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

Microcephaly / Small head circumference for gestational age

id	Study   Auto Kim (Controls exposed to LTG) (Topiramate) (Indications NOS), 2026Kim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026Christensen (Topiramate) (All indications) (Controls exposed to LTG), 2024Christensen (Topiramate) (All indications) (Controls unexposed, general population), 2024Blotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Veiby (Topiramate) (Controls unexposed, disease free) (Mixed indications), 2014	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 trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	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.
S19325 R81920	Kim (Controls exposed to LTG) (Topiramate) (Indications NOS), 2026	Microcephaly	1st trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.94 [0.16;5.67] C excluded (control group)	2/507   3/718	5	507		ref
S19318 R81851	Kim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026	Microcephaly	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	3.40 [0.79;14.59]	2/507   2,473/2,489,078	2,475	507		ref
S16072 R66699	Christensen (Topiramate) (All indications) (Controls exposed to LTG), 2024	Microcephaly (z-score for head circumference ≤3rd percentile for gestational week, sex, and country (including newborns with congenital malformations))	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.42 [0.95;2.11] C excluded (control group)	28/638   274/8,756	302	638		ref
S16040 R66579	Christensen (Topiramate) (All indications) (Controls unexposed, general population), 2024	Microcephaly (z-score for head circumference ≤3rd percentile for gestational week, sex, and country (including newborns with congenital malformations))	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	1.35 [0.92;1.99]	28/638   134,023/4,467,848	134,051	638		ref
S10173 R37180	Blotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019	Microcephaly (until 24 months of age, identifiable by: Q02; brain MRI; according to the EUROCAT definition)	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	5.81 [0.36;92.98] C excluded (control group)	1/517   1/2,997	2	517		ref
S10048 R36431	Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019	Microcephaly (until 24 months of age, identifiable by: Q02; brain MRI; according to the EUROCAT definition)	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	9.00 [0.20;50.80]	1/517   438/1,875,733	439	517		ref
S8595 R28611	Veiby (Topiramate) (Controls unexposed, disease free) (Mixed indications), 2014	Small for gestational age head circumference at birth (< 2.5th percentile)	throughout pregnancy	population based cohort retrospective	unexposed, disease free	Adjustment: Yes	7.21 [3.23;16.10]	7/48   18,514/771,412	18,521	48		ref
					Total	4 studies	3.47 [1.11;10.84]		155,486	1,710
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 10173, 16072, 19325