Cytomegalovirus Shedding Characteristics in Pregnant Women

Overview

The cCHIPS study is a feasibility study for larger scale multi-centre studies and is designed as a single-centre observational cohort, longitudinal, natural history study. The overarching aim of this study is to evaluate the feasibility of performing larger scale, multi-centre studies to evaluate the relationship between CMV shedding in pregnancy with congenital CMV (cCMV). There is no randomisation involved in this study and all participants will perform the same study procedures and receive treatment as usual. The primary (main) objective is to evaluate the prevalence (percentage of occurrence) of CMV shedding in saliva, urine and vaginal secretions of CMV seropositive women throughout pregnancy. The secondary objectives are to evaluate the quantity of CMV shedding in saliva, urine and vaginal secretions of CMV seropositive women throughout pregnancy, to compare the prevalence and quantity of CMV shedding in CMV seropositive women between different sources of shedding (saliva, urine or vaginal secretions) and different gestational stages, to identify risk factors for CMV shedding in CMV seropositive pregnant women, to evaluate the acceptability of the study procedures to the participating pregnant women, to evaluate the proportion of women approached who are recruited into the study and who are completing the study, and to evaluate the relationship between CMV specific cell mediated immunity (a type of immune protection following exposure to CMV) and CMV shedding in CMV seropositive pregnant women. The tertiary objective is to compare the evaluation of CMV specific T cell immune responses (a type of CMV specific cell mediated immunity) between the two commercially available CMV-specific T cell immune response assays which are QuantiFERON-CMV and CMV-ELISPOT assays. This study will aim to recruit 200 pregnant women. This study will be undertaken in parallel with a separate study called RACE-FIT (REC reference number 18/SC/0360, IRAS ID 239977), which will have ethical approval to screen pregnant women with children less than 4 years of age booked for their antenatal care at St George's Hospital, London, identified during the antenatal combined screening bloods appointment or the antenatal booking appointment, for their CMV serology status on a sample of blood collected as part of the screening process. As part of the ethical approval sought for the RACE-FIT study and the cCHIPS study, the pregnant women screened and found to be CMV seronegative will be eligible for recruitment into the RACE-FIT study and those screened and found to be CMV seropositive will be eligible and approached for recruitment into the cCHIPS study. The cCHIPS study aim to recruit over a 6 month period. The study involves four visits (Visit 1, Visit 2, Visit 3, Visit 4) for each participant. The total study period for each participant will be between 6 to 8 months.

The potential participants will be contacted via telephone, email and/or post by the study team. They will be screened for their eligibility, and if they are interested in participating, the first study visit (Visit 1) will be arranged where the written informed consent will be obtained then before any study related procedures. Visit 1 will be held as soon as possible following screening, aiming up to 16 weeks and 6 days gestational age (early in pregnancy). Visit 2 will be aimed to coincide with the routine 20 gestational week appointment or any time in second trimester from 17 weeks and 0 days gestational age to 27 weeks and 6 days gestational age (middle of pregnancy). Visit 3 will be aimed to coincide with the routine 28 gestational week appointment or any time in the third trimester from 28 weeks and 0 days gestational age onwards (late in pregnancy), Visit 4 will be aimed to coincide with the participant's routine admission on the labour ward or postnatal ward after giving birth, or anytime from the time of birth to 1 week postnatal age (postpartum period). At each study visit, the participants will be performing their own study samples of saliva, urine and vaginal secretions using the study specific self-sampling instructions provided. These self-samples will be tested for the presence and quantity of CMV DNA detected via a molecular technique called polymerase chain reaction (PCR). If consent is obtained, a blood sample will also be collected at each study visit to test for cellular mediated immunity. At the last visit, the participant will be offered to have her newborn baby tested for congenital CMV by collecting the newborn's saliva sample which will be tested for CMV DNA via PCR. At each study visit, the participant will complete a short questionnaire on the participant's contact with their child(ren)'s saliva and urine (to identify risk factors for CMV shedding). At Visit 1, the participant will complete a background questionnaire (also to identify risk factors for CMV shedding)and at Visit 4 a feedback questionnaire (to assess feasibility). Where possible the study visits and blood samples will be aimed to take place alongside the participants' routine antenatal appointments and routine blood tests respectively. At the end of the study, up to 20 participants will be invited to take part in a process evaluation in the form of an interview by phone, skype or face to face to explore in depth the experiences of participation in the study.