'Groundbreaking' Lifespan Data to be Developed with Down Syndrome Community

The Down Syndrome Research Group will embark on the largest Down syndrome study to date to collect data across the lifespan.

The Down Syndrome Research Group at Children's Hospital of Philadelphia is working with families in the Down syndrome community and collaborating institutions to collect valuable lifespan data, supported by more than $2 million in funding from the National Institutes of Health (NIH). The data will help advance research on how co-occurring conditions, social determinants of health, and ableism affect youths with Down syndrome.

"The goal of this research is to improve the health and well-being of children and adults with Down syndrome," said Mary Pipan, MD, a developmental behavioral pediatrician and Director of the CHOP Trisomy 21 Program. "Families come to our clinic so they can be sure they are doing everything possible to help their children live their best lives and flourish as members of their community. This research will help them in this endeavor."

As part of the INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Down Syndrome Cohort Development Program, researchers will gather data from medical records reviews, blood samples, and endocrine, nutrition, sleep, and neurocognitive evaluations to determine how these factors affect the medical and social health of patients in the Down syndrome community. Qualitative interviews and questionnaires will help researchers understand ethical situations that people with Down syndrome face, especially in terms of their involvement with decision-making and ableism.

"Some patients have historically been excluded from participating in certain studies due to concerns about their abilities to tolerate the procedures, but in reality, individuals with Down syndrome are capable of so much," said Andi Kelly, MD, MSCE, lead principal investigator and leader of the Down Syndrome Research Group at CHOP. "Feedback from the Down syndrome community has been invaluable for informing our next steps."

Mary Pipan, MD, (left) has helped organize the CHOP Buddy Walk since 2002.

Dr. Pipan's work through the Trisomy 21 Program and CHOP's Buddy Walk® fundraising event has fostered strong relationships between CHOP and families in the Down syndrome community that will lay the foundation for close partnership in future research. Dr. Kelly and colleagues will meet with a community advisory panel to create consent forms and a website that will be inclusive of learning differences and intellectual disabilities to optimize participants' understanding of what researchers are asking of them before making decisions to join the research study.

Melissa S. Xanthopoulos, PhD, MS, a psychologist in the Department of Child and Adolescent Psychiatry and Behavioral Sciences and the Sleep Center at CHOP, also develops storyboards that help explain research activities. Feedback collected from patients and families lets researchers understand how well a child is prepared to engage in research and if procedures could be made more accessible if facilitated by behavioral interventions.

For example, Drs. Xanthopoulos and Kelly previously found that at-home sleep assessments could reduce the potential burden and anxieties around sleeping in-hospital, making treatment more tolerable for patients. This finding was made in collaboration with Sleep Center Director Christopher Cielo, DO, who shared his expertise in obstructive sleep apnea, a condition for which individuals with Down syndrome are at higher risk.

From left to right, Andi Kelly, MD, MSCE; Christopher Cielo, DO; Melissa Xanthopoulos, PhD, MS.

In tailoring the assessments to better serve the population they want to help, the research team anticipate these modifications could lead to more participants and thus greater efforts to address obstructive sleep apnea in children with Down syndrome. Future studies could determine if treatment of obstructive sleep apnea and disrupted sleep could improve learning development, decrease behavior issues, and reduce dementia risk.

"This funding mechanism provides an opportunity to build on some of these projects with many more sites, so the impact can grow exponentially," Dr. Cielo said. "The foundational work that's been done at CHOP will find its way into this much larger program to help the Down syndrome community across the country and internationally."

CHOP researchers will work closely with external collaborators such as Sheela Magge, MD, MSCE, Director of the Division of Pediatric Endocrinology at Johns Hopkins, and Maria Sukie Rayas, MD, from the University of Texas Health Science Center at San Antonio. They are joined by a former CHOP physician Ignacio Tapia, MD, MS, who is now the Chief of the Division of Pediatric Pulmonology at the University of Miami Miller School of Medicine. Dr. Tapia and Dr. Rayas are looking forward to the opportunity to engage Spanish-speaking Down syndrome community members.

The medical phenotyping data generated by this study will be stored in the Crnic Institute Human Trisome Project®, a biobank with multi-omic capabilities spearheaded by Joaquin Espinosa, PhD, at the University of Colorado Anschutz Medical Campus, and will also be available through the INCLUDE Data Coordinating Center, managed by CHOP's Center for Data-Driven Discovery in Biomedicine. This NIH-funded study will be the largest Down syndrome study to date and will include infants through adulthood. Dr. Kelly and colleagues will focus specifically on pediatrics and young adults, and they anticipate the data will be useful in answering questions on how to improve quality of life across the lifespan.

Interactive data in one location could eventually help clinicians and general pediatricians link certain behavioral outcomes to clinical conditions, which would then point to different treatment options that may not have been considered previously.

"We don't have answers to so many questions," Dr. Xanthopoulos said. "We have hypotheses, but to be able to look at these data over the lifespan is going to be groundbreaking."