TT-CMV Observational Birth Cohort Study
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss, Hospital, Women's Studies |
| Therapuetic Areas: | Endocrinology, Other, Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/11/2015 |
| Start Date: | January 2010 |
| End Date: | July 2015 |
| Contact: | Cassandra D Josephson, MD |
| Email: | cjoseph@emory.edu |
| Phone: | 404-785-6499 |
Prevention of Transfusion-transmitted CMV (TT-CMV) in Lowbirth Weight Infants (LBWI; ≤1500 Grams) Using CMV Seronegative and Leukoreduced Transfusions.
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.
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.
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.
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.
Inclusion Criteria:
- All LBWIs whose weight is ≤ 1500 grams at birth
- LBWI is within first five days of life
Exclusion Criteria:
- LBWI not expected to live past first seven days of life
- LBWI has a severe congenital abnormality
- LBWI has received a RBC or platelet transfusion at another institution prior to
transfer
- LBWI has received an in-utero transfusion
- LBWI is clinically suspected of having toxoplasmosis, rubella, herpes infection(s) at
birth
- Refusal by the mother to grant consent for herself and/or refusal to grant consent
for her LBWI
- If the mother of the child has previously participated in this study
We found this trial at
3
sites
Emory University Hospital Midtown Emory University Hospital Midtown is a 511-bed community-based, acute care teaching...
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Grady Memorial Hospital Grady is an internationally recognized teaching hospital staffed exclusively by doctors from...
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Northside Hospital Northside Hospital-Atlanta (in Sandy Springs) opened in 1970. The original facility had 250...
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