WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.

koakes@mdedge.com

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