Sequence analyses of variable cytomegalovirus genes for distinction between breast milk- and transfusion-transmitted infections in very-low-birth-weight infants

Transfusion. 2018 Dec;58(12):2894-2902. doi: 10.1111/trf.14920. Epub 2018 Oct 19.

Abstract

Background: Cytomegalovirus (CMV) transmission to very-low-birth-weight infants (VLBWIs) sometimes induces serious clinical symptoms. Although breast milk is considered a major source of transmission, transfusion-transmitted CMV (TT-CMV) infection is often suspected when CMV disease develops after transfusion. Thus, it is clinically important to distinguish between transfusion-transmitted and breast milk-transmitted CMV infections.

Study design and methods: Study A: The incidence of acquired CMV transmission was prospectively investigated in 65 VLBWIs. Study B: To determine the transmission routes in 18 TT-CMV-suspected VLBWIs who had been reported in our hemovigilance system, we performed polymerase chain reaction for CMV DNA in fed breast milk and/or repository blood samples related to transfused leukoreduced blood products. Furthermore, we evaluated the identity of CMV strains in patients' urine/blood samples and fed breast milk by sequence analyses of variable CMV genes UL139 and UL146.

Results: Study A: Acquired CMV infection was found in 4 of 65 VLBWIs (6.2%). Study B: CMV DNA was detected in fed breast milk for 12 of 14 TT-CMV-suspected cases, for which breast milk was available. Furthermore, CMV DNA sequence-matching rates between fed breast milk and patients' urine/blood for both UL139 and UL146 genes were 100% or nearly 100% in 11 patients. In contrast, repository blood samples for 11 of 14 patients were CMV DNA negative.

Conclusion: CMV is principally transmitted through breast milk in VLBWIs. The risk of TT-CMV seems to be extremely low when using leukoreduced blood products. Sequence analyses of the variable CMV genes are useful for evaluating CMV transmission routes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism
  • Cytomegalovirus Infections* / genetics
  • Cytomegalovirus Infections* / metabolism
  • Cytomegalovirus Infections* / transmission
  • Cytomegalovirus* / genetics
  • Cytomegalovirus* / metabolism
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Female
  • Fetomaternal Transfusion*
  • Genes, Viral*
  • Genetic Variation*
  • Humans
  • Infant, Newborn
  • Infant, Very Low Birth Weight
  • Infectious Disease Transmission, Vertical*
  • Male
  • Milk, Human / virology*
  • Pregnancy
  • Sequence Analysis, DNA*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Chemokines, CXC
  • DNA, Viral
  • Viral Proteins
  • viral chemokine CXC-1, Cytomegalovirus