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Principal Investigator: Yanmin Zhu
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $89,500
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <0-11 years old><0-4 weeks old><AD/HD><ADHD><ASD><Active Follow-up><Address><Affect><Age><Anti-viral Agents><Attention deficit hyperactivity disorder><Autism><Autistic Disorder><Awareness><Benefits and Risks><Birth><CMV><Case Study><Cell Communication and Signaling><Cell Signaling><Child><Child Youth><Childhood><Children (0-21)><Chronologic Fetal Maturity><Clinical><Clinical Trials><Cytomegalovirus><Data><Deterioration><Development><Diagnostic tests><Disease><Disorder><Early Diagnosis><Early Infantile Autism><Early treatment><Effectiveness><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology><Epidemiology Research><Equilibrium><Fetal Age><Foundations><Ganciclovir><Gancyclovir><Gestational Age><Grouping><HCMV><Health><Hearing><Hearing Loss><Hepatitis><Hepatosplenomegaly><Hypoacuses><Hypoacusis><Icterus><Infant><Infantile Autism><Intracellular Communication and Signaling><Jaundice><Kanner's Syndrome><Knowledge><Longitudinal Studies><Longitudinal observation study><Longitudinal, observational study><Lung Inflammation><Medicaid><Microcephaly><Myocarditis><Neonatal><Neonatal Mortality><Neurologic><Neurologic outcome><Neurological><Neurological outcome><Newborn Infant><Newborns><Nordeoxyguanosine><Outcome><Parturition><Patients><Petechiae><Pneumonitis><Population><Predominantly Hyperactive-Impulsive Type Attention-Deficit Disorder><Predominantly Hyperactive-Impulsive Type Hyperactivity Disorder><Preventative strategy><Prevention strategy><Preventive strategy><Primary Prevention><Privatization><Process><Public Health><Pulmonary Inflammation><Randomized, Controlled Trials><Reporting><Research><Risk><Salivary Gland Viruses><Sample Size><Sampling><Scanning><Secondary Prevention><Signal Transduction><Signal Transduction Systems><Signaling><Symptoms><Testing><Treatment outcome><Trees><Update><Vaccines><Valcyt><Valganciclovir><Viral><Virus><Woman><active followup><adverse consequence><adverse outcome><ages><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><balance><balance function><biological signal transduction><cardiac inflammation><case report><cohort><congenital CMV><congenital cytomegalovirus><congenital cytomegalovirus infection><congenital infection><cytomegalovirus group><death among neonates><death among newborns><death in neonates><death in newborn><design><designing><detection method><detection procedure><detection technique><develop a vaccine><develop vaccines><development of a vaccine><developmental><dysfunctional hearing><early detection><early screening><early therapy><epidemiologic><epidemiologic investigation><epidemiological><epidemiology study><follow up><follow-up><followed up><followup><groupings><hearing challenged><hearing defect><hearing deficient><hearing deficit><hearing difficulty><hearing dysfunction><hearing impairment><high risk><improved><infancy><infant infection><infantile><infected infant><infected neonate><infected newborn><insight><interest><kids><long-term sequelae><long-term study><longitudinal outcome studies><longterm study><micrencephaly><microencephaly><mortality><mortality among neonates><mortality among newborns><mortality in neonates><mortality in newborns><neonatal death><neonatal demise><neonatal infection><neonate><newborn child><newborn children><newborn death><newborn infection><newborn mortality><novel><pediatric><pregnant><prevent><preventing><protective effect><randomized control trial><routine practice><screening><screenings><unborn child><vaccine development><youngster>