Cytomegalovirus transmission to preterm infants during lactation

https://doi.org/10.1016/j.jcv.2007.12.005Get rights and content

Abstract

Breastfeeding has a major impact on HCMV epidemiology. The incidence of postnatal HCMV reactivation during lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA can be isolated easily from cell and fat-free milk whey. Early onset of viral DNAlactia and virolactia as well as high viral load in milk whey are maternal risk factors for virus transmission. The dynamics of HCMV reactivation can be described by unimodal kinetics with interindividual variation. Virus reactivation during lactation is a self-limiting local process in the absence of systemic HCMV infection. Preterm infants below 1000 g birthweight and a gestational age below 30 weeks may be at high risk of acquiring a symptomatic HCMV infection. Several recent studies described low transmission rates and mostly asymptomatically infected neonates using frozen milk. Despite different freeze-storing procedures, HCMV transmissions occurred, and severe HCMV infections were observed. Few data exist on the long-term outcome of postnatally acquired HCMV infection via breast milk. To substantiate the international debate on the use of native or inactivated milk for feeding of preterm infants, additional data are necessary for better identification of mother–infant-pairs at risk for viral transmission and symptomatic infection early after birth.

Introduction

In the context of optimal infant and child health, growth, and development, the American Academy of Pediatrics recommends breastfeeding for healthy term infants as well as for preterm infants. Research in developed and developing countries provides strong evidence that human milk feeding decreases the incidence, and the severity of a wide range of infectious diseases including bacterial meningitis, bacteriemia, diarrhea, respiratory tract infection, necrotizing enterocolitis, otitis media, urinary tract infection, and late-onset sepsis in preterm infants (American Academy of Pediatrics, Section on Breastfeeding, 2005).

Breastfeeding has a major impact on the epidemiology of postnatal HCMV infection (Stagno and Cloud, 1994). Forty years ago, HCMV was first isolated from human milk (Diosi et al., 1967). The prevalence of virolactia, which is defined as the presence of infectious virus in milk, has been reported initially to be 27% during the first 3 months postpartum (Hayes et al., 1972). In a further study, HCMV was isolated more often in milk than in colostrum and 58% of the breast-fed term infants became infected. Morbidity among term infants was minimal (Stagno et al., 1980). In a study of unselected postpartum women, 32% (13/41) of seropositive mothers shed virus in breast milk; 69% (9/13) of their infants subsequently became infected. All of the term infants took an uneventful postnatal course, however, two preterm infants developed pneumonitis (Dworsky et al., 1983). In an additional study, hematological laboratory findings like neutropenia, lymphocytosis, thrombocytopenia and clinical findings like hepatosplenomegaly were described for the first time in 6 of 18 HCMV infected preterm infants and correlated with the time of onset of viruria. However, there was no apparent evidence for mother-to-child transmission (Yeager et al., 1983).

Using PCR technology, the rate of HCMV DNAlactia 4 weeks after birth was 92% (12/13) (Hotsubo et al., 1994). A protocol for separation of native milk into milk fat, milk cells and cell-free milk whey compartment (Hamprecht et al., 1998) prior to DNA extraction and PCR, resulted in a high incidence of HCMV reactivation in breastfeeding mothers of preterm infants (Vochem et al., 1998). In this paper it was first demonstrated, that the most immature preterm infants are at the greatest risk of acquiring an early and symptomatic HCMV infection.

Virus transmission from the breastfeeding mother to her infant can be subdivided into two different processes: (1) the HCMV reactivation of the seropositive breastfeeding mother results in HCMV primary infection of the infant in the case of a maternal transmitter; (2) neonates of maternal non-transmitters do not experience HCMV primary infection, despite the infants being exposed to the virus containing milk for weeks or months. Whether “silent” HCMV exposure of the preterm infant without acquiring primary infection has any impact on the clinical status of the infant or on long-term outcome is not yet known. However, several clinical studies used these long-term exposed infants without virus transmission as control group. The majority of maternal non-transmitters excrete HCMV DNA in milk in the range of 1000–20,000 copies/ml (Hamprecht et al., in preparation).

In the following we present data concerning principles of maternal virus reactivation, a case report of a severe HCMV primary infection in a preterm infant with subsequent ganciclovir therapy and a survey of all clinical studies analysing HCMV infection of preterm infants by breastfeeding.

Section snippets

Viral parameters for HCMV reactivation in milk

An obligatory first step for identification of mother–infant-pairs with risk for virus transmission is the prenatal or immediately postnatal determination of the maternal anti-HCMV IgG-serostatus. Studies on HCMV transmission by breast milk are based on qualitative and quantitative detection of viral DNA (DNAlactia) and infectious virus from milk using cell culture (virolactia). Recurrent HCMV infections in seropositive breastfeeding mothers show large interindividual variability concerning the

Case report of a severe course of breast milk-transmitted HCMV infection

An extremely premature and small for date female infant (GA 25 weeks, BW 490 g) was postnatally infected with HCMV through untreated breastmilk of her mother. Congenital HCMV infection was excluded by negative PCR from urine and throat swab in the first days of life.

Thrombocytopenia (nadir 20,000/μl) resulting from a bacterial infection resolved to a maximum of 228,000/μl on day 27 postpartum (p.p.), but then granulocytopenia (560/μl) occurred and platelets fell to a minimum of <5000/μl with

Clinical studies on HCMV transmission by breastfeeding

Three reports from our institution on HCMV transmission by breastfeeding mothers to their preterm infants (Hamprecht et al., 2001, Maschmann et al., 2001, Vochem et al., 1998) described a high incidence of HCMV reactivation in seropositive mothers (73 of 76 mothers, 96%) and a risk population of extremely immature preterm neonates facing high risk of acquiring early and symptomatic HCMV infection.

In recent years several other studies (Croly-Labourdette et al., 2006, Jim et al., 2004, Meier et

References (48)

  • Agence Française de Sécurité Sanitaire des Aliments. Recommandations d’hygiène pour la préparation et la conservation...
  • American Academy of Pediatrics, Section on Breastfeeding

    Breastfeeding and the use of human milk

    Pediatrics

    (2005)
  • H. Asanuma et al.

    Role of milk whey in the transmission of human cytomegalovirus infection by breast milk

    Microbiol Immunol

    (1996)
  • J.L.Y. Cheong et al.

    Gastrointestinal manifestations of postnatal cytomegalovirus infection in infants admitted to a neonatal intensive care unit over a five year period

    Arch Dis Child Fetal Neonatal Ed

    (2004)
  • S. Croly-Labourdette et al.

    Transmission du cytomégalovirus par le lait maternel cru aux enfants prématurés: etude épidémiologique pilote. Pilot epidemiologic study about transmission of cytomegalovirus from mother to preterm infant by breastfeeding

    Arch Pediatr

    (2006)
  • N. Curtis et al.

    Cytomegalovirus remains viable in naturally infected breast milk despite being frozen for 10 days

    Arch Dis Child Fetal Neonatal Ed

    (2005)
  • P. Diosi et al.

    Cytomegalovirus infection associated with pregnancy

    Lancet

    (1967)
  • S. Doctor et al.

    Cytomegalovirus transmission to extremely low-birthweight infants through breast milk

    Acta Pediatr

    (2005)
  • M. Dworsky et al.

    Persistence of cytomegalovirus in human milk after storage

    J Pediatr

    (1982)
  • M. Dworsky et al.

    Cytomegalovirus infection of breast milk and transmission in infancy

    Pediatrics

    (1983)
  • P. Gessler et al.

    Cytomegalovirus-associated necrotizing enterocolitis in a preterm twin after breastfeeding

    J Perinatol

    (2004)
  • K. Hamprecht et al.

    Detection of cytomegaloviral DNA in human milk cells and cell free milk whey by nested PCR

    J Virol Methods

    (1998)
  • K. Hamprecht et al.

    Transmission of cytomegalovirus infection through breast milk in term and preterm infants. The role of cell free milk whey and milk cells

    Adv Exp Med Biol

    (2000)
  • K. Hamprecht et al.

    Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding

    Lancet

    (2001)
  • Hamprecht K, Maschmann J, Vochem M, Speer CP, Jahn G. Transmission of cytomegalovirus to preterm infants by...
  • K. Hamprecht et al.

    Rapid detection and quantification of cell free cytomegalovirus by a high-speed centrifugation-based microculture assay: comparison to longitudinally analyzed viral DNA load and pp67 late transcript during lactation

    J Clin Virol

    (2003)
  • K. Hamprecht et al.

    Cytomegalovirus (CMV) inactivation in breast milk: reassessment of pasteurisation and freeze–thawing

    Pediatr Res

    (2004)
  • K. Hamprecht et al.

    Breast mild and cytomegalovirus infection in preterm infants

    Early Hum Dev

    (2005)
  • K. Hayes et al.

    Cytomegalovirus in human milk

    N Engl J Med

    (1972)
  • T. Hotsubo et al.

    Detection of human cytomegalovirus DNA in breast milk by means of polymerase chain reaction

    Microbiol Immunol

    (1994)
  • W.-T. Jim et al.

    Transmission of cytomegalovirus from mothers to preterm infants by breast milk

    Pediatr Infect Dis J

    (2004)
  • B.T. Kerrey et al.

    Breast milk as a source for acquisition of cytomegalovirus (HCMV) in a premature infant with sepsis syndrome: detection by real-time PCR

    J Clin Virol

    (2006)
  • B. Knorr et al.

    A haemophagocytic lymphohistiocytosis (HLH)-like picture following breastmilk transmitted cytomegalovirus infection in a preterm infant

    Scand J Infect Dis

    (2007)
  • H.C. Lee et al.

    Postnatal cytomegalovirus infection from frozen breast milk in preterm, low birth weight infants

    Pediatr Infect Dis J

    (2007)
  • Cited by (0)

    View full text