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Link to original content: https://pubmed.ncbi.nlm.nih.gov/31324220
Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability - PubMed Skip to main page content
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. 2019 Jul 19;14(1):180.
doi: 10.1186/s13023-019-1064-y.

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

Jill Clayton-Smith  1   2 , Rebecca Bromley  3   4 , John Dean  5 , Hubert Journel  6 , Sylvie Odent  7 , Amanda Wood  8   9 , Janet Williams  10 , Verna Cuthbert  11 , Latha Hackett  12 , Neelo Aslam  12 , Heli Malm  13 , Gregory James  14   15   16   17 , Lena Westbom  18 , Ruth Day  19 , Edmund Ladusans  20 , Adam Jackson  21 , Iain Bruce  22 , Robert Walker  23 , Sangeet Sidhu  24 , Catrina Dyer  25 , Jane Ashworth  26 , Daniel Hindley  27 , Gemma Arca Diaz  28 , Myfanwy Rawson  29 , Peter Turnpenny  30
Affiliations

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

Jill Clayton-Smith et al. Orphanet J Rare Dis. .

Abstract

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.

Keywords: Antiepileptic drug; Expert consensus; Fetal valproate syndrome; Guideline; Management; Teratogen.

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Conflict of interest statement

All participants in the process were asked to declare any conflicts of interest or competing interests. The authors declared that they had no competing interests.

Figures

Fig. 1
Fig. 1
Outline Of The Process Of Producing The Consensus Statement
Fig. 2
Fig. 2
Facial Features Associated With Valproate Exposure At Different Ages. Note the presence of anteverted nares, small mouth, thin upper lip, everted lower lip, flattening of philtrum, prominent midline to forehead. Features are attenuated but still apparent in young adult
Fig. 3
Fig. 3
Minor limb malformations Seen After VPA exposure. Note the hypoplastic and overlapping toes and flattening of the arches due to the joint laxity frequently seen in FVS
See this image and copyright information in PMC

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