Discussion
infectious diseases, anaemia, malaria, inflammation, hypophosphataemia, infection, Inflammation
INFECTIOUS DISEASES, ANAEMIA, MALARIA, INFLAMMATION, HYPOPHOSPHATAEMIA, INFECTION, IRON DEFICIENCY, INFLAMMATION
In resource-limited setting in sub-Saharan African, where adverse pregnancy and neonatal outcomes are common and malaria is highly endemic, treatment of women with moderate or severe anaemia in the second trimester of pregnancy with a single dose of up to 1000 mg ferric carboxymaltose was not significantly superior to standard of care in improving the primary maternal outcome of anaemia at 36 weeks' gestation or the primary neonatal outcome of birthweight. However, ferric carboxymaltose reduced iron deficiency and iron deficiency anaemia. Ferric carboxymaltose might be more effective in increasing haemoglobin in women with baseline iron deficiency, although the statistical evidence for this interaction was not strong. In this resource-constrained primary-care setting where exposure to infectious diseases was intense, ferric carboxymaltose was safe.We used pragmatic eligibility criteria for the trial so that the results could be translated into practice. We reasoned that in resource-limited primary antenatal health-care, screening with venous blood currently represents an insurmountable transformation of practice, as laboratory screening for anaemia in any form is seldom performed. Discrepancies between capillary and venous haemoglobin assessments are recognised,Our findings highlight the complexity of the determinants of anaemia in this setting. Inflammation was present in more than half of women at baseline, despite testing negative for The reduction in iron deficiency produced by ferric carboxymaltose could potentially provide benefits to mothers and their babies independent of effects on anaemia. 2021 data indicate that universal iron interventions in 8-month-old infants do not improve cognitive outcomes,Despite iron therapy, and accounting for recurrent intermittent preventive therapy, approximately half of women remained anaemic by 36 weeks' gestation; this might relate to the ongoing high prevalence of inflammation (∼36%) seen at this timepoint, perhaps due to causes beyond malaria. Previous randomised controlled trials and systematic reviews have suggested a benefit from iron supplementation on birthweight.Systematic reviews have indicated that intravenous iron might increase infection risk compared with oral iron (or no iron);Ferric carboxymaltose is known to induce transient hypophosphataemia due to FGF23-induced renal-phosphate losses;Several systematic reviews have indicated that intravenous iron is superior to oral iron in increasing haemoglobin and reducing anaemia prevalence during pregnancy; these reviews contain limited data from low-income countries, or from trials using modern intravenous formulations including ferric carboxymaltose.Hepcidin regulates iron access to the plasma from the diet and the reticuloendothelial system.Our trial has several strengths, and included women who face a high risk of adverse antenatal and perinatal outcomes (for whom optimising pregnancy outcomes is most crucial) using pragmatic eligibility criteria that could be implemented in the field. Limitations in our study design include the open-label design, but since ferric carboxymaltose is a dark solution, administering intravenous placebo would require a curtain, blindfold, or opaque tubing. Key efficacy outcomes were measured by masked personnel. Several major trials of intravenous iron in high-income settings, such as the IRONMAN study testing iron derisomaltose in heart failureFerric carboxymaltose can feasibly be delivered safely in resource-poor contexts where infection risk is high. Further exploration of the role that ferric carboxymaltose might play as part of the solution to the complex determinants of anaemia in sub-Saharan Africa is warranted.