VCOM Carolinas Research Day 2023

Clinical Case-Based Reports

Case Report: Congenital Cytomegalovirus Arley Rodriguez OMS-III and Lindsay Tjiattas-Saleski DO, MBA, FACOEP Self Regional Medical Center, Greenwood, SC and Edward Via College of Osteopathic Medicine, Spartanburg, South Carolina

Abstract # CBR-9

Discussion

Background

Hospital Course

Day 1: Physical examination revealed a diffuse petechial rash most prominent on forehead and face, but extending to the trunk, abdomen, and bilateral upper and lower extremities (Figure 2 and 3). A small head circumference was measured at 31.1 cm. Laboratory results revealed thrombocytopenia and hyperbilirubinemia. Due to concern for possible congenital viral infection or sepsis, the patient was transferred and admitted to the NICU for close monitoring. A sepsis screen was initiated and the patient was started on empiric ampicillin. A TORCH workup and phototherapy were initiated .

• Congenital cytomegalovirus infection is the most common congenital infection both worldwide and in the United States. • The overall prevalence is 0.67%, affecting 1 in every 150-200 live births in developed countries and 1 in 20-100 live births in developing countries. • The infection can lead to permanent sequelae in 15% to 18% of births, including death in 1%, neurocognitive sequalae in 5% to 15%, and hearing loss in 12%. • The outcome of congenital CMV infection depends upon the clinical pattern of disease at birth, as well as antiviral treatment provided in the newborn period. • Approximately 90% of neonates are asymptomatic, leading to underdiagnosis. Surveys have shown that women are less well informed about cCMV than they are about neural tube defects, fetal alcohol syndrome, Down syndrome, and toxoplasmosis, even though all these threats to healthy pregnancy are less common (Figure 1). • This is a case of a newborn presenting with petechiae, thrombocytopenia, and direct hyperbilirubinemia due to congenital cytomegalovirus. • This case report highlights the importance of including a TORCH workup when considering abnormal neonatal findings.

• CMV is spread in urine, saliva, cervical mucus, semen, stool, and breast milk. • Toddlers and young children commonly have silent CMV infections, thus pregnant women can lessen risk of contracting CMV by reducing contact and with proper hygienic measures. • Primary maternal CMV infection may be suspected if a woman has symptoms of fever, sore throat, fatigue, and swollen glands. • The diagnosis of congenital CMV should be considered in neonates who have signs, symptoms, and laboratory values suggestive of CMV infection (Table 1).

Clinical Presentation

Laboratory & Image Findings

Vision loss

Thrombocytopenia

Jaundice

Direct hyperbilirubinemia Elevated transaminases

Hepatosplenomegaly

Petechiae

Microcephaly

Hearing loss

Ventriculomegaly

Seizures Intracerebral calcifications Table 1. Clinical and laboratory findings suggestive of congenital CMV

• Intravenous (IV) ganciclovir and its orally available prodrug, valganciclovir, are the first-line antiviral agents of choice for treatment of congenital CMV disease. • The outcome of congenital CMV infection depends upon the clinical pattern of disease at birth, as well as antiviral treatment provided in the newborn period. Consequences of untreated cCMV include hearing loss, vision loss, intellectual disability and seizures. • Hearing evaluations are recommended every three to six months during the first three years of life and annually thereafter until at least 18 years of age. 1. Ssentongo P, Hehnly C, Birungi P, et al. Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries With Universal Screening. JAMA Network Open . 2021;4(8). doi:10.1001/jamanetworkopen.2021.20736 2. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. The “Silent” Global Burden of Congenital Cytomegalovirus. Clinical Microbiology Reviews . 2013;26(1):86-102. doi:10.1128/cmr.00062-12 3. Wilson K, Ellsworth L, Pesch MH. Congenital Cytomegalovirus Infection Presenting with Hyperbilirubinemia and Splenomegaly in a Term Infant with Trisomy 21. Case Reports in Pediatrics . 2020;2020:e2534629. doi:10.1155/2020/2534629 4. Vauloup-Fellous C, Picone O, Cordier AG, et al. Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Journal of Clinical Virology . 2009;46:S49-S53. doi:10.1016/j.jcv.2009.09.003 5. Marsico C, Kimberlin DW. Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. Italian Journal of Pediatrics . 2017;43(1). doi:10.1186/s13052-017-0358-8 6. ModernaTX, Inc. A Phase 3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age. clinicaltrials.gov. Published October 5, 2022. Accessed November 6, 2022. 7. Buca D, Di Mascio D, Rizzo G, et al. Outcome of fetuses with congenital cytomegalovirus infection and normal ultrasound at diagnosis: systematic review and meta‐analysis . Ultrasound in Obstetrics & Gynecology . 2021;57(4):551-559. doi:10.1002/uog.23143 8. Barber V, Calvert A, Vandrevala T, et al. Prevention of Acquisition of Cytomegalovirus Infection in Pregnancy Through Hygiene-based Behavioral Interventions: A Systematic Review and Gap Analysis. Pediatric Infectious Disease Journal . 2020;39(10):949-954. doi:10.1097/inf.0000000000002763 9. Baker CJ, American Academy Of Pediatrics. Red Book Atlas of Pediatric Infectious Diseases . American Academy Of Pediatrics; 2017. 10. Ronchi A, Zeray F, Lee LE, et al. Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection. Journal of Perinatology . 2019;40(1):89-96. doi:10.1038/s41372-019-0501-z 11. Boppana SB, Ross SA, Fowler KB. Congenital Cytomegalovirus Infection: Clinical Outcome. Clinical Infectious Diseases . 2013;57(suppl 4):S178-S181. doi:10.1093/cid/cit629 12. Basha J, Iwasenko JM, Robertson P, Craig ME, Rawlinson WD. Congenital cytomegalovirus infection is associated with high maternal socio-economic status and corresponding low maternal cytomegalovirus seropositivity. Journal of Pediatrics and Child Health . 2014;50(5):368-372. doi:10.1111/jpc.12502 13. CMV | Clinical Features for Healthcare Professionals | Cytomegalovirus | CDC. (n.d.). 14. Foulon I, De Brucker Y, Buyl R, et al. Hearing Loss With Congenital Cytomegalovirus Infection. Pediatrics. 2019;144(2):e20183095. doi:10.1542/peds.2018-3095 15. High Cytomegalovirus (CMV) DNAemia Predicts CMV Sequelae in Asymptomatic Congenitally Infected Newborns Born to Women With Primary Infection During Pregnancy. Forner G, Abate D, Mengoli C, PalùG, Gussetti N J Infect Dis. 2015;212(1):67. 16. Demmler-Harrison, Gail. Congenital cytomegalovirus infection: clinical features and diagnosis. UpToDate . April 2021. 17. Hearing Loss in Children With Asymptomatic Congenital Cytomegalovirus Infection. Lanzieri TM, Chung W, Flores M, Blum P, Caviness AC, Bialek SR, Grosse SD, Miller JA, Demmler-Harrison G, Congenital Cytomegalovirus Longitudinal Study Group Pediatrics. 2017;139(3) Epub 2017 Feb 16. 18. Pass, Robert F, and Ravit Arav- Boger. “Maternal and Fetal Cytomegalovirus Infection: Diagnosis, Management, and Prevention.” F1000Research , U.S. National Library of Medicine, 1 Mar. 2018. 19. Brennan- Krohn, Thea. “Congenital Cytomegalovirus Diagnosis.” American Society of Microbiology . ASM.org. Aug 2020. 20. Schleiss, Mark. “Congenital Cytomegalovirus: Impact on Child Health.” Contemporary Pediatrics . July 2018. Acknowledgements Thank you to the patient and patient's mother. References

Figure 2. Petechial rash on face of patient

Figure 3. Petechial rash on neck of patient

Day 3: Blood cultures and urine cultures remained negative, thus antibiotics were discontinued. Patient remained thrombocytopenic, but bilirubin levels stabilized. Phototherapy was discontinued. Day 4: The patient's urine PCR was positive for CMV. Infectious disease was consulted. IV ganciclovir was initiated, 6 mg/kg/dose every 12 hours. The patients auditory testing was normal. Day 5: Ultrasound encephalogram showed a normocephalic head and no evidence of intracranial or periventricular calcifications. Day 7: Patient's platelet level was trending up. Transitioned to PO valganciclovir, 16 mg/kg/dose every 12 hours. Day 11: Patient's laboratory values stabilized. Petechiae has mostly resolved. The patients' mother has been taught to administer PO valganciclovir. The patient was discharged with outpatient follow up.

Figure 1. Cytomegalovirus awareness versus number of children born with CMV. Courtesy of the National CMV Foundation.

Case Report

A 6 lb. 7.6 oz 37-week gestational age newborn female was spontaneously born vaginally to a GBS negative and O negative mother. The mother was HIV non reactive, Hepatitis B non-reactive, RPR nonreactive. She had a history of HSV but did not report lesions or outbreak at delivery. The pregnancy was complicated by suboptimal prenatal care, severe maternal depression requiring hospitalization, maternal chlamydia infection in the first trimester, maternal herpes infection (not on prophylaxis), maternal anemia, and maternal urine drug screen positive for marijuana. The mother failed a 1-hour Glucola and did not follow up for 3-hour Glucola.

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