Caregiver signaling questions in sickle cell disease

In this issue of Blood Advances, Dandar et al¹ have provided important data about school-age children that can assist sickle cell disease (SCD) health care providers in implementing the American Society of Hematology (ASH) 2020 guidelines for the prevention, diagnosis, and treatment of cerebrovascular disease.² Although developmental delays and disorders can occur for a variety of reasons, there is an elevated rate of these conditions in SCD due, in part, to SCD-related impacts on the central nervous system beginning in childhood.^2,3 The 2020 guidelines recommend that clinicians supervising the care of children with SCD conduct surveillance (using simplified signaling questions) to detect indicators of developmental delays in preschool-age children and concerns about neurodevelopmental or neurocognitive disorders in school-age children to support early identification and intervention.

There are significant empirical data and clinical experience to inform developmental surveillance in preschool-age children with extensive online resources available from the American Academy of Pediatrics (AAP) to guide clinicians.⁴ Empirical guidance on the most effective surveillance approaches in school-age children, particularly data specific to SCD, is much further behind that of preschool-age children. This is problematic because the risk of neurocognitive deficits increases with age in SCD,² meaning that surveillance for these concerns is needed across the life span. Dander et al demonstrated at least 2 key findings among children aged 8 to 17 years. First, the authors identified specific questions for parents related to learning and school performance that were useful for identifying children who showed neurocognitive deficits on formal testing. Although the individual signaling questions showed somewhat weaker sensitivity than would be desired as a stand-alone surveillance approach, if used as a set of questions, parents who endorsed any 2 of these questions about their child showed >80% sensitivity for significant cognitive impairment (see Dander et al, Figure 1). Additional studies and data will be important for improving our knowledge of how to best conduct surveillance in school-age children, but this is a good start to having empirically supported and SCD-specific surveillance approaches for this age range.

Surveillance methods represent relatively low-resource ways to identify children at higher risk, but formal cognitive testing is considered the gold standard for detecting neurocognitive deficits. In the data presented by Dander et al, the accuracy of the signaling questions is still low enough that many children with mild or significant cognitive impairment would be missed if this were the only approach used. A combination of surveillance at routine medical visits and intermittent formal screening for school-age children, when feasible, is likely to be superior to surveillance alone as has been found with preschool age children.⁵ As shown by Dander et al, the overall rates of mild and significant cognitive impairments were high and increased over time, with over half of the sample showing mild cognitive impairment and over one-fourth showing significant cognitive impairment. This highlights the need for surveillance and/or screening to identify this morbidity as early as possible, given the high proportion of children affected and the greater benefit of interventions delivered earlier in life.^6,7 It is likely that many of the children identified in the study by Dander et al had indicators of developmental concerns earlier in life that could be detected before school age,⁸ reinforcing the need for a life span approach. It is important to note that although ASH currently recommends screening following abnormal surveillance, screening can be bypassed for formal evaluation in situations in which the patient’s functional complaints indicate a high risk for cognitive impairment.² Many sickle cell providers, however, face challenges with wait times and access to cognitive evaluation services,⁹ which poses a challenge to the clinical process for cases with abnormal surveillance or other indicators of high risk. Developing sources for prompt referrals and access to evaluation and intervention (such as through outpatient therapies and school) are important considerations.

A notable methodological facet of the study by Dander et al is that surveillance questions were asked as part of a clinical interview, which is consistent with the recommendations for early childhood surveillance provided by the AAP.⁴ The AAP emphasizes surveillance is done best as a conversation between clinicians and parents. It is unknown whether the signaling questions evaluated in this study work similarly if done as part of written questionnaires. In our evaluation of preschool-age screening in SCD, we found that parent concerns elicited through a brief interview were more sensitive to delays found on formal screening than concerns elicited through written questions.¹⁰ 

Taken together, the work of Dander et al presents an important advancement in how to conduct empirically informed surveillance for school-age children with SCD. Health care providers supporting individuals with SCD are strongly encouraged to implement this guideline-based, low-resource method of detecting cognitive impairment.

Conflict-of-interest disclosure: The authors declare no competing financial interests.