Identifying early intervention strategies for sickle cell disease

King's NIH grant addresses barriers to early intervention  

by Stephanie Stemmler • September 27, 2022

Allison King, MD, PhD, and Elizabeth Taaffe (standing), clinical research coordinator for the Child Health and Education Laboratory, review study requirements and progress with a research participant.

 

Pediatric hematologist/oncologist Allison King, MD, MPH, PhD, is using her expertise in neurologic and cognitive functioning to redefine early intervention strategies for children with chronic diseases, particularly sickle cell disease (SCD).

King, a professor of occupational therapy, medicine, pediatrics, surgery and education in the Washington University Program in Occupational Therapy, studies how such diseases alter cognition and then how the environment influences early childhood development and participation.

“I want to know why children with SCD often have cognitive deficits and then identify ways to mitigate those deficits as they grow older,” she says.

Her decades-long research has resulted in growing awareness of the benefits of early screening and intervention services for children with sickle cell disease (SCD). This year, Tennessee’s Department of Education and Department of Intellectual and Developmental Disabilities added SCD to their list of pediatric conditions covered by early intervention services. State officials noted that the addition was prompted, in part, because of ongoing research by King and her colleagues. Now, King is using a $561,321 grant from the National Institutes of Health (NIH) to address barriers to early intervention as well as to create and improve developmental screening tools for children with SCD.

Prevalence

An estimated 2,000 children are born in the United States with SCD each year, making it the most common inherited blood disorder. Children with the disease often develop chronic anemia and have a higher risk for strokes and cognitive deficits.

Medically, researchers have addressed the issue of stroke risk and the link to cognitive problems. Numerous studies have found that silent strokes are a primary contributor to cognitive deficits in children with SCD. While the U.S. National Heart, Lung and Blood Institute has guidelines to support transcranial Doppler screening of children with SCD to check for hidden strokes, guidelines for cognitive screenings are not readily in use.

“The need for these screening tools is critical because half of all preschool-aged children with SCD have developmental delays,” stresses King. “We need to have protocols or a systemic method to assess young children and then offer evidence-based interventions that will ameliorate these deficits so that the children will be on par with their peers when they enter grade school.”

King’s work in the mechanisms behind SCD and its impact on early childhood development began while she was in medical school at the University of Missouri-Columbia. There, during an elective pediatric neurology rotation, she saw firsthand the benefits of rehabilitation in treating patients with neurologic deficits. She also helped to care for many children with SCD. She then transitioned to Washington University School of Medicine to complete a residency in pediatrics and a fellowship in pediatric hematology and oncology. Here, she connected and conducted clinical research with Michael DeBaun, MD, MPH, a renowned researcher who led a large, NIH-sponsored, international clinical trial in SCD. Called the Silent Cerebral Infarct (SIT) Multi-Center Trial, the groundbreaking study found that regular blood transfusions significantly reduced the recurrence of strokes in children with sickle cell anemia.

During that study, King pursued her own questions about cognitive delays and educational attainment, wondering if the deficits were caused by the disease itself or an environmental factor, such as poverty, stress, or lack of access to social and educational services. That research, subsequently published in the American Journal of Hematology in 2014, found that household per capita income is more associated with grade retention than is the presence of a silent stroke in children with SCD. The results showed her that both medical and educational interventions were needed to ensure that children with SCD could “catch up” developmentally with their peers when they entered school.

Joining the faculty at WashU, King used her first career development award to conduct cognitive assessments on children with SCD who did not have a history of stroke. She also reached out to Parents as Teachers, a local (now global) organization that works with school districts to support and provide resources to parents to enhance engagement and early learning. When some school districts started cutting back on the program, King applied for a grant from the U.S. Department of Health and Human Services to open WashU’s own Parents as Teachers service. “We launched it and approached families of children who were less than 3 years old,” King explains. “We did developmental testing at the beginning and end of their participation in the program and found that home visitations and the resources we provided dramatically increased cognitive development by half of a standard deviation point, which was significant.” It was this research that ultimately prompted the state of Tennessee to include early education intervention for children with SCD.

King now has multiple collaborators working with her to standardize a screening tool and referral process. They include school districts and colleagues from occupational therapy, neurology, pediatrics, public health, education, social work and psychology. Already, she and her team have surveyed almost 100 pediatricians in the region to find out how and when children with SCD are being screened for developmental delays. “In addition to the NIH grant to identify barriers and develop new screening tools, I have a separate grant that will allow us to build relationships and offer training and education within school systems,” she says. “The reality is that sickle cell is an invisible condition. Unless someone chooses to share that they or their child has the disease, no one really knows if you have it, so teachers may not consider a cognitive deficit versus a behavior problem.”

She adds, “We can’t be so myopic to think about this just as a blood disorder. By working on the factors that drive cognitive delays and creating evidence-based early intervention strategies, we can give kids the best opportunity to succeed.”