Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review

Abstract

SummaryThe World Health Organization recommends universal iron supplementation of 30–60 mg/day in pregnancy but coverage is low in most countries. Its efficacy is uncertain, however, and there has been a vigorous debate in the last decade about its safety, particularly in areas with a high burden of malaria and other infectious diseases. We reviewed the evidence on the safety and efficacy of antenatal iron supplementation in low‐income countries. We found no evidence that daily supplementation at a dose of 60 mg leads to increased maternal Plasmodium infection risk. On the other hand, recent meta‐analyses found that antenatal iron supplementation provides benefits for maternal health (severe anaemia at postpartum, blood transfusion). For neonates, there was a reduced prematurity risk, and only a small or no effect on birth weight. A recent trial showed, however, that benefits of antenatal iron supplementation on maternal and neonatal health vary by maternal iron status, with substantial benefits in iron‐deficient women. The benefits of universal iron supplementation are likely to vary with the prevalence of iron deficiency. As a consequence, the balance between benefits and risks is probably more favourable in low‐income countries than in high‐income countries despite the higher exposure to infectious pathogens.

Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection and Select for Attenuated Virulence in an Enteric Pathogen

“…It is important to note that the strain of mouse used for most of these studies has been C57BI/6 mice, which has a nonfunctional allele of Nramp1, a divalent metal (iron and manganese) transporter that renders them more susceptible to infections (Canonne-Hergaux et al, 1999; Fritsche et al, 2012; Loomis et al, 2014; Powell and Frelinger, 2017; Soe-Lin et al, 2009). In humans, clinical data support our findings that dietary iron supplementation provides beneficial outcomes, especially in developing countries where low iron status may be prevalent (Loukas et al, 2016; Mwangi et al, 2017; Oppenheimer, 1989, 1998, 2001). However in malaria endemic areas, iron supplementation was associated with a negative outcome for patients (Clark et al, 2014).…”

Safety of Oral and Intravenous Iron

“…In pregnant women at risk for malaria, concern has been raised about oral iron increasing the risk for this infection [15]. Iron is crucial for supporting growth of pathogenic organisms such as malaria, and early studies suggested that iron supplementation may increase the risk of this infection.…”

Reducing anaemia in low income countries: control of infection is essential

“…In a second recent placebo controlled trial in non-iron deficient, non-anaemic, pregnant women in Tanzania, iron supplementation did not increase placental malaria, although no benefit on birth weight or gestation duration was found, perhaps reflecting higher baseline iron status in this study population 42. These trials indicate that antenatal iron supplementation is safe even where malaria is highly endemic and malaria control strategies incompletely implemented (perhaps because of more developed host immunity and/or tolerance to pathogen load in adulthood),43 and has important benefits on maternal and neonatal health when iron deficiency is prevalent. Detailed investigations of potential risks from iron in pregnancy on other infections are still warranted.…”