Maternal iron deficiency anaemia

Overview

Maternal iron-deficiency anaemia is a pressing global health issue affecting approximately 37% of pregnant women worldwide, and a significant risk factor for maternal mortality, with around 20% of maternal deaths potentially attributable to complications stemming from this underlying condition. Although a global problem, prevalence increases up to four-fold in LMICs, where confounding factors such as widespread dietary deficiencies, increased risk of infections and inflammation inhibiting iron absorption, and gut conditions all play a role. The resulting inadequate maternal iron stores can lead to serious adverse maternal and neonatal outcomes, including preterm delivery, low birth weight, and impaired infant development. Maternal iron-deficiency related anaemia also has a profound impact on susceptibility to and severity of postpartum haemorrhage, which can have fatal consequences. Addressing iron-deficiency anaemia in pregnancy is essential for improving maternal and neonatal health, particularly in high-burden regions.

Unmet needs

Iron supplementation is the primary course of treatment and prevention for iron-deficiency anaemia. Despite the wide range of iron replacement options available, their effectiveness varies depending on the formulation and bioavailability (how much the body can use). While oral iron is widely used, it is often poorly absorbed and can cause side effects such as gastrointestinal discomfort, nausea, and constipation, leading to high rates of discontinuation. Adherence throughout pregnancy is also an issue, requiring women to continue to take daily pills for long periods. Intravenous iron formulations are also available, although access remains a major barrier in low-resource settings. In LMICs, even low-cost oral iron supplements are not always available where needed. There is an urgent need for more affordable, point-of-care diagnostic tools (specifically via improved biomarkers), and accessible, effective treatments for maternal iron-deficiency anaemia to enhance maternal and neonatal health outcomes.

Funding

In its first year of inclusion in the G-FINDER survey, maternal iron deficiency anaemia (IDA) funding totalled just $2.8m in 2023 and was provided by just two funders. The US NIH provided the vast majority of global funding ($2.4m, 86% of the total), with the remainder coming from the Australian NHMRC ($0.4m, 14%). This left maternal IDA with the second-lowest funding total of any condition included in the survey, only abortion received less.

There was no reported maternal IDA funding at all from the private or philanthropic sectors. This absence is probably partly due to the wide range of iron supplements already on the market and the resulting lack of commercial interest in developing new and better ones; but also, partly due to the G-FINDER survey’s currently limited coverage of the dietary supplement industry.

The largest single share of reported maternal IDA funding went to drug R&D, which totalled just over $1m (37% of the total). This included all $0.4m from the Australian NHMRC, which went to early-stage drug research conducted by the Walter and Eliza Hall Institute of Medical Research. The remaining drug funding, provided by the US NIH, was for a multicenter randomised Phase III trial of IV vs oral iron for treating iron-deficiency anaemia in pregnancy. Despite a total of 38 approved medicines for IDA, there is a disconnect between the availability of effective iron supplements and any realised improvements in maternal IDA globally.

Remaining funding – all of it from the NIH – was relatively evenly split between basic research ($0.8m, 29%) and diagnostics ($0.7m, 25%), with just 9% ($0.2m) going to dietary supplements, for a study of the feasibility of oral lactoferrin to prevent iron deficiency anaemia in obese pregnant women.

Funding for maternal iron deficiency anaemia

Product landscape & pipeline

Alongside limited funding, the R&D space for maternal iron-deficiency anaemia is not very dynamic. The medicines landscape is dominated both by broadly indicated iron products that have been marketed for a long time, and a lack of innovative approaches: there are only a small number of candidates in development compared to other conditions.

In total, 54 medicines are in use or active development for maternal iron deficiency anaemia. Of these, 39 products (72%) are already approved for use to treat the condition. While this number appears substantial, most of these products are simply different formulations of iron: 21 are variations of oral iron supplements, and eight are intramuscular/intravenous (IM/IV) iron. A further six products (15%) are iron in combination supplements, including iron and folate tablets commonly prescribed for both prevention and treatment of maternal iron deficiency anaemia and other pregnancy-related deficiencies, and multiple micronutrient supplements used for prevention only. Beyond iron supplements, there are three products classified as other dietary supplements. These include trofin and neotrofin, two novel anti-anaemics developed by the Cuban National Centre for Biopreparations (BioCen), and Punarnava Mandura, a traditional Indian Ayurvedic medicine. There is one biologic, lactoferrin, which is a milk-derived iron-binding glycoprotein capable of enhancing intestinal iron absorption and improving haemoglobin production, though its exact mechanism of action is unknown. While all 39 approved products have evidence of clinical use, two-thirds of these (26 products) are also subject to Phase IV investigations with ongoing clinical evaluation in the past three years.

There are only 15 candidates under investigation for maternal iron deficiency anaemia. None are formulations of oral iron, IV/IM iron or iron in combination supplements. Instead, almost all are dietary supplements (14 candidates), eight of which are traditional Indian Ayurvedic medicines, including Mandoor Bhasma, Ayastiladi Modak and Dhatri Lauha. Other dietary supplements being tested are traditional Chinese and Japanese medicines, bee pollen syrup, pumpkin seed extract and date syrup. The only non-dietary supplement under investigation is the biologic Lactobacillus plantarum 299v, a probiotic that targets the gut microbiome and has been demonstrated to enhance iron absorption in non-pregnant populations. Most candidates are in Phase II clinical trials (13 candidates, 87%). FeJuice, a nutritional formula from Serbia, made from a blend of fruits and vegetables, is the only truly novel compound under development. All other investigational candidates are repurposed from broad indications for iron deficiency, and perhaps understandably so. But it does indicate a pipeline that is largely void of true product innovation.

The current landscape of available products and investigational candidates for maternal anaemia fails to address the limitations of iron therapy, and particularly the greater challenges faced by populations living in LMICs, where risks are compounded and availability of medical care, for example for IV administration, is limited. At present, there are fewer investigational candidates than approved (suboptimal) products, and no completely new compounds are under development.

Maternal iron deficiency anaemia pipeline*

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*For two candidates, ferrous gluconate (IV) and sodium feredetate, current development stages are unclear, and they have therefore been excluded from this graph.