Giants in the Nursery
By Rita M. Rooney

Theirs is a gargantuan mission on behalf of Maryland’s youngest patients. At the core of the pediatric faculty’s commitment to children is a conviction that a child’s physiology is complex, totally unlike that of adults, and demanding sub-specialization in every medical disease affecting children. Nineteen divisions in the medical school’s department of pediatrics are staffed by 122 faculty member s who treat youngsters both as outpatients, and in a 100-bed state-of-the-art children’s hospital. Scientific investigation places the department among the top 20 grant recipients of NIH funding for pediatric research.

Steven J. Czinn, MD, professor and chair of pediatrics, is a clinician whose research has altered medical thinking about the cause of childhood ulcers. He refers to pediatric care at Maryland as “one of the state’s jewels.”

“I came here three years ago because of the exceptional faculty, and the opportunity to meet the diverse needs of children throughout Maryland,” Czinn says. “As a school of medicine, we draw residents from top tier training programs nationally. We continue to attract the best and brightest among faculty and students, largely due to our impressive resources, among them technology, space, and support staff.”

In 2008, the department of pediatrics—originally a division of medicine—celebrated its 60th anniversary. The occasion marked a community outreach initiative, working with hospitals and schools, promoting programs, and communicating with area physicians regarding the availability of services. Czinn explains the purpose is to increase awareness that will give children throughout the state the advantages of the unparalleled expertise and compassion found in an academic medical environment that places a high priority on personalized care. One example is the 24/7 presence in the emergency department of, not only a pediatrician, but a pediatrician whose sub-specialty is emergency medicine. Typical of outreach efforts, the pediatric emergency specialist sends a report on the treatment received by a patient to the area physician whenever the physician’s name has been provided by the family.

Combating Children’s Asthma
Asthma, a significant problem for the young throughout the country, nears epidemic proportions in Baltimore, where up to 20 percent of school age children have the disease, and where 46 percent of these youngsters have sought emergency care for an asthma-related problem in the past six months.

The department of pediatrics has long been recognized for its service to children with asthma, including its far-reaching Breathmobile, a free program that travels to Baltimore city schools to treat youngsters.

Commenting on specific efforts of the division he heads, Keyvan Rafei, MD, assistant professor of pediatrics, is emphatic about the care provided. “What we do here is not breakthrough science,” he says. “What we do is find innovative ways to more effectively translate existing knowledge in a clinical setting.”

Traditionally, an asthmatic child is seen in the emergency department and follow-up treatment is passed on to a primary care giver. Unfortunately, fewer than 10 percent of these young patients ever receive anything more than acute episodic management of their disease, and heavy medications for their symptoms.

The difference at Maryland is that care begins with an evidence-based approach to the treatment of acute asthma that optimizes treatment. “The cornerstone of our approach is the preferential use of metered dose inhalers with valved holding chambers (MDI-VHC),” Rafei reports. “In contrast to the more commonly used nebulization route for administering inhaled medications, MDI-VHC’s have been shown to be an effective modality that reduces side effects, shortens time spent in the emergency department, and decreases the need for hospitalizations.”
Although these benefits are widely known, Rafei says few institutions have been able to efficiently incorporate the use of MDI-VHCs in daily care, both in emergency and in hospitalized care.

He adds, “What makes our approach to asthma management comprehensive is that we don’t stop at innovative management of the acute asthma, but extend that to the management of the chronic underlying disease. We focus on a standardized approach, classifying the severity of the chronic asthma and tailoring an individualized action plan.”

The primary tool used in the program is a document called The 1-2-3s of Asthma that highlights differences between airway bronchospasm and inflammation, two distinct but related processes that underlie asthma symptoms. The document also outlines triggers that can lead to acute episodes, and finally pinpoints the approach for managing asthma, identifying symptoms that are frequently missed, and questioning parents about specifics that help physicians conclude whether a child’s asthma is intermittent or chronic persistent. This information is integrated with an individualized action plan for patients and parents.

“We can’t say our methods produce 100 percent compliance,” Rafei says. “However, we have been able to show that our children do better faster, and leave the hospital with a better understanding of what to do when symptoms occur.”

The Breathmobile is one dramatic example of Maryland’s determination to bring ongoing care to the children of Baltimore. Mary Beth Bollinger, DO, associate professor of pediatrics and director of the program, reports that the free care provided by the Breathmobile is available to Maryland families throughout Maryland, but focuses on 23 sites in Baltimore and another in Prince George’s County, where childhood asthma is most prevalent. Approximately 400 to 600 children are seen annually for evaluation, treatment and consistent follow-up care in the program which is funded entirely through grants.

“Asthma is a lifelong illness that responds to early control of symptoms,” Bollinger says. “The underserved children we treat are those with the most limited resources, as well as those with the highest prevalence and poorest control of asthma. We’ve been successful in significantly cutting the number of urgent care visits for these children, and reducing the number of asthma-related school absences.”
Rafei concludes, “We’re not the ones who discovered metered dose inhalers as more effective than nebulizers. We’re not the ones who first determined airway inflammation as a critical factor to be controlled. What we have done is take what we know to be effective and apply it in a better and more consistent way, and that’s not always easy to do.”

Perhaps not. However, in 2006, the Joint Commission on Accreditation in Hospitals recognized Maryland’s childhood asthma program for excellence in treating a specific disease and in 2008, renewed that certification with no recommendation for improvement.

Infants At Risk
As the largest division of neonatology in the state, Maryland has the best outcomes, including survival of infants born as early as 23 weeks. Premature and at-risk babies are treated by neonatologists whose published research is directed to many of the serious medical traumas that too often attend birth.

Cynthia F. Bearer, MD, PhD, professor of pediatrics and head of neonatology, is one of the most often cited authorities on the subjects of fetal alcohol syndrome and nutritional support for infants. Her vision for Maryland and for neonatology nationwide is the elimination of all environmental factors that threaten an infant’s life and well-being—from plastics to alcohol.

“We are currently screening for heavy metal concentrations in blood received from blood bank donors,” Bearer reports.
She explains that adults can walk around with much heavier metal concentrations in their blood than children. The process used to prepare blood for neonates doubles the metal concentration. She proposes using blood with low concentrations of heavy metal, which is therefore safer for preemies.

Bearer is a big believer in nutritional support for newborns, and claims there are many unanswered questions about the impact of nutrition on a preemie’s brain. Her extensive research on fetal alcohol syndrome leads her to suggest there may be other environmental factors, including nutritional deficiencies, that work through the same mechanisms as alcohol to impair neuro-development. Her research has shown that specific nutritional supplements can prevent some of the alcohol-induced changes seen in infants.

One percent of all babies born live have some degree of alcohol damage, and fetal impairment caused by alcohol is the leading known cause of mental retardation. So it becomes imperative to recognize an infant’s exposure—signs that may not appear for several years, often too late for effective intervention. Bearer has a patent on a procedure that determines if a newborn has been exposed to alcohol. It involves the testing of meconium, and informs doctors which women have been drinking during pregnancy and how badly the baby has been exposed. Bearer has been working with cohorts in Cleveland and Africa, and in both cases, the studies have been able to pinpoint which children will need neuro-developmental help. She is now proposing that the test be used as part of the routine testing required for all babies.

“Infants are tested for all kinds of rare metabolic diseases, but here is an issue that affects one percent of all babies,” she says. “If we can identify these children early in life, there are programs we can put in place to reduce many secondary disabilities incurred by these children, as well as to prevent the next exposed infant.”

Rose Marie Viscardi, MD, professor of pediatrics, is conducting NIH-funded research on Ureaplasma, an infection that contributes to chronic lung disease in about 20 to 30 percent of premature births.

“Although the presence of Ureaplasma can be detected through amniocentesis, there is some skepticism about testing for it on the premise that there is no way to treat it,” Viscardi says. “Our laboratory is very close to clinical trials with extremely low weight infants, to determine if azithromycin is effective in treating the condition.”

One of the most recent programs available to newborns is the whole body hypothermia method used for infants who do not receive sufficient oxygen in utero or during delivery, a situation that can lead to a form of brain damage called hypoxic ischemic encephalopathy (HIE). When the injury is severe, the insult to the brain can lead to severe developmental problems, even death. The unit now uses a cooling system in which the baby is placed on something resembling a heating pad for 72 hours, while cool water is consistently pumped from a machine into tubing inside the pad.

The procedure is a relatively new one that studies prove to be effective in saving lives and improving neurodevelopmental outcomes. Based on clinical signs, doctors determine if HIE is moderate to severe. If it is, these infants must receive the treatment within six hours of birth.”

Diagnosing Infections
James P. Nataro, MD, PhD ’87, professor of pediatrics, who heads the division of infectious diseases and tropical pediatrics, has a single-minded goal in his study of technology for diagnostic purposes.

“I’d like to put clinical microbiology laboratories out of business,” he says. Countering the statement to explain his reference to the way in which laboratories now work, he talks of the need to send a specimen to bacteriology, virology, parasitology, and mycology labs for batteries of tests, each time-consuming and requiring considerable expertise. Much of the division’s studies have focused on research in developing countries where setting up this kind of laboratory is prohibitive, but necessary to Nataro’s specialty

“In treating a child with an extremely high fever, you could be dealing with malaria or bacteria in the blood,” Nataro says. “If a child has dysentery, it could be caused by any one of several different pathogens, some of which are difficult to diagnose without molecular tests.”

His research has found a life-saving shortcut. By cracking open all the bacteria, viruses and cells in a particular stool, his lab has discovered it’s possible to identify the nucleic acid signatures. From that, the lab can examine a long list of pathogens, using microarray or mass spectrometry to search through the list simultaneously and make the diagnosis.

“A machine has been developed commercially that can identify the nucleic signatures,” Nataro reports. “We already have nucleic acids isolated from children in developing countries. Platforms have been developed and a list of suspect pathogens populated. We are now evaluating various multiple technologies head to head, and expect that, within a year, we will have a validated technology that will save time, and probably lives.”

He adds the research will undoubtedly find valuable application in the United States and abroad, any place where critical diagnosis of a specific agent is often impaired by costly and time-consuming lab work.

In another area of research, Dr. Czinn’s laboratory has made important inroads concerning H.pylori, an infection known to cause pediatric ulcers. The suggestion was originally discarded by a skeptical medical community that rejected the concept of a germ residing in a child’s stomach. His was one of the first labs to show the infection does affect children and causes ulcers. From that, his continued studies proved that the organism becomes a lifelong infection that, in some, leads to gastric cancer later in life. His lab, which has been funded by NIH for 20 years, holds patents on the oral vaccine to prevent the infection.

Commenting on the stature of the 122 pediatric specialists who comprise the department, Czinn says, “It is their reputation for unqualified excellence that draws patients from every corner of Maryland to this university. It is because of them, and because of our broad-based credentials in patient care and pediatric research that we are called on for second opinions for out-of-state patients. And it is because of them that children in this academic medical environment receive the compassionate care they might expect in a community hospital.”