DISSEMINATED

CYTOMEGALOVIRUS
Rinawati Rohsiswatmo
 Kasus 1 : By Ny DN
• Lahir tanggal 15 Maret 2023
• Bayi lahir dari ibu G1P0A0 26 minggu dengan HELPP Syndrome, BBL 725gr 🡪 tidak langsung
menangis, distress napas 🡪 CPAP 7-8 FiO2 30-100% namun tidak respon 🡪 intubasi dan terapi
surfaktan.

• Antibiotik ampisilin-gentamisin 🡪 eskalasi ke cefoperazone-sulbactam amikasin

• Mulai minum dengan ASI Donor selama 6 minggu.

• Hasil skrining mata saat di NICU didapatkan ROP Grade 2 OD yang regresi spontan.

Faktor risiko Ibu: HELLP syndrome, hiperkoagulasi, ISK, prematuritas

(sudah mendapatkan pematangan paru sebanyak 2 siklus)
 Riwayat Pemeriksaan Mata
• Hasil: FODS Plus -, vascular zone 1, DL (-), Ridge (-), Vasoproliferatif (-), Retinal hemorrhage OD
inferotemporal, Z 1
• Kesan: retina imatur zone 2, no ROP, retinal hemorrhage OD
12 April

• Hasil: FOD plus (-), Vascular zone 1-2, DL (-), Ridge (+), Temporal, Vasoproliferatif (-)
• FOD plus (-), vascular zone 1-2, DL (-), Ridge (-), vasoproliferatif (-)
• Kesan: retina imatur ODS, ROP stage 2 OD
26 April

• Hasil: FOD plus (-), Vascular zone 1-2, DL (-), Ridge (+), Temporal, Vasoproliferatif (-)
• FOD plus (-), vascular zone 1-2, DL (-), Ridge (-), vasoproliferatif (-)
• Kesan: ROP stage 2, Zone 2, Regressed Spontan
10 Mei

• Hasil: segmen ant tenang

• FODS plus-, vasc zone 2-3,white lesion/eksudat bbrp area ODS, perifer retina
• Kesan: Suspek chorioretinitis ODS dd/ white lesion e.c. ?
24 Mei
Pemeriksaan Laboratorium
Diagnosis 🡪 Postnatal CMV (?)
 Kasus 2 : Bayi A
• Bayi lahir dari ibu G3P2A0 usia 38 minggu BBL 2895gr, tidak langsung menangis, merintih, sianosis,
dirawat di NICU selama 3 hari dengan alat bantu napas
• Ditemukan peningkatan CRP dan diberikan antibiotik
13 Maret
• Curiga sindrom Down (belum konfirmasi genetik), serta ditemukan jari tangan berjumlah 6
2023
• Hasil echocardiography kesan small PDA

• Pasien pindah ke RS lain, dirawat di NICU selama 7 hari, perbaikan dan diperbolehkan pulang
17 Maret
2023

• Kontrol saat usia 14 hari 🡪 bayi tampak kuning 🡪 ada peningkatan bilirubin USG 2 fase tgl 11 April 2023
• Curiga kolestasis • Gangguan kontraksi kandung empedu ec?
7 April • Kemungkinan atresia bilier belum dapat
2023 • USG abdomen 2 fase tetapi belum konklusif 🡪 juga dicurigai atresia bilier
disingkirkan
• Ekoparenkim hati meningkat, suspek non
spesifik parenkimal disease
• Pankreas dan lien tervisualisasi, kedua
• Pasien berobat ke RSCM untuk second opinion ginjal dan buli tidak tampak kelainan
4 Mei 2023 • Tidak tampak ascites
 4 Mei 2023

Bayi usia 1 bulan 22 hari, dengan keluhan kuning sejak usia 14 hari, terdapat BAB dempul terus menerus.
Tidak ada demam.
BB saat ini 3075 gram

Status gizi :
Malnutrisi berkaitan dengan tersangka atresia bilier ditandai oleh BB/U, PB/U dan BB/U <-3 SD
Klinis gizi buruk
Failure to thrive
 Pemeriksaan Fisik
Tanda Vital: Aktif, tampak ikterik kramer 4
T 36,7oC
HR 135x/menit
Kepala: tidak ada deformitas, UUB datar
RR 44 x/menit
SpO2 98% room air
Mata: tidak anemis, tampak ikterik, tampak flat nasal bridge dan hipertelorism,
tidak tampak low set ear

Thoraks: tidak ada retraksi, simetris

Paru: vesikuler, rhonki/wheezing tidak ada

Jantung: S1/S2 normal reguler, tidak ada gallop/murmur

Abdomen: supel, organomegali tidak teraba, umbilikal tidak menonjol

Ekstremitas: akral hangat, CRT <3 detik, polidaktili manus dekstra, tidak tampak
simian crease, terdapat sandal gap
Hasil Laboratorium
Diagnosis 🡪 Congenital CMV (?)
Congenital CMV (cCMV)
Vs
Postnatal CMV (pCMV)
 Congenital CMV (cCMV) Vs Postnatal CMV
(pCMV)

Diagnosis of postnatal
Retrospectively diagnosing cytomegalovirus (pCMV) is based
Distinguishing between
congenital CMV (cCMV) relies on on exclusion of congenital CMV
congenital and postnatal
detecting the virus on the dried infection and detection of CMV
infection where CMV is detected
blood spot, collected as part of DNA, after day 21 of life*
after 3 weeks of life is
screening for congenital *from blood, urine, CSF, or respiratory
challenging
conditions. secretions (nasopharyngeal aspirate or
bronchoalveolar lavage)
Sample collected from saliva must be
obtained at least 1 hour after breast
feeding to avoid false-positive results

Kadambari S, Whittaker E, Lyall HPostnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?Archives of Disease in Childhood - Fetal and Neonatal Edition 2020;105:334-339.
Osterholm EA, Schleiss MR. Impact of breast milk-acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences? Rev Med Virol. 2020 Nov;30(6):1-11. doi: 10.1002/rmv.2117. Epub 2020 Jul 13.
PMID: 32662174; PMCID: PMC8173712.
 Congenital Cytomegalovirus Infection

Approximately 10% of infants with cCMV have clinical abnormalities at birth (symptomatic infection)
including evidence of disseminated disease and/or CNS involvement.

The vast majority (≈90%), however, will have no clinical manifestations present during the newborn
period (asymptomatic infection).

About 40–60% of symptomatic infants will suffer from permanent sequelae, with sensorineural hearing
loss (SNHL) being the most common, followed by cognitive impairment, retinitis, and cerebral palsy.

Suresh B. Boppana and others, Congenital Cytomegalovirus Infection: Clinical Outcome, Clinical Infectious Diseases, Volume 57, Issue suppl_4, December 2013, Pages S178–S181, https://doi.org/10.1093/cid/cit629
Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol. 2018 Apr;42(3):149-154. doi: 10.1053/j.semperi.2018.02.002. Epub 2018 Mar 2. PMID: 29503048.
 Clinical and Laboratory Findings
in Infants With Symptomatic
cCMV
Most infants with cCMV have no clinical findings at birth, and therefore,
the majority are not identified at birth.

Viral isolation by culture from urine or saliva has long been the gold
standard for identifying infants with cCMV.

Specimens should be collected from the infant within the first 2–3 weeks
of life to distinguish congenital from postnatally acquired CMV infection.

Newborn CMV screening is needed to identify infants who have asymptomatic cCMV and who
may be at risk for CMV-related SNHL 🡪 earlier diagnosis allows for an earlier institution of
interventions 🡪 result in better outcomes for children with CMV-related SNHL

Suresh B. Boppana and others, Congenital Cytomegalovirus Infection: Clinical Outcome, Clinical Infectious Diseases, Volume 57, Issue suppl_4, December 2013, Pages S178–S181, https://doi.org/10.1093/cid/cit629
Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol. 2018 Apr;42(3):149-154. doi: 10.1053/j.semperi.2018.02.002. Epub 2018 Mar 2. PMID: 29503048.
 Most Common Manifestations of pCMV
• May mimic bacterial sepsis 🡪 characterised by a triad of apnoeas,
bradycardias and grey pallor
Sepsis-like symptoms • CMV testing is often only performed when there is no clinical improvement
after first-line antibiotic treatment

• Acute hepatitis, jaundice, hepatomegaly and cholestasis are all recognized as

Hepatitis hepatobiliary complications

• Study of pCMV in preterms 🡪 Thrombocytopaenia (66%) and neutropaenia

Marrow suppression (34%) were frequently observed

• The association between pCMV infection and bowel inflammation, including

Intestinal NEC, strictures, volvulus and colitis, is well documented

Kadambari S, Whittaker E, Lyall HPostnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?Archives of Disease in Childhood - Fetal and Neonatal Edition 2020;105:334-339.
 Most Common Manifestations of pCMV
• CMV may cause lung disease 🡪 contributes to prolonged mechanical
ventilation.
Pneumonitis • Retrospective cohort study of 606 infants revealed an increased risk of
bronchopulmonary dysplasia (BPD)

• Bearing in mind the common central nervous system presentations of

congenitally acquired CMV, it is interesting that postnatal CMV infection in
Meningitis/encephalitis extremely premature infants has not been shown to cause meningitis or
encephalitis.

• Retinitis is very uncommon in children with pCMV but may be missed if a

Retinitis preterm infant has been discharged from an ROP screening service before
developing infection.

• CMV is an important cause of sensorineural hearing loss (SNHL) in infants with

congenital infection
Hearing • However, multiple population-based cohort studies have shown no association
between pCMV infection and sensorineural hearing loss.
Kadambari S, Whittaker E, Lyall HPostnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?Archives of Disease in Childhood - Fetal and Neonatal Edition 2020;105:334-339.
When should
a clinician
consider
testing for
pCMV?

Kadambari S, Whittaker E, Lyall HPostnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?Archives of Disease in Childhood - Fetal and Neonatal Edition 2020;105:334-339.
What to educate on CMV in pregnant women?

Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol. 2018 Apr;42(3):149-154. doi:
10.1053/j.semperi.2018.02.002. Epub 2018 Mar 2. PMID: 29503048.
 Summary
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).

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 (<1500g) pCMV can result
in a severe sepsis-like syndrome, with wide-ranging end-organ disease manifestations.