blood samples in a centrifuge

Are We Underestimating the Prevalence of Iron Deficiency?

September 3, 2021

Current test thresholds for detecting iron deficiency in women and children may be too low, according to a new study led by a Columbia researcher.

The new study found that physiological changes occur at test levels higher than the current thresholds, and about 30% of both women and children in the United States could be considered iron-deficient under the new thresholds proposed by the investigators. About 17% of premenopausal women and 10% of children in the U.S. population are now considered iron-deficient under the current thresholds.

“Under the existing guidelines, doctors detect people only with the more severe forms of iron deficiency,” says study leader Gary M. Brittenham, MD, the James A. Wolff Professor of Pediatrics at Columbia University Vagelos College of Physicians and Surgeons. “But they are neglecting many women and children with mild-to-moderate iron deficiency who are not anemic but still have ill effects from the lack of iron.”

The study was published this month in Lancet Haematology.

Iron deficiency is the world’s most common nutritional deficiency, but there has always been uncertainty about how to best detect it. By far, the most widely used method by physicians is to measure levels of ferritin, an iron protein in the blood, to estimate the body’s iron stores.

Under current guidelines, people are considered iron-deficient when ferritin levels drop below 15 µg/L in adults and 12 µg/L in children.

But these thresholds, defined by the World Health Organization, are based only on a small number of studies and detect only the more severe stages of iron deficiency.

Brittenham and other researchers believe human health is affected well before iron becomes so scarce. Adults with ferritin levels above the current threshold for deficiency can still experience fatigue, impaired physical performance, and decreased work productivity without being anemic. “This is a particularly critical oversight for children,” Brittenham says, “since studies suggest that even modest reductions in iron can impair brain development, possibly resulting in irreversible damage.”

In the new study, the researchers set out to determine the ferritin level at which physiological changes can be detected in blood tests.

They found that when ferritin dropped below 25 µg/L in women and 20 μg/L in children, the levels of two other proteins in blood began to change. Changes in these blood proteins indicate that under these ferritin thresholds, cells need more iron and fewer red blood cells are being produced.

“We think the thresholds determined by our physiological methods detect the true onset of iron deficiency,” Brittenham says, “whereas the WHO thresholds seem to identify a more advanced stage of iron deficiency.”

The new thresholds could help better identify individuals with health problems stemming from iron deficiency, treat patients at an earlier stage to prevent anemia, and help researchers better understand the health impacts of the early stages of iron deficiency.

“But it would be premature to adopt these thresholds now in clinical practice,” Brittenham cautions. “Our findings need to be confirmed, preferably by several studies, in populations here in the United States and around the world.”

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The study is titled “Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study.”

Other contributors: Zuguo Mei, O Yaw Addo, Maria Elena Jefferds, Andrea J Sharma, and Rafael C Flores-Ayala (all at the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA).

The researchers did not receive any funding for the study and declare no competing interests.