Breast Milk-Acquired Cytomegalovirus Infection and Disease in VLBW and Premature Infants

National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
PEDIATRICS (Impact Factor: 5.47). 05/2013; 131(6). DOI: 10.1542/peds.2013-0076
Source: PubMed


Very low birth weight (VLBW) and premature infants are at risk for developing postnatal cytomegalovirus (CMV) disease, including CMV-related sepsis-like syndrome (CMV-SLS) for which estimates [corrected] in the United States are lacking.

We performed a systematic review and meta-analysis to estimate the pooled proportions (and 95% confidence intervals) of VLBW and premature infants born to CMV-seropositive women with breast milk-acquired CMV infection and CMV-SLS. We combined these proportions with population-based rates of CMV seropositivity, breast milk feeding, VLBW, and prematurity to estimate annual rates of breast milk-acquired CMV infection and CMV-SLS in the United States.

In our meta-analysis, among 299 infants fed untreated breast milk, we estimated 19% (11%-32%) acquired CMV infection and 4% (2%-7%) developed CMV-SLS. Assuming these proportions, we estimated a rate of breast milk-acquired CMV infection among VLBW and premature infants in the United States of 6.5% (3.7%-10.9%) and 1.4% (0.7%-2.4%) of CMV-SLS, corresponding to 600 infants with CMV-SLS in 2008. Among 212 infants fed frozen breast milk, our meta-analysis proportions were 13% (7%-24%) for infection and 5% (2%-12%) for CMV-SLS, yielding slightly lower rates of breast milk-acquired CMV infection (4.4%; 2.4%-8.2%) but similar rates of CMV-SLS (1.7%; 0.7%-4.1%).

Breast milk-acquired CMV infection presenting with CMV-SLS is relatively rare. Prospective studies to better define the burden of disease are needed to refine guidelines for feeding breast milk from CMV-seropositive mothers to VLBW and premature infants.

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    • "Disease is typically not observed in term infants, but can be a substantial problem for low birth weight premature infants [13] [14]. Because of the virtual elimination of transfusion-associated CMV heralded by the advent of leukofiltration of blood products [15], essentially all CMV infections in premature infants are acquired from maternal breast milk [16] [17] [18]. As is the case for congenital CMV infections, many breast milk-acquired infections in premature infants are asymptomatic, but a substantial percentage can produce severe, occasionally lifethreatening disease, which can manifest as viremia, neutropenia , thrombocytopenia, hepatitis, pneumonia, enteritis, "
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    ABSTRACT: Fetal and neonatal infections caused by human cytomegalovirus (CMV) are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies.
    Clinical and Developmental Immunology 08/2013; 2013(1):501801. DOI:10.1155/2013/501801 · 2.93 Impact Factor
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    ABSTRACT: Aim: To assess the burden of congenital and perinatal cytomegalovirus (CMV) disease among infants hospitalized in neonatal intensive care units (NICUs). Methods: CMV infection was defined as a report of positive CMV viral culture or polymerase chain reaction at any time since birth in an infant hospitalized in a NICU reporting to California Perinatal Quality Care Collaborative during 2005-2010. Results: One hundred and fifty-six (1.7 per 1000) infants were reported with CMV infection, representing an estimated 5% of the expected number of live births with symptomatic CMV disease. Prevalence was higher among infants with younger gestational ages and lower birth weights. Infants with CMV infection had significantly longer hospital stays and 14 (9%) died. Conclusions: Reported prevalence of CMV infection in NICUs represents a fraction of total expected disease burden from CMV in the newborn period, likely resulting from underdiagnosis and milder symptomatic cases that do not require NICU care. More complete ascertainment of infants with congenital CMV infection that would benefit from antiviral treatment may reduce the burden of CMV disease in this population.
    Journal of Perinatal Medicine 12/2013; 42(3):1-7. DOI:10.1515/jpm-2013-0183 · 1.36 Impact Factor
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