Three Common Neonatal Infections: 2013

Roger G. Faix, M.D.The University of Utah

Primary Children’s Medical CenterIntermountain Medical Center

Importance of Cytomegalovirus(CMV)

Frequent pathogen in all human populations 70-80% of US adults are seropositive Up to 100% in the developing world

Importance 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

Cytomegalovirus CPE In Vivo

CMV 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

Importance 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

Importance 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 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 Infection

Congenital CMV Infection

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) 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 (CMV)

With congenital CMV infection, symptomatic disease occurs in 5-10%

With symptomatic presentation, 90+% will have severe neurodevelopmental sequelae (100% if microcephaly or intracranial destructive lesions)

Symptomatic Presentation Abnormal head size CNS lesions Calcifications Organomegaly Adenopathy Petechiae ‘Blueberry muffin’

Symmetric IUGR Hydrops Anemia Bony/dental lesions Deafness Chorioretinitis Numerous others

Congenital CMV

Congenital CMV

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

Congenital CMV: Hearing Loss >20 dB (Fowler et al, 1999)

05

1015

2025

3035

40

0 6 12 18 24 30 36 42 48 54 60 66 72

Months since birth

Hear

ing

loss

,%

Symptomatic Asymptomatic

What Determines Presentation?

Maternal infection – primary or recurrent Gestational timing of infection Maternal organism load Other factors to be determined

Congenital Cytomegalovirus (CMV)

N o rm a l1 0%

S eq u e lae9 0 % (se ve re )

S ym p to m a tic5 -1 5%

S eq u e lae5 -1 5%

m ild -m od

N o rm a l8 5 -9 5%

A sym pto m a tic8 5 -9 5%

C o ng e n ita l in fec tion4 0%

P rim a ry in fe c tion1 -4 % o f se ro n eg

Effect of GA at primary CMV infection on transmission and disease

Outcome 4-22 wk GA 16-27 wk GA 23-40 wk GA Total

Maternal primary CMV

33 10 26 69

Fetal infection 17 (51%) 6 (60%) 12 (46%) 35 (51%)

Symptomatic congenital

2 (12%) 1 (16%) 0 (0%) 3/37* (8%)

Severe sequelae 5 (29%) 0 (0%) 0 (0%) 5/37* (13%)

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

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 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 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 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 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

Quantity of CMV in urine with 42 days of GCV (Whitley, 1997)

0

1

2

3

4

5

6

0 7 14 21 28 35 42 49

Study days

pfu

log1

0

8 mg/kg 12 mg/kg

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

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 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

Early-onset GBS (EOGBS) in the Era of Intrapartum

Antibiotic Prophylaxis IAP)

GBS

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

EOGBS and ECMO

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…

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

Temp Instability Respiratory distress Neutropenia Thrombocytopenia Hypoperfusion Hypoglycemia

Pneumonia PPHN Focal erythema Arthritis Meningitis Others

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 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

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

RSV and ECMO

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 (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 (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 (RSV) Treatment

Supportive Careful attention to upper airway toilet Bronchodilators controversial (racemic epi-,

albuterol, DXM) Ribavirin very controversial