A Vanderbilt University Medical Center News and Public Affairs Publication GIVING / CHILDREN'S HOSPITAL / VANDERBILT UNIVERSITY
Vanderbilt Childrens Hospital
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In this issue: SUMMER 2010

Welcome letter
Big dreams for tiny babies
The thrill of discovery
A joint effort
Born too soon
The nature of nurture
Steeplechase benefits Children's Hospital
Friends and fashion

 

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The thrill of discovery

June 2010

The Division of Neonatology in the Department of Pediatrics at Vanderbilt University is nationally recognized for its innovative research and contributions to medical literature.

The faculty is committed to the discovery of new therapies to treat life-threatening neonatal illnesses and to translate these new discoveries into better ways to deliver care and improve outcomes. Clinical trials are currently under way to test novel treatments for infants with lung disease, patent ductus arteriosus, pulmonary hypertension, necrotizing enterocolitis, brain injury, life-threatening infections, birth defects and nutritional problems. The division’s research, funded by the National Institutes of Health, the March of Dimes, the American Heart Association and the Gerber Foundation, is helping to shape the way the nation cares for infants requiring neonatal intensive care. Research is divided into two categories: basic science research and patient-oriented research. Here, you’ll read about four families who have benefited from different therapies and interventions that are helping our youngest patients receive the best chance at a healthy life.

Preventing blindness

Retinopathy of prematurity (ROP) is a leading cause of irreversible blindness in children worldwide. In the United States it affects nearly 16,000 premature infants each year.

If detected early, it can be treated.

While the number of trained specialists willing to screen premature babies for ROP is decreasing, ophthalmologists at the Vanderbilt Eye Institute (VEI) are stepping up to ensure that the future will be bright for this group of children.

Photomicrograph of a newborn rat retina magnified 400 times shows blood vessels in orange and nerve processes in green. Courtesy Franco Recchia, M.D. Photomicrograph of a newborn rat retina magnified 400 times shows blood vessels in orange and nerve processes in green. Courtesy Franco Recchia, M.D. “We know that most children who are born early will develop some degree of ROP,” said Franco Recchia, M.D., chief of the Retina Division at VEI. “While it usually regresses spontaneously, there are still a significant number of patients who are at risk for vision loss if not treated with surgery.

“Of the babies we screen, about 10 percent require laser treatment and we do this procedure within 48 hours of diagnosis,” Recchia said. “When correctly applied, it reduces the chance of an unfavorable outcome by 90 percent.”

Recchia applauded a recent study that supported the treatment protocols utilized by ophthalmologists treating ROP.

Findings from a recent study, published in the Archives of Ophthalmology, provide some parameters for surgical intervention.

“Earlier treatment of ROP is certainly helpful to maintain the vision and decrease the chance of retinal detachment in very aggressive cases of ROP,” Recchia said. “However, early treatment may not be beneficial for all babies – some subgroups appear to have a worse visual outcome if they are treated early.

“This study further refines the criteria and decision-making process used to identify babies who would most benefit from the laser therapy and those who can be safely observed.”

Isabel Willers, who was treated surgically for an  aggressive form of ROP, plays with her twin Owen at home. Photo by Anne Rayner.Isabel Willers, who was treated surgically for an aggressive form of ROP, plays with her twin Owen at home. Photo by Anne Rayner.Born at 27 weeks gestation, twins Owen and Isabel Willers spent 10 weeks in the Neonatal Intensive Care Unit at Monroe Carell Jr. Children’s Hospital at Vanderbilt. Isabel was diagnosed with an aggressive form of ROP and received surgical treatment the next day. Owen was closely monitored.

Luckily for the Willers family, they were able to benefit from the preliminary findings. Vanderbilt doctors utilized the same clinical judgment that was ultimately defined by the study.

“Our daughter could have lost her eyesight,” said Elisabeth Willers, M.D., assistant professor of Medicine, Allergy, Pulmonary and Critical Care at Vanderbilt. “We’re very fortunate. Now she has perfect vision.”

“I cannot underscore how important these screenings are. Without this, the outcome of her vision would have been very different.” Recchia said.
Vanderbilt doctors recently began providing eye screenings for Erlanger Children’s Hospital in Chattanooga and for Niswonger Children’s Hospital at Johnson City Medical Center to ensure that at-risk babies receive the full range of care.

“The Willers twins were the two sides of the coin that this study looked at,” Recchia added. “And today, they both have perfect eyesight.” – Jessica Pasley


Big problems for small lungs

Joshua Speck runs the hallways of his Sparta, Tenn., home tethered to a 50-foot-long oxygen tube. He plays happily, constantly in motion, except when he gets hopelessly tangled.

Joshua Speck, free of his oxygen tube, plays in Nashville’s Dragon Park after a clinic visit. Photo by Susan Urmy.Joshua Speck, free of his oxygen tube, plays in Nashville’s Dragon Park after a clinic visit. Photo by Susan Urmy.“He’s always getting hung up with his tubing and saying, ‘Me stuck,’” says his father, Dennis Speck. “Nothing stops him and he’s not afraid of anything. You turn your back and he’s ready to climb up and jump off the furniture.”

Joshua weighed 585 grams at birth, or 1 pound, 4 ounces. He was born just 27 weeks into his 40-week gestation. Somewhere along the rocky road to his discharge from the hospital he was diagnosed with a serious chronic breathing disorder called bronchopulmonary dysplasia, or BPD.

Today, at the age of 3, he still cannot go more than two hours without his oxygen tube.

BPD is a chronic lung disease that occurs in 10,000 to 15,000 premature infants in the United States every year. Many of them are born with respiratory distress syndrome and require mechanical ventilation to help them breathe. Prolonged ventilator use is the leading cause of BPD.

“You may save their life but do terrible things to their lungs,” says Mildred Stahlman, M.D., professor of Pediatrics and Pathology at Vanderbilt University Medical Center. Stahlman, a pioneer in the field of neonatology, says even in the 1960s as she helped develop the use of mechanical ventilators to rescue premature infants, she knew some kind of damage was occurring, but discovering how the damage occurs and why, is something doctors and scientists have puzzled over for decades.

“There are just a million questions. You answer one question and it asks another,” Stahlman says.

Over the years, the questions have brought new discoveries that are building a very complex picture of BPD. Vanderbilt researchers are digging deep to find hope for babies and their families.

One path, taken by Vanderbilt neonatologist Mario A. Rojas, M.D., M.P.H., is exploring the reduction of the use of the mechanical ventilator in favor of gentler devices to blow air into a baby’s nose. Early evidence from efforts to trade finely-tuned control of air delivery for a reduction in the risk of infection and physical damage appears to keep babies healthier. But there are limits. Babies born at less than 27 weeks gestation don’t seem to benefit as much from a gentler touch.

Image of fetal mouse lung shows cells (blue), connected by two key proteins (green and red). Infection may  impair normal lung development by disrupting these connections. Courtesy Lance Prince, M.D., Ph.D. Image of fetal mouse lung shows cells (blue), connected by two key proteins (green and red). Infection may impair normal lung development by disrupting these connections. Courtesy Lance Prince, M.D., Ph.D. Lance Prince, M.D., Ph.D., assistant professor of Pediatrics and Tim Blackwell, M.D., Rudolph H. Kampmeier Professor of Medicine and chief of the Division of Allergy, Pulmonary and Critical Care, think exposure to infection – even before birth – may play an important role in the development of BPD. Early evidence suggests infections can “turn off the spigot” of a chemical critical to lung growth and development. Prince hopes that one day this chemical, called FGF10, might somehow be replaced in babies for whom the flow has already been turned off; or that something might be found to prevent infections from triggering such disastrous effects in the infant lung.

But what if oxygen, the elixir of life itself, is the cause of lung damage in the most vulnerable of premature infants?

“A premature infant has not had time to fully develop the mechanisms within the lungs to deal with higher levels of oxygen present outside the womb,” says Judy Aschner, M.D., Julia Carell Stadler Professor and director of the Mildred Stahlman Division of Neonatology.

Aschner and colleagues recently received a $2.4 million research grant from the National Institutes of Health to follow 250 premature infants through their first year of life. Vanderbilt will be searching for biomarkers that may help predict which babies are at higher risk for BPD. Aschner hopes this will lead to development of nutrition-based supplements to boost antioxidant protection in premature infants.

But ultimately, the best strategy is to prevent premature delivery in the first place.

“The lung in utero prepares itself for extra-uterine life in a very precise fashion, and if we interfere with that you don’t have the same sequence of events,” Stahlman points out. “For some babies it is a disaster no matter how you look at it. It is an emotional disaster for the parent.”
– Carole Bartoo

 

A complex disorder

On Christmas Day 2009, Danyel Harber received a tiny, precious gift. Her daughter, Izzy, entered the world weighing 1 pound, 10 ounces, 15 weeks ahead of schedule.

For the first 24 hours her doctors and nurses marveled at how well she was doing, but then things changed. She developed fluid around her heart, which required a rare and invasive procedure. A few days later, she started showing signs of something more ominous: necrotizing enterocolitis (NEC).

Izzy underwent surgery where doctors found two small holes in her bowel. They removed 3 centimeters of her intestines. A few days later, she developed an infection and became septic, signs that NEC was setting in.

“It’s been a roller coaster. That’s the best way to describe it,” Danyel says.

NEC claims the lives of 20 percent to 50 percent of its tiny victims. Izzy was one of the lucky ones. She went home in late April.

Necrotizing enterocolitis begins with an infection.

A single layer of cells line the intestine and separate us from the outside world where bacteria live and outnumber us 10 to one. At birth, a newborn’s intestine is relatively sterile. Once a baby starts taking milk – either formula or breast milk – bacteria proliferate and become the large “microbiome” inside their intestines.

Izzy Harber naps on her mother’s shoulder. She was discharged from the NICU in April and has been thriving at home. Photo by Joe Howell.Izzy Harber naps on her mother’s shoulder. She was discharged from the NICU in April and has been thriving at home. Photo by Joe Howell.For unknown reasons, something causes mild damage at the surface of these cells. When that happens, the normal bacteria that reside in the intestines stick to the epithelium, causing inflammation and damage to the bowel.

“The process happens very rapidly, and you can’t predict whom it’s going to happen to,” says Steve McElroy, M.D., assistant professor of Pediatrics at Vanderbilt University Medical Center. “It often happens within 12 hours, and is a very devastating disease for these babies.

“We’ve known about this disease about as long as there have been neonatologists,” he continues. “We’re not any better at treating it today than we were back in the 1970s. Part of that is because it’s a very complex disease. It’s a disease process that’s ripe for investigation.”

NEC affects 1 percent to 3 percent of babies admitted to intensive care nurseries. Primarily a disease of prematurity, it affects one in 10 infants born weighing less than 1,500 grams (3.3 pounds). About 2,700 infants die from necrotizing enterocolitis every year in the United States. Babies who survive have significantly increased risks of feeding problems, liver failure and developmental delays.

Only maternal breast milk is known to protect against NEC. Compared to breastfed-only babies, formula-fed infants are six to 10 times more likely to develop NEC, and babies fed both formula and mother’s milk are three times more likely to suffer from the disorder.

“We know breast milk is a very good thing to give these babies. We just don’t know what part of it is such a great thing,” McElroy says.

Many breast milk components have been studied, including epidermal growth factor (EGF). Investigators know EGF plays a role in NEC.

 Images show normal lining of the small intestine, left, and abnormal lining from a premature infant who underwent surgery for necrotizing enterocolitis. Courtesy Steve McElroy, M.D. Images show normal lining of the small intestine, left, and abnormal lining from a premature infant who underwent surgery for necrotizing enterocolitis. Courtesy Steve McElroy, M.D.“EGF promotes bowel healing by increasing the replication and migration of epithelial cells,” McElroy explains. “However, expression of EGF receptor is lower in premature infants compared to adults. EGF is important in preventing NEC, and premature infants have lower levels of the major receptor of EGF than adults.”

Some studies outside the United States show that probiotics (helpful bacteria) decrease the incidence of NEC in premature babies. The first study of this kind was done in Colombia, South America, where babies were given a combination of two probiotics.

“They were able to demonstrate an almost 50 percent decrease in the incidence of NEC from the year prior to the year it was being used,” says Mario A. Rojas, M.D., associate professor of Pediatrics at Vanderbilt.

Current research is also investigating the use of these helpful bacteria in acute and chronic diarrhea of infants and children, and in inflammatory bowel disease and colon cancer in adults. – Kathy Whitney


A vital vessel

The role of the ductus arteriosus (DA) is simple – it should stay open while a baby is in the womb and it should close after birth.

In this series of images, white arrows point to the ductus arteriosus as it closes and remodels into a rigid ligament. To watch a video of the same process: "Closing the gap," see below, or find it in the Media Gallery.  Courtesy of Jeff Reese, M.D.In this series of images, white arrows point to the ductus arteriosus as it closes and remodels into a rigid ligament. To watch a video of the same process: "Closing the gap," see below, or find it in the Media Gallery. Courtesy of Jeff Reese, M.D.The DA is a temporary heart vessel that routes blood from the pulmonary artery to the aorta, bypassing a fetus’ uninflated lungs. It usually constricts within 24-36 hours after delivery and turns into a stiff ligament during the next several weeks.

But that simple task becomes much more complicated in a premature birth, where up to 40 percent of DAs don’t close properly. This condition is called patent ductus arteriosus (PDA) and is one of the most common congenital heart defects.

There are two negative effects of PDA: excess blood flows through the open vessel causing lung injury, and normal blood flow is diverted away from the circulatory system, which can damage organs from lack of oxygen and nutrients.

Medication is sometimes successful at closing a PDA, but it can also constrict other blood vessels, further restricting blood supply and damaging organs.

If the medication fails to close the vessel, surgery is used as a last resort, and about 25,000 babies undergo this surgery each year in the United States.

That’s exactly what twin brothers Isaac and Eli Gannon faced a month after their premature birth.

At 24 weeks into the pregnancy, their parents Chris and Bekah Gannon discovered that Eli had a fatal condition called absent end diastolic flow. His blood flow to the placenta was malfunctioning, which overworked his heart and would eventually cause it to wear out and stop beating.

“It was like he had been constantly running a marathon his whole life,” Bekah explained.

The Gannons were given two options: continue the pregnancy knowing that Eli would die, but giving Isaac the chance to deliver closer to term; or deliver both babies early and give Eli a chance of survival.

Chris said the choice to deliver early wasn’t a hard decision.

“We knew it was a big decision, but we had the reassurance that both boys had a good chance of survival. To not give Eli a chance never sat right with me,” he said.

 Becca Gannon with Isaac, foreground, and her husband, Chris, with Eli, in the NICU at Children’s Hospital. Photo by Susan Urmy. Becca Gannon with Isaac, foreground, and her husband, Chris, with Eli, in the NICU at Children’s Hospital. Photo by Susan Urmy.The twins were delivered on Feb. 2 at 27 weeks gestation. Isaac came first at 2 pounds, 4 ounces, followed by Eli at 1 pound, 3 ounces.

It was discovered a few days after birth that both boys had PDA, a hallmark of prematurity. They went through two rounds of medication that closed the vessel partially, but still had to undergo surgery to complete the closure at 1 month old.

For both boys, this would be major surgery on top of the chronic lung conditions they were facing, and Eli had already had an exploratory bowel surgery.

Neonatologists Jeff Reese, M.D., and Robert Cotton, M.D., are conducting research in hopes of avoiding PDA surgery for babies.

“We face this in the NICU on a regular basis, and we try to do things medically to get the vessel to close. If we fail in our efforts, then we have to call the surgeons, and it would be best to avoid this major surgery in such fragile infants,” Reese said.

Reese has created a mouse model of PDA and is able to apply different therapies and directly observe the vessel’s response. 

“We’d like to know what causes the ductus to stay open, what causes it to close and why in preterm babies it doesn’t close,” he said.

These studies have already yielded results that could change the way neonatologists practice. Reese, working off previous PDA studies performed by Cotton, found that cimetedine, a drug commonly given to neonates to block ulcers, unintentionally relaxes the vessel.

Isaac and Eli both came through the PDA surgery with no complications, and their health began to improve once their blood was flowing properly. Issac was released from the NICU in early June and the Gannons hope Eli will go home this summer. – Leslie Hast

For more detailed versions of these stories, visit www.mc.vanderbilt.edu/lens.

 

 
Play Video

Closing the gap
Watch Vanderbilt researchers "close the gap" in a tiny, but crucial vessel as the cameras roll. To learn more about why research to close the ductus arteriosus is so important to the lives of tiny patients in our NICU, read "A vital vessel," within our "Thrill of discovery" story.


 

 

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