Pulmonary Complications of Cytomegalovirus Infection in Neonates and Infants: A Systematic Review of Case Reports and Pooled Analysis

Abstract

Background: Cytomegalovirus (CMV) causes intrauterine infections in 0.67% of neonates, with 12.7% displaying symptoms at birth. CMV can lead to severe multiorgan involvement, and mortality in symptomatic cases is around 30%. Pulmonary complications are rare in infants with CMV. This review assesses pulmonary complications and outcomes in infants with CMV infection. Methods: A systematic literature search was conducted using PubMed, SCOPUS and Ovid SP to retrieve case reports on pulmonary complications in infants with congenital or perinatal CMV infection. Descriptive analysis and pooled analysis were conducted for the case reports. Results: A total of 28 articles with 38 patients were included in this systematic review. The reported pulmonary complications in the case reports were CMV pneumonitis (34.2%), persistent pulmonary hypertension of the newborn (18.4%), emphysema and chronic lung disease (15.8%), diaphragmatic dysfunction (13.2%), lung cysts and calcifications (10.5%), Pneumocystis jirovecii infection (7.9%), pulmonary hypoplasia (5.3%) and bronchial atresia (2.6%). Seven (18.4%) of 38 patients passed away because of the pulmonary complications of CMV infection. Congenital transmission (P = 0.0108), maternal CMV (P = 0.0396) and presence of neonatal comorbidities (P = 0.0398) were independent risk factors for mortality. Conclusions: This systematic review demonstrated infrequent occurrence of severe pulmonary involvement in CMV infection but should be considered in infants with persistent or severe respiratory symptoms.

“Minimally symptomatic” congenital cytomegalovirus infection: latest data and emerging concepts

“…Only about 10-15% of infected neonates are born "symptomatic" with clinical and laboratory signs such as small for gestational age (SGA; <10% birth weight), intrauterine growth restriction (IUGR; ponderal index <10%), microcephaly, blueberry muffin rash representing extramedullary hematopoiesis, hepatosplenomegaly, anemia, petechiae, thrombocytopenia, jaundice, direct hyperbilirubinemia, elevated alanine amino transaminase (ALT), or chorioretinitis and rarely cataracts [12,13]. In addition, congenital CMV infection has been associated with pneumonitis and persistent pulmonary hypertension of the newborn [14][15][16]. Importantly, congenital CMV infection likely is an under-recognized cause of fetal and neonatal mortality globally [17][18][19][20][21][22].…”