Studies Focus on Optimizing Pediatric Care from Birth to Adulthood

Researchers share new findings on caring for preterm babies, children with cancer, and young people with sickle cell disease

(New Orleans, Dec. 12, 2022) – New research being presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition draws attention to previously overlooked issues in caring for babies and young people and sheds light on opportunities to improve the outlook for children with health challenges.

“These studies can inform ways to help children live long and healthy lives,” said press briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National in Washington, DC. “They will certainly be of interest to clinicians, and also to the families of children dealing with blood disorders or requiring special care.”

The first study expands the body of knowledge on long-term health outcomes of childhood cancer treatment, pointing to new opportunities for screening and early detection while underscoring the importance of finding gentler therapies that could help more children avoid these long-term health problems in the first place. In the second study, researchers report that preterm babies who are fed only formula show a higher risk of iron deficiency, suggesting that new guidance on feeding practices may be warranted to ensure all preterm babies maintain sufficient iron levels necessary for growth and development. The third study highlights how a data-sharing system could help people with sickle cell disease avoid dangerous blood transfusion complications and allow more young people to benefit from future curative therapies for this disease later in life.

Together, the studies highlight the challenges in and opportunities for improving care for babies and young people.

The press briefing will take place on Monday, December 12, at 12:00 noon Central time in press briefing room 346.

Study links accelerated aging in survivors of childhood Hodgkin lymphoma with neurocognitive impairment in middle age

902: Epigenetic Age Acceleration and Neurocognitive Function Among Long-Term Survivors of Pediatric Hodgkin Lymphoma: A Report from the St. Jude Lifetime Cohort

In a new study, people treated for Hodgkin lymphoma in childhood showed accelerated aging and had higher rates of neurocognitive impairment by their late 30s compared to their peers. The study analyzed “biologic age,” a marker of changes to gene expression that accrue over a person’s lifetime, based on the level of DNA methylation measured in blood samples. The findings suggest childhood cancer survivors may benefit from additional screening or interventions to mitigate aging-related cognitive declines starting in early adulthood.

“We found that biologic aging is associated with long term neurocognitive impairment in Hodgkin lymphoma survivors,” said AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester School of Medicine and Dentistry in New York. “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”

The study involved nearly 500 participants in their late 30s; 215 were survivors of childhood Hodgkin lymphoma and 282 did not have cancer in childhood. Participants submitted blood samples and underwent a series of validated neurocognitive tests to assess attention, processing speed, memory, and executive function.

Researchers found that the difference between biologic age and chronologic age was on average 7.7 years greater among Hodgkin lymphoma survivors compared with the control group, suggesting that their cancer or cancer treatment prematurely accelerated their aging. Overall, more than 80% of Hodgkin lymphoma survivors showed evidence of accelerated epigenetic aging compared with just 23% in the control group.

Among survivors of childhood Hodgkin lymphoma, those with more accelerated epigenetic aging performed significantly worse in terms of memory, learning, attention, and executive function compared with those who had less evidence of premature aging. Although the observed degree of impairment may not be readily apparent to friends or family members, researchers said it was clinically significant and could likely be noticed by the survivors themselves, in instances such as small lapses in memory.

“These types of memory issues are something people tend to notice first with aging-related disorders like Alzheimer’s and dementia,” said Dr. Williams. “I hope our study brings awareness to the fact that these underlying biologic changes are not only associated with heart disease and other chronic conditions that we have been aware of in survivors, but also with poor neurocognitive function.”

The association likely reflects the long-term effects of cancer treatments rather than the cancer itself, researchers said. They noted that treatment regimens used today are somewhat different from those several decades ago, so children currently being treated for cancer now may not necessarily develop the same degree of accelerated aging.

The researchers are continuing the study to examine changes over time. Other related studies are examining rates of early-onset dementia and Alzheimer’s disease in survivors of childhood cancer.

AnnaLynn M. Williams, University of Rochester School of Medicine and Dentistry, will present this study during an oral presentation on Monday, December 12, 2022, at 3:00 p.m. Central time in 291-292.

Formula-fed preterm babies are at a higher risk of iron deficiency than breastfed babies

3638: Formula Feeding Significantly Increases Risk of Iron Deficiency in Very Preterm Infants during the First 4-6 Months of Life

Among babies born before 31 weeks gestation (considered “very preterm”), those fed only with formula were more likely to have iron deficiency even though they had higher iron intake than babies who were breastfed, according to a study conducted in Canada. Iron deficiency in infancy is associated with cognitive, social, and emotional problems later in life.

“Just because a baby is on iron-rich formula, we should not assume all of their iron needs are being met, since iron from the formula may not have the same absorption as iron from breast milk,” said Grace Power, a third-year medical student at Dalhousie University in Nova Scotia, Canada. “These findings suggest we might need to rethink some of the guidelines for iron supplementation.”

Since formula contains more iron than breast milk, the Canadian Pediatric Society has issued guidance recommending iron supplementation for breastfed but not formula-fed preterm babies; however, to date there has been little research into how feeding type influences the iron stores in these babies. The American Academy of Pediatrics doesn’t offer guidance on iron supplementation in preterm babies with respect to the type of feeding.

For the study, researchers analyzed health records from 392 very preterm infants born in Nova Scotia from 2005-2018. Since all preterm babies born in the province are followed through a single medical center, the data set is considered to be representative of the general Canadian population in terms of patient demographics and health care protocols. About three-quarters were exclusively fed iron-rich formula and one-quarter were partially or exclusively breastfed. Researchers extracted data on feeding practices, iron intake from formula and iron supplements, and iron levels in the blood taken at four and six months of age (with ages corrected for prematurity by subtracting the number of weeks early each baby was born from its actual age).

The study revealed that babies who were exclusively formula-fed had a significantly higher daily iron intake than babies who were breastfed. Nonetheless, more than 36% of formula-fed babies and just over 20% of breastfed babies were iron deficient, suggesting that higher iron intake in formula does not always translate into higher iron stores in the blood.

Researchers said one likely explanation is that components of breast milk that are not found in formula, such as hormones, help to increase the absorption of iron into the baby’s bloodstream. Even consuming a mix of breast milk and formula was found to be protective, indicating that exclusive breastfeeding is not required for babies to derive this benefit. Formula-fed babies who were born earlier, those who were born smaller, and those who had received blood transfusions, were found to be at greater risk for iron deficiency than other formula-fed infants.

“We should not assume a one-size-fits-all approach to iron supplementation,” said Ms. Power. While more research is needed to inform future guidelines, in the meantime, Ms. Power suggested that preterm babies could benefit from closer monitoring, especially those who are exclusively fed formula. “If iron stores are checked in time and babies are regularly supplemented with iron as needed, we can still prevent iron deficiency.”

Too much iron can also be harmful, so researchers cautioned that careful monitoring is important to ensure the right balance. Future studies on the topic could help confirm the findings and inform future guidelines, researchers noted.

Grace Power, Dalhousie University, will present this study during a poster presentation on Monday, December 12, 2022, at 6:00 p.m. Central time in Hall D.

National system for sharing data from blood transfusions would save lives and money, according to projections

885: A US-Wide Red Blood Cell Alloantibody Exchange Can Decrease Mortality and Produce Cost Savings in the Care of Alloimmunized Patients with Sickle Cell Disease

Getting a blood transfusion can be life-saving, but it also carries the risk of a dangerous immune reaction, especially for people who have received a previous blood transfusion or have been pregnant. According to projections from a new study, establishing a central repository to share data on patients’ blood antibodies would not only significantly reduce the risks patients face but also cut health care costs by helping patients avoid prolonged hospitalization for serious transfusion complications.

“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, Yale University School of Medicine in Connecticut. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction, or DHTR.”

A DHTR occurs when transfused blood triggers an immune response in the days or weeks following a blood transfusion. It results from the presence of proteins called alloantibodies, which can circulate in the blood after a pregnancy or previous blood transfusion. Although rare, DHTRs can be fatal and often require prolonged hospitalization, making them burdensome for patients, families, and health systems.

To confirm that the blood selected for transfusion is likely to be safe for a patient and prevent DHTRs, doctors can check donated blood against the patient’s alloantibody profile. While the information needed to do this often exists, it is typically not shared between different health systems in the United States, leaving doctors to select blood without access to this critical information.

For the study, researchers used a computer simulation to estimate the costs and benefits of establishing a U.S. alloantibody exchange – a central repository for alloantibody data that doctors could access from any U.S. health care system. They estimated how such a repository would affect DHTR mortality and associated health care costs among people with sickle cell disease (SCD), who face a particularly high rate of DHTRs due to their relatively frequent need for blood transfusions. The results project that an alloantibody exchange would significantly reduce the cumulative lifetime risk of dying from a DHTR from 5.7% to 2.4% for people with SCD who have alloantibodies and bring a cumulative net savings of up to $1.5 billion over the lifetime of the population of such individuals in the U.S. today.

The study provides a conservative estimate of benefits since it did not account for benefits in people who require blood transfusions for conditions other than SCD. Researchers noted that an alloantibody exchange would also help to reduce health risks and care costs among other patient populations not included in the model, such as people who require blood transfusions during cancer treatment.

“It’s saying that we can do two things at the same time – we can save lives and save costs,” said Dr. Goshua, whose lab is the first in the U.S. focused on quantitative decision analytic modeling in classical (non-malignant) hematology. “It should be a no-brainer.”

The researchers also found their model’s calculations were comparable to the demonstrated benefits of a real-world alloantibody exchange in the Netherlands, offering further validation of the study findings.

George Goshua, MD, MSc Yale University School of Medicine, will present this study during an oral presentation on Monday, December 12, 2022, at 3:15 p.m. Central time in New Orleans Theater C.

Additional press briefings will take place throughout the meeting on health equity, advances in blood cancer research and care, novel drug development, and selected late-breaking abstracts. For the complete annual meeting program and abstracts visit www.hematology.org/annual-meeting. Follow ASH and #ASH22 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2022 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH’s flagship journal, Blood (www.bloodjournal.org), is the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), is the Society’s online, peer-reviewed open-access journal.

Contacts:

Leah Enser, ASH, [email protected]
Kira Sampson, ASH, [email protected]
Brianne Cannon, FleishmanHillard, [email protected]