Clinical Spotlight: Cardiac Neurodevelopmental Program

As survival has improved dramatically for children with even the most serious forms of heart disease, neurodevelopmental disabilities have been increasingly recognized. These can affect not only school performance, but also future employment, quality of life and social relationships.

Now in its 8th year, the Heart Center’s Cardiac Neurodevelopmental Program (CNP) continues to lead the field in both research and clinical operations. Janice Ware, PhD, Medical Director of the CNP, describes it as a specialized clinical program providing comprehensive neurodevelopmental evaluation and short-term behavioral treatment to children from birth to 24 years with congenital heart disease (CHD) and other severe heart conditions.  Examples include:

  • Complex congenital heart disease, repaired and unrepaired, with and without associated genetic syndromes
  • Cardiomyopathy and other forms of severe acquired heart disease
  • Pre- and post-cardiac transplant

The CNP’s clinical services are provided by a multidisciplinary team of specialists in cardiology, cardiovascular genetics, neurology, neuropsychology, nursing, psychology, and special education. The program emphasizes earliest possible detection of developmental problems in order to maximize each child’s developmental potential. CNP provides unique continuity of follow-up from infancy to early adulthood.

“Our work emphasizes collaboration and coordination with pediatric cardiology care teams, primary care pediatricians, medical specialty providers, early intervention program staff, schools and special education teams, and local behavioral health providers,” says Ware.

The CNP is designed to complement ongoing services, not replace them. As Ware explains, “Our goal is to supplement current developmental and educational practices with input from clinicians who have specialized training and experience in caring for children with severe CHD.”

Innovating in research and clinical practice

The CNP developed as a natural evolution of the landmark research conducted here at Children’s by cardiologist Jane Newburger, MD, and developmental neuropsychologist David Bellinger, PhD. Over the past 25 years, Newburger, Bellinger, and their colleagues have extensively studied the development of children with many different forms of CHD. Their work has produced characteristic profiles of these children. These “developmental signatures” represent recognized neurodevelopmental patterns that serve as universal guides to the medical, developmental and educational needs of children with early histories of CHD.

Since the  inception of the Boston Children’s CNP in 2008, nearly two dozen new cardiac neurodevelopmental programs have been established at other institutions in the U.S., Canada and abroad. The programs work together through a newly established Cardiac Neurodevelopmental Outcomes Collaborative, a clinical research consortium that will conduct multi-site studies and share data resources. Children’s staff psychologist Anjali Sadhwani, PhD, biostatisticians Christian Stopp, MS, and David Wypij, PhD, and research nurse Carolyn Dunbar-Masterson, MS, have developed and implemented a detailed database that is being used as a model for replication by the national consortium.

CNP research interests include the work of pediatric neurologist Caitlin Rollins, MD. Rollins is focusing her research on prenatal identification of early brain injury in fetuses with CHD, through the use of fetal brain imaging technology. The CNP cardiovascular geneticist, Amy Roberts, MD, is leading efforts to recognize genetic links to cardiovascular conditions associated with neurodevelopmental disabilities.

In addition to laboratory research, the CNP is focused on developing innovative treatment programs for its patients.


  • Samantha Butler, PhD, and Jayne Singer, PhD, CNP staff psychologists, designed a model of neurobehavioral consultation services for CNP’s youngest patients on the Cardiology Inpatient Service prior to hospital discharge. The care model focuses on helping parents address the frequent feeding and sleeping problems that develop after hospital discharge.

School-age children

  • Johanna Calderone, PhD, CNP Psychology Research Fellow, is working with school age children with CHD to test the effectiveness of a specialized cognitive behavioral treatment approach in remediating the frequently observed attention and executive function deficits in the CNP patient population.
  • CNP clinical services for children 6 months to 24 years are provided at both our Boston location and our Waltham site. CNP will extend clinical services using an Integrated Health Care model by incorporating Brandi Henson, PsyD, CNP staff psychologist, into the Child Heart Associates pediatric cardiology practice in Worcester, MA. Henson’s work will include parent and staff consultation services as well as the start-up of parent psycho-educational groups to address typical child behavior and special education concerns often seen in the pediatric CHD population.

Teens and young adults

  • CNP support of older patients includes an initiative with Michelle Gurvitz, MD, cardiologist in the Boston Children’s Hospital Adult Congenital Heart (BACH) group. CNP staff members are working with Gurvitz to help young adults with CHD to transition from pediatric services into adult care.

Genetics research uncovers clues in the codes

Exactly why some children with complex CHD develop neurodevelopmental delays is still somewhat a mystery. “There are multiple hypotheses, and they’re not mutually exclusive,” says Amy Roberts, MD, a genetic cardiologist at the Boston Children’s Hospital Heart Center.

The side effects of surgery, such as oxygen deprivation during bypass, are commonly thought to be to blame. Others suspect problems with the in utero environment. But these factors are not the whole story.

“Even in studies that have measured every known risk factor, only one third of neurodevelopmental disabilities in children with CHD can be explained by factors related to the child’s heart disease, medical history or family factors,” notes Jane Newburger, MD, MPH, director of the Cardiac Neurodevelopment Program at Boston Children’s.

Perhaps there is a genetic component?

In a recent study published in Science, a team of researchers from seven hospitals (Boston Children’s, Brigham and Women’s Hospital, Children’s Hospital of Philadelphia, Columbia, Mount Sinai, Yale and University of California Los Angeles), examined the whole genomes of 1,213 patients with complex CHD, looking for genetic indicators that a child will have developmental delays alongside his or her CHD.

The group focused on “de novo” mutations, or mutations that are not inherited. Their question: Is there a difference in the rate of de novo variants in patients with and without CHD?

To find out, the researchers looked at de novo variants in genes that contribute to heart and brain development.  These genes are referred to as “high heart” and “high brain” genes.  Roberts also calls them “master regulators,” because they have widespread effects on the body’s most vital organs.

CHD patients with de novo variants in these genes exhibited more developmental delays than CHD patients without those variants.

Roberts emphasizes that genetic factors may not only contribute to neurodevelopmental disabilities by affecting brain structure and microstructure, but also may influence the body’s response to the stresses of heart disease. For instance, there might be genetic variants that make children better or less able to tolerate oxygen deprivation or anesthesia.

“We can’t yet tell individual patients whether or not they will suffer developmental delays based on genetic factors,” says Roberts. “But in the future, we’d like to be able to tell parents if their child is in the low, medium or high risk group.”

What’s next?

In the next stage of this research, a subgroup of patients who took part in the first study, and thus have had their genome sequenced, will be evaluated by MRI and specific tests for cognitive function. The results will be analyzed to uncover any patterns that point to potential genetic indicators for developmental issues. Newburger is national co-chair for this study, which is a joint endeavor of the Pediatric Cardiac Genetics Consortium (PCGC) established by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

“This is a very exciting time,” Roberts says. “We’re using a much more advanced approach than before.  It’s a genome-wide analysis, so the research is looking at all of a patient’s genes, not just a few. And it’s a large group of subjects; patient data are compiled from five-partner institutions across the country. We’re in the beginning stages of some very ambitious research.”

Additional information about CNP and its services in Boston, Waltham, or at the new site in Worcester can be obtained by contacting CNP Director, Janice Ware, PhD, at 617-355-5721 or by calling CNP Program Coordinator, Donna Donati at 617-355-3401 for intake and patient enrollment information.

For additional information on how to refer patients, please visit the Cardiac Neurodevelopmental Program webpage.

*The published study was supported by the National Heart, Lung and Blood Institute (NHLBI) and, in Boston, by the Kostin Family Innovation Fund (other centers had other grant sources). The ongoing work is supported by the NHLBI and the National Institute of Child Health and Human Development and, in Boston, by the Kostin Family Innovation Fund.