Landmark Malawi trial boosts iron levels in pregnant women

A world-first study exploring new ways to fight anaemia in developing nations has found a single iron infusion can significantly reduce iron deficiency in pregnant women, compared with daily tablets.

The World Health Organization (WHO) currently recommends oral iron taken twice daily as the standard of care in developing nations, but adherence to this treatment is poor.

The finding, driven by a collaboration between Australian and Malawian researchers, paves the way for more effective health policies to reduce the global health burden of anaemia, which remains one of the most avoidable causes of illness and death in resource-poor nations. 

The research is published in The Lancet.

At a glance

• First trial to give ferric carboxymaltose (FCM) iron infusions to pregnant women in a developing nation. FCM is a common treatment for iron-deficient pregnant women in high-income countries like Australia.
• The study showed a single iron infusion given during the second trimester significantly reduced iron deficiency in pregnant women, compared to daily iron supplements currently recommended by the WHO. 
• The Malawi-based trial of 862 women could lead to urgently needed new treatment options for iron deficient women in resource-poor communities. 

Iron deficiency is a major public health burden in resource-poor countries and a key precursor to anaemia – a condition affecting nearly half of all pregnancies in Africa. It occurs when a person lacks oxygen-carrying red blood cells (haemoglobin) and iron.

While the WHO recommends oral iron tablets taken twice daily for pregnant women in sub-Saharan Africa, less than 30% of the population consumes this recommended dose.

Ferric carboxymaltose (FCM) is a 15-minute iron infusion treatment widely given to iron-deficient pregnant mothers in developed countries.

In efforts to find more effective ways of treating iron-deficient patients, WEHI researchers worked with Malawian scientists at the Training Research Unit of Excellence and Kamuzu University of Health Sciences to compare FCM to standard-of-care oral iron.

Half of the Malawian women (431) in their second trimester received FCM, while the other half took standard-of-care oral iron. 

Professor Sant-Rayn Pasricha, a leading anaemia expert and Division Head in WEHI’s Population Health and Immunity Division, said the trial was four times larger than the one conducted to bring FCM onto the market.

“When we first set out to do this trial, people thought we were trying to achieve the impossible,” Professor Pasricha, also a haematologist, said.  

“We proved that FCM can not only be safely administered in a complex resource-limited setting like Malawi, but can also reduce the iron deficiency component of anaemia by around 60% – a significantly better result than the oral iron currently recommended in these populations.

“The results show women who received FCM throughout the trial had a substantial reduction in iron deficiency and iron deficiency anaemia during their third trimester, at delivery and 4-weeks post-partum. 

“This will open a whole new field of research that was previously thought impossible and could help transform health policies in vulnerable communities. 

“I’m tremendously excited that a medicine widely used in high-income nations might have an application to help women in Sub-Saharan Africa and other resource-poor settings. Our next task is to identify those women who have the best chance of benefiting from the IV treatment.”

Unique health challenges

Pregnant women with anaemia are at elevated risk of complications, including post-partum haemorrhage, stillbirth and low birthweight.

Despite the substantial improvements in iron levels, the trial found FCM was not superior to oral iron in reducing the overall burden of anaemia in pregnant women and did not reduce incidences of low birthweight or anaemia in women at the time of delivery.

Researchers say this is because anaemia can be driven by more than iron-deficiency in developing nations.

“For example, conditions like malaria and HIV, which are common in parts of Sub-Saharan Africa, can drive up inflammation in the body and prevent access to stored iron,” Professor Kamija Phiri, a leading epidemiologist and Director of the Training and Research Unit of Excellence, said. 

“Additionally, haemoglobinopathies – a group of inherited blood disorders predominantly affecting red blood cells – are common in the region and cause anaemia.”

Professor Pasricha says the results emphasise the urgent need for new mechanisms to address these unique health challenges.

“Over half of participants had inflammation in their bodies, despite testing negative for malaria,” he said.

“With some parasites able to hide in the placenta during pregnancies, it is likely that current tests are not sensitive enough to help us understand a mother’s complete health status and flow-on risks to her unborn child. 

“While you can do a blood test to detect determinants of anaemia, like ferritin, in developed nations, there is no such tool in place for these parts of the world to measure iron status.

“Our study shows there is an urgent need for field-friendly testing capabilities for iron status and causes of anaemia, which will provide critical insight into how and where medicines like FCM should be used.”

With FCM remaining an expensive treatment option, researchers hope the promising results of the trial can encourage philanthropic efforts to further research the intervention and make it more accessible to women in low-income settings.

The research team is currently tracking the mothers involved in this study and their babies to assess whether the intervention will impact on anaemia prevalence, post-partum depression and child neurodevelopment.

The study, “Ferric Carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial,” is published in The Lancet. (DOI:10.1016/S0140-6736(23)00278-7).
The research was funded by the Bill & Melinda Gates Foundation and a National Health and Medical Research Council (NHMRC) Investigator Grant awarded to Professor Pasricha. 

WEHI authors: Sant-Rayn Pasricha, Ricardo Ataide, Rebecca Harding, Danielle Clucas, Sabine Braat.