Association of Maternal and Child Anemia With Brain Structure in Early Life in South Africa.

Importance: Anemia affects millions of pregnant women and their children worldwide, particularly in low- and middle-income countries. Although anemia in pregnancy is a well-described risk factor for cognitive development, the association with child brain structure is poorly understood. Objective: To explore the association of anemia during pregnancy and postnatal child anemia with brain structure in early life. Design, Setting, and Participants: This neuroimaging nested cohort study was embedded within the Drakenstein Child Health Study (DCHS), a population-based birth cohort in South Africa. Pregnant individuals were enrolled into the DCHS between 2012 and 2015 from 2 clinics in a periurban setting. Mother-child pairs were assessed prospectively; follow-up is ongoing. A subgroup of children had brain magnetic resonance imaging (MRI) at age 2 to 3 years from 2015 to 2018. This study focused on the 147 pairs with structural neuroimaging and available hemoglobin data. Data analyses were conducted in 2021 and 2022. Exposures: Mothers had hemoglobin measurements during pregnancy, and a subgroup of children had hemoglobin measurements during early life. Anemia was classified as hemoglobin levels less than 11 g/dL based on World Health Organization guidelines; children younger than 6 months were classified using local guidelines. Main Outcomes and Measures: Child brain volumes of global, subcortical, and corpus callosum structures were quantified using T1-weighted MRI. Linear regression models were used to analyze the associations between maternal and child anemia with child brain volumes, accounting for potential confounders. Results: Of 147 children (mean [SD] age at MRI, 34 [2] months; 83 [56.5%] male) with high-resolution MRI scans, prevalence of maternal anemia in pregnancy was 31.3% (46 of 147; median [IQR] gestation of measurement: 13 [9-20] weeks). Maternal anemia during pregnancy was significantly associated with smaller volumes of the child caudate bilaterally (adjusted percentage difference, -5.30% [95% CI, -7.01 to -3.59]), putamen (left hemisphere: -4.33% [95% CI, -5.74 to -2.92]), and corpus callosum (-7.75% [95% CI, -11.24 to -4.26]). Furthermore, antenatal maternal hemoglobin levels were also associated with brain volumes in the caudate (left hemisphere: standardized β = 0.15 [95% CI, 0.02 to 0.28]; right hemisphere: β = 0.15 [95% CI, 0.02 to 0.27]), putamen left hemisphere (β = 0.21 [95% CI, 0.07 to 0.35]), and corpus callosum (β = 0.24 [95% CI, 0.09 to 0.39]). Prevalence of child anemia was 52.5% (42 of 80; median [IQR] age of measurement: 8.0 [2.7 to 14.8] months). Child anemia was not associated with brain volumes, nor did it mediate the association of maternal anemia during pregnancy with brain volumes. Conclusions and Relevance: In this cohort study, anemia in pregnancy was associated with altered child brain structural development. Given the high prevalence of antenatal maternal anemia worldwide, these findings suggest that optimizing interventions during pregnancy may improve child brain outcomes.