TARGET-EU: Risk of adverse birth and neurodevelopmental outcomes in children born alive to fathers exposed to valproate versus levetiracetam for generalised epilepsy

11/05/2026
22/05/2026
EU PAS number:
EUPAS1000000999
Study
Planned
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Study summary
No information provided.
Study identification

EU PAS number

EUPAS1000000999

Study ID

1000000999

Official title and acronym

TARGET-EU: Risk of adverse birth and neurodevelopmental outcomes in children born alive to fathers exposed to valproate versus levetiracetam for generalised epilepsy

DARWIN EU® study

No

Study countries

Netherlands
Spain

Study description

Background:
Multiple studies have suggested that the intake of valproate for pregnant women during pregnancy has a negative effect on pregnancy outcomes. The evidence regarding the effect of paternal valproate exposure on offspring is much less clear, with multiple recent studies presenting contradictory results.
Therefore, new evidence is needed for regulatory decision-making, particularly regarding how methodological aspects may affect study results.
Objectives:
The primary objective is to estimate the cumulative incidence of death, major congenital malformations, ADHD and autism in offspring born alive to fathers diagnosed with generalised epilepsy exposed to valproate compared to levetiracetam.
Methods:
We will conduct an observational cohort study following the target trial emulation approach in combination with the estimands framework using linked electronic health records from the Valencian Health Integrated Database (García-Sempere et al, 2020), a comprehensive database of longitudinal electronic health records of the Valencia region in Spain. Eligible individuals are males of reproductive age (≥ 18 years) diagnosed with generalised epilepsy exposed to valproate or levetiracetam. In the primary analysis, the hypothetical strategy is used for treatment switch and the treatment policy strategy is used for treatment discontinuation; a principal stratum strategy is used where the principal stratum consists of those who father live births. A Poisson regression is used to estimate relative risks, weighted by the propensity score. Because of challenges in uniquely defining time-zero, the sequential trial approach is also employed.

Study status

Planned
Research institutions and networks

Institutions

Teamit Institute
Spain
First published:
12/03/2024
Institution Other ENCePP partner

Networks

Contact details

Carlos González Poses

Primary lead investigator

Study timelines

Date when funding contract was signed

Planned:

Study start date

Planned:

Data analysis start date

Planned:

Date of final study report

Planned:
Sources of funding
EMA
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable