Cytomegalovirus transmission to preterm infants during lactation
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
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