Levetiracetam (All indications)

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.
S12775
R48762		 Bjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2022 Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) (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 0.71 [0.32;1.57] C
excluded (control group) 		7/1,017   49/5,073 56 1,017
ref
S12776
R48763		 Bjørk (Levetiracetam) (Controls unexposed NOS), 2022 Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) (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 1.59 [0.76;3.33]
excluded (control group) 		7/1,017   38,437/4,463,879 38,444 1,017
ref
S12777
R48764		 Bjørk (Levetiracetam) (Controls unexposed, sick), 2022 Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.06 [0.49;2.30] 7/1,004   267/21,634 274 1,004
ref
S10071
R46403		 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
S9020
R46404		 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
S9022
R46406		 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
S9962
R46407		 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
S9932
R46408		 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
S9958
R46409		 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 4 studies 1.83 [0.88;3.83] 4,594 1,667
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[0.49; 2.30]2741,00438%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 2 2.50[0.90; 6.60]4,28462130%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Huber-Mollema (Levetiracetam), 2019Huber-Mollema, 2019 3 0.72[0.08; 6.75]5309%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bjørk (Levetiracetam) (Controls unexposed, sick), 2018Bjørk, 2018 4 4.54[1.28; 16.06]311222%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 39% 1.83[0.88; 3.83]4,5941,6670.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.83[0.88; 3.83]4,5941,66739%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 4 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 2.01[0.49; 8.25]3051,01673%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 2 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 1.53[0.67; 3.53]4,5581,62544%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 2 All studiesAll studies 1.83[0.88; 3.83]4,5941,66739%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.73.31.3660.000Bjørk (Levetiracetam) (Controls unexposed, sick), 2022Coste (Levetiracetam) (Controls unexposed, NOS), 2020Huber-Mollema (Levetiracetam), 2019Bjørk (Levetiracetam) (Controls unexposed, sick), 2018

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9962, 9932, 10071, 12775, 12776

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.35[1.27; 4.36]49,6391,65022%NABjørk (Levetiracetam) (Controls unexposed NOS), 2022 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Bjørk (Levetiracetam) (Controls unexposed, disease free), 2018 3 unexposed, sick controlsunexposed, sick controls 2.01[0.49; 8.25]3051,01673%NABjørk (Levetiracetam) (Controls unexposed, sick), 2022 Bjørk (Levetiracetam) (Controls unexposed, sick), 2018 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.11[0.60; 2.04]891,6806%NABjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2022 Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Huber-Mollema (Levetiracetam), 2019 Bjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2018 40.510.01.0