Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; A consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability

Research output: Contribution to journalArticle


Background: A pattern of major and minor congenital anomalies, facial dysmorphic features, and neurodevelopmental difficulties, including cognitive and social impairments has been reported in some children exposed to sodium valproate (VPA) during pregnancy. Recognition of the increased risks of in utero exposure to VPA for congenital malformations, and for the neurodevelopmental effects in particular, has taken many years but these are now acknowledged following the publication of the outcomes of several prospective studies and registries. As with other teratogens, exposure to VPA can have variable effects, ranging from a characteristic pattern of major malformations and significant intellectual disability to the other end of the continuum, characterised by facial dysmorphism which is often difficult to discern and a more moderate effect on neurodevelopment and general health. It has become clear that some individuals with FVSD have complex needs requiring multidisciplinary care but information regarding management is currently lacking in the medical literature. Methods: An expert group was convened by ERN-ITHACA, the European Reference Network for Congenital Malformations and Intellectual Disability comprised of professionals involved in the care of individuals with FVSD and with patient representation. Review of published and unpublished literature concerning management of FVSD was undertaken and the level of evidence from these sources graded. Management recommendations were made based on strength of evidence and consensus expert opinion, in the setting of an expert consensus meeting. These were then refined using an iterative process and wider consultation. Results: Whilst there was strong evidence regarding the increase in risk for major congenital malformations and neurodevelopmental difficulties there was a lack of high level evidence in other areas and in particular in terms of optimal clinical management. The expert consensus approach facilitated the formulation of management recommendations, based on literature evidence and best practice. The outcome of the review and group discussions leads us to propose the term Fetal Valproate Spectrum Disorder (FVSD) as we feel this better encompasses the broad range of effects seen following VPA exposure in utero. Conclusion: The expert consensus approach can be used to define the best available clinical guidance for the diagnosis and management of rare disorders such as FVSD. FVSD can have medical, developmental and neuropsychological impacts with life-long consequences and affected individuals benefit from the input of a number of different health professionals.


  • Jill Clayton-Smith
  • Rebecca Bromley
  • John Dean
  • Hubert Journel
  • Sylvie Odent
  • Amanda Wood
  • Janet Williams
  • Verna Cuthbert
  • Latha Hackett
  • Neelo Aslam
  • Heli Malm
  • Gregory James
  • Lena Westbom
  • Ruth Day
  • Edmund Ladusans
  • Adam Jackson
  • Iain Bruce
  • Robert Walker
  • Sangeet Sidhu
  • Catrina Dyer
  • And 5 others
  • Jane Ashworth
  • Daniel Hindley
  • Gemma Arca DIaz
  • Myfanwy Rawson
  • Peter Turnpenny
External organisations
  • Aston University
  • Murdoch Children's Research Institute
  • University of Helsinki
  • University College London
  • Skåne University Hospital
  • Hospital Clínic of Barcelona
  • Royal Manchester Children's Hospital
  • Aberdeen Royal Infirmary
  • Centre Hospitalier Bretagne Atlantique
  • CHU Hôpital Sud, Rennes
  • The Fetal Anti-Convulsant Trust (FACT)
  • Helsinki University Central Hospital
  • Great Ormond Street Hospital. London
  • National Hospital for Neurology and Neurosurgery
  • Guardian Medical Centre
  • Salford Royal NHS Foundation Trust
  • Breightmet Health Centre
  • Manchester Centre for Genomic Medicine
  • Royal Devon & Exeter Hospital
  • University of Manchester
  • University Hospital of South Manchester NHS Foundation Trust
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Health Care Service and Management, Health Policy and Services and Health Economy


  • Antiepileptic drug, Expert consensus, Fetal valproate syndrome, Guideline, Management, Teratogen
Original languageEnglish
Article number180
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 2019 Jul 19
Publication categoryResearch