title: Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study.
abstract: OBJECTIVE
  Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low-birth-weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, as well as the efficacy of approaches to prevent CMV transmission, are poorly characterized.
  
  
  OBJECTIVE
  To estimate the risk of postnatal CMV transmission from 2 sources: (1) transfusion of CMV-seronegative and leukoreduced blood and (2) maternal breast milk.
  
  
  METHODS
  A prospective, multicenter birth-cohort study was conducted from January 2010 to June 2013 at 3 neonatal intensive care units (2 academically affiliated and 1 private) in Atlanta, Georgia. Cytomegalovirus serologic testing of enrolled mothers was performed to determine their status. Cytomegalovirus nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. A total of 539 VLBW infants (birth weight, ≤ 1500 g) who had not received a blood transfusion were enrolled, with their mothers (n = 462), within 5 days of birth. The infants underwent serum and urine CMV NAT at birth to evaluate congenital infection and surveillance CMV NAT at 5 additional intervals between birth and 90 days, discharge, or death.
  
  
  METHODS
  Blood transfusion and breast milk feeding.
  
  
  METHODS
  Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT.
  
  
  RESULTS
  The seroprevalence of CMV among the 462 enrolled mothers was 76.2% (n = 352). Among the 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI, 4.2%-9.2%); 5 of 29 infants (17.2%) with postnatal CMV infection developed symptomatic disease or died. A total of 2061 transfusions were administered among 57.5% (n = 310) of the infants; none of the CMV infections was linked to transfusion, resulting in a CMV infection incidence of 0.0% (95% CI, 0.0%-0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence, 15.3%; 95% CI, 9.3%-20.2%).
  
  
  CONCLUSIONS
  Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants whose care is managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00907686.
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia2Department of Pathology, Children's Healthcare of Atlanta, Atlanta, Georgia3Aflac Cancer Center and Bloo.
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Josephson
authors.affiliation: Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Caliendo
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Knezevic
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Neeta
authors.initials: N
authors.lastname: Shenvi
authors.affiliation: Neonatology Associates of Atlanta, Northside Hospital, Atlanta, Georgia.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hinkes
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia8Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Ravi M
authors.initials: RM
authors.lastname: Patel
authors.affiliation: New York Blood Center, New York, New York.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hillyer
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia.
authors.forename: John D
authors.initials: JD
authors.lastname: Roback
mesh_terms: D015331:Cohort Studies; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000635:transmission*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000209:etiology*; D019102:Infant, Very Low Birth Weight; D008297:Male; D008895:Milk, Human / Q000382:microbiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D065227:Transfusion Reaction