Posts

preterm baby

Validating a better way to stratify BPD risk in vulnerable newborns

preterm baby

Factoring in the total number of days that extremely preterm infants require supplemental oxygen and tracking this metric for weeks longer than usual improves clinicians’ ability to predict respiratory outcomes according to bronchopulmonary dysplasia severity.

Factoring in the total number of days that extremely preterm infants require supplemental oxygen and tracking this metric for weeks longer than usual improves clinicians’ ability to predict respiratory outcomes according to bronchopulmonary dysplasia (BPD) severity, a research team led by Children’s National Hospital writes in Scientific Reports. What’s more, the researchers defined a brand-new category (level IV) for newborns who receive supplemental oxygen more than 120 days as a reliable way to predict which infants are at the highest risk of returning to the hospital due to respiratory distress after discharge.

About 1 in 10 U.S. infants is born preterm, before 37 weeks gestation, according to the Centers for Disease Control and Prevention. That includes extremely preterm infants who weigh about 1 lb. at birth. These very low birthweight newborns have paper thin skin, frail hearts and lungs that are not yet mature enough to deliver oxygen throughout the body as needed. Thanks to advances in neocritical care, an increasing number of them survive prematurity, and many develop BPD, a chronic lung disease characterized by abnormal development of the lungs and pulmonary vasculature.

“About half of the babies born prematurely will come back to the hospital within the first year of life with a respiratory infection. The key is identifying them and, potentially, preventing complications in this high-risk population,” says Gustavo Nino, M.D., a Children’s National pulmonologist and the study’s lead author.

For decades, the most common way to stratify BPD risk in these vulnerable newborns has been to see if they require supplemental oxygen at 36 weeks corrected gestational age.

“The problem with this classification is it doesn’t take into account the very premature babies who are on oxygen for much longer than other babies. So, we asked the question: Can we continue risk stratification beyond 36 weeks in order to identify a subset of babies who are at much higher risk of complications,” Dr. Nino says.

The longitudinal cohort study enrolled 188 infants born extremely preterm who were admitted to the neonatal intensive care unit (NICU) at Children’s National and tracked their data for at least 12 months after discharge. The team used a multidimensional approach that tracked duration of supplemental oxygen during the newborns’ NICU stay as well as scoring lung imaging as an independent marker of BPD severity. To validate the findings, these U.S.-born newborns were matched with 130 infants who were born preterm and hospitalized at two NICUs located in Bogotá, Colombia.

“Babies who are born very preterm and require oxygen beyond 120 days should have expanded ventilation of the lungs and cardiovascular pulmonary system before going home,” he notes. “We need to identify these newborns and optimize their management before they are discharged.”

And, the babies with level IV BPD risk need a different type of evaluation because the complications they experience – including pulmonary hypertension – place them at the highest risk of developing sleep apnea and severe respiratory infection, especially during the first year of life.

“The earlier we identify them, the better their outcome is likely to be,” Dr. Nino says. “We really need to change the risk stratification so we don’t call them all ‘severe’ and treat them the same when there is a subset of newborns who clearly are at a much higher risk for experiencing respiratory complications after hospital discharge.”

In addition to Dr. Nino, Children’s National study co-authors include Awais Mansoor, Ph.D., staff scientist at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI); Geovanny F. Perez, M.D., pediatric pulmonologist; Maria Arroyo, M.D., pulmonologist; Xilei Xu Chen, M.D., postdoctoral fellow; Jered Weinstock, pediatric pulmonary fellow; Kyle Salka, MS, research technician; Mariam Said, M.D., neonatologist, and Marius George Linguraru, DPhil, MA, MSc, SZI principal investigator and senior author. Additional co-authors include Ranniery Acuña-Cordero, Universidad Militar Nueva Granada, Bogotá, Colombia; and Monica P. Sossa-Briceño and Carlos E. Rodríguez-Martínez, both of Universidad Nacional de Colombia.

Funding for research described in this post was provided by the National Institutes of Health (NIH) under award Nos. HL145669, AI130502 and HL141237. In addition, the NIH has awarded Dr. Nino an RO1 grant to continue this research.

newborn in incubator

A bronchopulmonary dysplasia primer to guide clinicians and researchers

newborn in incubator

Six months in the writing, the “Bronchopulmonary Dysplasia Primer” published recently by Nature Reviews will be the gold standard review on this topic for years to come.

The term bronchopulmonary dysplasia, or BPD, was first coined in 1967 to describe a chronic lung disease of preterm newborns after treatment with supplemental oxygen via mechanical ventilation in an effort to save their lives. Back then, infants had 50-50 odds of surviving.

In the intervening years, survival has improved and the characteristics of BPD have evolved. Now, BPD is the most common complication of preterm birth for infants born at fewer than 28 weeks’ gestation, as more and more newborns survive premature birth. Hence, the primer.

“The contributing authors are some of the biggest thinkers on this topic,” says Robin H. Steinhorn, M.D., senior vice president, Center for Hospital-Based Specialties, at Children’s National Hospital and author of the section about BPD diagnosis, screening and prevention. “This document will guide clinical education and investigators in the field of BPD. I anticipate this will be the definitive review article on the subject for the next several years.”

Gestational age and low birth weight remain the most potent predictors of BPD. Some 50,000 extremely low gestational age newborns are born each year in the U.S. About 35% will develop some degree of BPD, according to the primer authors.

These newborns are introduced to life outside the womb well before their lungs are ready. Indeed, the pulmonary surfactants needed for normal lung function – a complex mixture of phospholipids that reduce surface tension within the lungs – don’t differentiate until late in pregnancy. Infants who persistently need respiratory support after the 14th day of life are at the highest risk of being diagnosed with BPD at 36 weeks, the coauthors note.

A number of complicating factors can come into play, including maternal diet; fetal exposure to maternal smoking and infection; structural issues such as pre-eclampsia; acute injury from mechanical ventilation and supplemental oxygen; as well as the body’s halting efforts to repair injured, inflamed lung tissue.

“The good news is the number of the smallest and youngest preterm infants who survive extreme preterm birth has steadily increased. Neonatal intensive care units, like our award-winning NICU, now routinely care for babies born at 22 weeks’ gestation,” Dr. Steinhorn says.

Treatment strategies include:

  • Reducing exposure to intubation and ventilation.
  • Leveraging respiratory stimulants, like caffeine.
  • Postnatal steroid therapy.

“Children’s National Hospital is the only center in our immediate region that provides comprehensive care for infants and children with severe BPD,” Dr. Steinhorn adds. “As the population of vulnerable and fragile infants has grown, we have invested in the equipment and the personnel – including at the Hospital for Sick Children Pediatric Center (HSC) – to create a very safe and supportive environment that improves survival and quality of life.”

Some preterm infants spend their first 9 to 10 months of life at Children’s National, and their days are filled with concentrated physical, occupational and speech therapy, as well as music and play therapy to hasten their rehabilitation.

Once their medical condition stabilizes, they transition to HSC to focus more intently on rehabilitation.

“We see HSC as filling a very important role in their care. When our children graduate to HSC, they are going for ongoing care of their lung disease, but also their ongoing rehabilitation. At HSC, they focus on creating the most normal life that we can possibly create and, over time, that is a life free of ventilators and tracheostomy tubes.”

In addition to Dr. Steinhorn, BPD Primer co-authors include Bernard Thébaud, Children’s Hospital of Eastern Ontario; Kara N. Goss, University of Wisconsin-Madison; Matthew Laughon, The University of North Carolina at Chapel Hill; Jeffrey A. Whitsett and Alan H. Jobe, Cincinnati Children’s Hospital Medical Center; Steven H. Abman, Children’s Hospital Colorado;  Judy L. Aschner, Joseph M. Sanzari Children’s Hospital; Peter G. Davis, The Royal Women’s Hospital; Sharon A. McGrath- Morrow, Johns Hopkins University School of Medicine; and Roger F. Soll, University of Vermont.

Financial support for the research described in this post was provided by the National Institutes of Health under grant Nos. U01HL122642, U01HL134745, RO1HL68702, R01HL145679, U01HL12118-01 and K24 HL143283; the Australian National Health and Medical Research Council; the Canadian Institute for Health Research; Stem Cell Network and the Ontario Institute for Regenerative Medicine.

newborn baby

Directly measuring function in tiny hearts

newborn baby

The amount of blood the heart pumps in one minute can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates the first clinical study of direct cardiac output measurement in newborns.

The amount of blood that the heart pumps in one minute (cardiac output) can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates a paper published online Dec. 17, 2019 in the Journal of Pediatrics and Neonatal Medicine. The research, conducted by Children’s National Hospital faculty, is believed to be the first clinical study of direct cardiac output measurement in newborns.

Right now, cardiac output is measured indirectly in the nation’s neonatal intensive care units (NICU) using newborns’ blood pressure, heart rate, urine output and other indirect measures. However, these techniques can produce imprecise readings in children. And the field lacks a feasible “gold standard” to measure cardiac output in newborns.

The COstatus monitor already uses ultrasound dilution – the expected decrease in the velocity of blood when saline is injected, producing a dilution curve. A Children’s National research team used ultrasound dilution in their small pilot study to gauge the feasibility of directly measuring cardiac output in newborns.

“Infants who stand to benefit most from directly monitoring cardiac hemodynamics are often so sick they already have central venous access,” says Khodayar Rais-Bahrami, M.D., an attending neonatologist at Children’s National and the study’s senior author. “Using the COstatus monitor in these children would enable the clinical team to personalize care based on the newborn’s current hemodynamic status, while introducing minimal fluid during measurements,” Dr. Rais-Bahrami adds.

COstatus monitor

The COstatus Monitor uses an extracorporeal loop attached to arterial and venous lines to measure cardiac output using ultrasound dilution. The research team injected 1mL/kg of body temperature saline into the loop and performed up to two measurement sessions daily.

The research team recruited 12 newborns younger than 2 weeks old who already had central venous and arterial access. The venous line of the arteriovenous AV loop is connected to the umbilical venous catheter while the COstatus monitor’s arterial line is connected to the umbilical arterial catheter. During measurement sessions, two injections of solution are injected into the venous loop, allowing for two measures of cardiac output, cardiac index, active circulating volume index, central blood volume index and systemic vascular resistance index.

Infants enrolled in the pilot study underwent up to two measurement sessions per day for up to four days, for a total of 54 cardiac hemodynamic measurements. The newborns ranged from 720 to 3,740 grams in weight and 24 to 41.3 weeks in gestational age.

The infants’ mean cardiac output was 0.43L/min and increased with gestational age. By contrast, the mean cardiac index was 197mL/kg/min and changed little with infants’ increasing maturity – either by gestational age or postnatal age. Two of the study participants were undergoing therapeutic cooling for hypoxic-ischemic encephalopathy and had their measurements taken during cooling and after rewarming.

“Although this study size is small, it demonstrates that this minimally invasive technique can safely be used in newborns to directly measure cardiac hemodynamics,” says Simranjeet S. Sran, M.D., a Children’s National neonatalogist and the study’s lead author. “This technology may allow for more precise and personalized care of critically ill newborns in a range of disease states – real-world utility in NICUs that serve some of the youngest and sickest newborns,” Dr. Sran adds.

The research team notes that direct measurement by ultrasound dilution revealed a stark increase in cardiac index as infants undergoing therapeutic hypothermia were rewarmed, raising questions about whether indirect measures using other technology, such as echocardiography, underestimate hypothermia’s effect on hemodynamics.

In addition to Drs. Rais-Bahrami and Sran, Mariam Said, M.D., also a Children’s National neonatalogist, was a study co-author.