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pediatrics

Gastroenterology

New technology eases management of liver disease

Children’s of Alabama is using FibroScan to help patients with liver disease. (Stock photo)

With obesity in children steadily rising, more young patients are coming to Children’s of Alabama with a form of fatty liver disease that can greatly imperil their health. But determining the progression of liver disease can be a thorny process. To smooth that path, Children’s recently invested in an increasingly popular technology called FibroScan, helping University of Alabama at Birmingham (UAB) pediatric physicians to deftly and comprehensively manage children’s care.

Using a technique known as transient elastography, FibroScan was the first FDA-approved device of its kind and is considered an aid to managing liver disease. Quick, noninvasive and painless, it uses an enhanced form of ultrasound to send vibrations into the liver to measure its stiffness, which typically indicates fibrosis or scarring. “The more quickly the wave passes through the liver, the more stiff the liver is,” Children’s transplant hepatologist David Willcutts, M.D., explained.

By assessing the severity of scarring—and the potential for cirrhosis—FibroScan can help diagnose or monitor the progression of various liver conditions. These range from less-common cystic fibrosis-associated liver disease to more-prevalent autoimmune liver diseases and metabolic dysfunction-associated steatotic liver disease (MASLD). The latter—which can also result from genetic predisposition—essentially makes the liver unable to process the high amounts of extra calories a person is consuming, spurring inflammation.

David Willcutts, M.D.

About one-third of the patients in Children’s Hepatology Clinic, which serves about 500 ongoing patients each year, have suspected or confirmed fatty liver disease.

“We will be using this for almost every patient with confirmed fatty liver disease, so we can measure the baseline stiffness of the liver when they first see us,” said Willcutts, who’s also an assistant professor of pediatrics at UAB. “The machine also provides a CAP (controlled attenuation parameter) score as a surrogate of fat content of the liver, which is useful for the growing numbers of adults—and unfortunately, children—in our country with fatty liver disease. It’s one of the rising conditions leading to adult liver transplants.”

FibroScan is a welcome alternative to invasive liver biopsies and other forms of elastography that require a separate radiology appointment. A FibroScan exam takes just minutes, offering little disruption for young patients and faster treatment decisions for physicians. The new equipment arrived in the summer of 2025.  

“One of the big selling points of this technology is it makes the patient experience much easier because it can be done within a clinic visit and will save them a visit with radiology, which involves a separate appointment elsewhere in the hospital or even at another Children’s facility,” Willcutts said. “It’s a one-stop kind of assessment.”

By keeping close tabs on a patient’s liver stiffness, FibroScan offers Children’s specialists the ability to understand “how much runway we have before we need to do potentially invasive assessments and other therapies,” Willcutts said.

While the goal is always to avert lasting damage to the liver, the presence of cirrhosis is generally thought to be irreversible. FibroScan can help doctors pinpoint “how close we’re getting to that and if the patient needs a biopsy—or a repeat biopsy—to evaluate scarring at the microscopic level and make sure we’re not missing something before it’s too late to act upon it,” he explained.

FibroScan results can also help physicians tailor treatments to patients’ precise stage of liver damage, including certain medications that can be tricky for the liver to process.

“Children’s is a referral center for pediatric liver disease in Alabama because we’re the only liver transplant center in the state,” Willcutts said. “Being able to offer FibroScan helps us elevate our level of care and offer smoother visits and a convenient assessment of liver disease that we didn’t have before.”

Nephrology

Leading-Edge Technology May Change Kidney Transplant Monitoring and Help Other Specialties

In the UAB Spatial Core Lab, researchers are using spatial transcriptomics to examine specific regions within tissue samples.

A breakthrough technology that allows doctors to study the precise regions of a kidney transplant that are involved in rejection could transform how doctors learn about kidney transplant biology, potentially leading to new diagnostic tests or treatments for children.

The technology, called spatial transcriptomics, is a leading-edge technique that lets researchers see which genes or proteins are active in very specific regions of tissue samples, such as those from a kidney biopsy. Unlike traditional methods that study tissue samples as a whole without regard for the location of important signals from the tissue, this technique allows researchers to examine custom-shaped regions of interest containing just a few cells in their natural environment.

Think of it as having a detailed map that shows not just what’s happening in a city, but precisely in which neighborhoods each activity occurs.

“There’s been decades now of data showing that gene expression patterns coming from a transplant are a little bit more sensitive for problems coming from a kidney transplant,” said Michael Seifert, M.D., director of the University of Alabama at Birmingham (UAB) Spatial Core and medical director of pediatric renal transplantation at Children’s of Alabama. “The problem is that we’ve never exactly known where those signals are coming from. Are they coming from cells in the kidney that we care about or are they coming from cells in the kidney that may not be as relevant?”

For instance, signals from immune system cells would be extremely relevant, he said, but could be distinct from those coming from the endothelial cells lining blood vessels.

With this technique, “we can look at a picture of a kidney biopsy on our instrument screen and take your mouse and draw a shape around it, and it will profile everything in that shape while ignoring everything else around it,” he said. It can even profile a certain cell type within the shape.

The Spatial Core team (from left): Pooja Nagaraj, MS, CCRP, Michael Seifert, M.D., Miguel Melendez-Ferro, Ph.D.

The technology itself isn’t destined for routine clinical use, Seifert said. “I can’t foresee a scenario where I would do a biopsy and then use spatial transcriptomics to make a diagnosis, because it’s a very labor-intensive, time-intensive and cost-intensive technique.”

Instead, he said, “my hope is that this will allow us to have a deeper understanding of the processes involved in transplants doing well but also transplants doing poorly. That will help us design better management programs, whether that’s using existing medicines in different ways or designing new medicines that can be more targeted and more effective than what we currently have available.”

Understanding exactly which parts of the kidney are affected by rejection also opens the door to personalized transplant care.

“Every cell in the kidney behaves differently depending on where it sits,” Seifert said. “This technology lets us uncover the heterogeneity—that is, the differences—within the tissue,” including if the problem lies in the blood vessels or the tubules or the parts of the kidney that generates urine. “I hope that’ll allow us to understand the signals that vary from person to person so we can really apply that more personalized technique.”

Thus, rather than treating all kidney transplant patients the same way, doctors could tailor anti-rejection treatments based on what is happening in an individual child’s kidney. This would, however, require advances in the spatial transcriptomics technology to make it faster and less expensive.

Spatial biology is not limited to the study of kidney transplant diseases. Seifert and his team in the UAB Spatial Core are working with specialists in other disciplines throughout Children’s and UAB, including ophthalmology, oncology and pulmonology. “We’re open to collaborating with any investigator with a good question that spatial biology can answer,” he said.

In fact, he sees spatial biology as an important technique for understanding all diseases in children. “I think what’s come out of this is an appreciation that the spatial context is incredibly important in so many of the diseases that we study.”

Orthopedics

How Dogs Are Transforming Pediatric Orthopedic Procedures

Dr. Michael Conklin and Shelby with a patient. (Photo courtesy of Judith Thomason)

What goes in must come out—including the metal pins used to hold bones together while fractures heal. “It probably takes 15 seconds to remove three pins,” Children’s of Alabama pediatric orthopedist Michael Conklin, M.D., said. “But, of course, kids are very scared about that.”

Enter Shelby. The 50-pound standard poodle is trained to sit on the examining table and cuddle with children while Conklin grasps the pins with a tool resembling a needle-nosed plier and pulls them out.

Basically, Shelby serves as a distraction, he says. “We tell the child to pet the dog and look toward the dog and not look at me on the other side of them, not worry about what I’m doing.”

Shelby remains calm no matter what, even with a screaming child. “She just sits there calmly and doesn’t do all the dog things that you and I know and love about our dogs,” Conklin said. “She’s trained to just be there for comfort.”

And it works. Well, for about two-thirds of patients. The rest “freak out no matter what,” Conklin said, but even then, Shelby has an effect. “It seems as if they return back to their baseline calm quicker after the procedure.”

Shelby also helps parents. “There’s a lot of value in the parents seeing that we’re trying to do our best for their child,” Conklin said. “Even though they know their child’s having to go through a procedure . . . it keeps us in good stead with them.”

Shelby’s brother, Foster, works with his sister at the Children’s South location as part of the Pups Unleashing Patient Smiles (PUPS) program, which is one of three branches of Children’s of Alabama’s animal-assisted program, PetsRX. Another branch involves longtime Children’s partner, Hand-in-Paw, which provides therapy dogs at Children’s of Alabama’s main hospital to provide comfort and distraction. The third is a hospital-based medical dog program which includes golden retrievers Wanda and Sydney to assist with scary or painful procedures. Meanwhile, suspected victims of child abuse—who are served by the Children’s Hospital Intervention and Prevention Services Center (CHIPS)—are assisted by dogs from the Help Empower Restore Overcome (HERO) Program with the Alabama Office of Prosecution Services.

The dogs aren’t just a cute addition. There is good science behind their use in the pediatric setting, with studies finding that animal-assisted therapy (AAT) can help children recover more quickly after surgery by improving mood and alertness, reducing perceived pain, and contributing to lower heart rates and blood pressure readings.[1],[2],[3] 

Animal-assisted therapy is also safe for the dogs, with studies showing no signs of stress or fatigue in therapy dogs when the programs are properly managed.[4] At Children’s, the dogs are overseen by a staff handler and rotated to ensure their well-being.

Soon, Shelby and Foster may be part of the scientific literature. Conklin and his team are conducting a randomized trial to evaluate the dogs’ effectiveness, comparing outcomes between patients who receive the therapy dog intervention and those who receive standard care. They are monitoring the child’s heart rate before, during and after the procedure to track how quickly they return to baseline and using a standardized anxiety scale that assesses facial expression, leg movement, activity, crying and consolability.

The goal is to, hopefully, show positive data that will pave the way for broader adoption of such programs.


[1] Calcaterra, V, Veggiotti, P, Palestrini, C, et al. Post-Operative Benefits of Animal-Assisted Therapy in Pediatric Surgery: A Randomised Study. PLoS ONE. 2015; 10.

[2] Braun C, Stangler T, Narveson J, Pettingell S. Animal-assisted therapy as a pain relief intervention for children. Complement Ther Clin Pract. 2009;15(2):105-109.

[3] López-Fernández, E., Palacios-Cuesta, A., Rodríguez-Martínez, A. et al. Implementation feasibility of animal-assisted therapy in a pediatric intensive care unit: effectiveness on reduction of pain, fear, and anxiety. Eur J Pediatr 183, 843–851 (2024). https://doi.org/10.1007/s00431-023-05284-7

[4] Palestrini C, Calcaterra V, Cannas S, et al.  Stress level evaluation in a dog during animal‐assisted therapy in pediatric surgery. Journal of Veterinary Behavior: Clinical Applications and Research. 2017; 17. https://doi.org/10.1016/j.jveb.2016.09.003.

Pulmonology

Bringing Asthma Care Closer to Home in Alabama’s Black Belt

Dr. Isabel L. Virella-Lowell with a patient.

Dallas, Marengo, Perry and Wilcox counties, part of the Black Belt (so named for its rich, dark soil), are four of the poorest counties in Alabama. They also have some of the highest rates of childhood asthma—nearly 12% compared to the state’s 8%—and are severely underserved when it comes to medical care. Two of the counties don’t even have a pediatrician.

Yet just 4% of the more than 5,000 patients seen at Children’s of Alabama’s Specialty Asthma Clinic hail from those areas. “We realized these kids weren’t getting to us for help,” pediatric pulmonologist Isabel L. Virella-Lowell, M.D., said. “But Medicaid data showed a high number of asthma-related claims from the area. So we knew there was a gap.”

One reason is distance, with families having to drive up to three hours to reach Birmingham. Thus, many children receive care only during asthma flare-ups at urgent care clinics or emergency rooms rather than ongoing, preventive treatment, said Children’s and University of Alabama at Birmingham (UAB) Pediatric Asthma Program Director Teresa G. Magruder, M.D. Without a primary care physician overseeing their child’s asthma, families find themselves caught in a cycle of crisis-driven care.

So instead of hoping kids will come to Birmingham, Virella-Lowell and Magruder are bringing their expertise to the Black Belt. Their mission: improve those dismal asthma statistics by engaging the community at a grass-roots level.

The initiative began when Children’s and UAB infectious disease specialist Claudette Poole, M.D., spent time in the area studying water sanitation and parasites. She kept hearing about an asthma crisis and recruited Virella-Lowell and Magruder.

The three applied for and received a Health Resources and Services Administration (HRSA) grant, which provides salary support for the core team and local community and health care partners. It also helps fund the virtual continuing medication education (CME) Project ECHO sessions, health fairs and supplies—such as spirometers and educational materials.

Magruder and Virella-Lowell stress the community-based approach of their efforts rather than having Children’s swoop in for just a few months. “We are really trying to improve the capacity of the community and their understanding of delivering asthma care in their own communities,” said Magruder. That means educating the front-line people caring for children, including school nurses, teachers, daycare workers and parents, while providing access to subspecialty care for the severe high-risk patients.

“If the community doesn’t buy in, if they are not engaged, if they’re not supportive, then there’s a limited amount of good we can do,” Lowell said.

“There’s some fatigue in these communities from programs that come and go,” Magruder added. “We know it takes time to build trust.”

The two doctors are also partnering with local physicians at Selma Pediatrics and Whitfield Regional Hospital in Demopolis. They hope to open a monthly clinic in 2026 in a space provided by Selma Pediatrics, so families don’t have to travel so far for specialty care.

They are also educating clinicians and others who see children with asthma through the aforementioned CME approach Project ECHO (which stands for Extension of Community Healthcare Outcomes), an interactive program that helps clinicians address their own cases. “It’s incredibly important that local physicians are comfortable managing asthma. And asthma care has changed a lot through the years,” said Lowell, who noted the recent release of new guidelines for diagnosing and treating the disease. The program, which is virtual, is available to any clinician throughout the state and beyond who’s interested in maintaining their expertise in pediatric asthma.

The Alabama State Asthma Coalition, a statewide group with a diverse mix of experts including environmental experts and respiratory educators, is also playing a role. The coalition helped train the first group of community health workers and hopes to continue that work.

Given that asthma affects one out of 10 children, it must be managed locally, Lowell said. “There’s no way that we will ever be able to manage all the really sick asthmatics here at Children’s. So it’s incredibly important that local pediatricians and family doctors are comfortable managing asthma.”

“Our goal is to raise the level of asthma care across the state,” Magruder said, “not just at Children’s, but everywhere kids need it.”

Endocrinology

Long-Term Effects of Gestational Diabetes on Kids

A new study from Children’s of Alabama shows the lasting impact of gestational diabetes on the child. (Stock photo)

New findings from a follow-up study at Children’s of Alabama and the University of Alabama at Birmingham (UAB) shed light on how a mother’s health during pregnancy may influence her child’s body weight well into adolescence—especially if that pregnancy was complicated by gestational diabetes. Led by pediatric endocrinology fellow Mary Margaret Barr, M.D., the new analysis builds on the foundational HAPi (Health After Pregnancy) study, conducted by  Paula Chandler-Laney, Ph.D., who directs UAB’s Ph.D. program in nutrition.

That original study assessed the health of 219 children ages 4 to 10. Mothers were divided into three groups based on her health during pregnancy: normal weight mothers without gestational diabetes (group 1); overweight or obese mothers without gestational diabetes (group 2); and overweight or obese mothers with gestational diabetes (group 3). Health-related data collected on the children included body mass index (BMI), waist-to-hip ratios, blood pressure and metabolic markers like glucose and cholesterol levels.

Barr’s research, which she presented at the Pediatric Endocrine Society annual meeting in May, went a step further. She reviewed electronic health records of 139 of the original study group to see how each group’s BMI Z-score—a metric that adjusts BMI for a child’s age and sex—changed as they entered adolescence.

As anticipated, children in group 3 (whose mothers had gestational diabetes and obesity) started off with higher BMI Z-scores that continued to trend upward through adolescence. “These were kids exposed to higher sugars while they were growing inside mom,” Barr said. Another key finding: Of all the children who had normal BMI Z-scores at the time of the original HAPi study (ages 4-10), those exposed to gestational diabetes (group 3) were significantly more likely to become overweight in adolescence.

Group 1—the control group—maintained healthy BMI levels over time, with only a slight rise in average BMI Z-score, which is often seen at adolescence.

The surprise came with group 2. These children, born to mothers with overweight or obesity but no gestational diabetes, initially had higher BMI Z-scores—even higher than group 3 at the study’s start. But over time, most of these children saw improvements in their BMI. “They started off big and then they got better,” Barr said. “Eventually, they ended up in the same range as the children born to normal weight mothers.”

This unexpected trend persisted even after adjusting for factors like maternal BMI, maternal education, household income and the number of children in the home. “These moms were of lower income, most of them below the poverty line, and had a lower education status,” she said. “You would have expected them to parallel group 3 and get worse over time. But they didn’t.”

The reason for the disconnect isn’t clear. “Nothing else stood out except for the child’s BMI during the HAPi study,” she said. “If you were heavier during the HAPi study, you were more likely to wind up heavier in adolescence. But it wasn’t a super strong correlation.”

Although none of the children developed diabetes during the follow-up period, Barr found a handful of prediabetes cases in groups 2 and 3.

The research provides a clue for pediatricians to intervene early in children with a high risk of obesity and/or diabetes. If the pediatrician knows the mother’s pregnancy weight and gestational diabetes history, they can be aware that the child may have a higher risk for obesity in the future. “So it’s probably more important to start earlier with healthy habits, a varied diet with less fried food, more vegetables, reasonable expectations of portion sizes, and exercise and movement,” Barr said.

While gestational diabetes and maternal obesity both increase a child’s risk for obesity, Barr’s findings suggest that gestational diabetes carries a more lasting impact than exposure to obesity alone. “We don’t fully understand the relationship between genetics, environment and exposures” on childhood obesity, she said. “But this data gives us another piece of the puzzle.” Her next step after publication is to expand the dataset to include maternal weight and metabolic health since the original study ended.

Urology

A new protocol for kidney tests in spina bifida patients

A new study shows that ultrasound is not enough to monitor kidney health in children with spina bifida. (Stock photo)

For decades, doctors have relied heavily on ultrasound scans to monitor kidney health in children with spina bifida, the most common permanently disabling birth defect in the U.S. People with spina bifida tend to develop end-stage renal disease up to 20 years earlier than the general population, so keeping a close watch on kidney health from a young age is important, says Children’s of Alabama pediatric urologist Stacy Tanaka, M.D. “Then if there’s a concern, it can be acted upon early and not ignored.”

Current guidelines from the Spina Bifida Association (SBA) recommend annual screening with ultrasound to look for hydronephrosis—a condition in which the urine backs up into one or more kidneys—as a sign of kidney function, and blood tests like serum creatinine, to measure overall kidney health. But with kids, Tanaka says, “the practice pattern was that a lot of people were only doing renal ultrasound.”

Now a new study from Tanaka and her Children’s colleague David Joseph, M.D., as well as other kidney experts from around the country, shows that ultrasound alone is not enough to assess kidney health. “We basically use ultrasonography as a reflection of renal function,” Joseph said, but few, if any, studies assessed its accuracy in determining renal function.

Stacy Tanaka, M.D.

The study’s genesis came during a multidisciplinary meeting in 2003 of specialists who treat children with spina bifida. “The bottom line from all disciplines at that time was that nobody was really treating this population with evidence-based care,” Joseph said.

To change that, the Centers for Disease Control and Prevention and the SBA established the National Spinal Bifida Patient Registry (NSBPR), to which 20 spina bifida clinics submit data to help develop evidence-based care. In addition, nine clinics established a urologic protocol to manage and preserve initial renal function in young children with spina bifida (UMPIRE). The NSBPR and UMPIRE provided the data set Joseph and Tanaka used to determine the effectiveness of renal ultrasound vs. blood test to assess renal function.

The two registries included data on 2,500 children ages 1-18 with myelomeningocele, the most severe form of spina bifida. All had had an ultrasound and blood test within six months to determine estimated glomerular filtration rate (eGFR), a marker of kidney health.

The results were striking: ultrasound-based detection of hydronephrosis had only about a 25% sensitivity for identifying children with signs of chronic kidney disease in the UMPIRE study and 24% in the NSBPR cohort. That means kidney damage in three out of four children was going undetected. The poor sensitivity held even when researchers looked only at severe hydronephrosis, which had an even worse sensitivity rate–just 6% to 11%. “The renal ultrasound by itself wasn’t all that good,” Joseph said, “but that didn’t surprise us.”

David Joseph, M.D.

The findings challenge current practice and suggest that blood tests measuring kidney function should be routinely performed alongside ultrasound, not just when ultrasound results look concerning, as some clinicians practice. The team at Children’s prefers testing for cystatin C rather than creatinine because of the test’s improved and more accurate ability to obtain an eGFR.

One reason clinicians may eschew blood tests is that it involves needles, Tanaka said, which be traumatizing for children. Ultrasound, on the other hand, is noninvasive, easily available, and can be performed by technicians.

“The ultrasound is very helpful and important,” Joseph said, “but you need to recognize that it may not be telling you about renal function or injury to the kidney.” The findings have already changed practice at Children’s, where all kids with spina bifida now receive both tests during kidney health screening.

Ideally, the next study would randomize kids to either double testing or ultrasound alone, but that requires significant funding, particularly since the children would need to be followed for years.

This study was conducted with very little financial support, Tanaka said. “It represents a labor of love for everyone at all nine UMPRIE centers who have been involved in this project,” Joseph added.

Nephrology

Reducing hypertension numbers in children—and adults

The Children’s of Alabama Hypertension Clinic aims to help children in the short-term and long-term. (Stock photo)

Successfully stemming rising rates of cardiovascular disease in adults needs to start in childhood. But with mounting numbers of children and adolescents developing high blood pressure—a trend driven largely by skyrocketing obesity rates—this objective is getting harder to achieve. Enter the Pediatric Hypertension Program at Children’s of Alabama, which, with its steady growth, seeks to break the cycle.  

The Hypertension Clinic, which operates three half-days each week, now sees about 45 patients weekly, a 10-fold increase from 14 years ago, says Daniel Feig, M.D., Ph.D., director of the Division of Pediatric Nephrology at Children’s, who was recruited in 2011 to oversee the clinic’s development and expansion.

High blood pressure—defined in adults and children 13 years and older as a reading of 130/80 mm Hg or higher—is relatively unusual in healthy young patients, affecting 2-3% of typical children and adolescents. (For younger children, the definition of hypertension is a statistical one, based on greater than 95th percentile for age, sex and height.) But children with obesity—who account for nearly 20% of all Americans under 18—have a 20-30% rate of hypertension, says Feig, also the Margaret Porter Professor of Pediatrics at University of Alabama at Birmingham (UAB).

Daniel Feig, M.D.

“There’s a fairly large number of kids with high blood pressure, and one of the major concerns is how we can impact the long-term epidemic that results in cardiovascular disease in adults,” he said. “Controlling hypertension in adults hasn’t gone very well—only about half of those diagnosed have even remotely effective control. This impacts their cardiovascular disease and stroke risk.”

“The only way we can get this under control is by prevention,” Feig added. “If we can make an impact in children and adolescents, we can push back cardiovascular disease in adults.”

Drawing patients from across Alabama as well as some from eastern Mississippi and western Georgia, the Children’s Hypertension Program provides ongoing care for about 2,200 children. But this “catchment area” is likely home to about 70,000 young people with high blood pressure who are undiagnosed. Part of the problem is that many pediatricians aren’t comfortable diagnosing or treating the condition, Feig explains.

When patients come to Children’s, they’re often set up with ambulatory blood pressure monitoring equipment they wear for 24 to 48 hours to measure blood pressure a few times each hour while doing normal activities. The technology enables Children’s clinicians to tease out who actually has hypertension and not blood pressure spikes resulting from factors such as exertion, nervousness or pain.

Once diagnosed, Feig and pediatric nurse practitioner Jessica Edmondson collaborate with dietitians, pharmacists, social workers and others at Children’s to ensure patients benefit from a multidisciplinary approach to treatment. Ultimately, they’re trying to prevent both short- and long-term health implications resulting from hypertension, including heart thickening, retinal damage and even impairments in cognitive function.

It’s a daunting task, Feig acknowledges. “Anything we can do to reduce the numbers right now has a domino effect that reduces long-term target organ damage and long-term cardiovascular risk,” he said. “We’re not at a point where we can reverse the trajectory in 70,000 undiagnosed kids in Alabama, but we can positively impact a good number of kids, improve their health and quality of life, and gain the opportunity to gradually access more and more of them.”

Neonatology

Extended CPAP Shows Promise in Preemies

Research at Children’s and UAB shows that keeping premature infants on CPAP longer may improve lung growth.

Research at Children’s of Alabama and the University of Alabama at Birmingham suggests that keeping premature babies on nasal continuous positive airway pressure (CPAP) longer than currently practiced could significantly improve respiratory outcomes, potentially changing how neonatologists approach respiratory care for the smallest patients.

Early use of CPAP is standard for preterm infants unable to breathe on their own. It helps avoid invasive ventilation and minimizes the risk of lung injury while also increasing lung volume, which could stimulate lung growth and development.

Zaki Yazdi, M.D.

Children’s neonatologist Zaki Yazdi, M.D., conducted a pilot study as part of his fellowship to see whether extending CPAP beyond traditional stopping points benefited premature infants. Yazdi’s study, published in Archives of Disease in Childhood: Fetal & Neonatal, showed that continuing CPAP reduced episodes of drops in heart rate and oxygen levels in preterm infants. These positive findings align with groundbreaking research published this year in the American Journal of Critical Care Medicine, suggesting that extending CPAP promotes lung growth in babies born prematurely.

“We know CPAP helps premature babies with respiratory distress syndrome and apnea of prematurity,” Yazdi said. “The question we were trying to answer was: When is the best time to stop CPAP? We hypothesized that if you were to continue CPAP for a 24-hour period instead of going down to nasal cannula, you would have fewer drops in your oxygen level.”

Yazdi and the Children’s neonatology team, including neonatologist Colm P. Travers, M.D., randomized 36 infants born before 34 weeks gestation to either stop CPAP when they met Children’s traditional criteria (minimal oxygen support and few apnea episodes) or continue for an additional 24 hours. The primary outcomes were oxygen levels and other vital sign changes.

Colm Travers, M.D.

Babies who remained on CPAP an additional 24 hours experienced significantly fewer episodes of intermittent hypoxemia—defined as oxygen saturation below 85% for 10 seconds or longer—compared to those transitioned to low-flow nasal cannula. The CPAP group also had fewer heart rate drops and spent less time with low oxygen saturations.

“Even though all the markers we traditionally look at say this baby should be ready to come off CPAP, perhaps there are some more subtle things that we wouldn’t normally pick up on that suggest staying on CPAP could be helpful,” Yazdi said.

Extended CPAP isn’t without risks. Prolonged treatment can delay oral feeding, since many hospitals avoid feeding babies while on CPAP. There’s also risk of nasal breakdown from the CPAP mask interface, increased costs, and potential complications like feeding intolerance from swallowing air. However, Yazdi’s study found no negative effects during the 24-hour extension period.

The team has now received funding from the National Institute of Child Health and Human Development’s Neonatal Research Network to perform a much larger study examining extended CPAP’s effects on lung development. The multicenter, randomized clinical trial—led by UAB—will involve approximately 860 babies. Unlike Yazdi’s 24-hour study, neonates randomized to the longer CPAP arm will remain on the support for at least two weeks or until they are 34 weeks post-menstrual age. The children will then be followed for two years to assess lung function development and long-term respiratory outcomes, making it the largest controlled trial of extended CPAP to date. 

Already, Yazdi said, he and other neonatologists have noticed “a little bit of creep” toward keeping babies on CPAP longer at Children’s and other institutions.

“I don’t think we’re ready to say that this is definitely the best way to go yet,” Travers said. “But preliminary data that’s very promising suggests we need to do this larger trial to see if there’s any long-term benefit.”

“This could redefine what the standard of care could be,” Yazdi said.

Neonatology

Gut fungi can predict BPD, study shows

Research shows that the gut composition of fungi in the second week of life predicts the later development of BPD.

By Jeff Hansen (UAB)

Extremely preterm newborns who weigh less than 3.3 pounds have immature lungs that often require high levels of ventilation oxygen in the hospital. This contributes to the chronic lung disease bronchopulmonary dysplasia, or BPD, the most common cause of death for these tiny infants. BPD exacts a devastating toll on the immature lung.

In one of the most extensive studies of the microorganisms in the intestines of very preterm infants, University of Alabama at Birmingham (UAB) and University of Tennessee Health Science Center researchers show that the gut composition of fungi in the second week of life predicts the later development of BPD, weeks to months before diagnosis of that disease. They analyzed gut fungi in the first true non-meconium stool produced before two weeks of life and found that the fungal intestinal microbiome—known as the mycobiome—of infants who later developed BPD differed in community diversity, composition and interconnectivity from the infants who never got BPD, as measured by the most up-to-date bioinformatic techniques. The researchers did not find significant differences in the bacterial microbiome in those first true stools.

To show causality, researchers transferred samples of the first true stool that predicts BPD or the first true stool of newborns who did not get BPD into female mice to give them a pseudo-humanized gut microflora. In a mouse model of BPD, newborn pups from those BPD dams showed an increased in the severity of lung injury compared with newborn pups from the no-BPD dams. In loss-of-function experiments, when the female mice with the BPD-predictive stool transplant were treated with an antifungal agent before birth, that inhibition of perinatal fungal colonization reduced lung injury in the newborn pups. In contrast, a gain-of-function experiment, where the perinatal fungal colonization of dams was augmented with a species of Candida fungus common in mice, amplified BPD severity in the newborn pups.

Kent Willis, M.D.

“These findings demonstrate that features of the initial intestinal fungal microbiome are associated with the later development of BPD in premature neonates and exert a microbiome-driven effect that is transferable and modifiable in mouse models,” said Children’s of Alabama neonatologist Kent Willis, M.D., who’s also an assistant professor in the UAB Department of Pediatrics Division of Neonatology. “This suggests causality, and it suggests that the gut fungi may represent a therapeutic target in newborn lung disease.”

Willis and Ajay J. Talati, M.D., University of Tennessee Health Science Center, Memphis, Tennessee, co-led the study, published in Microbiome.

“Collectively, our analyses demonstrate that the composition of the intestinal mycobiome of infants who did not develop BPD was more uniform,” Willis said. “In contrast, those who eventually developed BPD had more disparate mycobiomes. This suggests that a particular pattern of mycobiome development may be necessary to impart resistance to the development of BPD, and failure to do so in various ways is associated with disease development.”

The first defecations of newborn infants are meconium, composed from materials ingested while in the uterus. The first true stools in the second week, the ones analyzed by Willis and Talati, are digested milk. It is known, Willis and Talati say, that fungi in adults are vital members of the human microbiota; but compared to bacteria, their non-pathological and non-parasitic functions are still poorly understood, especially in newborns.

This prospective observational cohort study included newborn stool samples collected over six years from 2017-2020 in Memphis and 2021-2022 in Birmingham. The 64 very-preterm infants in the study who did not develop BPD had an average birthweight of 2.5 pounds, and the 38 very-preterm infants who did develop BPD had an average birthweight of 1.6 pounds. Only one of the 64 no-BPD infants in the study died, while six of the 38 BPD infants died.

Neonatology

A closer look at the effects of chorioamnionitis on premature babies

The majority of preterm births stem from chorioamnionitis. (Stock photo)

The vast majority of preterm births—especially “micro-preemies” born at 22 or 23 weeks’ gestation—stem from a single cause: chorioamnionitis, an inflammation of the placenta and membranes surrounding the fetus. But Children’s of Alabama neonatologist Viral Jain, M.D., is on a mission to determine why this insidious condition occurs, the ways it affects babies’ health, and how to stop it.

Occurring in an estimated 1% to 5% of births in the United States, chorioamnionitis—often shortened to chorio—can be hard to spot. It’s typically diagnosed using clinical signs of inflammation such as fever or elevated heart rates in either the mother or the baby. But chorio often eludes clinical diagnosis, silently causing damage to the placenta and triggering preterm birth, says Jain, also an assistant professor in the Division of Neonatology at the University of Alabama at Birmingham (UAB).

Viral Jain, M.D.

“It’s a huge reason why neonatology exists, as such,” he explained. “It’s the body’s reaction when there’s inflammation to deliver the baby preterm, and all the complications that come with a preterm baby are due to chorio. In addition, the inflammation also causes direct damage to the developing organs of the baby.”

Some of the extensive research conducted on chorio has focused on its causes, which may include infection, environmental chemicals, smoking and bleeding. But scientists still have a poor understanding of why it happens, Jain notes, as well as how to catch it early enough to stop premature delivery.

Much of Jain’s research has delved into chorio’s potential health implications for babies once they’re born—and the effects can be devastating. One of his studies shows that the incidence of cerebral palsy is far higher in infants born when chorio progresses to such a severe extent it becomes funisitis, or inflammation of the umbilical cord. Jain’s findings have been somewhat controversial, he acknowledges, since cerebral palsy is already known to affect more preterm infants than those born after full-term pregnancies.

“We chose the most severe chorio babies for the study to clearly show that it affects cerebral palsy development,” Jain said. “We found that it’s about 50-50—so half the risk of cerebral palsy was from being born pre-term due to chorio, and half was the direct injury coming from inflammation to the developing brain.”

To help predict the cerebral palsy risk of these infants while they’re still in the neonatal intensive care unit (NICU)—when early intervention can more easily be planned—Jain’s research has also used MRI to look for specific markers in the brain suggesting a high risk of the disabling condition.

“We showed that chorioamnionitis insult, which started at birth, continues in these babies and that we can see those changes in the MRI and that they lead to cerebral palsy,” he said. “This means you can start early intervention on those babies to capture or reduce some of the damage.”

Another of Jain’s studies suggests that infants born early due to chorio have chronic lung damage. “It creates an immune cell dysfunction in the lung that there is continuous damage happening,” he explained. In addition to requiring longer ventilator and oxygen treatment, these babies “end up developing what we call BPD, or bronchopulmonary dysplasia, which is neonatal chronic lung disease.”

Ultimately, Jain says, his research—which has been funded by the American Heart Association and National Institutes of Health—seeks to learn how chorio propagates so doctors can impede its damage.

“The goal is to find out what treatment we can give so when it’s just mild we can stop the progression and it won’t become full-blown chorio and end up delivering the baby preterm,” he said. “If we can do that, we can prevent a lot of organ damage to the lung or brain.”  

For more information on Jain’s work on chorio, listen to this episode of the Children’s of Alabama PedsCast podcast.