Pharmacoepidemiology of Antiviral Treatment for Congenital Cytomegalovirus in Neonates

Haejung Yoon; Daniel K Benjamin; Reese H Clark; Matthew Laughon; Rachel G Greenberg; Ashley Stark

doi:10.5863/JPPT-25-00149

Pharmacoepidemiology of Antiviral Treatment for Congenital Cytomegalovirus in Neonates

J Pediatr Pharmacol Ther. 2026 Feb;31(1):161-169. doi: 10.5863/JPPT-25-00149. Epub 2026 Feb 9.

Authors

Haejung Yoon¹, Daniel K Benjamin², Reese H Clark³, Matthew Laughon¹, Rachel G Greenberg^{4

5}, Ashley Stark⁶

Affiliations

¹ University of North Carolina at Chapel Hill School of Medicine (HY, ML), Chapel Hill, NC.
² Clemson University (DKB), Clemson, SC.
³ Pediatrix Center for Research Education, Quality, and Safety (RHC), Sunrise, FL.
⁴ Department of Pediatrics, Duke University School of Medicine (RGG), Durham, NC.
⁵ Duke Clinical Research Institute (RGG), Durham, NC.
⁶ University of Chicago, Comer Children's Hospital (AS).

Abstract

Objective: The objective was to assess the pharmacoepidemiology of ganciclovir and valganciclovir for treatment of congenital cytomegalovirus (cCMV), adverse events, and hearing screen outcomes in infants treated with antiviral therapy.

Methods: We included infants discharged from Pediatrix Medical Group neonatal intensive care units (NICUs) between 2010 and 2020. We calculated the number of infants with cCMV and the proportion treated per year. We identified infants with cCMV treated with antivirals and used logistic regression models to compare adverse events (neutropenia, thrombocytopenia, and hepatic dysfunction) before and during treatment. Hearing screen outcomes were assessed using a logistic regression model as our primary analysis, with further sensitivity analyses to allow for the possibility of endogenous treatment.

Results: A total of 465 infants from 144 sites met our inclusion criteria, of whom 262 received antiviral treatment. From 2010 to 2020, the annual number of infants with cCMV fell by one-third and the proportion of infants receiving antiviral treatment more than doubled. Neutropenia (absolute neutrophil count ANC <1000 μL) was significantly more common among infants receiving antiviral treatment after adjustment for gestational age and postnatal age (OR 3.2, 95% CI: 1.4-7.3). Neither thrombocytopenia nor hepatic dysfunction was associated with treatment. The primary logistic regression analysis and sensitivity analyses indicated that antiviral exposure was associated with elevated risk of hearing screen failure.

Conclusions: Our data support previous studies identifying neutropenia as an adverse effect of antiviral treatment. In our cohort of infants with cCMV, treatment was associated with increased likelihood of failed hearing screen; this finding could be a result of unmeasured confounding variables or other limitations of retrospective analysis. Further studies should focus on identifying which infants with cCMV will most likely benefit from treatment, the optimal duration of treatment, and long-term outcomes.

Keywords: antiviral agents; cytomegalovirus; hearing; liver diseases; neutropenia; thrombocytopenia.