Tag: iron deficiency

Intravenous Iron is Faster and Better than Oral Form for Pregnant Women

Photo by Marcelo Leal on Unsplash

Researchers found that an intravenous iron preparation, ferric carboxymaltose, works faster and better than an oral iron tablet taken by mouth for the treatment of anaemia, with comparable safety. The findings were published in Lancet Global Health.

Anaemia is a common cause of ill-health or death in mothers and their babies, especially in sub-Saharan Africa and South-East Asia where more than four out of ten pregnant women have the condition. A sizeable proportion of pregnant women in Nigeria proceed to giving birth while still anaemic despite taking iron tablet for prevention during pregnancy. Some reasons for this are that some women do not tolerate the tablets because of side effects like diarrhoea, nausea, or vomiting, or they forget to take the tablets. Available iron preparations given through drip in Nigeria like iron dextran have been associated with high risk of severe side effect, while iron sucrose needs repeat dosing. There is a need for an effective and safer alternative to overcome these problems. 

A team of researchers in a recently concluded clinical trial, called the IVON TRIAL, tested ferric carboxymaltose, which is new in Nigeria and most of sub-Saharan Africa. 

They compared the effectiveness and safety of this medicine with that of a popular tablet preparation, ferrous sulphate, which is currently being used to treat anaemia in Nigeria. They found that this new medicine given intravenously works faster and better for anaemia treatment than oral iron tablets; and it is as safe as the tablet. 

The study enrolled 1056 pregnant women, aged 15–49 years, who were between five and seven-and-half months pregnant and had anaemia with haemoglobin measurement less than 10 g/dL.

“We used a web-based platform to assign them to treatment groups. Half of the women were treated with one dose of iron given in drip through the vein while half took iron tablets three times a day till they gave birth”, says Ochuwa A. Babah, a doctoral student at the Department of Global Public Health, Karolinska Institutet and one of the authors of the paper. 

Their haemoglobin levels and iron levels were checked, and they were screened` for depression at specific time points. They were followed-up until six weeks after delivery to collect more data from mother and baby. Blood was collected from the baby’s cord at delivery to know if the medicine affected the baby’s phosphate level.

Works better for iron deficiency anaemia

Only one dose of iron (ferric carboxymaltose) given by drip through a vein during pregnancy causes a faster rise in blood level after four weeks compared to iron tablet taken by mouth three times every day. The drip iron also corrects low body iron better than iron tablets. The side effects of the drip iron are comparable to that with iron tablets, with no adverse effect on the babies. 

“These findings are reassuring because pregnant women often reject new medicines because of fear of harm to their babies. We now have evidence that implementing the use of this new iron via drip (ferric carboxymaltose) in regions where many pregnant women suffer anaemia like Africa, will be a valuable step towards reducing the proportion of pregnant women who suffer from this condition and its complications”, says Ochuwa A. Babah and continues:

“The pregnant women were willing to accept iron via drip during pregnancy, supported by their families. The healthcare workers were ready to administer iron via drip but identified a need to increase staff strength and possibly medicine subsidy. We know from the clinical trial that the intravenous iron is effective and safe, so we are already liaising with the Federal Ministry of Health, Nigeria to add it to the essential drug list.”

Source: Karolinska Institutet

Over Half of Iron Deficiency Cases Unresolved After Three Years

Photo by National Cancer Institute on Unsplash

Over half of people with iron deficiency were found to still have low iron levels three years after diagnosis, and among patients whose condition was effectively treated within that timeframe, they faced longer-than-expected delays, pointing to substantial gaps in appropriate recognition and efficient treatment of the condition, according to a study published in Blood Advances.

Iron deficiency is common, and affecting up to 40% of adolescents and young women. Previous work reported that up to 70% of cases go undiagnosed in high-risk populations, such as those with bleeding disorders, issues with malabsorption, or women who menstruate.

“Iron deficiency is probably a bigger problem than we realise. I’ve seen a lot of cases where people don’t have anaemia, but they are walking around with very little to no iron in their body and it can have a big impact on how people feel in their day-to-day life,” said Jacob Cogan, MD, assistant professor of medicine at the University of Minnesota and the study’s lead author. “Iron deficiency can be challenging to diagnose, but it’s easy to treat. Our findings underscore the need for a more coordinated effort to recognise and treat iron deficiency to help improve quality of life.”

If untreated, low iron stores can lead to mood changes, fatigue, hair loss, exercise intolerance, and eventually anaemia. The condition is generally first treated with oral iron supplementation, and if low iron levels persist after a few months or the patient reports side effects, intravenous (IV) iron is started.

For this study, the researchers retrospectively analysed medical records from one of Minnesota’s largest health system database and identified 13 084 adults with a laboratory diagnosis of iron deficiency (defined as a ferritin value of 25ng/mL, with and without anaemia) between 2010 and 2020 who had available follow-up data for three years.

In the study, iron deficiency was d or less. Patients had to have at least two ferritin values – one initial value and at least one more within the three-year study period. Adequate treatment and resolution was defined as a subsequent ferritin value of at least 50ng/mL. Most patients received some form of treatment, consistent across sex.

Of the 13,084 patients included in the study, 5,485 (42%) patients had normal iron levels within three years of diagnosis, while 7,599 (58%) had persisting iron deficiency based on low ferritin levels. Only 7% of patients had their iron levels return back to normal within the first year of diagnosis.

Factors associated with a higher likelihood of getting iron levels back to normal included older age (age 60 and up), male sex, Medicare insurance, and treatment with IV iron alone. Additionally, compared with patients who were still iron deficient, those whose condition was resolved had more follow-up blood work to check ferritin values (six vs four ferritin tests). Of note, younger patients, females, and Black individuals were most likely to remain iron deficient or experience longer lags in getting their iron stores back to a healthy level.

Even among patients whose iron levels were restored to normal during the study duration, it took nearly two years (the median time to resolution was 1.9 years), which researchers say is longer than expected and signals missed opportunities to more effectively manage the condition. While there was no data to look at whether anaemia iron deficiency was more apt to be treated, Dr Cogan says it’s reasonable to think this might be the case as iron deficiency without anaemia is harder to recognise.

“Two years is too long and well beyond the timeframe within which iron deficiency should be able to be sufficiently treated and resolved [with oral or IV treatments],” said Dr Cogan. “The numbers are pretty striking and suggest a need to put systems in place to better identify patients and treat them more efficiently.”

As with trends showing persisting iron deficiency, Dr Cogan attributes the delays in resolution to the diagnosis either being missed or not treated to resolution. He added that there is a clear need for education about non-anaemic iron deficiency and who is at high risk, more universal agreement on the best ferritin cut off for diagnosis, and efforts to create an iron deficiency clinic or pathway to “assess and treat patients more efficiently and get people feeling better faster.”

The study was limited by its reliance on EMR data and retrospective nature, which prevented researchers from determining why ferritin tests were ordered for patients or the cause of their iron deficiency.

Source: American Society of Hematology

Obese and Overweight Children at Risk of Iron Deficiency

Photo by Patrick Fore on Unsplash

Children and young people who are overweight or obese are at significantly higher risk of iron deficiency, according to a study by nutritional scientists at the University of Leeds.

Researchers from the School of Food Science and Nutrition examined thousands of medical studies from 44 countries involving people under the age of 25 where levels of iron and other vitamins and minerals had been recorded alongside weight. They found that iron deficiency was associated with both underweight and overweight children and adolescents.

By contrast, zinc and vitamin A deficiencies were only observed in children who were undernourished, leading researchers to conclude that iron deficiency in overweight children is probably due to inflammation disrupting the mechanisms that regulate iron absorption.

The results of the research appear in the journal BMJ Global Health.

Iron deficiency in children has a negative effect on brain function, including attention, concentration and memory, and can increase the risk of conditions, such as autism and ADHD.

It is already recognised as a problem in adults living with obesity, but this research is the first to look at the association in children.

Lead author Xiaomian Tan, a Doctoral Researcher in the University of Leeds’ School of Food Science and Nutrition said: “The relationship between undernutrition and critical micronutrients for childhood growth and development is well established, but less is known about the risk of deficiencies in iron, vitamin A and zinc in children and adolescents who are overweight or obese, making this a hidden form of malnutrition.

“Our research is hugely important given the high prevalence of obesity in children. We hope it will lead to increased recognition of the problem by healthcare practitioners and improvements in clinical practice and care.”

Hidden hunger

Historically the problem has been linked to malnutrition and is a particular concern for lower- and middle-income countries where hunger may be the leading cause of mortality for young children.

Increasingly though it is being recognised that vitamin and mineral deficiencies can also occur in people who are overweight and obese and who have a nutrient-poor but energy-dense diet, something which has been described as ‘hidden hunger’.

In high-income countries it is associated with ultra-processed foods that are high in fat, sugar, salt, and energy but in lower- and middle-income countries obesity is often associated with poverty and monotonous diets with limited choices of staples such as corn, wheat, rice, and potatoes.

Many developing countries are now facing a double burden of malnutrition alongside overnutrition due to the rapid increase in the global prevalence of obesity in recent decades, especially in children aged between five and 19.

Undernutrition versus overnutrition

The research also highlights differences in focus between higher income countries and developing nations, with most studies in Africa and Asia focusing on undernutrition and those from North America and Europe focusing entirely on overnutrition.

The researchers say this is particularly concerning as both Africa and Asia are experiencing the highest double burden of malnutrition due to economic growth and the transition to a western-style high-sugar, high-fat diet.

Between the years 2000 and 2017, the number of overweight children under the age of five in Africa increased from 6.6 to 9.7 million, and in Asia that figure rose from 13.9 to 17.5 million. At the same time, there was an increase in the number of stunted children under 5, from 50.6 to 58.7 million in Africa.

Research supervisor Bernadette Moore, Professor of Nutritional Sciences in Leeds’ School of Food Science and Nutrition, said: “These stark figures underscore the fact that the investigation of micronutrient deficiencies in relation to the double burden of malnutrition remains critically important for child health.

“By the age of 11 here in the UK, one in three children are living with overweight or obesity, and our data suggests that even in overweight children inflammation leading to iron deficiency can be an issue.

“Iron status may be the canary in the coalmine, but the real issue is that prolonged inflammation leads to heart disease, diabetes and fatty liver.”

Increasing physical activity and improving diet have been shown to reduce inflammation and improve iron status in children and the researchers are now calling for further studies into the effectiveness of these interventions.

They also believe that more research is needed into micronutrient deficiencies and the double burden of malnutrition and overnutrition in countries where there are currently gaps in data.

Source: University of Leeds

Iron is Critical for Neutrophils as Well as Red Blood Cells

Red blood cells, platelets and T cells. Source: CC0

In a surprising discovery published in Science Advances, turning off the two proteins that regulate iron uptake results in not only anaemia but also in neutrophil levels plummeting. Iron deficiency, a known defence mechanism against infectious pathogens, can therefore a double-edged sword, as it simultaneously curbs the defensive power of this important arm of the innate immune system.

Iron is an indispensable component, needed for the blood pigment haemoglobin. The iron supply to the cells is controlled by the two proteins IRP-1 and IRP-2. If the cell lacks iron, IRP-1 and IRP-2 crank up the production of the various iron transporter proteins that take iron into the cell. IRP-1 and IRP-2 also ensure that an equally dangerous excess of iron does not occur.

IRP-1 and IRP-2 are essential for survival: mice lacking both control proteins during embryonic development die while still in the womb. But what happens when IRP-1 and IRP-2 fail in adult mice? A team led by Bruno Galy at the German Cancer Research Center (DKFZ) has now investigated this by shutting down IRP production in mice.

As the researchers had expected, the most striking change after IRPs were switched off was a pronounced decrease in red blood cells. Due to the lack of haemoglobin, these erythrocytes reached only a minimal size.

However, the researchers were surprised to see that white blood cells also decreased, mainly due to a deficiency of neutrophils, which account for up to two-thirds of white blood cells in humans.

The neutrophil decline was not caused by a mass die-off but a developmental blockade in the haematopoietic system: the precursor cells in the bone marrow no longer develop into mature neutrophils – an iron-dependent process. Other types of white blood cells, such as monocytes, were unaffected by the IRP-dependent developmental blockade.

Iron limitation is a double-edged sword

“This strong iron dependence of neutrophils was previously unknown. It possibly affects the immune defence against bacterial pathogens,” said senior author Bruno Galy. Yet iron deficiency is one of the body’s defence strategies in bacterial infections since many pathogens are dependent on iron. The body hoards the metal in certain cells to cut off access for pathogens, limiting their ability to replicate.

Galy is involved with another study also in Science Advances, which shows that iron deficiency in blood serum, as typically occurs with infections, leads to a decrease in neutrophils in mice and limits the ability of these immune cells to fight bacteria. “Iron deficiency apparently modulates the innate immune system. It suppresses the maturation of neutrophils and also throttles their defensive power,” commented Bruno Galy. “The limitation of available iron is apparently a double-edged sword: On the one hand, the body thereby prevents bacteria from spreading. On the other hand, the function of an important arm of the innate immune system suffers.”

Inflammation often leads to anaemia, as can be experienced by cancer patients. The researchers next want to investigate whether iron deficiency in chronic inflammation also impairs immune function.

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)