Low HCMV DNA Copies Can Establish Infection and Result in Significant Symptoms in Extremely Preterm Infants: A Prospective Study

Abstract

Breast milk (BM) is the main source of human cytomegalovirus (HCMV) infection. We examined whether the number of HCMV DNA copies in BM is related to HCMV infection in very low birth weight (VLBW) infants. We identified 11 pairs of VLBW infants and mothers. BM samples were collected every week until 10 weeks postpartum. Urine samples were collected from the infants within 1 week, at 6 to 8 weeks, at discharge, and whenever HCMV infection was suspected. HCMV DNA in BM was positive in 7 of 11 mothers and reached a peak at 4 to 5 weeks postpartum. Of the 11, 5 infants were determined to be infected from positive HCMV DNA in the urine, despite the fact that BM was used after being frozen. Of the five, four infected infants exhibited symptoms between 35 and 60 days of age. Symptomatic infants had longer stays and slower weight gain. The HCMV infection rate is high in very preterm infants. A new strategy to prevent HCMV infection other than freezing should therefore be established.

High Rate of Symptomatic Cytomegalovirus Infection in Extremely Low Gestational Age Preterm Infants of 22-24 Weeks' Gestation after Transmission via Breast Milk

“…Between 4 and 6 weeks postpartum, HCMV can be isolated from breast milk in up to 100% of HCMV IgG-positive mothers [1,2]. Very immature preterm infants are at the greatest risk of developing symptomatic HCMV infection via breast milk [3,4,5,6]. Previous reports on HCMV infection in preterm infants via breast milk have suggested that infected infants did not have any long-term sequelae [7,8] but new data from 2012 and 2013 showed a negative influence of HCMV infection on cognitive development [9,10].…”

Transmission of human cytomegalovirus via breastmilk and potential risks to very preterm infants

“…While in Gambia HCMV excretion in colostrum and genital tract were observed in 100% of congenitally infected, and 48% of early infected infants 10 , a study from Japan showed, that in seven cases of very low birthweight (VLBW) infants the initial viral load in breastmilk in the first week p.p. ranges between 10 and <1000 copies/mL HCMV DNA 11 . In contrast, an Italian group detected viral DNA in 31 out of 57 (54%) colostrum samples 12 .…”

“…However, other observations seem to be important in the context of prevention 11 . An inverse correlation between milk HCMV-specific IgG avidity and HCMV load was also found 20 .…”

“…All additional parameters included were self-limiting and there was no impact on neonatal outcome parameters like intracranial hemorrhage, periventricular leucomalacia, retinopathy of prematurity and necrotizing enterocolitis (NEC) 30 . However, a large number of cases and case seriesincluding a case from our department which was observed later on -describe severe illness in VLBW infants including pneumonia requiring artificial ventilation, hepatitis and gastrointestinal involvement, with some infants needing antiviral treatment with (val)ganciclovir 11,26,28,[31][32][33][34][35][36][37] . The onset of viral excretion was detected at day 6 post partum (p.p.)…”

New short-term heat inactivation method of cytomegalovirus (CMV) in breast milk: impact on CMV inactivation, CMV antibodies and enzyme activities

“…Transmission to breastfed infants occurs from 6% (depending on pretreatment like heating or cryopreservation) to 59% (native milk), and symptomatic CMV infection may occur in up to 4% 7. Whereas term newborns usually do not show clinical signs of infection,8 preterm infants are more likely to show clinical signs of CMV infection, from mild thrombopenia or leukocytopenia, icterus to severe sepsis-like symptoms 5 9–18. Therefore, different ways of CMV inactivation in breast milk have been tested, from freezing19–24 to short-term pasteurisation,21 25 microwave heating24 as well as ultraviolet C irradiation 26.…”