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Three Common Neonatal Infections: 2013. Roger G. Faix , M.D. The University of Utah Primary Children’s Medical Center Intermountain Medical Center. Importance of Cytomegalovirus (CMV). Frequent pathogen in all human populations 70-80% of US adults are seropositive

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three common neonatal infections 2013

Three Common Neonatal Infections: 2013

Roger G. Faix, M.D.

The University of Utah

Primary Children’s Medical Center

Intermountain Medical Center

importance of cytomegalovirus cmv
Importance of Cytomegalovirus(CMV)
  • Frequent pathogen in all human populations
    • 70-80% of US adults are seropositive
    • Up to 100% in the developing world
  • Transmission usually involves prolonged intimate contact with infected body fluid
  • Infection ≠ Disease – usually asymptomatic in immunocompetent subjects
  • Among immunocompromised, CMV is a leading cause of morbidity and mortality
  • One of at least 8 human herpesviruses
    • DNA genetic material
    • Latency – lifelong potential dormancy
    • Persistence – may shed virus for years
    • Reactivation- latent virus may become actively shed again
  • Congenital infection (acquired in utero, present at birth): 0.5 – 2.5% of liveborns, (10,000-50,000/year in US)
  • Natal infection (acquired during passage through infected birth canal): 10-35% of liveborns; detectable after 3 weeks
  • Post-natal infection (acquired after birth): up to 100% in some populations; breast milk, day care, contact with infected fluid
  • Natal and postnatal infections usually are asymptomatic in newborns, but
    • VLBWs may develop sepsis-like condition and other syndromes
    • May cause significant disease if subject later immunocompromised
    • May serve as a source for transmission to high risk individuals
importance of congenital cmv
Importance of Congenital CMV
  • Major cause of morbidity and death for embryo, fetus, and neonate
  • Wide array of potential responsible agents for congenital infection - important to identify which responsible
  • CMV most common cause of congenital infection in US by far
congenital cmv infection2
Congenital CMV Infection
  • Potential for intervention
  • Limitations of therapy
    • Effective therapy may arrest further injury, BUT
    • May not reverse injury that already occurred
    • May not immediately stop injury
congenital cytomegalovirus cmv
Congenital Cytomegalovirus (CMV)
  • Mother usually asymptomatic
  • Transmission from mother to fetus hematogenous or transamniotic
  • Father may be source of infection or multiple other sources
  • DNA analysis useful for epidemiologic investigations
congenital cytomegalovirus cmv1
Congenital Cytomegalovirus (CMV)
  • With congenital CMV infection, symptomatic disease occurs in 5-10%
  • With symptomatic presentation, 90+% will have severe neurodevelopmentalsequelae (100% if microcephaly or intracranial destructive lesions)
symptomatic presentation
Abnormal head size

CNS lesions





‘Blueberry muffin’

Symmetric IUGR



Bony/dental lesions



Numerous others

Symptomatic Presentation
congenital cytomegalovirus cmv2
Congenital Cytomegalovirus (CMV)
  • With congenital CMV infection, 90%+ are usually asymptomatic at birth
    • 10-15% of these may develop later sequelae, usually relatively mild
      • Hearing loss (SNHL)
      • Enamel hypoplasia
      • Seizure disorders
      • Learning disorders
what determines presentation
What Determines Presentation?
  • Maternal infection – primary or recurrent
  • Gestational timing of infection
  • Maternal organism load
  • Other factors to be determined
effect of ga at primary cmv infection on transmission and disease
Effect of GA at primary CMV infection on transmission and disease

*32 of original 69 were terminated or otherwise lost before birth

congenital cmv2
Congenital CMV
  • Much lower risk in mother who is seropositive at start of pregnancy, BUT absolute number of those who are seropositive is so much greater that absolute number of resultant infants with symptomatic CMV is significant
  • Up to 40% of those with symptomatic congenital CMV result from mothers who were seropositive at start of pregnancy
diagnosis of congenital cmv
Diagnosis of Congenital CMV
  • Many other pathogens may cause congenital disease that mimic CMV
  • It is important to determine the presence/absence of these organisms
    • Some are amenable to specific therapy
    • Many are associated with very different sequelae and care needs
diagnosis of congenital cmv1
Diagnosis of Congenital CMV
  • Viral culture (urine, saliva) up to age 3 weeks – congenital detected more quickly due to high viral load
  • PCR up to 3 weeks of age OR blood spot from newborn screen
diagnosis of congenital cmv2
Diagnosis of Congenital CMV
  • TORCH titers - very limited utility
    • IgG- specific usually transplacental
    • IgM-specific antibody – diagnostic if + in first 3 weeks; does not exclude if negative
treatment of congenital cmv
Treatment of Congenital CMV
  • Treat signs/symptoms as detected
  • Longitudinal assessment for SNHL
  • Ganciclovir (GCV)
    • IV 6 weeks; CVC requirement
    • 50% thrombocytopenia, neutropenia
    • Does ↓frequency and severity of SNHL
    • Sparse data re: other CMV issues
    • Chorioretinitis usually treated
treatment of congenital cmv1
Treatment of Congenital CMV
  • Valganciclovir – oral prodrug converted to GCV upon absorption; sparse neonatal data, but what there is appears promising
  • Problems with all
    • Not eradicate latency
    • Viral infection recurs once stop
    • Not reverse established injury
utah state law 2013 session
Utah State Law – 2013 Session
  • All newborn infants who fail hearing screen must undergo testing for congenital CMV
  • Parents of all infants found to be positive, must be offered counseling re: treatment, consequences
prevention of congenital cmv
Prevention of Congenital CMV
  • Infection control and universal precautions remain critical
    • At home, school, hospital, all settings
    • High potential (not always avoidable) for contacting infected fluids of asymptomatic, actively shedding individuals
  • Although dramatic decreases in frequency since adoption of universal screening and IAP, still #1 cause of early-onset sepsis in term infants in US
  • Frequent cause of mortality (5-10% of affected) and morbidity
suspicion aroused if no iap and
Suspicion aroused, if no IAP and…
  • No antenatal culture
  • Culture obtained, but results unavailable
  • History GBS UTI
  • History maternal chorioamnionitis
  • History prior infant with EOGBS
  • Unexplained POL
  • ROM >18 hours
suspicion aroused if iap given but
Suspicion aroused, if IAP given but…
  • Negative culture may be false-negative
  • IAP with erythromycin or clindamycin may be ineffective
  • IAP with penicillin or cefazolin may be ineffective if given <4 hrs prior to delivery
eogbs presenting signs
EOGBS – Presenting Signs
  • Temp Instability
  • Respiratory distress
  • Neutropenia
  • Thrombocytopenia
  • Hypoperfusion
  • Hypoglycemia
  • Pneumonia
  • PPHN
  • Focal erythema
  • Arthritis
  • Meningitis
  • Others
treatment for eogbs
Treatment for EOGBS
  • Supportive
  • Culture
    • Blood
    • CSF
    • Focal areas
  • Empirical treatment
    • Ampicillin and Gentamicin
    • If +, covert to PCN G – 400,000U/kg/d
treatment for eogbs1
Treatment for EOGBS
  • Follow-up culture to assure sterilization
  • Duration
    • 7-10 after sterilization, if + blood only
    • 14-21 after sterilization, if CSF+
    • 14+ after resolution of sequestered focus
respiratory syncytial virus rsv
Respiratory syncytial virus (RSV)
  • Paramyxovirus: RNA, many strains
  • Mother or other contacts (family, healthcare staff) symptomatic or mild URI
  • Spread by contact with respiratory droplets, not aerosol
respiratory syncytial virus rsv1
Respiratory syncytial virus (RSV)
  • Neonatal signs: rhinorrhea, wheezing, pneumonia, lethargy, irritability, apnea; in preterms, absent or minimal respiratory signs is not unusual
  • Diagnosis
    • culture/PCR
    • IFA or EIA of NP swab (only 80-90% sensitive)
respiratory syncytial virus rsv2
Respiratory syncytial virus (RSV)
  • Prevention: RSVIg (IM or IV)
    • Controversial based on cost-benefit analyses, lack of data re: mortality and need for vent
    • Nonetheless recommended by AAP in select circumstances and widely used, including SLC
respiratory syncytial virus rsv3
Respiratory syncytial virus (RSV)
  • Infection control:
    • Careful attention to handwashing
    • Minimizing hand-eye contact
    • Barrier precautions
    • Discouraging visiting by infected family, work by infected staff
respiratory syncytial virus rsv4
Respiratory syncytial virus (RSV)
  • Treatment
    • Supportive
    • Careful attention to upper airway toilet
    • Bronchodilators controversial (racemicepi-, albuterol, DXM)
    • Ribavirinvery controversial