Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in the US, affecting one
in every 200 infants each year. Approximately 10% of newborns impacted by cCMV have symptoms at birth,
such as small size for gestational age, jaundice, petechiae/purpira, and hepatosplenomegaly. Symptomatic
cCMV is associated with a higher risk of long-term sequelae and mortality. Despite its significant clinical
consequences, cCMV remains one of the least recognized and understood viruses that can spread from
pregnant patients to their unborn children.
There is an urgent need for high-quality evidence on the risks of long-term neurologic and non-neurologic
sequelae and on the benefits of available treatments for these outcomes among cCMV infected infants. While
neurologic sequelae are commonly reported in cCMV infected infants, the available evidence has significant
limitations (e.g., limited follow-up and sample sizes) preventing accurate quantification of the risks of long-term
neurologic sequelae attributable to cCMV infection. While several studies have reported cases of non-
neurological adverse outcomes among infants and children with cCMV, including hepatitis, pneumonitis, and
myocarditis, it is currently unknown whether cCMV infection leads to long-term non-neurologic sequelae.
Whereas randomized controlled trials have demonstrated the effectiveness of ganciclovir and valganciclovir in
preventing hearing deterioration, improving hearing and early neurodevelopmental milestones in symptomatic
infants before the age of 2, it remains unclear whether antivirals also reduce the risks of late-onset hearing loss
and long-term neurologic and non-neurologic sequelae.
Using nationwide cohorts of publicly (Medicaid, 2000-2020) and privately (MarketScan, 2003-2021) insured
neonates (≈ 29 million, both cohorts to be updated as new data become available during the course of the
study), which provide a unique, highly representative sample of the overall US neonatal and pediatric
population, as well as sophisticated epidemiologic design and analytic approaches and novel tree-based
scanning signal detection methods, we will address the following specific aims: (i) to quantify the risks of
neurologic long-term sequelae among infants with clinically recognized cCMV; (ii) to conduct a systematic
surveillance of newborns with clinically recognized cCMV to detect signals of adverse long-term non-neurologic
health consequences. For both aims, the effect of antiviral treatment on the risk of these neurologic and non-
neurologic outcomes will be evaluated.
By harnessing the power of existing real-world data, the proposed studies will have an immediate and
important public health impact by informing the value of universal screening, early antiviral treatments and
vaccines, as well as by raising awareness among patients and clinicians.
