Response to Zhang et al.

We appreciate the thoughtful comments by Zhang and colleagues¹ regarding our article “Detection of iron deficiency in children with Down syndrome.”² We agree that ferritin, while a useful measure for identifying iron deficiency/iron deficiency anemia, can be elevated in the setting of comorbidities.³ Therefore, the interpretation of its value needs to be considered in the context of the child’s whole medical history and evaluation. Similarly, comorbidities such as malnutrition may falsely lower serum transferrin.⁴ As noted in our paper, we agree that bone marrow evaluation is the gold standard for evaluating iron stores, but this is invasive and not practical. At our institutions, we do make use of soluble transferrin receptor measurement to help distinguish iron deficiency anemia versus anemia of chronic disease. To be cost-efficient these measures are not obtained on all patients, but are introduced in a tiered evaluation as needed. We agree that many other factors can affect red cell distribution width (RDW); however, similar to the utility of ferritin, the RDW value needs to be considered in the setting of the child’s entire medical history and condition.

In summary, through our investigation of a large number of individuals with Down syndrome at multiple different institutions, we provide evidence to support a systematic approach of laboratory testing and clinical follow up. However, for children with comorbidities, referral to a provider with expertise in hematology, including review of the peripheral blood smear and a trial of iron replacement over time, can help clarify the extent, etiology, and management of an individual’s iron deficiency and iron deficiency anemia. Further research will help to parse out the contributions of nutrition, infection, autoimmunity, metabolic diseases, antibiotic usage, and other variables in children with Down syndrome and iron deficiency/iron deficiency anemia.