April 2022 – An update on the CMV GAP Project

Following the success and learning from RACE-FIT, a follow-on project has evolved – CMV GAP: primary prevention of cytomegalovirus in pregnancy, addressing the gaps – which CMV Action are very pleased to be members of.
The aim of the project is to establish and build effective partnerships with policy makers and stakeholders to identify policy priorities and to gather the essential evidence required to fully inform policies to reduce the risk of CMV infection in pregnancy. The first activity of the project was to hold a policy round table (see previous article) to engage with policy makers and key stakeholders to identify policy priorities and evidence gaps that need to be filled in order to routinely recommend CMV risk reduction measures in pregnancy. Round table participants agreed that:
• CMV risk reduction messages should be universally available
• A short film should be released rather than further research to test efficacy/effectiveness.
The next steps will deliver a policy podcast, a policy briefing and an application for further research funding. The second planned project activity is to determine the proportion of women at risk of primary CMV infection in pregnancy and the rates of CMV infection in the first trimester of pregnancy by testing blood samples routinely collected at antenatal booking at representative sites in England. Six sites have been identified to take part in the CMV seroprevalence and seroincidence study. Samples from each site, collected over a two- month period, will be sent to Southampton Specialist Virology Centre where data will be extracted. The third project activity will evaluate the process with the aim of investigating ways of implementing, sustaining or enhancing CMV educational interventions in real-world routine antenatal care settings.

We will report back on findings when these are available.

July 2021 –  Roundtable Discussions on Integrating CMV Risk Reduction Measures into Routine Antenatal Care

Sarah Dewar, Chair of Trustees and Sharon Wood, Project Manager of CMV Action, recently took part in a roundtable discussion organised by Dr. Chrissie Jones and members of the original RACE-FIT (Reducing Acquisition of CMV Through Antenatal Education) project team. 

Following the success and learning from RACE-FIT, a follow-on project has evolved – CMV GAP:  primary prevention of cytomegalovirus in pregnancy, addressing the gaps – which CMV Action are very pleased to be members of.

Our work has highlighted that pregnant women and families affected by CMV express that they felt let down that they were not told about CMV during their pregnancy, and therefore did not have the opportunity to make decisions for themselves about reducing their risk of catching CMV.  Sarah gave a presentation on the experiences of our support volunteers speaking with women and families facing a CMV diagnosis.

The CMV GAP team believe a digital antenatal intervention in the form of a short educational film, made in consultation with pregnant women and families living with CMV, could be integrated into antenatal care to educate women about CMV, without burdening antenatal healthcare professionals. Women and their partners would then feel empowered to make changes to reduce their risk of CMV and thus avoid the heartbreak that we so often hear about.

The roundtable brought together representatives from government departments, medical experts, healthcare colleges and bodies, as well as a number of patient-representative charities and organisations to discuss gaps which need to be addressed, and actions that need to be taken in order to ensure that CMV risk reduction messages are integrated into antenatal care.

The discussions proved to be very useful, both in break-out groups and as a main group, and a number of suggestions and ideas will now be taken forward by the team in a further step to ensure CMV awareness is routinely and effectively available.

We will bring you further news on future action as they develop.

February 2020 – Update on Reducing Acquisition of CMV through antenatal Education (RACE-FIT)  

CMV Action has been delighted to be involved in the RACE-FIT project – to develop an educational intervention to reduce the risk of acquiring CMV infection in pregnancy, co-designed with pregnant women and families affected by CMV.  Phase I of the project has now been completed.  Messages from interviews with families affected by CMV informed the storyline of a moving educational film and significantly contributed to the final product.

Phase II of the project has been concerned with the recruitment of women to take part in the study, with 3795 pregnant women approached to participate.  The study specifically looked for women believed to be most at risk of contracting the virus – those in their second, or subsequent pregnancy, with another child or children under the age of four.  95% of pregnant women ‘at risk of CMV’ were willing to have CMV serology tested; the original assumption was 70%, so this was a fantastic result.

Following serology testing, women who tested seronegative –  the cohort required for the study  – and who agreed to take part were recruited to RACE-FIT.  Work on this stage will be completed and analysed by May 2020 and the team hope to submit a final report for publication in the summer of this year. 

A further funding application has been submitted to follow up on this important work to the National Institute of Health Research (NIHR) and we are pleased to report that the application has passed its first stage.  The proposed research will be a 12-month project to establish and build effective partnerships with policy makers and stakeholders to identify policy priorities and to gather the essential evidence needed to fully inform policies to reduce the risk of CMV infection in pregnancy, and if successful, should commence in July this year. 

We will bring you further news of the results of the RACE-FIT study, and the NIHR funding application as soon as they are available. Many congratulations to everyone involved for all the hard work and great results achieved to date. 

October 2018 – Reducing Acquisition of CMV through Antenatal Education (RACE-FIT)

CMV Action are delighted to be taking part in this UK research project which aims to assess an educational intervention to reduce the risk of catching cytomegalovirus (CMV) infection in pregnancy.

CMV is the most common infection to be contracted before birth and about 20% of babies infected with CMV in this way will have permanent health problems, such as hearing loss, learning delay or physical impairments.  Simple hygiene measures may reduce the risk of catching CMV whilst pregnant, and therefore, also the risk of passing on the infection to the unborn baby.  In the UK, pregnant women are not routinely told about these hygiene measures.

Before we can embark on a large-scale study to determine the effectiveness of an education intervention in reducing CMV infection in pregnancy, the feasibility of such a large study has to be assessed.  Doctors at St. Georges University of London, in partnership with CMV Action, are working together with experts from Kingston University, University College London and Cambridge University to develop and educational material.  The study has been funded by the National Institute for Health Research (NIHR) and approved by the NHS Research Ethics Committee.

To date, phase I of the project has been completed. In the first phase interviews and focus groups with pregnant women and families affected by CMV were conducted. This helped the team to understand the levels of knowledge about CMV amongst pregnant women and how messages about reducing the risk of catching CMV are best delivered. Families who have a child affected by CMV and responded to our call to take part, generously shared their stories of how CMV has affected their child and their family. These experiences were instrumental in shaping the narrative for the production of a film, which is now being  tested in a randomised controlled trial to understand if this can increase knowledge and understanding about CMV and whether it is effective at helping women to modify their behaviour to try to reduce the risk of catching CMV infection in pregnancy.  Women who are having antenatal care at St George’s Hospital are being asked if they would like to take part in the trial. 

There have been two promising phase II trials into a vaccine for CMV. One trial (Pass et al 2009) was undertaken in adolescent and young adult women with a particularly high risk of acquiring primary CMV infection (e.g. a substantial proportion had a toddler at home) . The study found that a glycoprotein B (gB) vaccine gave 50% protection against acquiring a primary CMV infection for those who had not been infected before. These suggest that a gB vaccine may be able to prevent congenital CMV transmission in women of childbearing age.

However one of the main complications in developing a vaccine is the fact that congenital CMV infection does not just occur when a woman catches CMV for the first time when pregnant. It can also occur if she has pre-existing immunity but then catches a new strain of the virus. A further phase II study on glycoprotein B vaccine was carried out on transplant patients (Griffiths et al. 2011). The results of this trial were significant because it increased protection against CMV infection in those who had never had a strain of CMV before (seronegative) and those who had previously caught a different strain of the virus (seropositive).

The National Institute for Clinical Excellence (NICE) currently do not recommend routine antenatal screening for CMV. This because there is currently no way of preventing transmission of the virus to an unborn baby and no way to determine whether a baby will be born with problems.

A study in the US is testing whether CMV Immunoglobulin therapy may reduce the risk of transmission when given to pregnant women experiencing a primary CMV infection. This follows mixed results from previous studies of immunoglobulin therapy in Italy.  The US study is due to report in 2019.

In the meantime, CMV Action is working with researchers to try and secure funding for a pilot to test out how CMV screening in pregnancy could work within the NHS.

We will continue to campaign for change.

The UK National Screening Committee (NSC) recently held a consultation reviewing the evidence for whether to screen new-born babies for cytomegalovirus (CMV).  Screening does not currently take place in the UK and the consultation called for new evidence which the Committee could use to consider a change in this policy.

CMV Action prepared a number of responses to the consultation (working with a consortium of eminent medics working in the CMV field who also submitted a response), pointing out that CMV is a significant public health burden in the UK and that there are a number of practical steps that can be taken to reduce its impact whilst research is underway to address evidence gaps.   We also called for discussions about how research could be prioritised in the UK to advance specific details of how universal new-born screening for congenital CMV could be carried out effectively.

Unfortunately, there was no new substantial evidence to change the committee’s recommendation not to screen.

Based on the last UK NSC review of this condition that occurred in March 2022.

Screening for congenital CMV (cCMV) is not recommended because:

• we are not sure if tests reliably show which babies with cCMV will suffer long-term health problems
• it is likely that screening will find a larger number of babies with the infection who will not have problems from it than those who will
• there is a lack of evidence that early treatment following screening leads to better outcomes than later treatment after symptoms
• currently, it is not clear what is the best way of treating children who do not have symptoms

The UK NSC will engage with stakeholders and the NHS to help improve awareness and knowledge of CMV among the public and health care professionals.

CMV Action understands the reasoning behind the decision but calls for a multidisciplinary team effort to critically evaluate how the possibility of universal CMV screening for neonates can be taken forward.  We believe that maintaining a three year review cycle for CMV is not sufficient as major publications continue to add to the evidence that universal screening is both desirable and likely to be cost effective in the future. 

The full recommendation can be found at: https://legacyscreening.phe.org.uk/cytomegalovirus

Newborns with hearing loss

In many cases CMV hearing loss is progressive and gets worse over time. Gancyclovir treatment may be able to prevent a baby’s hearing loss from getting worse. However it must be started before a baby is 1 month old and very few babies are currently diagnosed with CMV this early. 

A series of studies in the UK have been investigating rapid diagnostics to test babies who fail their newborn hearing screen for CMV.  This would enable more babies to benefit from antiviral treatment.  Results so far are positive.

BEST 1 – (The Benefits, feasibility and acceptability of Extended Screening Testing in newborn babies who are referred for further hearing assessment after their neonatal screen)

What was the purpose of the study?

To examine the feasibility, acceptability and effectiveness of screening for cCMV infection in newborn infants who are referred following universal newborn hearing screening and specifically compare:

• The additional parental anxiety generated by raising the possibility of CMV infection over and above that of ‘failing’ the hearing screen.
• How easy it is to get urine or saliva specimens and which one parents prefer.
• The ability to complete cCMV screening, return a result to the family and GP and commence treatment of cCMV if needed by 28 days of life.

How did researchers go about testing this?

In total, 411 participants were recruited from Newcastle and south west London between August 2010 – October 2012. Parents of newborns who did not pass their initial newborn hearing test were approached by screeners to be contacted by the study team. Study packs were sent to parents’ homes which contained consent forms, anxiety questionnaires, saliva and urine swabs.  Parents were asked to collect saliva or urine samples themselves at home and post them back to the researchers along with completed questionnaires

What is the status of the study? Complete

What were the results?

• Over 98% of samples were processed within the first 3 weeks of life.
• Six newborns were found to have congenital CMV (3 with hearing loss and all 3 were treated with valganciclovir within the first month of life).
• There was no difference in anxiety levels between parents of babies who had a saliva swab taken to test for CMV compared to controls.
• 97% (217/223) of parents who responded to the questionnaires stated that they thought screening for cCMV using a saliva swab in babies who were referred after their initial hearing screen was a good idea.
• The major limitation in the study was that only 40% of all eligible recruits took part due to research procedures including inherent problems with postal recruitment.
• In September 2011, of the completed parental questionnaires returned, 97% (76/78) felt that salivary swabs were easier to collect than urine and 96% (72/75) indicated their preference for saliva over urine collection. The study team deemed that urine collection was not a practical screening method and recommended that saliva swabs only be collected.

Where can I find out more?

Full details are in the clinical trials register

An academic paper reporting the results was published in the Archives of Disease in Childhood

BEST 2: (The Benefits, feasibility and acceptability of Extended Screening Testing in newborn babies who are referred for further hearing assessment after their neonatal screen)

What is the purpose of the study?

This next stage was to run a study that would be closer to a ‘real life’ model with saliva swabs for CMV testing taken by newborn hearing screeners, not researchers  The objective was to assess whether it is feasible to integrate testing for cCMV into the newborn hearing screening programme by enabling hearing screeners to take saliva samples at the point of referring a baby for further hearing tests. 

How did researchers go about testing this?

By training newborn hearing screeners in South West London to take saliva swabs, rather than posting out packs to parents at home.  Researchers tracked the number of babies referred for additional hearing screening who successfully had a saliva swab taken and asked the hearing screeners for their views.

What is the status of the study? Complete

When were the results? The BEST 2 study showed that this model is feasible.  Newborn hearing screeners felt confident doing the tests and they were able to test nearly 80% of babies referred for further hearing assessment

2013 Re: Length of antiviral treatment

What research was carried out?

The first big trial of oral antiviral treatment reported in 2013. The main purpose of the study was to compare a 6-week course to a 6-month course of the oral drug valganciclovir in babies born with CMV aged less than 30 days. The study was carried out between 2008 and 2013. It was primarily based in the US but 2 out of the 109 study participants came from the UK.

All babies in the study took valganciclovir by mouth for 6 weeks. At the end of the 6 week period, babies were assigned by chance to receive either valganciclovir or placebo (inactive substance) to complete the 6 months of antiviral treatment. Information about hearing loss and developmental milestones was followed up for 2 years.

What did the results say?

The results showed a small positive improvement in the babies who had 6 months of treatment compared with 6 weeks. This improvement was statistically significant when babies were followed up at 12 and 24 months.

There was a slight improvement in levels of hearing loss in those who got 6 weeks of the drug, but a greater improvement was seen in those who got 6 months of treatment.

The infants who got 6 months of treatment also scored higher on parts of the Bayley Scales of Infant and Toddler Development. The differences were statistically significant for language composite and receptive communication.

There was a slight increase in side effects in babies who had six months of treatment.

However this was not at levels of major toxicity. Levels of low white blood cells were also much better than in the previous ganciclovir study.

What is new about this research?

There is now better evidence about the benefits and risks of valganciclovir. Previously, the only published evidence on benefits of CMV treatment was about the intravenous antiviral drug ganciclovir. Over the past few years, some doctors have been prescribing the oral version of the drug, valganciclovir, instead as it is less invasive for babies. This was based on two very small scale studies which suggested that the drug is safe to use and has fewer short term side effects than ganciclovir.

This study compares the benefits and risks of longer vs. shorter valganciclovir treatment. Previous studies have only looked at 6 weeks of treatment.

This study included babies with a wider range and severity of CMV symptoms than previous studies. Previous studies have treated babies with central nervous system symptoms such as brain calcifications and hearing loss. This study included babies who had e.g. low platelet count or petichiae without central nervous system symptoms.

However, this research didn’t directly compare the benefits and risks of valganciclovir treatment with those of ganciclovir treatment or not getting any treatment at all.

What does this mean for families in the UK?

Its exciting to see more research being carried out into treatment options. The results of this study may mean that UK doctors prescribe a longer course of antivirals for babies. However it is important to remember that there are no statutory guidelines for treating and managing CMV in the UK. Recommendations about type and length of treatment will still be made by individual doctors. 

The reason that there are no universal guidelines on treatment is that it is a very complex picture. Little is known about the long-term benefits and risks. There are short term side effects which may be a bigger issue for some babies than others. And whilst there are encouraging signs about benefits the effects are small and do not cover all the potential symptoms of CMV. 

Further valganciclovir studies are in the pipeline, the picture on antiviral treatment may evolve further over coming years. This study established collaboration between USA and UK and that these centres will be working on more research.

As a result, CMV Action feels that any family who is interested in considering treatment for their baby should have the opportunity to discuss this with an expert who is familiar with the latest research. We therefore recommend that families ask for a referral to their nearest paediatric infectious diseases specialist, or at the very least ensure that their doctor speaks to such a specialist before making recommendations about treatment.

Where can I find out more?

A full description of the research and the results available so far are on the clinical trials website.

The abstract summarising the results.

Would toddlers with CMV benefit from anti viral treatment?

The headline results of this trial have been discussed with the paediatric infectious diseases doctors in the UK who were responsible for recruiting eligible children with congenital CMV infection. They, in turn, have given the results to the families who volunteered for the study. We would now like to share the main results with other parents through the CMV Action website.

Valganciclovir has previously been shown in a randomised clinical trial to help stabilise the hearing of children who were under one month of age when treatment started. The valganciclovir toddler trial aimed to see if the same benefit was found for older children.

The trial recruited children aged from one month of age up to their fourth birthday who had congenital CMV infection and sensorineural hearing loss. They were randomised to receive either valganciclovir or a matching placebo for six weeks. Hearing was measured at the start of the study and again 6 months later.

The results showed that valganciclovir did not produce any unexpected side effects. The drug reduced the quantity of CMV (the viral load) found in urine or saliva samples. However, the drug did not have any effect on hearing. We conclude that this drug offers no benefit to children of this age and so cannot be recommended.

It is not clear why this drug works in young babies but not older children. One possible explanation is that the drug may gain access in babies to the inner ear structures where CMV is replicating, but not in older children. Another possibility is that the damage to the hearing of babies may be caused by the virus directly whereas, in older children, it may be caused by their ability to cause inflammation in the ear as their immune system matures. The doctors will now discuss how another clinical trial could be designed to address these possibilities and keep CMV Action informed.

We will update with the full trial results when they are published.

CMV Action continue to highlight the importance of timely follow-up and treatment as necessary for any babies who fail their newborn hearing tests.

2021 Study re: Quality of Life of Children with congenital CMV – University of Southampton

Many thanks to those who have responded.  This is now closed.  We will publish the results in due course.

Would you like to be involved in a study about the quality of life of children with congenital CMV?

Researchers at the University of Southampton are carrying out a research study about the quality of life and behaviour of children and young people affected by congenital Cytomegalovirus (CMV). They are inviting families who have a child who has been affected with congenital CMV (even if they have no problems from CMV) to participate in this study. This will help them to evaluate the impact that congenital CMV has on children and young people in the UK. CMV Action has agreed to help them with this study by approaching families affected by CMV.

If you agree to take part in the study, you will be sent some online questionnaires to complete at a time that suits you. The questionnaires will ask about your child’s physical, emotional, psychological and social functioning. There will also be a questionnaire asking about your own wellbeing. Depending on your child’s age, you may also be sent some questionnaires for your child to complete, if they are able, to about their opinions on their own physical, emotional, psychological and social functioning. The questionnaires will take no longer than 25 minutes for you to complete and 15 minutes for your child to complete. You can complete them at home.

The information you give us will help us to assess the quality of life of children and young people with congenital CMV in the UK. You will also receive a £20 gift voucher when we receive your questionnaires to thank you for your time.

Taking part in this study is completely voluntary. You can choose whether you would like to take part or not.

You will be sent some more information about the study.

The results of this study will form part of a Masters project and we plan to share the results on the CMV Action website and publish the data in an academic journal.

2020 Study re: Cognition and Behaviour in Children affected by CMV – University of Huddersfield

Thank you to those who took part in our study into cognition, behaviour and cCMV. We have had an incredible response from the CMV Action community, and met our targets already, so we have now closed the study. Thank you once again to anyone who took part – and also to anyone who planned to and didn’t get the chance! It is volunteers like you who make our research possible.

We now have the exciting job of analysing all of this new data. This will take us a few months, but CMV Action will feature an update on what we find out when the results are available. Those of you who took part and said you’d like to hear will also receive a summary direct to your inbox.

If you have any questions, please feel free to contact me directly on j.retzler@hud.ac.uk.

Take part in a new research study into cCMV and child development

Hello,

I am a researcher in developmental psychology based at the University of Huddersfield. I am contacting you because you are on the mailing list for CMV Action. I am trying to understand more about how differences in the way children’s brains process information might explain differences in how they behave in everyday life. I want to find out whether these differences between children are related to whether or not they had CMV at birth.

If you have a child aged between 5 and 11, you can get involved with this online study, whether or not your child had CMV at birth. If you have more than one child, you may complete this study once for each child. To thank you for taking part in the study, we will provide you with a £5 voucher for www.amazon.co.uk.

The study has an online parent questionnaire for you to complete (15 to 20 minutes), and then some short online computer games for your child (15 minutes), so you must both be in the room if you decide to take part. It should take no more than a total of 35 minutes.

If you are interested, the link below provides more information and an opportunity to take part:

https://huddersfieldbss.eu.qualtrics.com/jfe/form/SV_br0MOpzrBD2sQ3r

If you have any questions, please feel free to contact me directly on j.retzler@hud.ac.uk.

Kind regards,

Dr Jenny Retzler

https://pure.hud.ac.uk/en/persons/jenny-retzler | Twitter: @jenny_retzler

01484 471474

Department of Psychology (EK1/12)

University of Huddersfield, HD1 3DH, United Kingdom

Researcher: Kate Ralph (Medical Sciences Masters Student at University of Southampton)

ERGO ID: 61440

Supervisors: Dr Christine Jones (Associate Professor of Paediatric Infectious Diseases), Dr Kim Bull (Lecturer in Psychology)

Knowledge and attitudes among health care professionals and the public

Two independent surveys were developed to gather information on knowledge of and attitudes towards CMV infection during pregnancy. The first (CMV Action 2016 in partnership with St. George’s Hospital, London) gathered information from antenatal health care professionals about their knowledge of CMV and other diseases, and measured knowledge of risk factors in pregnancy, CMV prevention and attitudes towards prevention (see the aims and methods of the survey here).

The second was a survey of over 1000 British women aged 18–44 (ComRes 2014), which gathered information from the general public to assess prior knowledge of CMV and attitudes towards self-care in pregnancy, what measures respondents would take to prevent CMV infection during pregnancy, and views on who should give advice and information to pregnant women.

Read more about the results of this research in this article written for the MIDIRS Midwifery, vol 27, no 1, March 2017, pp 33-36.

So far there have not been any large scale studies in the UK looking at proportions of children born with CMV and the overall burden of the disease (a lot of the research evidence comes from other developed countries).