Researchers Examine Obesity, Cardiovascular Risks in Down Syndrome

Children with Down syndrome (also known as Trisomy 21) are prone to obesity. Their families may be concerned about their future risks for cardiovascular problems as well as their quality of life.

Although Down syndrome is the most common chromosomal anomaly in humans, affecting about 5,000 babies born each year and more than 350,000 people in the U.S., the population is understudied, according to Andrea Kelly, MD, MSCE, an attending physician in the division of Endocrinology and Diabetes at The Children’s Hospital of Philadelphia, and Sheela N. Magge, MD, MSCE, director of research in the division of Endocrinology and Diabetes at Children’s National Health System.

They are both principal investigators of a multidisciplinary team — including experts in pediatric growth and metabolism, psychology, cardiology, and statistics — that is studying body composition measures and cardiometabolic risk factors in 150 adolescents with Down syndrome and in a matched control group.

In the typically developing pediatric population, body mass index (BMI, a calculation based on weight and height) is the standard way in the U.S. to screen for obesity. If a child or teen’s BMI is high, it could be an indicator of higher risk for certain health problems such as heart disease, high blood pressure, and type 2 diabetes. Yet, the usefulness of BMI in individuals with Down syndrome is not known in that it might not be appropriate as a one-size-fits-all marker for obesity.

“Children and adults with Down syndrome tend to have short stature,” Dr. Kelly said. “We don’t know if BMI truly reflects body fat or adiposity in a group with altered body proportions. We wanted to explore that a little bit more, especially since older data suggested they might be protected from cardiovascular disease.”

The first-ever BMI charts for children with Down syndrome became available in the fall based on previous research conducted at CHOP by Babette Zemel, PhD, (also a co-investigator on the current study). The charts do not represent an ideal distribution of BMI, but only describe BMI distribution among the study participants. The current investigations should help to put these charts into better context and will compare them to the Centers for Disease Control and Prevention’s BMI charts, in order to give clinicians more guidance on how to screen patients with Down syndrome for excess body fat and associated health symptoms.

The study team aims to determine if BMI is the best way to define obesity in teens with Down syndrome or if there is another measure of body composition that could better predict cardiovascular and metabolic risk in this patient population. For example, the researchers are performing dual-energy X-ray absorptiometry scans to estimate study participants’ body fat. They also are looking at novel markers of cardiometabolic risk by performing subparticle analysis of the participants’ lipids and blood sugars. And they are using technology called pulse wave velocity to assess cardiac end organ injury.

“We are exploring these traditional and novel markers because if children with Down syndrome and obesity need to be more aggressively managed, we need to pay attention to that,” said Dr. Kelly, who also is an associate professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

Based on pathology studies conducted in the late 1970s, a belief that individuals with Down syndrome are protected from cardiovascular disease has persisted. But more recent research has contradicted this theory, suggesting that death from cardiovascular disease was more than six times great in the Down syndrome population, Drs. Kelly and Magge pointed out.

In addition to taking a comprehensive look at the relationship between BMI and cardiovascular risk factors, the study team wants to know more about the teens’ perceptions of their quality of life and if families identify any barriers to promoting exercise and a healthy lifestyle for their children with Down syndrome. The study participants will wear an armband accelerometer that monitors their physical activity for a week.

Eventually, the investigators hope to use this research to build a foundation for future weight loss interventions and prevention programs that are targeted to pediatric populations with special needs.

“We’d like to work with the study team and ask, how can we prevent this from happening?” Dr. Kelly said. “Most families are very aware that their children are at risk for gaining excess weight, but we don’t know the best way for them to minimize that risk.”

At a Trisomy 21 Research Initiative meeting in October, Drs. Kelly and Magge gave an update on their research project to colleagues from the Intellectual and Developmental Disabilities Research Center at CHOP and Penn as well as other investigators from Kennedy Krieger Institute, Boston University, and University of California, Irvine. This meeting fostered a dialogue between these institutions and examined the Trisomy 21 research being done, in order to find potential extensions or amplifications of this work.

For more information on the IDDRC, contact Kristen Hearty at heartyk@email.chop.edu.