Lamotrigine (Epilepsy)

Neuro-developmental disorders (as a whole)

id	Study   Auto Bjørk (Controls unexposed, NOS), 2022Bjørk (Controls unexposed, sick), 2022Charlton (Controls unexposed, disease free), 2017Charlton (Controls unexposed, sick), 2017Bromley (Controls unexposed, disease free), 2013Bromley (Controls unexposed, sick), 2013Rihtman, 2013Dean, 2007	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.
S12723 R47992	Bjørk (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: No	1.04 [0.84;1.30] C excluded (control group)	81/5,073   68,295/4,463,879	68,376	5,073		ref
S12722 R47989	Bjørk (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	0.83 [0.65;1.06]	81/5,073   443/21,634	524	5,073		ref
S8124 R24954	Charlton (Controls unexposed, disease free), 2017	Neurodevelopmental disorders (at 6 years old)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, disease free excluded	Adjustment: No Matched	0.42 [0.03;6.86] C excluded (control group)	0/122   58/6,048	58	122		ref
S8127 R24957	Charlton (Controls unexposed, sick), 2017	Neurodevelopmental disorders (at 6 years old)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: No	0.20 [0.01;3.47] C	0/122   9/472	9	122		ref
S6604 R18109	Bromley (Controls unexposed, disease free), 2013	Neurodevelopmental disorder (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: Yes	4.06 [0.55;22.20] excluded (control group)	2/30   4/214	6	30		ref
S6603 R18106	Bromley (Controls unexposed, sick), 2013	Neurodevelopmental disorder (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No	4.64 [0.21;101.27] C	2/30   0/26	2	30		ref
S6295 R24816	Rihtman, 2013	Children: special education (mean age 4-5 years old)	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No	1.24 [0.08;20.50] C	1/42   1/52	2	42		ref
S6673 R18469	Dean, 2007	Neurodevelopmental disorder (mean age in years: m1=1.5 and m0=15.25)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No	1.73 [0.07;40.78] C	0/4   3/46	3	4		ref
					Total	5 studies	0.84 [0.66;1.06]		540	5,271
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 6604, 8124, 12723