Experts from 13 national bodies, including seven Royal Colleges, have joined forces to launch new practical guidance to support doctors and other health professionals around valproate use in women and girls in their reproductive years.
The ‘pan-College’ advice is based on 2018 regulations issued by the Medicines and Healthcare Products Regulatory Authority (MHRA) around the prescribing and dispensing of valproate - but looks at the more challenging issues that clinicians across primary and specialist care might encounter in daily practice. These include transition from paediatric to adulthood services, competence to consent to treatment, and confidentiality.
Valproate is licensed for use only in the treatment of epilepsy and bipolar disorder as it carries significant risk of birth defects and developmental disorders in children born to women who take the drug in pregnancy.
The MHRA regulations state that valproate should not be prescribed to women in their reproductive years without a pregnancy prevention plan (PPP), unless a girl or woman suffers from a type of epilepsy that is not responding to other treatments.
The authors of the new guidance take a pragmatic approach, considering issues through life stages. It does not profess to answer every complex ethical issue but brings together data and best practice from the collaborating bodies across the UK, as well as signposting to a wide range of helpful resources.
Mr Edward Morris, Vice President of Clinical Quality at the Royal College of Obstetricians and Gynaecologists, said: “Most women with epilepsy have straightforward pregnancies. But careful management of the condition is needed before conception and during pregnancy, because there are risks which need to be minimised and are associated with maternal use of valproate and birth defects and developmental disorders in children.
“We welcome the publication of this guidance that provides further clarification for healthcare professionals on the use of valproate.”
Professor Helen Stokes-Lampard, Chair of the Royal College of General Practitioners, said: “Valproate use is now under strict regulation and we have clear guidance that it should not be prescribed to women in their reproductive years unless there are exceptional circumstances – but complex situations can occasionally arise.
“The care of women with epilepsy can span GP and specialist care and I do hope this guidance will provide much-needed support to doctors across all medical specialties, helping them to act in the best interests of the individual girl or woman, and ultimately improve the care we provide to our patients.
“Producing this report has taken a huge amount of work and I thank everyone who has been involved and contributed to it.”
Professor Sanjay Sisodiya representing the Royal College of Physicians and the Association of British Neurologists said: "The regulations around valproate have been well publicised. Their implementation in practice can throw up difficult situations. We hope that this document will provide both practical guidance and an illustration of the general approach which will be of value to clinicians.
“We hope also that the joint provenance of the guidance will ensure consistent messages for clinicians and patients. We realise that additional changes may occur and intend to update the document over time."
Dr Angelika Wieck from the Royal College of Psychiatrists, said: “Managing mental health is particularly important for childbearing girls and women. Although valproate is an effective drug for the treatment of bipolar disorder, when taken during pregnancy it often causes serious problems in the physical and mental development of the baby.
“The new MHRA regulations are designed to minimise exposure in pregnancy and the Royal College of Psychiatrists welcomed the opportunity to contribute to this important guidance to support clinicians in implementing the new regulations and providing the most effective and safe care possible.”
Royal College of Paediatrics and Child Health Clinical Lead, Dr Daniel Hawcutt said: “The dangers of valproate to the unborn child are now well recognised, so prescribing in women is now limited. However, it can be an effective medicine to treat seizures, especially in children.
“This pan-College advice is designed to help paediatric neurologists, as well as other groups, implement the MHRA toolkit and pregnancy prevention programme appropriately across all age groups, and in those with particularly complex circumstances including pre- and peri-pubertal girls, or those with complex neurodisability.”
Birte Harlev-Lam, Executive Director for Professional Leadership at the Royal College of Midwives, said: "This is clear and helpful guidance that supports the recent MHRA publication regarding Sodium Valproate in pregnancy.
“It adds to and harmonises the information health professionals provide when discussing pregnancy with young adults and women who may be taking or could be prescribed Sodium Valproate. It is a great example of the multidisciplinary team working in collaboration for the benefit of the people we care for."
Carmel Bagness, Professional Lead Midwifery and Women's Health at the Royal College of Nursing, said: “The RCN is pleased to have played a part in producing this new guidance, which will be welcomed by midwives and nurses, setting out the evidence and pathways of care recommended for girls and women who may be at risk from valproate use pre- conception and during pregnancy.
“The guidance recognises the extra support needed by women with epilepsy when they become pregnant, and the difficult decisions that sometimes need to be taken. Having clinically-backed information on best practice will be a great help to nursing and midwifery staff.”
Notes to editors
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Valproate should only be prescribed as long as girls and women are on a pregnancy prevention programme, ideally long acting reversible contraception (LARCs). It is equally essential that women should not stop taking valproate without medical advice. Women and girls are advised to seek advice from their GP and/or specialist team before conception or as soon as they are aware that they are pregnant. For those with epilepsy, the lowest effective dose of the most appropriate anti-epileptic drug should be prescribed and they should be looked after by a specialist team throughout pregnancy.
RCOG published Green-top Guidelines on epilepsy in pregnancy in 2016. This guideline summarises the evidence on maternal and fetal outcomes in women with epilepsy (WWE). It provides recommendations on the care of WWE during the prepregnancy, antepartum, intrapartum and postpartum periods.
Based on this guidance, RCOG has developed an information leaflet for women with epilepsy.
In 2018, the CMDh endorsed a strengthened regulatory position on valproate. The RCOG welcomed this action to reduce the risk of physical and developmental problems in children born to mothers who have taken valproate during pregnancy. This guideline recommends that exposure to sodium valproate and other anti-epileptic drugs should be minimised by changing the medication prior to conception, as recommended by an epilepsy specialist after a careful evaluation of the potential risks and benefits.