Asymptomatic DNAemia Heralds CMV-Associated NEC: Case Report, Review, and Rationale for Preemption

Abstract

Human cytomegalovirus (CMV) infection may be acquired in very low birth weight and extremely low birth weight (ELBW) infants from breast milk. The clinical relevance of such infections is uncertain. There is no consensus on whether screening breast milk for CMV, freezing/pasteurizing milk before feeding, or performing virological monitoring on at-risk infants is warranted. We describe an ELBW infant who acquired CMV postnatally from breast milk and developed CMV sepsis syndrome and clinical evidence of necrotizing enterocolitis (NEC) at ∼5 weeks of age. The availability of serial dried blood spots from day of life (DOL) 4 to 21, coincidentally obtained for a metabolic study, provided the novel opportunity to retrospectively test for and quantify the magnitude of CMV DNAemia. DNAemia was present for several weeks before the onset of severe CMV disease, first being noted on DOL 18 and increasing in magnitude daily to 4.8 log10 genomes/mL on DOL 21, approximately 8 days before the onset of abdominal distension and 15 days before the onset of CMV sepsis syndrome and NEC. After surgical resection, supportive care, and ganciclovir therapy, the infant recovered. This case underscores the importance of including CMV infection in the differential diagnosis of sepsis and NEC in premature infants. This case also suggests the value of prospective virological monitoring in at-risk low birth weight and ELBW infants. Future studies should examine the potential utility of preemptive monitoring for, and possibly treatment of, CMV DNAemia in premature infants, which may herald the onset of serious disease.

Neonatal gastrointestinal involvement and congenital cytomegalovirus

“…Most of the studies revealed a possible association between CMV infection and enteritis, 22 17,25,33,36,37,39,40,44,63,65 often with finding of CMV inclusions in histological intestinal samples. It is debatable whether the virus has a role in the pathogenesis of the diseases, either directly or as a secondary super-infection after the acute phase of the enterocolitis.…”

“…Born at 37 WGA, birth weight 2490 g Berardi et al, 2011 (Modena, Italy) 58 Acquired CMV colitis and anaemia in a 2 months old infant with previous surgery for ileum-caecal valve atresia. Born at term, birth weight 3255 g Irizarry et al 2011 (Tampa, FL, USA) 59 Congenitally infected infant with primary CMV enterocolitis, successfully treated with oral valgancyclovir Bar-Meir et al, 2012 (Chicago, IL, USA) 33 CMV NEC in 26 WGA premature infant, birth weight, 864 g. Onset: 29 th day of life Refai et al, 2012 (Brighton, UK) 60 CMV enterocolitis acquired in the 5 th week of life in a term newborn (birth weight 3700 g) Lee et al 2012 (Los Angeles, CA, USA) 61 CMV enterocolitis in a premature newborn (27+4 WGA, birth weight 1130 g, onset at 34 th day of life) Unl soy Aksu et al 2013 (Ankara, Turkey) 53 Description of CMV enteritis and jejunal stricture in a preterm infant Hendriks et 17 Postnatal acquired CMV with septic syndrome and NEC in a 24+5 WGA preterm infant, birth weight 800 g, onset in the 5 th week of life Tran et al, 2013 (Baton Rouge, LA, USA) 63 NEC and CMV in a premature infant (25+1 WGA, birth weight 653 g). Onset at 48 th day of life but history of feeding difficulties after the first week of life Louazon et al, 2014 (Bron Cedex, France) 64 CMV enterocolitis, onset at 10 weeks of age.…”

“…16 Very low birth weight and extremely low birth weight newborns are at higher risk of symptomatic CMV infection, most commonly secondary, acquired through breast milk. 17 Maternal primary CMV infection or reinfection during pregnancy are the cause of neonatal congenital infection, with a mean risk of transmission of 40% (24-75%), 3,18 lower in the first three months (36%) than in the last three months of gestation (78%). 3,19 Considering all the infected newborns, only 5 to 10% are symptomatic at birth, in particular with neurodevelopmental delay signs and sensorial hearing loss.…”

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

“…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.)…”

Iatrogenic injury and unexpected hospital death in the newborn

“…Cytomegalovirus infection can present as thrombocytopenia, respiratory distress, or can mimic necrotizing enterocolitis. 30 Outbreaks of bloodstream infections can occur in a single nursery or other hospital unit secondary to bacterial contamination of intravenous medication or parenteral nutrition. Clusters of neonates in several different intensive care nurseries have died in recent years due to contamination of total parenteral nutrition with Gram-negative enterobacteria.…”