Iron Deficiency Anaemia in Mothers and Infants from a South African Birth Cohort: Prevalence and Profile in the Context of Inflammation

ABSTRACT Objectives The scarcity of epidemiological data on anaemia in low- and middle-income countries, coupled with poor characterisation of overlapping risk factors in high-risk settings and contrasting approaches to the assessment of iron status with inflammation, represent critical gaps to address. This study aimed to characterise the prevalence and profile of iron deficiency anaemia, including adjustment for inflammation, in pregnant and postpartum women, as well as infants from South Africa. Methods Mother-child dyads ( n =394) were recruited (2021-2022) for the Khula birth cohort study in Cape Town, South Africa. Haematological metrics (haemoglobin, mean corpuscular volume [MCV]), iron metrics (serum ferritin and soluble transferrin receptor [sTfR]), and inflammatory biomarkers (highly sensitive C-Reactive Protein [ hs CRP]; Alpha-1 Acid Glycoprotein [AGP]) were obtained from mothers antenatally and postnatally, as well as from infants 3-18 months after birth. World Health Organisation (WHO) guidelines were used to classify anaemia and iron deficiency. The extent to which inflammation impacted iron deficiency was assessed using two methods: Method A: higher serum ferritin thresholds for classifying iron status in participants with inflammation (WHO), Method B: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia (BRINDA) regression which corrects serum ferritin levels based on inflammatory biomarker concentrations. Results Prevalence of anaemia was 34.74% (107/308) in pregnancy and 22.50% (54/240) in mothers at 3-6 months postpartum. Of their infants, 46.82% (125/267) and 48.10% (136/283) were anaemic at least once by 6-12 months and 12-18 months, respectively. When accounting for inflammation using Method A, the prevalence of maternal iron deficiency (regardless of anaemia), increased from 18.35% (20/109) to 55.04% (60/109) in pregnancy, and from 11.97% (28/234) to 46.58% (109/234) postnatally. Similarly, using Method B, the estimated prevalence of maternal iron deficiency increased to 38.53% (42/109) in pregnancy, and 25.21% (59/234) postnatally. In infants at 12-18 months, the prevalence of iron deficiency increased from 19.79% (19/96) to 31.25% (30/96) and 32.29% (31/96) using Methods A and B, respectively. Approximately half of anaemia cases in mothers antenatally (50%; 20/40) and postnatally (45.10%; 23/51), and infants at 12-18 months (55.56%; 10/18), were attributable to iron deficiency. However, there was little overlap in the estimated prevalence of microcytic anaemia (based on MCV) and iron deficiency anaemia (based on adjusted serum ferritin) in pregnant and postpartum mothers, as well as infants at 3-6 and 6-12 months. At these timepoints, microcytic anaemia underestimated the likely proportion of anaemia cases attributable to iron deficiency. Conclusion This is one of the first studies to report the true prevalence of iron deficiency anaemia in South African mothers and infants, and the extent to which it may be underestimated if inflammation is not accounted for. Additionally, the results indicate that, while microcytic anaemia classification may be a valid proxy for iron deficiency anaemia in infants over 1 year of age, it seems less useful for pregnant and postpartum mothers and younger infants within the context of inflammation. Overall, the findings contribute to a global effort to understand the complex aetiology of iron deficiency anaemia, informing guidelines for optimised detection, prevention, and intervention in high-risk communities.