Transcript Necrotizing Enterocolitis: Progress, Problems, and Prospects

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
 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)
40
Hearing loss,%
35
30
25
20
15
10
5
0
0
6
12
18
24
30
36
42
48
54
Months since birth
Symptomatic
Asymptomatic
60
66
72
What Determines Presentation?
Maternal infection – primary or recurrent
 Gestational timing of infection
 Maternal organism load
 Other factors to be determined

Congenital Cytomegalovirus (CMV)
Primary infection
1-4% of seroneg
Congenital infection
40%
Symptomatic
5-15%
Normal
10%
Sequelae
90% (severe)
Asymptomatic
85-95%
Sequelae
5-15%
mild-mod
Normal
85-95%
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
IgG-
titers - very limited utility
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)
6
pfu log10
5
4
3
2
1
0
0
7
14
21
28
Study days
8 mg/kg
12 mg/kg
35
42
49
Treatment of Congenital CMV
– oral prodrug
converted to GCV upon absorption;
sparse neonatal data, but what there is
appears promising
 Problems with all
 Valganciclovir
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