What medicine can do now for babies born too soon.
Of the hundred odd nights they spent in Duke Hospital’s intensive care nursery, the one Jim and Tara Glandorf learned that their son was showing signs of kidney failure may have been the worst.
Aiden had weighed just two pounds when he was born at 26 weeks with twin sister Olivia, who was even tinier but much stronger than her brother.
Modern medicine had already saved their young lives more than once. Both had spent time on special ventilators and received surfactant, a drug specially developed to open up their immature lungs — a therapy Duke neonatologists helped make possible.
Aiden had also weathered two spinal taps to test for meningitis and survived bleeding in his brain, a serious and common problem in extremely low birth weight infants.
But that night, Aiden turned a shade of gray, and “My husband just lost it,” says Tara. “We thought we were going to lose our son. A doctor came in and didn’t say anything, but just put her arm around Jim. There were many babies in the nursery that needed attention; it just meant the world to us that she would do that.”
It would be three and a half months and many more agonizing nights after the twins’ birth, but Aiden would go home with his parents and sister. Within 24 hours, his kidneys responded to treatment, and he was back to his pink, if still fragile, self.
The Glandorfs know now that preemies are like that. It’s one step forward, two steps back, until the day your child “hits that magic corner, and it’s just eating and growing to come home,” Tara says.
They know that, while they can’t see those same doctors breaking new research ground when they leave the nursery for the lab, the Duke team manifests hope for parents in other ways, sending signals that small lives are big, bold, and completely capable of saving here.
It’s a quiet arm around a shoulder; an oxygen tube placed in a tub for a bubbling, triumphant first bath; the imprint on a piece of paper of a tiny foot that, each week, grows bigger and bigger and bigger, until one day, one family at a time, they get to go home.
Thirty years ago, most babies as small as Aiden and Olivia Glandorf never made it to that first bath, much less their front porch. Today, they have a 90 percent survival rate — and despite the medical challenges they face early on, most of them catch up with their full-term peers by elementary school.
Moreover, advances in treatment are saving infants at ever-younger gestational ages and smaller birth weights. Duke has an excellent reputation for helping some of the most critical patients who are a part of the preterm boom — infants born weighing less than 1,000 grams (2.2 pounds) — and even babies as tiny as one pound have a fighting chance.
That’s not to minimize the challenges. Preterm births are on the rise nationally, and especially in North Carolina, which had one of the highest rates in the country in 2003 — 13.6 percent of all live births in the state — due in part to fertility treatments and increasing maternal age. The rate of disability is not increasing, thanks to dramatic advances in both neonatology and maternal-fetal medicine, but the average infant born at 24 weeks still requires a three- to four-month hospital stay.
Marshalling enough resources to provide the high-intensity care all these tiny patients need is a big challenge — as is finding new treatments to improve their odds even further.
Even at a major medical center like Duke, “It was dark days just a few years ago,” says neonatology division chief Ronald Goldberg, MD. “In 1996 we had only four neonatologists to cover two hospitals, no fellows, and no funding from the National Institutes of Health. Our physicians were interested in basic science and clinical research, but when you have such a large service load, it gets difficult to find the time.”
Under the leadership of Goldberg and associate director David Tanaka, MD, the division has undergone a growth spurt as impressive as a thriving newborn’s: today it includes 12 neonatologists, 17 nurse practitioners, and six fellows, an expansion in staffing that has come along with a similar rise in research funding — some $16 million from the NIH alone last year.
To keep up with its exploding patient population, the division has expanded from 42 to 68 beds at Duke and Durham Regional hospitals, with plans to add 12 more at Duke.
In March, Duke Neonatology also began providing care at a new, 12-bed unit at Alamance Regional Hospital.
A delicate balance
There’s no doubt that the best place for growing a baby is the womb, but these neonatal units are getting better and better at mimicking the most critical elements of that environment — and making amends for what they can’t.
In the Intensive Care Nursery (ICN), bright lights are kept to a minimum, the isolettes cozy warm, with a carefully calibrated network of machines and tubing delivering oxygen and food to lungs and stomachs pressed into use before they were quite ready.
Despite such considerations, preemies are inevitably exposed to all kinds of “noxious stimuli,” as neonatologist Ricki Goldstein, MD, puts it: “Noise, pain, touch, feeding and suctioning tubes being put in their mouths, bright lights in their eyes… Their whole sensory processing system is disrupted, and that can lead to developmental issues,” ranging from chronic lung disease to feeding problems and neurodevelopmental disorders.
In some cases, in fact, the very interventions needed to save preemies can also injure their delicate bodies — a conundrum Duke researchers are tackling by finding new ways to minimize the risks and maximize the benefits.
One such therapy still hotly debated in the neonatology community is high-frequency ventilation (HFV) — a special respirator that helps premature babies threatened by respiratory failure. Duke neonatologists were involved in early development and testing of this mode of ventilation, use of which has since been expanded to older children and adults.
“When it’s used right, it saves lives and reduces the risk of chronic lung disease in babies with lung failure,” says Goldberg. “But the data also show that when it isn’t used right, it can cause lung or brain injury.”
Duke neonatology researchers have defined protocols for using HFV safely, thereby allowing babies to take advantage of the therapy’s considerable benefits.
While a standard respirator for preemies “breathes” 40 to 60 times per minute, babies on HFV breathe 600 times a minute, taking in just a fifth of a teaspoon of oxygen with each puff.
“A baby on HFV actually vibrates,” says Goldberg. “The closest analogy I can think of is the very short, rapid breaths of a panting dog. By providing shorter breaths and more of them, HFV carries far less risk of overinflating and injuring the baby’s lungs.”
Similarly, William Malcolm, MD, a pediatrician who specializes in neonatal convalescent care, has developed a potential way to ameliorate the serious complications that can result from treatment of necrotizing enterocolitis (NEC).
Infants with NEC have an infection in the intestinal wall that can lead to perforation of the intestine, requiring resection of part of the bowel and an ostomy.
While these surgeries are lifesaving, they can also cause infants to become dangerously dehydrated and unable to absorb proper nutrients. Poor growth and liver failure can result. Through a two-year study, Malcolm found that adding microlipids to formula or milk slows down the rate of stomach emptying as well as small bowel transit time, increasing nutrient absorption.
“Adding this fat-containing emulsion to the diet is of nutritional value as well,” says Malcolm, who presented his findings at a Pediatric Academic Societies meeting this spring. “We also noticed that the babies had a significant increase in growth and a significant decrease in ostomy output, which meant they were able to wean off their IV nutrition.”
Partners in many places
Many of the research studies carried out in the ICN are funded through the Neonatal-Perinatal Research Institute (NPRI), a multimillion-dollar, multidisciplinary program begun shortly after Goldberg’s arrival that combines explorations in neonatology with expertise from more than a dozen other areas at Duke University, from cell biology to engineering.
In one of the most promising cross-disciplinary partnerships, NPRI researchers teamed with Duke cardiologist and pulmonologist Jonathan Stamler, MD, to test how a drug that Stamler had previously developed might be useful in treating persistent pulmonary hypertension (PPH) in babies.
A potentially deadly condition, PPH causes blood vessels within the lungs to constrict, severely limiting the amount of oxygen that can be pumped through the body.
Stamler’s discovery, ethyl nitrite (ENO) in inhalation form, was shown to successfully treat PPH in all seven full-term infants enrolled in a 2002 Duke study led by Goldberg. A second Phase I study to test safety and dosage requirements over a longer period of treatment time is planned.
Although ENO’s safety has not yet been tested for preterm infants, it holds promise for preemies, in whom PPH is a common problem.
“We expect some diseases of preterm infants may benefit from ENO,” says Michael Cotten, MD, assistant clinical professor. “But we always want to make sure these things work on big babies first.”
Indeed, one of the major problems facing neonatology is a shortage of information about preemies; despite the recent gains in their survival rates, finding enough infants to produce definitive research results is still too great a challenge for most individual neonatology centers.
To that end, Duke recently was approved for a second five-year term in the NIH-sponsored Neonatal Research Network, which it joined in 2000.
The network, a national consortium of 16 clinical research centers, combines the vast expertise of its member researchers while offering large study populations — outcomes of more than 3,000 preterm infants are collected annually, with a database that now includes more than 40,000 subjects.
At Duke, Cotten is spearheading an effort to gather 1,000 genomic samples from extremely low birth weight babies, drawing from the network’s collective patient pool.
When complete, the samples stored in the Duke Center for Human Genetics DNA bank will comprise the largest such collection to date, giving investigators a treasure trove of information to use in teasing out genes linked to diseases associated with extreme prematurity.
More immediately, Duke neonatologists such as Richard Auten, MD, are leveraging the network’s resources to investigate whether the preemies can benefit from the current intervention of choice for respiratory failure in full-term infants — inhaled nitric oxide (NO), a drug whose FDA approval for use in humans originated through a multicenter study coordinated by Duke.
While the drug is not yet approved for use in premature infants, Duke recently participated in an NIH-sponsored multicenter trial to determine whether inhaled NO can prevent chronic lung disease of prematurity. Study results were presented in May at the Pediatric Academic Societies annual meeting.
Small patients, big commitment
Efforts like these get preterm infants closer to going home. And while discharge usually is a happy day for parents, it can also mean new developmental challenges for their children, from feeding struggles to delays in motor skills, according to Goldstein, an associate clinical professor of pediatrics who directs Duke’s Special Infant Care Clinic (SICC).
To help them adjust to life on the outside, 75 percent of babies discharged from the ICN are enrolled in the SICC, a neurodevelopmental and medical follow-up clinic where patients are followed by a multidisciplinary team that includes neonatologists, a pediatrician, a psychologist, and physical, occupational, and speech therapists until they reach age three.
Infants visit the clinic at regular intervals and whenever developmental concerns arise until the clinic staff “graduates” them to community care.
Under a three-year grant from The Duke Endowment, Goldstein has supervised an early intervention program called “Community Pathways.” The program funds developmental family specialists, who teach families about early intervention programs while infants are still hospitalized and help them access the resources available to them in their communities when they return home.
Goldstein hopes that the program’s excellent results will justify this position becoming a permanent one in the pediatrics department. As part of the grant, she also is completing a traveling effort throughout North Carolina to educate well-child care providers and community interventionists who may be rusty on the care of preterm infants — especially given the advances over the last decade that have allowed babies to be saved at earlier points in gestation.
Those advances have preserved the family dreams of parents like Jim and Tara Glandorf, who say that, without Duke, they would never have had the pleasure of watching their now-toddler twins giggle and grow.
“We have an opportunity to give a child who didn’t have any chance a good life,” division chief Goldberg says.
“It’s a very humbling experience. It’s what motivates us. And it’s hard to beat giving that to parents. The Talmud says that if you save a life, you save the universe. How exciting is that?”
For more information on Duke Neonatology, visit neonatology.mc.duke.edu. To read more from Dr. Goldstein on post-discharge care of preemies, visit dukemedmag.mc.duke.edu.
Staff reports contributed to this article.
Article Copyright 2006 DukeMed magazine
Published in DukeMed, Spring/Summer 2006.