Lamotrigine (All indications)

ASD (Autism spectrum disorder): Diagnosis

id	Study   Auto Bjørk (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2022Bjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2022Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Wiggs (Lamotrigine), 2020Cohen-Israel (Lamotrigine), 2018Bromley (Lamotrigine) (Controls unexposed, disease free), 2013Bromley (Lamotrigine) (Controls unexposed, sick), 2013	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.
S12727 R48005	Bjørk (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 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	1.13 [0.91;1.40] excluded (control group)	82/7,950   38,437/4,463,879	38,519	7,950		ref
S12728 R48008	Bjørk (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 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: No Controls: epilepsy indication	0.83 [0.65;1.07] C	82/7,950   267/21,634	349	7,950		ref
S8978 R30437	Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 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	1.30 [0.70;2.40]	10/2,813   4,254/1,707,707	4,264	2,813		ref
S8956 R30331	Wiggs (Lamotrigine), 2020	Austism Spectrum Disorder (after 2 years of age)	at least 1st trimester	population based cohort retrospective	unexposed, sick	Adjustment: Yes	0.66 [0.27;1.58]	-/-   -/11,298	-	-		ref
S8941 R30223	Cohen-Israel (Lamotrigine), 2018	Autism (a majority between 6-12 years old)	1st trimester	retrospective cohort	unexposed, disease free	Adjustment: No Matched	0.33 [0.01;8.20] C	0/83   1/83	1	83		ref
S8933 R35207	Bromley (Lamotrigine) (Controls unexposed, disease free), 2013	Autistic Spectrum Disorders (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No	1.81 [0.20;16.76] C excluded (control group)	1/30   4/214	5	30		ref
S8936 R35208	Bromley (Lamotrigine) (Controls unexposed, sick), 2013	Autistic Spectrum Disorders (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No	2.68 [0.10;68.88] C	1/30   0/26	1	30		ref
					Total	5 studies	0.87 [0.70;1.09]		4,615	10,876
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 8933, 12727

Umbrella review (other published meta-analyses)