Zonisamide (All indications)

Major congenital malformations

id	Study   Auto The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022The NAAED (Controls unexposed, disease free) (Indications NOS), 2022Meador (Zonisamide) (Controls exposed to Lamotrigine, sick), 2020Meador (Zonisamide) (Controls unexposed, disease free), 2020Meador (Zonisamide) (Controls unexposed, sick), 2020Tomson (Zonisamide), 2018Källén (Zonisamide) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013Källén (Zonisamide) (Controls unexposed, NOS) (Indications NOS), 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.
S10197 R37373	The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.77 [0.24;2.51] C excluded (control group)	3/205   44/2,333	47	205		ref
S10242 R37514	The NAAED (Controls unexposed, disease free) (Indications NOS), 2022	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	1.47 [0.41;5.26] C	3/205   12/1,201	15	205		ref
S10199 R37379	Meador (Zonisamide) (Controls exposed to Lamotrigine, sick), 2020	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.75 [0.19;16.25] C excluded (control group)	1/13   5/110	6	13		ref
S10200 R37383	Meador (Zonisamide) (Controls unexposed, disease free), 2020	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No	4.33 [0.37;51.42] C excluded (control group)	1/13   2/106	3	13		ref
S10201 R37387	Meador (Zonisamide) (Controls unexposed, sick), 2020	Major congenital malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.17 [0.07;20.72] C	1/13   1/15	2	13		ref
S10202 R37389	Tomson (Zonisamide), 2018	Malformed Offspring	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.93 [0.11;33.69] C	0/9   74/2,514	74	9		ref
S10206 R37396	Källén (Zonisamide) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013	Relatively severe malformations	early pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	14.15 [1.25;159.56] C excluded (control group)	1/3   37/1,084	38	3		ref
S10207 R37398	Källén (Zonisamide) (Controls unexposed, NOS) (Indications NOS), 2013	Relatively severe malformations	early pregnancy	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: No	15.42 [1.40;170.04] C	1/3   49,499/1,575,847	49,500	3		ref
					Total	4 studies	2.23 [0.81;6.18]		49,591	230
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 10206, 10199, 10200, 10197