Delayed iron does not alter cognition or behavior among children with severe malaria and iron deficiency

Andrew S. Ssemata, Meredith Hickson, John M. Ssenkusu, Sarah E. Cusick, Noeline Nakasujja, Robert O. Opoka, Maria Kroupina, Michael K. Georgieff, Paul Bangirana, Chandy C. John

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition. Methods: In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment. Results: All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 μmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from −0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06). Conclusions: Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up. Impact: The optimal time to provide iron therapy in children with severe malaria is not known. The present study shows that delay of iron treatment to 28 days after the malaria episode, does not lead to worse cognitive or behavioral outcomes at 12-month follow-up.The study contributes new data to the ongoing discussion of how best to treat ID in children with severe malaria.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalPediatric Research
Issue number3
StatePublished - Sep 1 2020

Bibliographical note

Funding Information:
We thank the study participants, their families, and the study team, including clinical officers, nurses, laboratory technologists, and data entry personnel. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (grant number 3U01HD064698) and the Fogarty International Center (grant number D43 NS078280).

Publisher Copyright:
© 2020, International Pediatric Research Foundation, Inc.


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