Antenatal Maternal Anaemia and Infant Brain Structure: 3T and 64mT MRI Findings from South Africa

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 64mT in infancy. The aim of this study was to assess the impact of antenatal maternal anaemia on infant brain structure across the first two years of life, using conventional high-field (3T) and ultra-low-field (64mT) MRI. This neuroimaging sub-study 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 approximately 3, 6, 12, 18, and 24 months of age. Anaemia was classified using WHO thresholds and neuroimaging data was 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 approximately 12 months. In the ultra-low-field subsample, infants born to anaemic mothers had 3.77% smaller ICV (β=-0.24, p =0.004) and 3.32% smaller putamen volumes (β=-0.18, p =0.04) 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 the corpus callosum (β=-0.13, p =0.037). Maternal anaemia in pregnancy was associated with 3.70% and 4.29% smaller caudate nucleus at 18 and 24 months of age, respectively. Similarly, infants born to anaemic mothers had 4.18% smaller corpus callosum volumes by 12 months and 7.10% 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 two-fold; (1) informing the feasibility of ultra-low-field MRI for use in low- and middle-income countries, as well as (2) the timing and optimisation of targeted recommendations for anaemia management in both practice and policy.