Association of Adverse Hearing, Growth, and Discharge Age Outcomes With Postnatal Cytomegalovirus Infection in Infants With Very Low Birth Weight

Weimer, Kristin E. D.; Kelly, Matthew S.; Permar, Sallie R.; Clark, Reese H.; Greenberg, Rachel G.

doi:10.1001/jamapediatrics.2019.4532

Cited by 45 publications

(87 citation statements)

References 63 publications

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“…Another important recent study that may have major implications for our understanding of the neurodevelopmental consequences of pCMV infection was recently reported by Weimer and colleagues. 62 As noted, cCMV infection is well recognized to be a major cause of SNHL, 17 but this association had not been noted in the context of pCMV infection. 53 This group examined the prevalence of failed hearing screens, the calculated postnatal age, and somatic growth parameters at discharge in VLBW infants with pCMV infections (and uninfected controls) at the time of NICU discharge.…”

Section: Potential Long-term Neurodevelopmental Complications Of Pcmentioning

confidence: 99%

“…However, in the Weimer study, NEC did not stand out as a complication of pCMV infection, although an association between pCMV infection and BPD was confirmed. Weimer et al also observed that viral infection was associated with an increased postnatal age at discharge of nearly 12 days and a lower weight‐for‐age z‐score, suggesting that CMV infection prolonged hospitalization and had a negative impact on infant growth 62 . An impact of delayed hospital discharge on the overall cost of care was not investigated, but this issue should be examined in future cost–benefit analyses 66…”

Section: Breast Milk‐acquired Post‐natal CMV Infectionsmentioning

confidence: 99%

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Impact of breast milk‐acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences?

Osterholm

Schleiss

2020

Reviews in Medical Virology

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Maternal-fetal transmission of cytomegalovirus (CMV) represents the most common infectious cause of long-term neurodevelopmental disability in children. Congenital CMV (cCMV) infection is associated with microcephaly, seizure disorders, cognitive disability, developmental delay, and sensorineural hearing loss (SNHL). Of these disabilities, SNHL is the most common, affecting approximately 10% of infants with cCMV. Although the sequelae of cCMV are well recognized, it is much less clear what long-term morbidities may occur in neonates that acquire post-natal CMV infection. Post-natal CMV (pCMV) infection is most commonly transmitted by breast-feeding, and in full-term infants is of little consequence. However, in preterm, very-low birthweight (VLBW) infants (<1500 g), pCMV can result in a severe sepsis-like syndrome, with wide-ranging end-organ disease manifestations. Although such shortterm complications are well recognized among clinicians caring for premature infants, the long-term risks with respect to adverse neurodevelopmental outcomes remain controversial. In this review, we provide an overview of the clinical manifestations of breast milk-acquired pCMV infection. In particular, we summarize studies that have examined-sometimes with conflicting conclusions-the risks of long-term adverse neurodevelopmental outcome in VLBW infants that acquire pCMV from breast milk. We highlight proposed preventive strategies and antiviral interventions, and offer recommendations for high-priority areas for future basic science and clinical research.

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Section: Potential Long-term Neurodevelopmental Complications Of Pcmentioning

confidence: 99%

Section: Breast Milk‐acquired Post‐natal CMV Infectionsmentioning

confidence: 99%

Impact of breast milk‐acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences?

Osterholm

Schleiss

2020

Reviews in Medical Virology

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“…Short-term sequelae include hepatosplenomegaly, hepatitis, altered hematological parameters (neutropenia, lymphocytosis, thrombocytopenia), pneumonia, and sepsis-like syndrome (SLS) [ 11 , 18 , 19 ], followed by bronchopulmonary dysplasia (BPD) and/or necrotizing enterocolitis (NEC) [ 11 , 18 , 19 , 20 , 21 , 22 ].…”

Section: Short- and Long-term Sequelae In Preterm Infants With CMVmentioning

confidence: 99%

“…A matched retrospective cohort study including a large number of VLBW infants from many neonatal intensive care units (NICUs) in the United States showed that post-natal CMV infection via breast milk statistically increased risks of death and BPD [ 21 ]. A multicenter cohort study showed that postnatal CMV infection in VLBW infants correlated with an 80% relative increase in the risk of having a failed hearing screen, increased postnatal age at discharge, lower weight at 40 weeks post menstrual age (PMA) and an increased risk of BPD, but not an augmented risk of NEC [ 22 ].…”

Section: Short- and Long-term Sequelae In Preterm Infants With CMVmentioning

confidence: 99%

Literature Review and an Italian Hospital Experience about Post-Natal CMV Infection Acquired by Breast-Feeding in Very Low and/or Extremely Low Birth Weight Infants

et al. 2021

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Breastfeeding is recommended for all neonates due to a known variety of beneficial effects, but infants can be infected by cell-associated bacteria and viruses from breast milk, such as cytomegalovirus (CMV). The majority of CMV-seropositive breastfeeding women have a viral, self-restricted reactivation, can shed the virus in the milk for about 12 weeks after delivery, and can transmit the infection to their offspring. Post-natal CMV-infected term infants are mainly asymptomatic, while very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) infants may present with severe disease, short-term sequelae ranging from abnormalities in laboratory indexes to sepsis-like syndrome, and long-term sequelae such as developmental problems. Thus, the use of thermally treated maternal milk for VLBW/ ELBW infants may be indicated to prevent/reduce the risk of CMV transmission. Different techniques, with varying efficacy in eradicating CMV and maintaining the activity of biological compounds in milk are available: long/short pasteurization, freeze-thawing, the use of microwaves, and ultraviolet-C irradiation. In our NICU, the use of maternal raw milk is always strongly recommended for term/preterm infants, but to reduce risk of CMV transmission, freeze-thawing mother’s own milk is used in neonates with GA ≤ 30 weeks or/and weight ≤ 1000 g, usually regardless of serological maternal condition, as CMV screening is not routinely offered to pregnant women and the milk of seroimmune mothers is not evaluated for CMV reactivation, as its rate is similar to seroprevalence. Over the last 4 years, we had 10 VLBW/ELBW newborns in our NICU with late-onset sepsis and negative cultures. In these cases, the research of CMV DNA in neonatal urine or saliva, for the diagnosis of post-natal symptomatic infection (once congenital transmission has been excluded) may be useful and not invasive. The take-home message we would like to share is that acquired CMV infection should be considered in VLBW/ELBW infants breastfed by seropositive mothers and presenting severe symptoms—particularly sepsis with negative cultures. This could allow pediatricians to make better-quality diagnoses, perform supportive therapy, provide antiviral treatment if needed, or establish a “pre-emptive” therapy for these high-risk neonates.

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“…Long-term neurological sequelae are observed in 16.8–18.8% of children with congenital CMV ( 5 ). Recently, it has also been suggested that post-natally acquired CMV infections can produced long-term neurodevelopmental sequelae in very-low-birthweight premature infants ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Impairment in neurocognitive function following experimental neonatal guinea pig cytomegalovirus infection

et al. 2020

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BACKGROUND: Cytomegalovirus (CMV) is a leading infectious cause of neurologic deficits, both in the settings of congenital and perinatal infection, but few animal models exist to study neurodevelopmental outcomes. This study examined the impact of neonatal guinea pig CMV (GPCMV) infection on spatial learning and memory in a Morris water maze (MWM) model. METHODS: Newborn pups were challenged intraperitoneally (ip) with a pathogenic red fluorescent protein (RFP)-tagged GPCMV, or sham-inoculated. On days 15–19 post-infection (pi), pups were tested in the MWM. Viral loads were measured in blood and tissue by quantitative PCR (qPCR), and brain samples collected at necropsy were examined by histology and immunohistochemistry. RESULTS: Viremia (DNAemia) was detected at day 3 pi in 7/8 challenged animals. End-organ dissemination was observed, by qPCR, in lung, liver, and spleen. CD4 + and CD8 + T-cell infiltrates were present in brains of challenged animals, particularly in periventricular and hippocampal regions. Reactive gliosis and microglial nodules were observed. Statistically significant spatial learning and memory deficits were observed by MWM, particularly for total maze distance travelled (p<0.0001). CONCLUSION: Neonatal GPCMV infection in guinea pigs results in cognitive defects demonstrable by the MWM. This neonatal guinea pig challenge model can be exploited for studying antiviral interventions.

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Association of Adverse Hearing, Growth, and Discharge Age Outcomes With Postnatal Cytomegalovirus Infection in Infants With Very Low Birth Weight

Cited by 45 publications

References 63 publications

Impact of breast milk‐acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences?

Impact of breast milk‐acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences?

Literature Review and an Italian Hospital Experience about Post-Natal CMV Infection Acquired by Breast-Feeding in Very Low and/or Extremely Low Birth Weight Infants

Impairment in neurocognitive function following experimental neonatal guinea pig cytomegalovirus infection

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