Sepsis- like syndrome in premature infants can be caused by acquired postnatal CMV infection, as reported by several studies , [6–8]. In order to elucidate the role of breastfeeding in transmission of CMV infection, this study has analysed prospectively both maternal CMV reactivation during lactation and the clinical outcome of primary infection of breastfed preterm infants. In breast milk whey CMV DNA is detectable with more reliability than in unfractionated milk or milk cells [9–12]. A very high proportion of CMV reactivation in longitudinally screened seropositive mothers during lactation has been found by RT-PCR, as viral DNA has been detected in breast milk from 40 out of 57 seropositive mothers (70.17%).
The mechanism of CMV reactivation in human milk, and the role of milk cells and cell-free virus in vertical transmission are still unknown . Maternal risk factors for CMV transmission are considered to be early excretion of viral DNA and infectious virus in milk whey. The duration of breastfeeding has been related to the acquisition of CMV infection by term infants. Viral load in breast milk has not been correlated to CMV transmission. Kinetic PCR analysis performed on breast milk indicated that some samples collected during the first week after delivery were negative to CMV; viral DNA became detectable in most of the samples in the third week, but the copy number increased in the total samples examined from the 4th to the 6th week and decreased thereafter. Since the incubation time of CMV infection is between 30 and 120 days, mother-to-infant infections transmitted via breast milk should not occur until at least 6 weeks after delivery. However, more detailed studies are needed to elucidate the kinetics of CMV reactivation in the milk to reveal clearly risk factors for transmission. In only one case CMV DNA was detected in the urine 8 weeks after delivery. The newborn was not deliveried vaginally, therefore he might not have acquired CMV infection from vaginal secretions during the birth process. Hamprecht et al. have reported that the transmission of CMV from breastfeeding mothers to their preterm infants could result in symptomatic CMV infections, such as sepsis-like disease, and that the early onset of symptomatic infections occurs only in extremely immature preterm infants [4, 12].
In a previous study, all term infants shed CMV into urine over a long period, and all of them had normal clinical courses without sequelae, but two preterm infants developed pneumonia . Without giving sufficient evidence for breast milk as the maternal source of postnatal virus transmission, other reports have described symptomatic cytomegalovirus infection of preterm infants with clinical symptoms including neutropenia, thrombocytopenia, hepatosplenomegaly, and pneumonia [14, 15]. In our study, we have observed CMV transmission in only 1 of 47 (2.5%) preterm infants, who had clinical symptoms related to CMV infection (sepsis-like symptoms and hepatosplenomegaly), although the viral load and detection rate (70.2%) of CMV DNA in the breast milk were high. The discrepancy between our study and other reports may not be associated with the studied population, since the mean gestational age and birth weight were similar (29 vs 29 weeks; 1158 vs 1100 g, respectively), rather with the difference in breast milk storage. In fact, before feeding, the breast milk has been kept and preserved at -20°C for 72 hours long care of in our lactarium. Hamprecht et al. previously have reported that 25% of preterm infants had acquired CMV infections, after feeding with raw breast milk refrigerated at 4 to 10°C for a maximum of 12 hours [10–12]. CMV infections have not been observed in CMV seronegative preterm infants, fed with banked human milk which was either pasteurized or frozen [14–17]. However, while detection of CMV after heating (72°C for 10 seconds) tested negative, freezing can reduce only partially CMV infectivity, especially when the virus load was high . This may explain the occurrence of the transmission of CMV in one infant.
In conclusion, our study confirms that CMV transmission through breast milk can cause a severe clinical course in preterm infants but freezing could highly decrease the transmission rate. Because breastfeeding is healthy and wide spread, and the number of preterm infants is increasing in the most developed countries, a new procedure for gentle virus inactivation of seropositive breast milk is being assessed in our laboratory, to prevent CMV transmission to extremely preterm infants in the future [19, 20].