Severe Neutropenia in Infants With Congenital Cytomegalovirus on Antiviral Therapy

Abstract

AIM: To describe European real-life experience of severe neutropenia (SN) during ganciclovir (GCV) and/or valganciclovir (VGCV) treatment in infants with congenital cytomegalovirus (cCMV) infection and identify risk factors associated with the development of SN. METHODS: A multicenter retrospective cohort study from the European cCMVnet registry included infants with confirmed cCMV infection treated since 2011 with GCV and/or VGCV. Details of treatment, including age at initiation, route of administration and duration, are described. Prevalence and risk factors associated with the development of SN, defined as neutrophil count of <500 cells/mm 3 , were analyzed. RESULTS: Overall, 566 children with confirmed cCMV treated with antivirals were included; 165 (29.7%) were born prematurely (gestational age <37 weeks). Administration of intravenous GCV, alone or in combination with oral VGCV, was associated with prematurity and date of birth before 2017. SN occurred in 102 infants (18%). Multivariate logistic regression analysis identified 2 independent risk factors for the development of SN: prematurity almost doubled the risk of developing SN [odds ratio (OR) = 1.961; 95% confidence interval (CI): 1.163-3.300], while the risk of developing SN increased by 11% for every 1000 neutrophils decrease in the absolute neutrophil count at baseline (OR = 1.104; 95% CI: 1.031-1.192). When term newborns were analyzed alone, baseline absolute neutrophil count remained an important risk factor for developing SN. CONCLUSIONS: In children with cCMV treated with GCV/VGCV prematurity and low pretreatment neutrophil counts are associated with an increased risk of developing SN. This is important for patient management, and when informing parents about treatment side effects.