8601: Neonatal Enterovirus and Human Parechovirus Viral Sepsis: Natural History and Predictors of Morbidity and Mortality (DMD 19-0026)

Background

Enteroviruses (EVs) and Human Parechoviruses (HPeVs) are primarily acquired during the period shortly before, during and immediately after giving birth. The virus occurs from contact of the newborn to the mother who is shedding EV or HPeV during delivery. In the 1980s and 1990s, the Collaborative Antiviral Study Group (CASG) conducted a series of studies of the treatment of neonatal HSV infection that has considerably reduced the rate of disease occurring and death from the virus. This raises the potential that therapy against viruses, called antivirals, for neonatal EV or HPeV sepsis could produce similar improvements in outcomes for these diseases. Given that there are approximately three times more cases of neonatal EV sepsis than of neonatal HSV disease, such an advance would be highly impactful.

Antiviral treatment for newborn EV or HPeV sepsis is needed, but not yet commercially available. Medications against these viruses are under development, and some have progressed to clinical trials. As no proven effective medication (other than supportive care) for neonatal EV infections currently exists, and since these infections are associated with unacceptably high rates of occurrence and death, there is a strong need to identify any study medications that would benefit these newborns.

This study will be the first large, multi-state look at the viral causes of neonatal sepsis conducted. Data from smaller studies as well as the CASG treatment study of neonatal EV sepsis suggest that the rate of occurrence and death is high, and this study will accurately calculate the precise rate of occurrence and death figures by viral pathogen in this highly vulnerable neonatal population. This, in turn, will provide the data needed to support studies of antiviral drugs active against EVs and HPeVs that are in the development pipelines of drug companies.

The main reason for this research study is to get a better understanding of what causes neonatal viral sepsis and to determine the impact of the infection on the babies’ health. Enterovirus and human parechovirus are very common in the population and can cause neonatal viral sepsis. By gaining a better understanding of the condition, we hope this information can be used to guide diagnosis and treatment of babies with neonatal viral sepsis in the future. This study does not include treatment for neonatal viral sepsis.

This study will enroll 72 babies in the entire study.

The study team will see the baby on study day 1. If your baby is still in the hospital or being seen by the clinical care team, the study team will see your baby on study days 2, 3, 5, 7, 10, and 14, and study months 1 and 3. Each study visit will take between 30 and 60 minutes.

What Happens During This Study?

  • A small amount of blood (approximately 2 teaspoons over the 3 months that your baby is in the study) will be collected for the study to determine the presence and the amount of the virus (EV or HPeV) that is in your baby’s blood.
  • We will review your baby’s medical records for information on when they were born, date of admission to the hospital, any problems that they had when they were first born, results of lab tests done by your baby’s clinical team looking at their general health (liver, kidney and how their body is fighting the infection).
  • If your baby’s doctor performed any test to look at their heart (echocardiogram), we will record the results in the study database.
  • The study doctors will also do a physical exam to collect information on your baby’s overall health, including height, weight, head circumference, temperature, and size of their liver, spleen, and presence of any rash, problems breathing or irritability, color of their skin, and soft spot on the head.
  • If your baby had blood or other body fluids taken for laboratory tests as part of their clinical care, we may obtain any leftover samples from the hospital lab.

To be eligible to participate, your baby must:

  • Have a signed informed consent from parent(s) or legal guardian(s)
  • Be less than or equal to 30 days of life at onset of symptoms
  • Weigh 1,670 grams or more
  • Be suspected or proven to have neonatal viral sepsis
  • Have one or more of the following:
    • ALT >2 times upper limit of normal (ULN)
    • Platelet count 1.5 ULN
    • Abnormal cardiac function as measured by echocardiography

Your baby is not eligible to participate if they have:

  • Known or suspected bacterial, HSV, CMV, or adenovirus sepsis

How to participate?

In order to participate in a study, you must contact the study coordinator or investigator of any of the participating institutions by phone or by email.