TT-CMV Observational Birth Cohort Study
Condition: Cytomegalovirus Disease
MeSH terms: Cytomegalovirus Infections
Study type: Observational

Summary: 
      The spread of viruses through transfusions is the cause of serious illness and death in
      recipients whose immune systems are unable to fight infection. Another group of patients
      whose immune systems are underdeveloped and can be affected by a particular virus known as
      cytomegalovirus (CMV) is low birthweight infants (LBWIs). CMV can be spread through the
      placenta, during the birth process, through breast milk, while in the hospital or while
      caring for someone carrying the virus as well as through a transfusion, known as
      transfusion-transmitted (TT-CMV).

      The spread of TT-CMV in LBWIs can be curtailed by transfusing blood products that are CMV
      negative as well as to filter the white cells in blood that carry the virus (leukoreduction).
      The purpose of this study is to see if the use of these two strategies can lower the spread
      of CMV through a transfusion. How "safe" the blood actually is through leukoreduction is not
      known and CMV still occurs in LBWIs. It is not clear whether this approach is optimal or
      whether additional safety steps are needed to completely prevent TT-CMV. Specific actions
      that could tell us when virus has reached the blood product or breast milk is to test each of
      these to determine if virus slipped "unnoticed" and/or when the product was not thoroughly
      filtered.

      In this study, the investigators believe that the use of both prevention strategies will
      result in a lower rate of TT-CMV, and that the "cause" of TT-CMV may be found in the presence
      of CMV at the DNA level or by unfiltered white cells that remain in the blood product. Thus,
      the most significant clinical question that remains to be addressed is whether this double
      strategy for transfusion safety actually provides a "zero CMV-risk" blood supply or whether
      further safety measures (DNA testing + 100% leukoreduction) must be used to protect this
      extremely vulnerable patient group from CMV infection. This birth cohort study will be done
      with 6 participating NICUs, and will study both CMV positive and negative mothers in order to
      estimate the rate and pathway of CMV transmission to the LBWI who receives a transfusion.
      Another study goal is to compare or link any CMV infection by either transfused units where
      the virus was undetected, or filter failure. If CMV disease occurs, the investigators will be
      able to describe the course and outcome in LBWIs who develop TT-CMV.
    

Detailed description: 
      The primary aim of this birth cohort study is to estimate the incidence of TT-CMV in LBWIs
      who receive a combination of CMV-seronegative + leukoreduced blood products. That is to say,
      the effectiveness of the two strategies coupled together will be assessed in the prevention
      of TT-CMV in at-risk LBWI born to CMV-negative and CMV-positive mothers.

      The following hypothesis relates to this primary aim, that the incidence of TT-CMV is
      elevated in the population of LBWIs born the CMV-positive mothers. According to reports in
      the literature, breakthrough TT-CMV infection will occur at low rates (< 2.5% incidence) in
      LBWIs of CMV-negative mothers transfused with seronegative plus leukoreduced blood
      components.

      The secondary aim of this study is to detect CMV DNA and/or elevated residual WBC counts in
      blood components transfused to LBWIs and to determine whether these results are related to
      episodes of breakthrough TT-CMV in this study population.

      Original sample size considerations were based on estimating and comparing the rates of
      TT-CMV infection in VLBW infants born to CMV-seropositive mothers or CMV-seronegative
      mothers. Assuming a 2.55% TT-CMV rate for infants born to CMV-seropositive mothers and a 0.5%
      TT-CMV rate for infants born to CMV-seronegative mothers, a sample size of 650 infants per
      group would need to be recruited to detect a difference of approximately 2% in the TT-CMV
      rate with 80% power (2-sided Fisher's exact test at the 5% significance level).

      After three years of accrual and follow-up the incidence of TT-CMV was 0%. Sample size
      calculations were revised using a 95% confidence interval for a single group of VLBW infants
      regardless of maternal CMV serostatus. The necessary sample size was 300 transfused VLBW
      infants based on a one-sided exact 95% confidence interval for a single proportion of 0.0
      with an upper bound of 0.01.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Low birthweight infants in NICU.
      
Biospecimen description: 
      Whole Blood, Urine, Breast Milk
    
Keywords: Transfusion Transmitted Cytomegalovirus (TT-CMV); Low birthweight infants (LBWIs); Leukoreduction and filter failure; CMV Seronegative blood products