Gillian Dohrn

Iron deficiency—when there’s too little iron in the blood—may affect a quarter of the world’s population, and in particular, women of reproductive age. Symptoms can include fatigue and shortness of breath, and without treatment, iron deficiency can progress to anemia, a condition characterized by low red blood cell count that can cause more severe heart and health problems.

There is a simple blood test for iron deficiency that measures ferritin—a protein in the blood that stores iron—but it’s not part of a standard checkup in most countries, including the United States. Further, the World Health Organization has, for decades, earmarked 15 micrograms per liter of ferritin as the threshold for low iron, which is too low, according to some experts, and does not reflect the true prevalence of iron deficiency. This lack of standardization creates blind spots, leaving many symptomatic individuals without access to treatment.

“We know for a fact that we’re missing people who are truly iron deficient,” says 

 an assistant professor of medicine (medical oncology and hematology) at Yale School of Medicine. Goshua led a team that explored the benefits and costs of screening adult women for iron deficiency and recently 

Their work is especially timely, given that the American Society of Hematology, an international task force of researchers and clinicians tackling blood disorders, convened a panel last year to establish the first medical practice guidelines for iron deficiency. The panel’s results are expected next year, and Goshua hopes his team’s work will help inform the experts’ decision.

“We believe this is how we start an important conversation that has been ignored for decades,” says Goshua, who is also a member of Yale Cancer Center.

 and 38% of reproductive age women are iron deficient. Worldwide, this issue may impact as many as 2 billion people.

“This is a problem that’s actually pretty easy to solve,” says Goshua. “We know exactly what iron does, and we know what deficiency looks like.”

Most of the body’s iron winds up in hemoglobin, a protein found in red blood cells that binds and transports oxygen to cells and tissues. Iron is absorbed from food, meaning that poor nutrition and issues with nutrient absorption due to disease or gastrointestinal disorders can deplete iron levels. Iron deficiency develops when red blood cells can’t make enough hemoglobin to meet the body’s demand for oxygen.

As a result, people often experience fatigue, shortness of breath, changes in mood, and restless legs. Goshua says these are “the kinds of things that have historically been normalized.” Part of the reason iron deficiency is underreported is because the symptoms aren’t always considered pathological.

Over time, iron deficiency can progress into anemia. But, by the time anemia presents, a person may have experienced “months or years of unnecessary symptomatology,” Goshua notes.

This is a problem that’s actually pretty easy to solve. We know exactly what iron does, and we know what deficiency looks like.
George Goshua, MD, MSc

In the new study, Goshua and his team focused on reproductive-age women, because they experience the highest rates of iron deficiency. Pregnant women are also prone to consequential iron losses, with the rate of deficiency increasing throughout pregnancy.

One recent study found that in developed countries, 84% of pregnant women experience iron deficiency during their third trimester, which can interfere with fetal brain development and deplete a baby’s baseline iron stores. Pregnant women with anemia face greater risk of preeclampsia, preterm birth, and post-partum hemorrhage.

The researchers created a model based on data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey collected between 2003 and 2020 from 3,490 female patients aged 12 to 21. To test the efficacy of screening at different thresholds, they simulated three different lifetime scenarios: no screening, annual screening at 15 micrograms of ferritin per liter, and annual screening at 25 micrograms per liter. Their model captured iron loss through the reproductive years, at the median age of 51, and after menstruation ceased.

Annual iron screening at 25 micrograms per liter maximized lifetime benefits without amplifying risk such as unnecessary treatment and allergic reaction. This threshold is still conservative, Goshua notes, considering that some experts flag anyone with iron levels below 50 micrograms per liter as deficient.

Over-the-counter oral iron is the leading strategy for treating iron deficiency. It is cheap and effective but also causes constipation and abdominal pain in 40% of users. Intravenous iron is the other option and is often tolerated better. A single infusion can boost iron levels for anywhere from 10 months to multiple years, says Goshua, making it a choice treatment for people with more significant depletion or underlying health issues.

“There is a subset of folks who actually report an improvement in their symptoms within hours or days of the infusion finishing, which is pretty remarkable,” he adds.

Ultimately, the study’s findings show regular screening has clear value.

“The population health benefits are there,” says Goshua.

The Goshua Lab is supported by the National Institutes of Health (awards 1K01HL175220 and CA016359) and Yale University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The lab is also supported by the NOMIS Foundation, the Frederick A. DeLuca Foundation, Yale Cancer Center, and Yale Bunker Endowment.

Articles

Iron deficiency affects a significant portion of the global population, particularly women of reproductive age, and can lead to anemia if untreated. Despite its prevalence, iron deficiency is often underdiagnosed due to non-standardized screening practices. A study led by Dr. George Goshua suggests that raising the ferritin threshold for screening could improve diagnosis and treatment. The study emphasizes the importance of regular screening, especially for women, and highlights the effectiveness of oral and intravenous iron treatments. The findings aim to inform upcoming guidelines by the American Society of Hematology.

Iron deficiency affects millions globally, especially women, yet remains underdiagnosed. Regular screening can prevent severe health issues and improve lives.