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Johns Hopkins Pediatricians to Study Newborn Bloodstream Infections, Pulmonary Hypertension - 01/28/2015

Johns Hopkins Pediatricians to Study Newborn Bloodstream Infections, Pulmonary Hypertension

Release Date: January 28, 2015
premature baby

Johns Hopkins Children's Center neonatologist Azadeh Farzin, M.D., and pediatric lung specialist J. Michael Collaco, M.D., M.B.A., M.P.H.M., have joined a team of physician-scientists from Johns Hopkins in East Baltimore and sister institution All Children's Hospital in St. Petersburg, Fla., on the hunt for biomarkers to improve the diagnosis and treatment of serious childhood diseases.

Farzin and Collaco, each of whom will receive $100,000 in research support over two years as part of the Child Health Translational Research Career Development Award, will delve into two of the most confounding neonatal conditions: bloodstream infections and pulmonary hypertension.

Their work is part of a research initiative known as iPICS (institution-wide Prospective Inception Cohort Study), a constellation of some 15 studies spanning the Baltimore and St. Petersburg campuses designed to identify key predictors of disease and health among infants and children. Other ongoing projects include research into the mechanisms of blood clot formation in children, indicators of impending cardiac arrest among critically ill children hospitalized in intensive care and brain injury in newborns. Beyond disease-specific outcomes, researchers have launched a parallel study called PREDICT (Prospective Research on Early Determinants of Illness and Children's Health Trajectories), which follows healthy children and their parents over time to glean insights about the role of genetic, epigenetic and environmental factors that precipitate the development of common diseases in childhood and throughout life. The findings of this research could reveal important clues and illuminate preventive strategies about conditions like diabetes and heart disease that emerge later in life but have their earliest roots in childhood.

"This is a vital cross-hospital research collaboration, the fruits of which will help reshape our understanding of childhood disease and health," says All Children's Hospital President Jonathan Ellen, M.D., professor of pediatrics and vice dean at the Johns Hopkins University School of Medicine. "Pediatric medicine occurs at the intersection of public health, biomedical discovery and research on clinical outcomes, and each one of our iPICS projects is uniquely positioned to provide insights about how one, more or all of these variables contribute to disease and health in children."

Historically, treatments in pediatric medicine have been informed by extrapolation from research conducted in adults. IPICS is posed to change that.

"Insights generated by these studies will redefine the field of pediatrics by providing much-needed and long-overdue evidence about disease and health in newborns, infants and children whose unique physiology renders them vastly different from adults, making the traditional reliance on data derived from adults both antiquated and problematic," says David Hackam, M.D., Ph.D., surgeon-in-chief and co-director of the Johns Hopkins Children's Center.

"Dr. Fazin's and Dr. Collaco's projects are perfect illustrations of that notion," Hackam adds.

Farzin's research focuses on developing tests that quickly and accurately detect the presence of life-threatening bloodstream infections in premature newborns. Premature babies have underdeveloped immune systems that render them vulnerable to dangerous bacteria. One in four extremely premature newborns develop invasive bloodstream infections, which can cause organ injury, developmental and neurologic damage and - in about one-third of cases - death. But because a definitive test to determine the exact kind of bacterium causing the infection can take up to three days, many babies with symptoms suggestive of infection receive pre-emptive treatment with potent antibiotics that target a wide range of bacteria, an approach that can have serious side effects and can make bugs impervious to drugs.

To increase the speed and accuracy of diagnosis, prevent unnecessary treatment and ensure that the antibiotic of choice will precision-target the bug causing the infection, Farzin has homed in on a set of chemicals - some of them found in saliva and some secreted by the lining of the blood vessels - believed to rise precipitously in early infection. Farzin's work will help determine if such chemicals can detect severe newborn infections quickly, reliably and accurately. Salivary chemicals would have the added benefit of allowing repeat, painless and easy testing, eliminating or reducing the need for frequent, painful blood draws, which can be especially problematic in babies because of insufficient blood volume.

Farzin, who is an assistant professor of pediatrics at the Johns Hopkins University School of Medicine, completed a fellowship in neonatology with additional training in pediatric infectious diseases at the University of California Los Angeles, and a pediatric residency at Cincinnati Children's Hospital. She received her medical degree at the University of Cincinnati.

Collaco's work focuses on uncovering new ways to predict, detect and monitor pulmonary hypertension in newborns and track how well the disease responds to treatment. Neonatal pulmonary hypertension - a dangerous condition marked by persistently elevated pressure in the artery carrying blood from the heart to the lungs - develops as a result of severe lung disease of prematurity and can be fatal in as much as 38 percent of babies who develop it. The disease occurs in nearly 4,000 newborns in the United States each year, a number expected to grow as a result of successes in neonatal medicine that have allowed more severely premature and sicker babies to survive. A single biomarker, a hormone known as NT-proBNP, is the only measure in use to detect the presence of the disease and monitor its progression, but the accuracy of the test is highly variable in newborns due to fluctuations in the levels of the hormone in the very young.

However, one of Collaco's mentors, pediatric cardiologist Allen Everett, M.D., has identified another candidate biomarker - a protein known as hepatoma-derived growth factor, known to fuel blood vessel growth and precipitate tumor development. Recent studies from Johns Hopkins have shown this protein is markedly elevated among adults with pulmonary hypertension, and Collaco and team believe this also may be the case in infants. A protein that quickly and accurately reveals how the disease evolves and whether a child is responding to treatment is critically needed. Such a biomarker would reduce the need for complex and, at times, invasive tests, including cardiac catheterization and heart ultrasounds generally needed to diagnose pulmonary hypertension. Another aspect of Collaco's research will be identifying risk factors that render newborns more likely to develop the disease.

Collaco is an assistant professor of pediatrics at the Johns Hopkins University School of Medicine. He earned his medical degree at Case Western Reserve University and completed a pediatric residency and fellowship training in pediatric pulmonary medicine at Johns Hopkins.