Antenatal maternal anaemia and infant brain structure: high-field (3 T) and ultra-low-field (64 mT) MRI findings from South Africa

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Abstract
With the evolution of ultra-low-field MRI and the recognition of antenatal maternal anaemia as an important driver of altered neurodevelopment in toddlers and children, it is critical to determine whether these effects are detectable at ultra-low-field (64 mT) in infancy. The aim of this study was to assess the impact of antenatal maternal anaemia on infant brain structure across the first 2 years of life, using high-field (3 T) and ultra-low-field (64 mT) MRI. This neuroimaging substudy was embedded within Khula, an observational population-based birth cohort in South Africa. Pregnant women were enrolled antenatally and postnatally. Mother-child dyads (n = 394) were followed prospectively with a subsample attending neuroimaging at ∼3, 6, 12, 18 and 24 months of age. Anaemia was classified using World Health Organization thresholds, and neuroimaging data were processed using MiniMORPH. Linear mixed-effects models were used to investigate associations between antenatal maternal anaemia status and absolute regional infant brain volumes using high-field and ultra-low-field MRI. In repeated measures high-field (n = 195) and ultra-low-field (n = 341) infant neuroimaging subsamples, the prevalence of antenatal maternal anaemia was 28.24% (37/131) and 29.76% (61/205), respectively. Maternal anaemia in pregnancy was associated with altered child brain structure across both MRI systems, with group differences becoming detectable at ∼12 months. In the ultra-low-field subsample, infants born to anaemic mothers had 3.77% smaller intracranial volume (β = −0.24, P = 0.004) and 3.32% smaller putamen volumes (β = −0.18, P = 0.040) across the first 2 years of life. The interaction between antenatal maternal anaemia and age was significant for the caudate nucleus (β = −0.13, P = 0.038) and corpus callosum (β = −0.15, P = 0.007). Antenatal maternal anaemia was associated with 3.70% and 4.29% smaller caudate nucleus volumes at 18 and 24 months of age, respectively. Similarly, infants born to anaemic mothers had 4.39% smaller corpus callosum volumes by 12 months and 6.27% smaller corpus callosum volumes by 24 months. Postnatal child anaemia and antenatal maternal iron deficiency status were not associated with total or regional child brain volumes in the ultra-low-field subsample from this cohort. Maternal anaemia remained a robust predictor of volume differences in sensitivity analyses. This study is the first to demonstrate that the impact of maternal anaemia in pregnancy on child brain structure is detectable as early as infancy. The implications of this research are 2-fold: (i) informing the feasibility of ultra-low-field MRI in low- and middle-income countries and (ii) the timing and optimization of targeted recommendations for anaemia management in practice and policy.
Funding Information
  • Wellcome Leap
  • The First 1000 Days (222076/Z/20/Z)
  • Wellcome Trust International Training Fellowship (224287/Z/21/Z)
  • Wellcome Trust Centre for Mitochondrial Research (224287/Z/21/A)
  • Gates Family Foundation (INV-023509)
  • Gates Family Foundation (INV-047888)
  • Gates Family Foundation (INV-090982)
  • Developing Excellence in Leadership, Training, and Science in Africa (Del-22-002)
  • Science for Africa Foundation
  • Wellcome Trust
  • Foreign, Commonwealth and Development Office
  • European and Developing Countries Clinical Trials Partnership
  • European Commission
  • National Institute for Health and Care Research
  • NIHR Maudsley Biomedical Research Centre

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