TABLE 3.

High priority areas for future research

Research Question	Rationale
Correlates of protective immunity against pCMV transmission	Transmission by breast milk is common and ubiquitous but not inevitable - either in term infants or VLBW premature infants. What are the maternal/infant immune responses that block transmission in some (but not all) cases?
Virological correlates of transmission	Are there differences in viral strains/genotypes that either augment or deter pCMV transmission? Is transmission more common in setting of maternal re-infection than reactivation? What is the impact of magnitude and/or duration of viral load during lactation?
How does CMV infect the nursing infant?	Where does virus enter the breast-fed baby (oropharyngeal epithelium, small bowel mucosal, lymphoid vs epithelial cells)? Is CMV transmitted as free virus or cell-associated virus? What are the relative roles of fusion vs endocytosis in virus access? Animal models should be developed to assess.
Can CMV be inactivated prior to breast feeding?	Could eliminate CMV infectivity of breast milk following addition of agent(s) to milk.
Should women be screened for CMV antibodies prior to administration of breast milk?	Could identify “high-risk” situations in which pasteurization, immune based therapies, or anti-virals would be warranted.
Should breast milk be tested by PCR or rapid, point-of-care assays prior to administration to VLBW infant?	CMV-positive breast milk could be treated/pasteurized prior to feeding.
Should VLBW infants have periodic CMV surveillance PCRs in course of clinical care to monitor for DNAemia or viral shedding?	Identify babies at risk for CMV end-organ disease; inform and direct decision-making by clinicians regarding other NICU therapies (eg, steroids for BPD). Identify infants that might benefit from pre-emptive antiviral therapy that in turn could prevent CMV end-organ disease (lung disease, CMV sepsis syndrome) and, possibly, neurodevelopmental sequelae.
What is the long-term neurodevelopmental impact of pCMV infection in VLBW infants?	Studies to date are inconclusive; data on increased numbers of newborn hearing screen referrals in VLBW infants with pCMV infection do not necessarily translate to SNHL; impact on neurodevelopmental outcomes still unresolved; controlled, prospective clinical trials are needed.