Measuring neurodevelopment in iron-deficient children in sub-Saharan Africa: A systematic review of evidence and gaps.

Anemia and iron-deficiency anemia are prevalent in sub-Saharan Africa (SSA) and linked to impaired brain and developmental outcomes. Progress in understanding these effects is constrained by inconsistent developmental measurement and minimal neuroimaging. This review evaluated how brain growth, cognition, and developmental status have been measured among children under five exposed to anemia, iron deficiency (ID), or iron-deficiency anemia (IDA) in SSA, to assess the availability, reliability, and limitations of neurodevelopmental measurement approaches and implications for comparability and interpretation. A systematic review (PROSPERO CRD42024529208) was conducted following PRISMA guidelines. Six databases were searched for English-language studies published between Jan 1, 2013, and Apr 30, 2024, aligning with the WHO 2013-2025 global nutrition targets. Eligible studies included children aged 0-5 years in SSA exposed to anemia, ID, or IDA and reporting neurodevelopmental outcomes. Findings were synthesized narratively to characterize measurement heterogeneity, reliability reporting, and neuroimaging use. Evidence quality was appraised narratively based on study design and reporting completeness. Of 2254 records screened, 19 studies from nine countries met inclusion criteria. Fourteen studies assessed developmental status, 13 assessed cognition, and only three measured brain outcomes using MRI or near-infrared spectroscopy. Substantial heterogeneity in measurement constructs, assessment tools, cultural adaptations, scoring approaches, and timing of assessment precluded quantitative meta-analysis. Reliability reporting was limited, with psychometric indices reported in seven of 14 developmental studies and nine of 13 cognitive studies. Only three studies incorporated direct measures of brain structure or function, limiting opportunities to relate behavioral outcomes to brain development. Marked measurement heterogeneity, sparse reliability reporting, and the near-absence of neuroimaging constrain epidemiological inference, cross-study comparability, and mechanistic understanding of neurodevelopmental outcomes associated with anemia and ID in SSA. Strengthening culturally grounded assessment frameworks and more equitable, accessible approaches to objective brain measurement are priorities for improving measurement precision and understanding iron-related developmental outcomes.