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

Abstract

ImportanceAnemia 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.ObjectiveTo explore the association of anemia during pregnancy and postnatal child anemia with brain structure in early life.Design, Setting, and ParticipantsThis 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.ExposuresMothers 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 MeasuresChild 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.ResultsOf 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 RelevanceIn 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.

Association between maternal hemoglobin concentration and educational attainment in mid-childhood in a high-resource obstetric setting: a prospective cohort study

“…Previous studies examining the relationship between maternal iron status and neurodevelopment aged 4-5 years have shown mixed results, with either no association 24 , or possible positive benefit from higher maternal iron status on memory 25 and attention 26 . A small South African study specifically assessing brain morphology found that maternal anemia, but not childhood anemia, was associated with smaller brain volumes and altered structural brain development at 2-3 years 27 .…”

Persistent Impact of Antenatal Maternal Anaemia on Child Brain Structure at 6-7 Years of Age: A South African Child Health Study

“…Findings regarding the association between antenatal maternal anaemia and child brain structure at 2–3 years of age in this cohort have been published [ 4 ]. The current study is focused on the 6–7 year timepoint, at which 157 children had both useable structural neuroimaging data (see neuroimaging measures section below) and maternal haemoglobin data for inclusion in analysis.…”

“…While the importance of this first 1000-day window is well-known, recent research is providing increasing evidence to support a renewed focus on optimising antenatal maternal well-being for improved neurodevelopmental outcomes in children [ 1 ]. In recognizing the foetal origins of brain health and the persistent impact of early risk, maternal anaemia during pregnancy is an important health priority for targeted prevention and intervention strategies [ 4 ].…”

“…Given the scarcity of MRI studies in LMICs [ 30 , 31 ] and the particularly high prevalence of anaemia in Africa [ 6 ], a neuroimaging sub-study of the Drakenstein Child health Study (DCHS; South African birth cohort) [ 32 , 33 ] investigated the associations between antenatal maternal anaemia, postnatal child anaemia, and child brain structure at 2–3 years of age [ 4 ]. In this cohort, maternal anaemia during pregnancy was associated with smaller volumes of the bilateral caudate, left putamen, and total corpus callosum in the child brain.…”

Multivariate and Regional Age-Related Change in Basal Ganglia Iron in Neonates

“…maternal diabetes and hypertension), showing low cord ferritin levels at delivery are related to slower auditory brainstem responses in neonates tested 48 hours after birth (Amin et al 2013). Further evidence related to iron and brain development comes from work demonstrating maternal somatic iron during pregnancy was related to infant brain volume (Wedderburn et al 2022).…”