoste (Levetiracetam) (Controls unexposed, NOS), 2020 1 unexposed, sickunexposed, sick 1.06[0.56; 2.01]4531,004 -NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 1 exposed to other treatment, sickexposed to other treatment, sick 0.41[0.02; 9.32]211 -NAArkilo (Levetiracetam), 2015 1 Tags Adjustment   - No  - No 0.41[0.02; 9.32]211 -NAArkilo (Levetiracetam), 2015 1   - Yes  - Yes 1.11[0.66; 1.86]10,4681,6250%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 2 All studiesAll studies 1.08[0.65; 1.80]10,4701,6360%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Arkilo (Levetiracetam), 2015 30.25.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 12772, 12773

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.44[0.87; 2.39]78,3201,6380%NABjørk (Levetiracetam) (Controls unexposed NOS), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 2 unexposed, sick controlsunexposed, sick controls 1.06[0.56; 2.01]4531,004 -NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.60[0.32; 1.15]931,0280%NABjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2022 Arkilo (Levetiracetam), 2015 20.510.01.0