Levetiracetam (All indications)

ASD (Autism spectrum disorder): Diagnosis

id	Study   Auto Bjørk (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2022Bjørk (Levetiracetam) (Controls unexposed NOS), 2022Bjørk (Levetiracetam) (Controls unexposed, sick), 2022Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020Coste (Levetiracetam) (Controls unexposed, NOS), 2020Huber-Mollema (Levetiracetam), 2019	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimester	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S12775 R48182	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 R48184	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 R48186	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 R36655	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 R30714	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 R30740	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
					Total	3 studies	1.40 [0.75;2.61]		4,563	1,655
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

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 10071, 12775, 12776