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Table 5 Recommendations For The Management Of Fetal Valproate Spectrum Disorder

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

Recommendation Agree
+++ > 75%
++  51–74%
+ < 50%
Evidence Strength
 Diagnosis should be made by a clinician with expertise in the area based on the stated diagnostic criteria +++ B
 Microarray analysis and Fragile X studies should be undertaken and other syndromic diagnoses suggested by history and clinical findings ruled out [53] +++ A
 The diagnostic process should include a developmental/neuropsychological assessment [53] ++ A
Preconception Counselling
 Treatment with VPA should be supervised by a doctor specialising in the area who will offer advice according to EMA and country-specific guidance [2, 61] +++ A
 Women and girls taking VPA who find themselves pregnant should not stop taking their medication without consulting their doctor [61] +++ A
 Possible genetic causes for the mother’s seizures should be considered and investigated if appropriate [62] +++ A
 Recurrence risks for seizures in a child should be assessed and communicated [62] ++ B
 As for all pregnancies, folic acid should be taken from 2 to 3 months before conception and continued until 12 weeks [63]. The dose to be taken varies between countries. After the first trimester doses high doses are not recommended or justified [64,65,66] ++ A
Pregnancy and Neonatal Period
 In pregnancies where VPA is being taken women should seen in a joint obstetric/neurology clinic [63] ++ B
 Ultrasound scans should be carried out at around 13 and 20 weeks depending on country. Additional scans are not needed if the heart can be visualised adequately at 20 weeks ++ B
 The ultrasonographer/radiologist should be made aware of a history of VPA exposure and the type of structural anomalies which are associated and can be looked for especially on scan +++ B
 If a major fetal malformation is detected on antenatal scans, discussion as to the most appropriate place for delivery should take place after detection of the anomaly [63] +++ B
 The neonatal check [67] should be carried out by a professional with knowledge of FVSD. Special care should be taken to visualise the palate directly and to check for submucous cleft palate, to look for radial ray defects, talipes and ridging of the metopic suture indicating metopic synostosis. ++ B
 If spinal dysraphism is suspected clinically e.g. the presence of dermal sinus, a skin dimple which is very large (> 5 mm) or high on the back or if there is ultrasound evidence of a spinal cord anomaly, the child should be referred to a paediatric neurosurgeon for clinical assessment and further imaging. Small sacral skin dimples/pits can be safely ignored [68, 69]. + B
 Midwifery/paediatric staff should be alert for signs of hypoglycaemia and blood sugar should be checked if these occur [70]. +++ B
 Breast feeding should be encouraged [71, 72]. Feeding should be established before discharge home +++ A
 Airway symptoms should prompt assessment by a suitably experienced airway surgeon [73]. Assessment may include rigid airway endoscopy under GA to exclude laryngeal abnormalities and tracheomalacia. +++ B
 If signs of drug withdrawal are present these should be treated [70, 74] +++ A
 If talipes is present referral should be made to a physiotherapist/or paediatric orthopaedic surgeon as required [75] +++ B
 Before discharge, arrangements for follow-up of the baby with a paediatrician and/or other specialists should be put in place. This professional will be responsible for coordination of health surveillance and care +++ B
 A renal ultrasound should be arranged after birth for all VPA exposed infants [18, 19] +++ A
 A one-off cardiac echocardiogram should be arranged [18, 19] +++ B
 An epilepsy nurse should see the mother after delivery to review her seizures and medication and discuss childcare and contraception. ++ B
Paediatric Surveillance: General Points
 At all ages, if malformations, medical problems or developmental problems are detected the paediatrician should refer the child on to the appropriate specialist +++ B
 Height, weight and head size should be measured at each paediatric visit and plotted on the appropriate growth charts +++ B
Enquiry about hearing and vision problems should be made at each visit [27, 47] +++ B
 If developmental problems are suspected at any stage referral should be made for a comprehensive developmental assessment +++ A
Paediatric Assessment and Health Surveillance of Infants
 In addition to the routine health checks by the health visitor, a paediatric appointment should be arranged at the age of six to eight weeks and further review at 9 months ++ B
 A full examination should be carried out in the first year to detect malformations. This should include detailed examination of the hands and forearms to look for signs of radial ray defect. Minor signs of this may include a hypoplastic thumb or flat thenar eminence ++ B
 Hip stability should be checked and ultrasound scan arranged if any concerns ++ B
 Where talipes is resistant to treatment or where there are abnormal neurological signs in the legs imaging of the spine should be carried out [69, 75] +++ A
 If there are clinical concerns about head shape or growth the child should be promptly referred to a Craniofacial Unit for evaluation and possible treatment [76, 77] +++ B
 A developmental history should be taken and development should be assessed +++ B
 An ophthalmological examination including orthoptic assessment, full ocular examination (to look for iris and chorioretinal coloboma, cataract and other abnormalities), and cycloplegic refraction should be carried out during the first 6 months of life [78] +++ B
 Early intervention for hearing loss is indicated to limit impact on development +++ B
Paediatric Surveillance At 18 months
 Health and development should be reviewed by a paediatrician or an appropriately trained health professional at 18 months +++ B
 A screen for autism spectrum disorder/social communication disorder should be undertaken by the community paediatrician +++ B
Surveillance During Childhood
 After the 18 month check progress should be reviewed by an appropriate health professional on an annual basis until school age, with a check being carried out prior to starting school. Thereafter appointments should be arranged the year before leaving junior school (age 10) and the year before public exams (age 13–14). ++ B
 If there are concerns about speech and language a referral for formal assessment by a speech and language therapist should be made by 2.5 years ++ B
 Joint hypermobility should be considered as a cause in those presenting with leg pains and assessed by Beighton score [79]. If score > 6 referral to a paediatric physio should be made and an age appropriate graded exercise programme administered to build up core muscle strength and endurance. This might also include swimming and soft play. Special requirements for joint hypermobility should be included in the individualised educational plan. +++ B
 Offer referral to a physiotherapist for fatigue management and advice on management of joint laxity and posture where these are prominent features +++ B
 Where there are foot deformities or flat feet referral to a podiatrist for orthotics should be made [80] +++ A
 Good posture and spinal strengthening exercises should be recommended ++ B
 Enquiry about sleep disordered breathing should be made at each surveillance visit +++ B
 Children with impaired hand function should be referred to an occupational therapist +++ B
 An ergonomic assessment of the school environment should be undertaken if required by an occupational therapist to ensure that the environment is suited to any specific needs of the child ++ B
 An annual ophthalmic assessment to look for amblyopia, strabismus, refractive error and other abnormalities should be carried out. Spectacles should be prescribed as appropriate, and treatment for amblyopia and strabismus carried out as required. +++ B
 Regular hearing assessment, including otoscopy should be carried out on all children and adolescents with FVSD ++ B
 Specific enquiry should be made about symptoms of urinary tract infection and enuresis. If present these should be managed in the standard way +++ B
 Development should be assessed and enquiry should be made about school progress at each visit +++ B
 Where developmental problems are identified a referral to a psychologist should be made so that appropriate specialist advice can be given to schools +++ B
 By virtue of having a mother with epilepsy children with FVSD may be at increased risk of seizures. If these occur they should be managed in the standard way. Genetic testing for seizure predisposition genes should be considered [62] +++ B
 Children with objective cognitive impairment should have an individualised educational plan or equivalent drawn up and be offered tailored input with their education +++ B
 Educators of children with FVSD should be provided with information about the condition and about strategies to best support affected individuals ++ B
Management of Adolescents With FVSD
 The need for extra time or a scribe should be assessed when taking examinations ++ B
 Health and social care service managers in children’s and adults’ services should work together in an integrated way to ensure a smooth and gradual transition from paediatric to adult care and individuals with FVSD should be involved in the transitional arrangements wherever possible. +++ A
 Annual assessment by an optometrist for refractive error is recommended +++ B
Management of Adults With FVSD
 A designated general practitioner should be identified to coordinate care ++ B
 An individualised educational plan should remain in place with annual reviews as long as it is necessary. In some countries this is also allowable for adults +++ B
 An annual health check for medical problems in learning disabled patients should be carried out by the general practitioner [81] ++ B
 Weight should be monitored at the annual check and dietary advice given if overweight for height +++ B
 Referral to a podiatrist should be undertaken where foot posture remains abnormal +++ B
 An occupational therapy referral should be made so that an ergonomic assessment of the workplace or educational setting should be carried out and adaptations made for any special needs +++ B
 Offer referral to a physiotherapist for fatigue management and advice on management of joint laxity and posture +++ B
 Annual assessment by an optometrist for refractive error should be recommended +++ B
Anaesthetic Management Of The Individual with FVSD
 Preoperative evaluation should include a full assessment of potential risk factors including a cardiological assessment and ENT evaluation of the upper airway. +++ B
 Dysmorphic features such as micrognathia, small mouth and cleft palate should be assessed as they can alert the anaesthetist to a potentially difficult airway and difficult endotracheal intubation +++ B
 Anaesthetists should have a high index of suspicion to subglottic narrowing and ENT presence may be required to examine the lower airway in full. +++ B
 Postoperative care will require monitoring for apnoeas in neonates and infants. +++ B
  1. A Supported by evidence from literature or full consensus
  2. B Considered best practice in the area but lack of specific evidence