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

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 milktransmitted 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-CMVsuspected 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-CMVsuspected 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. ABBREVIATIONS: BM-CMV = breast milk-transmitted CMV; CMV = cytomegalovirus; JRCS = Japanese Red Cross Society; LOD = limit of detection; PCR = polymerase chain reaction; TT-CMV = transfusiontransmitted CMV; VLBWI = very-low-birth-weight infantFrom the * The number of tested repository blood samples is the same as the number of transfused blood products. † Homology (the repository blood sample vs. patient) is 64.6% for the UL139 gene and 68.6% for the UL146 gene. 16 ‡ CMV DNA was detected in the testing conducted at the hospital. § Homology (the repository blood sample vs. patient) is 89.3% for the UL139 gene and 78.1% for the UL146 gene. FFP = fresh-frozen plasma; NT = not tested; PC = platelet concentrate; PCR = polymerase chain reaction; RBC = red blood cell. TRANSFUSION Volume 58, December 2018FURUI ET AL.

High prevalence of breastmilk‐acquired cytomegalovirus infection in jaundiced infants

“…About 30%‐50% of neonatal CMV infections are caused by recurrent infection in pregnant women, and the pathogenesis of BM‐acquired CMV infection may be relevant to immunodeficiency of the infants. The BM‐acquired CMV infection rates in premature and low‐birthweight infants differ among countries; however, there are few data about BM‐acquired CMV infection in jaundiced neonates . Our study results show that the BM CMV‐DNA (+) rate was 32.67% (98/300 cases) and the BM‐acquired CMV infection rate was 18.37% (18/98 cases) among the 300 pathologically jaundiced infants.…”

Prospective cohort study for postnatal cytomegalovirus infection in preterm infants

“…17 Furthermore, in 2018, it was reported that 4/65 (6.2%) of very low birth weight infants fed frozen-thawed breast milk were infected with pCMV. 6 The route of transmission was identified by CMV DNA as breast milk. The slight differences in study participants may have affected the results.…”

“…3 Transfusion of CMV-negative blood products has also been recommended, as pCMV infection can also occur with blood transfusions. [4][5][6] CMV is present in the cervical or vaginal secretions of mothers with a history of infection and can be transmitted to the baby during vaginal delivery. 1 Although pCMV infection is generally a subclinical infection in term infants, preterm infants can develop severe symptoms such as sepsis-like syndrome (SLS), pneumonia, necrotizing enterocolitis (NEC), hepatitis, enteritis, biliary stasis, hepatomegaly, elevated liver enzymes, thrombocytopenia, and neutropenia.…”

CMV screening of group‐specific orders—good stewardship of the blood supply

“…[6][7][8] The major risk of transmission occurs in low-birthweight infants as a result of breastfeeding from a CMV-infected mother. 9,10 In addition to finding CMV-seronegative RBCs, another challenge of the IRL is to identify unexpected antibodies and provide compatible blood. Immunization to RBCs antigens may result from transfusion, transplantation, from pregnancy, needle sharing, or injections of immunogenic material.…”