Zonisamide (All indications) updated on 04-22-2025

Major congenital malformations

id	Study   Auto Battino (Zonisamide) (Epilepsy), 2024The Australian Pregnancy Register of Antiepileptic Drugs (Mixed indications) (Controls exposed to LTG), 2024The Australian Pregnancy Register of Antiepileptic Drugs (Mixed indications) (Controls unexposed, sick), 2024The Kerala Registry for Epilepsy and Pregnancy (Epilepsy) (Controls exposed to Lamotrigine), 2024The Kerala Registry for Epilepsy and Pregnancy (Epilepsy) (Controls unexposed, sick), 2024The NAAED (Zonisamide) (Controls exposed to LTG) (Indications NOS), 2024The NAAED (Zonisamide) (Controls unexposed, disease free) (Indications NOS), 2024The UKIEPR (Epilepsy) (Controls exposed to Lamotrigine), 2024The UKIEPR (Epilepsy) (Controls unexposed, sick), 2024Meador (Zonisamide) (Controls exposed to Lamotrigine, sick), 2020Meador (Zonisamide) (Controls unexposed, disease free), 2020Meador (Zonisamide) (Controls unexposed, sick), 2020Källén (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 specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S16589 R69659	Battino (Zonisamide) (Epilepsy), 2024	Major congenital malformations (MCMs)	early pregnancy	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.13 [0.15;8.37] C	1/29   110/3,584	111	29		ref
S17206 R72090	The Australian Pregnancy Register of Antiepileptic Drugs (Mixed indications) (Controls exposed to LTG), 2024	Major congenital malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.71 [0.09;31.98] C excluded (control group)	0/6   20/406	20	6		ref
S16207 R67137	The Australian Pregnancy Register of Antiepileptic Drugs (Mixed indications) (Controls unexposed, sick), 2024	Major congenital malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.42 [0.12;47.87] C	0/6   7/207	7	6		ref
S17202 R72082	The Kerala Registry for Epilepsy and Pregnancy (Epilepsy) (Controls exposed to Lamotrigine), 2024	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	6.47 [0.21;202.45] C excluded (control group)	0/3   1/50	1	3		ref
S17203 R72084	The Kerala Registry for Epilepsy and Pregnancy (Epilepsy) (Controls unexposed, sick), 2024	Major congenital malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	3.92 [0.18;85.02] C	0/3   16/340	16	3		ref
S16191 R67084	The NAAED (Zonisamide) (Controls exposed to LTG) (Indications NOS), 2024	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.59 [0.18;1.89] C excluded (control group)	3/240   52/2,461	55	240		ref
S16181 R67073	The NAAED (Zonisamide) (Controls unexposed, disease free) (Indications NOS), 2024	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	1.09 [0.31;3.81] C	3/240   15/1,311	18	240		ref
S17182 R72026	The UKIEPR (Epilepsy) (Controls exposed to Lamotrigine), 2024	Major malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.84 [0.05;14.09] C excluded (control group)	0/25   49/2,098	49	25		ref
S17183 R72028	The UKIEPR (Epilepsy) (Controls unexposed, sick), 2024	Major malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.80 [0.05;13.81] C	0/25   13/541	13	25		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
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	7 studies	1.68 [0.75;3.78]		49,667	319
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, 17206, 17202, 16191, 17182