Detection of iron deficiency in children with Down syndrome

Genet Med. 2020 Feb;22(2):317-325. doi: 10.1038/s41436-019-0637-4. Epub 2019 Aug 16.


Purpose: Current American Academy of Pediatrics guidelines for children with Down syndrome (DS) recommend a complete blood count (CBC) at birth and hemoglobin annually to screen for iron deficiency (ID) and ID anemia (IDA) in low-risk children. We aimed to determine if macrocytosis masks the diagnosis of ID/IDA and to evaluate the utility of biochemical and red blood cell indices for detecting ID/IDA in DS.

Methods: We reviewed data from 856 individuals from five DS specialty clinics. Data included hemoglobin, mean corpuscular volume, red cell distribution width (RDW), percent transferrin saturation (TS), ferritin, and c-reactive protein. Receiver operating characteristic curves were calculated.

Results: Macrocytosis was found in 32% of the sample. If hemoglobin alone was used for screening, all individuals with IDA would have been identified, but ID would have been missed in all subjects. RDW had the highest discriminability of any single test for ID/IDA. The combination of RDW with ferritin or TS led to 100% sensitivity, and RDW combined with ferritin showed the highest discriminability for ID/IDA.

Conclusion: We provide evidence to support that a CBC and ferritin be obtained routinely for children over 1 year old with DS rather than hemoglobin alone for detection of ID.

Keywords: Down syndrome; iron deficiency; iron deficiency anemia; macrocytosis; trisomy 21.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / diagnosis
  • Anemia, Iron-Deficiency / diagnosis*
  • C-Reactive Protein / analysis
  • Child
  • Child, Preschool
  • Down Syndrome / metabolism*
  • Erythrocyte Indices / genetics
  • Erythrocytes, Abnormal / metabolism
  • Female
  • Ferritins / analysis*
  • Ferritins / blood
  • Hematologic Diseases / metabolism
  • Hemoglobins / analysis
  • Humans
  • Infant
  • Iron / metabolism
  • Male
  • Mass Screening / methods
  • ROC Curve


  • Hemoglobins
  • C-Reactive Protein
  • Ferritins
  • Iron

Supplementary concepts

  • Macrocytosis, Familial