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Neonatology

How Children’s Neonatologists Are Playing a Crucial Role in Complex Surgeries

Children’s neonatologists work with surgeons on many types of complex cases. (File photo)

In the Level IV Neonatal Intensive Care Unit (NICU), Children’s of Alabama cares for some of the sickest neonates in Alabama and the surrounding region. The unit, which expanded in 2025, frequently receives referrals from other hospitals for surgical and subspecialty care. Often, the babies cared for on the unit have conditions that require complex surgeries. In these cases, neonatologists work with surgeons and other specialists to manage the patient’s care. Jaw distraction is one example of a procedure they may manage.

Jaw Distraction Surgery and the Role of Neonatology

For some infants, a small or recessed jaw creates serious problems with breathing and feeding. Jaw distraction surgery—also called mandibular distraction osteogenesis—is an option that may dramatically improve outcomes for these patients. While the surgery itself is performed by craniofacial surgeons, the care before and after is deeply collaborative. Neonatologists play a central role in guiding babies and families through every step of the process.

Physicians typically consider jaw distraction surgery for young infants, often within their first month or two of life. Babies with the condition often work harder to breathe normally. They also may have difficulty feeding by mouth because the small jaw narrows the airway. If growth alone doesn’t lead to improvement, then a multidisciplinary team, including neonatologists, craniofacial surgeons, and often ear, nose, and throat (ENT) surgeons, evaluates whether jaw distraction could improve their symptoms and quality of life.

Surgeons focus on the technical aspects of lengthening the jaw, but before and after the operating room, neonatologists manage the airway, ventilation, nutrition and pain control. After the procedure, the baby returns to the NICU sedated and temporarily paralyzed. This protects the infant’s airway and allows the surgical site to heal while the jaw is gradually lengthened over several days. During this time, infants require ventilator support, careful airway management, pain control and nutritional support.

“This isn’t a procedure we recommend lightly,” Children’s of Alabama neonatologist Hannah Hightower, M.D., explained. “Protecting the airway is our number one concern for infants who undergo this surgery.” Because surgeons place hardware in the jaw, any movement could risk complications. This also means post-op babies cannot be held. This period can be especially hard on new parents who may have already begun holding and feeding their child.

As recovery progresses, collaboration becomes increasingly important. Neonatologists and surgeons work together to determine when it is safe to reduce sedation, remove the breathing tube and transition the baby off respiratory support. “Then, we begin working on the infant’s oral skills, because our ultimate goal is for the family to be able to feed their baby at home,” Hightower said. Many of these infants require tube feeding at first, but most eventually learn to feed by mouth.

Even in ideal cases, infants typically remain hospitalized for several weeks as they recover, learn to eat and prepare for discharge. Parents play a significant role as the baby’s recovery progresses, becoming actively involved in feeding and comforting their child. Success after jaw distraction is measured in practical, meaningful ways, such as improved breathing without respiratory support and the ability to take feeds by bottle.

Though the procedure can seem daunting, Hightower emphasizes its impact. Jaw distraction surgery can transform the course of an infant’s life—turning a situation marked by breathing struggles and feeding challenges into one where a baby can go home, breathe comfortably and be fed by their family. “It’s remarkable how a child who is working to breathe and unable to eat may improve and gain these skills post-surgery,” Hightower said. “Being able to send a child home doing those normal baby things is a big deal for the parents.”

February 16, 2026 by
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.

July 24, 2025 by
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.

July 23, 2025 by
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.

July 23, 2025 by
Neonatology

Using mitochondrial genetics to predict BPD

Researchers at Children’s and UAB are exploring how mitochondrial function may help predict BPD risk.

Bronchopulmonary dysplasia (BPD), a chronic lung condition affecting some extremely preterm infants, continues to be a significant clinical challenge in neonatology. While often lifesaving, supplemental oxygen can be a key contributor to long-term pulmonary complications in this vulnerable population. At Children’s of Alabama and the University of Alabama at Birmingham (UAB), researchers are exploring how mitochondrial function may hold the key to understanding and preventing BPD.

Jegen Kandasamy, M.D., an associate professor in the Division of Neonatology at UAB, leads a multidisciplinary team supported by a research grant dedicated to studying mitochondrial dysfunction in BPD. The research centers on individual differences in how mitochondrial DNA (mtDNA) haplogroups—genetic variations inherited maternally and varying by ethnicity—may influence an infant’s susceptibility to lung injury from oxygen exposure, particularly hyperoxia.

“Hyperoxia is a double-edged sword,” Kandasamy said. “It’s essential for survival, yet it introduces oxidative stress that preterm lungs are poorly equipped to handle. Our research is aimed at understanding how mitochondrial genetics impact that response.”

Using collected blood samples and clinical data from preterm infants, Kandasamy’s team is working to identify mtDNA haplogroups associated with higher BPD risk. The goal is to develop precise, genetically informed risk profiles that allow for early intervention. Hopefully, this will improve outcomes while addressing racial disparities in BPD prevalence and severity.

An especially promising area of research is platelet bioenergetics. By measuring how platelets utilize mitochondrial energy, the researchers hope to identify specific biomarkers that reflect systemic mitochondrial health and may help predict BPD risk. “Platelets are easy to access and give us a real-time snapshot of mitochondrial function without invasive procedures,” Kandasamy noted.

The team is also studying mitophagy, the elimination of damaged mitochondria through autophagy, and its role in lung development. Emerging evidence suggests that impaired mitophagy contributes to persistent mitochondrial dysfunction, exacerbating lung injury in preterm infants. As a result of this new evidence, the group is also evaluating the potential of thyroid hormone supplementation as a therapeutic strategy to restore mitochondrial function and mitigate lung damage.

By integrating clinical data with mouse models, the UAB team is uniquely positioned to investigate both the mechanistic underpinnings of BPD and potential interventions. The collaborative effort spans neonatology, mitochondrial biology and pediatric pulmonology, creating a comprehensive research environment.

“Our ultimate aim is to shift the paradigm from reactive to predictive personalized neonatal care,” Kandasamy said. “Understanding how mitochondrial genetics intersect with environmental exposures can help us identify at-risk infants earlier and intervene more effectively.”

July 23, 2025 by
Neonatology

Pandemic Practices and Neonatal Health Issues

A study led by Children’s researchers shows the link between pandemic health behaviors and neonatal health issues.

By Hannah Echols, UAB

Studies show that social distancing and other public health measures during the COVID-19 pandemic effectively reduced the spread of the deadly virus. However, they had unanticipated effects such as reduced health care accessibility and utilization, especially in high-risk populations.

Researchers at Children’s of Alabama and the University of Alabama at Birmingham (UAB) evaluated potential effects of pandemic-related behavior changes on neonatal mortality and preterm birth rates. A correlation was found between the social distancing index, a measure of overall social distancing behaviors observed, and higher rates of neonatal and early neonatal mortality, as well as preterm birth, when assessed with a lag period. Results were published in July in JAMA Network Open.

“COVID-19 affected the health care systems globally, and many lives were lost; it is important to learn from this experience to prepare better for possible future health crises,” said Vivek Shukla, M.D., assistant professor in the UAB Division of Neonatology and lead author of the study. “We need to understand how changes in health behavior affected outcomes, whether people had limited access to care or healthy habits were altered.”

Maternal pregnancy complications increase the risk of preterm delivery and neonatal morbidity. These complications are a major contributor toward neonatal mortality. During the COVID-19 pandemic, pregnant women encountered substantial obstacles in accessing health care. 

According to the American Medical Association, 81 percent of physicians were providing fewer in-person visits when surveyed in July and August of 2020 than pre-pandemic and the average in-person visits fell from 95 to 57 per week.

“The observed correlations may be due to changes in health care access during periods of increased social distancing, such as fewer prenatal visits,” said Rachel Sinkey, M.D., associate professor in the UAB Division of Maternal-Fetal Medicine and co-author of the study. “These appointments are important to catch and address complications that could be life-threatening to both mom and baby.”

Defining the trend

The population-based study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics. The team evaluated neonatal mortality and preterm birth rates from 2016 to 2019 and compared them to 2020 rates. In unadjusted comparison, the rates appeared to be lower. When adjusted for a declining trend observed in the 2016-2019 period using an Auto Regressive Integrated Moving Average model, the rates were not significantly different.

Shukla further analyzed the correlation between the Social Distance Index—which indicated overall population mobility during the pandemic—and neonatal mortality and preterm birth rates in 2020. On a first look, there was no significant correlation; but when a lag period was added, higher SDI was associated with higher neonatal mortality rates with a two-month delay and with higher preterm birth rates with a one-month delay.

“With these in-depth analyses, we could account for the effect of a potential delay, or lag time, receiving access to care could have on the mortality and preterm birth rates,” Shukla said.

“The results indicate a need for more in-depth studies on the unintended effects of pandemic-related health behavior changes,” he added. “Conducting additional studies is an important step for providers and public health experts to better prepare in case there is a next public health crisis.”

January 8, 2025 by
Neonatology, Pulmonology

Improving lung function for COPD and BPD patients

A study led by Children’s researchers shows that inhalation of live Lactobacilli reduces inflammatory markers in BPD and COPD.

By Jeff Hansen, UAB

In preclinical models, the inhalation of a mixture of living Lactobacilli bacteria attenuated pulmonary inflammation and improved lung function and structure for the chronic lung diseases bronchopulmonary dysplasia (BPD) and chronic obstructive pulmonary disease (COPD).

This study, published in the journal Nature Communications, determined the mechanism of this live biotherapeutic product—a powder mixture of living Lactobacilli bacteria—to reduce neutrophilic inflammation and reduce a broad swath of inflammatory markers in BPD and COPD, says Charitharth Vivek Lal, M.D., a neonatologist at Children’s of Alabama and the University of Alabama at Birmingham (UAB). Lal co-led the research with Amit Gaggar, M.D., Ph.D., a UAB pulmonologist.

Their findings “provide a paradigm for the progression of structural lung disease,” Lal said, because they identify the Lactobacilli as critical to regulating lung protease activity that is linked to the destruction caused by matrikine generation, extracellular matrix turnover and chronic neutrophilic inflammation that damages air sacs in the lungs. 

A possible protective role for Lactobacilli in the lung and the possible use of Lactobacilli to treat chronic lung disease had its foundation in 2016 when Lal and UAB colleagues discovered that the airways of infants with severe bronchopulmonary dysplasia had decreased numbers of Lactobacilli, increased numbers of proteobacteria and increased concentrations of proteobacterial endotoxin. In this latest study, the UAB researchers provided a mechanism of action for the Lactobacilli treatment to decrease downstream disease development and showed safety and effectiveness of the live biotherapeutic treatment in a mouse pup model for BPD and three mouse models of COPD. 

Bronchopulmonary dysplasia develops in some extremely premature infants after damage induced by high oxygen tension or mechanical ventilation needed to keep them alive. COPD occurs in older people, especially smokers, and kills about 130,000 Americans a year and about 3 million more worldwide.

“Inhaled live biotherapeutic products show promise in addressing common pathways of disease progression that in the future can be targeted at a variety of lung diseases,” Lal said. “Preclinical animal data is suggestive, and safety of the potential drug in humans will be tested in a forthcoming clinical trial. Human adult safety data in COPD will help de-risk the pathway to approval for use of the drug in bronchopulmonary disease infants.”

The UAB researchers hypothesized that mouse models of BPD would show heightened levels of acetylated proline-glycine-proline, or Ac-PGP, an extracellular matrix-derived peptide, as had been seen in premature infants with BPD.

This was demonstrated in BPD mouse models, and gain- or loss-of-function studies showed the impact of Ac-PGP. Intranasal instillation of Ac-PGP increased neutrophilic inflammation and lung degradation. When an inhibitor of Ac-PGP was given with the Ac-PGP, markers of neutrophilic inflammation decreased and lung structure improved.

Researchers then showed that a proprietary Lactobacilli blend of L. planatarum, L. acidophilus and L. rhamnosus performed best in synergy to reduce the inflammatory proteinase MMP-9, which helps release the Ac-PGP from extracellular matrix. Furthermore, supernatant from Lactobacilli growth medium also reduced MMP-9 at a similar magnitude as live Lactobacilli bacteria. 

A key finding was that L(+) lactic acid, which is produced in Lactobacilli growth medium supernatant, reduced MMP-9 in vitro, showing an important role for this lactic acid as an anti-inflammatory molecule. Researchers found that live Lactobacilli in the lungs provided an ongoing, sustained release of L(+) lactic acid in a controlled and well-tolerated manner.

A major technological advance reported in the study was creating the inhaled Lactobacilli powder through particle engineering—particles small enough to reach deep into the lungs while preserving viable bacteria. This live biotherapeutic product was then tested in the BPD and COPD models. In the COPD mouse models, the blend successfully reduced inflammation in the lung microenvironment whether treated concurrently or post-injury, showing anti-inflammatory effects, decrease of several pro-inflammatory markers and elevation of the anti-inflammatory marker IgA. 

An interesting finding was the favorable performance of the live biotherapeutic product. It reduced MMP-9 and other pro-inflammatory cytokines as effectively as—or in some cases better than—fluticasone furoate, a United States Food and Drug Administration-approved inhaled corticosteroid found in COPD combination therapies. 

Safety and biodistribution studies in one of the COPD mouse models showed that inhalation of the bacterial powder did not initiate adverse reactions or disease, and the Lactobacilli did not translocate to distal tissues or accumulate in the lungs.

January 8, 2025 by
Neonatology

Innovative Lung Testing for Preemies

A device developed by Children’s of Alabama neonatologists is showing promise at measuring lung function in premature babies.

One of the most important parameters of a premature baby’s health status is respiratory health. How well are their lungs working? What long-term respiratory complications might occur from the premature birth? Yet assessing lung function in these fragile newborns has long been a complex and invasive process.

“Right now, we diagnose lung disease based on whether a baby needs oxygen or not,” Children’s of Alabama neonatologist Colm P. Travers, M.D., said. “But we don’t know how severe their lung disease is and what type of lung disease they have.”

Measuring lung function in children and adults is as simple as having them blow hard into a plastic tube. Pulmonary function testing in neonates, however, requires complicated equipment as well as sedation or anesthesia, limiting its use outside of research studies.

Colm Travers, M.D.

So, Travers and his team have brought a decades-old technology used in adults called forced oscillation technique (FOT) to the NICUs at the University of Alabama at Birmingham (UAB) and Children’s. They worked with the device manufacturer to develop a machine designed for small babies. It sends sound waves into the lungs while the infant is sleeping and breathing naturally. The sound waves then bounce off the lungs, providing information on stiffness and resistance in the airways. It can be performed in less than 30 seconds, non-invasively, without sedation and repeated over time. It typically takes just a few minutes to set up and can be used soon after birth.

“It’s well suited to neonates because it doesn’t need any effort on behalf of the baby,” Travers said. “Oscillometry is also able to tell you the severity and the type of lung disease a baby has.” In addition, he said, it’s an ideal tool to use in research because of its simplicity and accuracy.

The Children’s team has already used the device in more than 600 neonates. They published the first results of their work in 2020, which demonstrated the feasibility of using oscillometry in healthy newborns and those with respiratory disorders. Now, they’re in the midst of a larger study funded by the National Heart, Lung, and Blood Institute involving 550 babies with the goal of establishing normative data for infant lung function and tracking outcomes, such as asthma and wheezing, in early childhood.

“We’re also using it in our NICU to see whether babies respond to certain medications,” Travers said. This approach could help doctors quickly determine if a treatment is effective or if they need to pursue alternative options.

The use of FOT at Children’s is still only in the research phase. Travers says he and his team are still following the infants until they are 2 years old. “In the future, we hope to see the infants back around the time they are starting school so we can see how they are doing in terms of exercise capacity and lung function,” he said.

Eventually, Travers hopes FOT will become standard of care not only in his NICU, but in hospitals everywhere.

August 7, 2024 by
Neonatology

Risk factors for BPD-PH in preterm infants

Studies led by Children’s neonatologists show early indicators of bronchopulmonary dysplasia with pulmonary hypertension.

It’s well-known that preterm infants are prone to breathing difficulties due to their underdeveloped lungs. But the most common lung disease in these babies, bronchopulmonary dysplasia (BPD), is only recently becoming better understood more than a half-century after it was first described.

Now, Children’s of Alabama neonatologist Samuel Gentle, M.D. is expanding that knowledge by focusing on the most severe type of BPD—the form associated with pulmonary hypertension (PH)—in research that teases out contributing factors to this deadly disease.

It’s a major threat: nearly half of preterm infants develop BPD, which can lead to long-term breathing and health problems. About 20% of these babies also develop PH, and an estimated 40% of them will die of BPD-PH before turning 2 years old.

Samuel Gentle, M.D.

“This is a disease for which there’s growing research interest. It can be lethal, is not uncommon in extremely preterm infants, and we have little understanding of how to prevent or treat it,” said Gentle, who’s also an assistant professor of neonatology at the University of Alabama at Birmingham (UAB). “And children who do survive have long-term complications that persist into adulthood. It’s not a disease they just grow out of.”

“I’ve also had many interactions with families who lost a child to this,” he added. “Oftentimes, a child will be stable and doing well, and then collapse. I’ve seen how this can ravage a family.”

Since research has been scant about what causes the development of BPD-PH—as well as how to screen, treat and prevent it—Gentle wanted to fill the vacuum. Currently, a single ultrasound of the heart is the standard diagnostic method, though UAB performs this testing more frequently.

“We need to get better at identifying this disease in real time, rather than doing ultrasounds at arbitrary time intervals,” Gentle said. “Even with UAB’s testing approach, I believe it will become possible to diagnose it sooner, allowing earlier initiation of PH-targeted therapies.”

Along with UAB colleagues, Gentle published two studies that assessed factors that may contribute to BPD-PH in preterm babies. Published in the American Journal of Respiratory and Critical Care Medicine, they found two important associations: The duration of intermittent hypoxia events and the presence and persistence of a patent ductus arteriosus (PDA) after birth are both novel risk factors for BPD-PH.

In the first study, Gentle found that infants who experienced intermittent hypoxia events lasting longer than one minute were twice as likely to develop BPD-PH. “If an infant has longer intermittent hypoxia events, we might be more proactive in screening that infant for BPD-PH,” he said.

In the second study, preterm babies born with BPD-PH between 22 and 28 weeks’ gestation were more likely to have a PDA vessel that stayed open longer than 28 days. Babies with longer PDA duration were also more likely to die due to complications of BPD-PH than infants with only BPD. “The PDA could be interfering with the development of pulmonary vasculature resulting in PH,” Gentle said.

UAB will be participating a multicenter trial to determine whether closing PDAs with a catheter-closure device might lower the risk of this PH variant. But far more study is needed, Gentle pointed out.

“While this research focused on a specific phenotype of BPD, we need a comprehensive approach to identifying each infant’s specific type of lung disease from which we can decide on the best therapeutic course for every child,” he said.

August 6, 2024 by
Neonatology

Improving outcomes for babies with neonatal encephalopathy

Children’s of Alabama neonatologist Vivek Shukla, M.D. is leading an effort to better understand neonatal encephalopathy.

In neonatology, few conditions pose as complex a challenge as neonatal encephalopathy, a condition that encapsulates various disorders characterized by depressed mental or neurological states in newborns. That is why Vivek Shukla, M.D., and his team are taking a multipronged approach to improve outcomes for infants affected by this condition.

Cause and challenges

According to Shukla, director of the Neuro-NICU at Children’s of Alabama, neonatal encephalopathy stems from multiple factors, ranging from fetoplacental, infection, genetic and metabolic disorders. On many occasions, neonatal encephalopathy results from perinatal hypoxic-ischemic events, usually right before or as a baby is delivered.

Diagnosis presents a challenge, often relying on meticulous review of the history and thorough physical examinations. Shukla says it can be difficult to identify the cause quickly, prompting the need for specialized tests. Techniques such as MRI with newer imaging sequences and EEG play pivotal roles in better understanding the neurological intricacies contributing to this condition.

Shukla emphasizes that while strides have been made, adverse outcomes in neonatal encephalopathy—especially from suspected perinatal hypoxic-ischemic events—remain the most common contributor to long-term impairment in children. Around one in three babies with moderate or severe encephalopathy faces severe disability or succumbs to the condition, signifying a need for continued improvement.

The team approach

Multidisciplinary teams together with engaged families are crucial in providing holistic care while infants receive treatment, Shukla says. This collaborative approach extends beyond NICU discharge, ensuring continuous support and intervention to enhance a baby’s developmental journey.

In the Children’s Neuro-NICU, Shukla leads just such a team. This multidisciplinary team includes neonatologists (Hope Arnold, M.D., neonatology fellows and pediatric residents), pediatric neurologists specializing in neonatal neurology (Stephen Walker, M.D., Salman Rashid, M.D., and pediatric neurology residents), pediatric developmental-behavioral specialists focusing on child development (Myriam Peralta-Carcelen, M.D.), a pediatric rehabilitation medicine specialist (Erin Swanson-Kimani, M.D.), interdisciplinary therapists, and dedicated nursing staff. “We collaborate closely to provide comprehensive care for newborn infants, integrating expertise across multiple disciplines to enhance neurological outcomes and support developmental milestones from infancy through early childhood,” Shukla said.

To address neonatal encephalopathy, the team has implemented several strategies:

  • Involvement in several clinically important studies to improve the outcomes of infants suffering from neonatal encephalopathy
  • Working to develop an early and individualized risk-prediction model for infants with neonatal encephalopathy using advanced machine learning and brain MRI images
  • Collaborating with researchers from other institutes to investigate novel biomarkers and utilize machine learning to enhance the understanding and prediction of therapeutic hypothermia responses
  • Working to develop and validate machine learning models to predict the risk of seizures in newborn infants using EEG data, video recordings and clinical information
  • Conducting clinical trials to study interventions including pharmacologic and developmental interventions aimed at improving survival and neurological outcomes

History of treatment

Over the years, advancements have transformed treatment strategies, particularly in babies with suspected perinatal hypoxic-ischemic encephalopathy. Therapeutic hypothermia—cooling newborns to reduce metabolic demand for up to 72 hours—curbed brain injury post-insult in NIH-funded randomized controlled trials, including in babies treated by the team at Children’s. “For babies with moderate to severe encephalopathy, adverse outcomes are much more likely. Therapeutic hypothermia certainly reduces longer-term complications, but there are still opportunities to serve these infants better. That is why we’re continuing research on other options, including treatments that improve the overall outcomes in these children,” Shukla said.

Newer research avenues explore stem cell therapies, medications and interventions beyond therapeutic hypothermia. Additionally, vigilance in monitoring and managing seizures, which are more likely to affect these infants, has become integral to care protocols. Shukla’s team is actively engaged in clinical trials, paving the way for more effective treatments to enhance outcomes beyond the existing therapeutic approaches.

The future

Shukla says urgency and passion continue to drive ongoing research efforts. Neonatal encephalopathy continues to challenge neonatal care, but ongoing research and innovative therapies offer hope for better outcomes. The dedication of the Children’s of Alabama and University of Alabama at Birmingham (UAB) health care teams and the integration of pioneering treatments are pivotal in reshaping the journey for these vulnerable newborns.

August 2, 2024 by