cCHIPS version 1.0
Research type
Research Study
Full title
An Observational, Longitudinal, Natural History, Feasibility Cohort Study to Evaluate the Characteristics of Cytomegalovirus Shedding in CMV Seropositive Women Throughout Pregnancy
IRAS ID
257710
Contact name
Paul Heath
Contact email
Sponsor organisation
St George's University of London
Duration of Study in the UK
1 years, 8 months, 1 days
Research summary
Summary of Research
Congenital cytomegalovirus (cCMV) the most common congenital infection (infection acquired from birth) in the UK. It is difficult to diagnose CMV infection in pregnancy as it does not produce a characteristic illness and it can also affect women who have previously been infected with it (known as being CMV seropositive).As the opportunities to diagnoses and treat babies affected with cCMV are currently limited, preventing the infection is a high priority. A better understanding of the characteristics, natural history and factors associated with CMV infection in pregnancy is needed to achieve this.
This study will investigate the importance of CMV shedding (viral excretion into bodily fluids)and cellular mediated immunity (a type of immune protection), and their relationship with each other, in CMV seropositive pregnant women, which could also give a valuable insight into their importance and relationship with cCMV.
Those eligible for the study are CMV seropositive pregnant women with children aged less than 4 years who are booked in St George's Hospital for their routine antenatal care.
The study period for each participant is approximately 6 months over four study visits (early in pregnancy, midway through pregnancy, late in pregnancy and soon after birth). Informed consent will be obtained at the first visit. At each visit, samples of saliva, urine and vaginal secretions will be collected, as well as blood if consent was obtained. Participants will complete a contact (with their children)questionnaire at each visit, a sociodemographic questionnaire just at the first visit and a study feedback questionnaire at the last (fourth) visit. Most visits will coincide with their routine appointments, if not at a suitable clinical setting within the study team's sites or in the participant's home.
The study will be run by St. George’s, University of London, in collaboration with St George's University Hospitals NHS Foundation Trust.
Summary of Results
Background Cytomegalovirus (CMV) infection in human is transmitted horizontally through contact with bodily fluids excreting CMV, known as CMV shedding, of another human infected with or carrying CMV (being CMV-seropositive), where young children are a common source of CMV infection. CMV infection in a pregnant woman commonly causes no direct harm to herself but can cause significant harm to her infant when transmitted vertically. The prevention or treatment of maternal CMV infection is crucial, and to achieve this, a better understanding of its epidemiology is vital. This project aimed to increase the understanding of the epidemiology of CMV shedding in CMV-seropositive women during pregnancy.Methods
CMV-seropositive pregnant women living with young children were invited to take part in an ethically approved study to collect samples of their saliva, urine and vaginal secretions to test for CMV DNA via PCR, of blood to test for CMV-specific T-cell immune responses using the CMV QuantiFERON and CMV-ELISPOT assays, as well as surveys to capture the hygiene and contact related activities they had with their young children when the samples were taken, over three serial time-points in pregnancy and after delivery.Results
804 women were screened for CMV serology, revealing a CMV seropositivity rate of 54.2%. 160 women were enrolled into the observational study and 74.4% completed the study. 18.8% of women shed CMV at least once at any point in pregnancy (3.1% in saliva, 10.6% in urine and 13.8% in vaginal secretions). There was no difference to the proportion and quantity of detected CMV shedding by different sites and gestational stages. Just over two-thirds of women had detected CMV-specific T-cell immune responses tested with CMV-QuantiFERON and nearly all with CMV-ELISPOT. The average CMV-ELISPOT count is higher when CMV-QuantiFERON is positive.
There was no association between sociodemographic and CMV shedding in pregnancy. Association with CMV shedding in pregnancy was also not seen in the CMV-QuantiFERON. There was an association between lower CMV-ELISPOT count against pp65 antigen and CMV shedding in the second trimester. Association with CMV shedding in the second trimester was also seen with higher reported frequency of using alcohol gel when cleaning wet nappies. Our study structure and procedures were mostly acceptable in a UK population with the opportunity to identify some areas that could be improved on for future large-scale trials.Conclusions
We have gathered important and valuable data on CMV shedding, CMV seroprevalence and CMV specific T-cell immune responses, in CMV-seropositive women during pregnancy in a UK population, with several potential factors identified that needs to be further explored to ascertain its potential association with CMV shedding. We anticipate a future large-scale trial would be feasible where we have gathered considerable data to inform the planning of this.REC name
London - Brent Research Ethics Committee
REC reference
19/LO/0161
Date of REC Opinion
20 Mar 2019
REC opinion
Further Information Favourable Opinion