Differing definitions of iron deficiency lead to divergent estimates of prevalence, study finds

In a recent study published in JAMA Network Open, researchers investigated how different ways of defining iron deficiency (ID) impact the prevalence estimates of this common disorder among women.

Their results indicate that using higher serum ferritin (SF) thresholds significantly increases the diagnosis rate of ID, potentially leading to improved treatment and declines in related morbidity.

Study: Prevalence of Iron Deficiency Using 3 Definitions Among Women in the US and Canada. Image Credit: angellodeco/Shutterstock.comStudy: Prevalence of Iron Deficiency Using 3 Definitions Among Women in the US and Canada. Image Credit: angellodeco/Shutterstock.com

Background

More than two billion people across the world, particularly children and young women, are affected by ID, which leads to various health issues, including fatigue, cold intolerance, epithelial and mucosal abnormalities, menstruation-related disturbances, pica, impaired muscular performance, and adverse outcomes related to pregnancy.

Previous research on ID prevalence among women in the United States and Canada has been limited and varied. Traditionally, ID diagnosis combines low serum iron levels, SF, and transferrin saturation (TS), but many studies use SF alone.

The Hemochromatosis and Iron Overload Screening Study (HEIRS) defined ID using combined TS and SF criteria, while the World Health Organization (WHO) definition uses SF alone to diagnose ID.

Another definition from the National Health and Nutrition Examination Survey (NHANES) sets a higher SF threshold for iron-deficient erythropoiesis (IDE).

About the study

This cross-sectional study compared ID prevalence in the HEIRS cohort using three definitions to understand how diagnostic criteria influence prevalence estimates and inform clinical practice and population studies.

Conducted from 2001-2003, the HEIRS study recruited 101,168 multiethnic adults aged 25 and older from primary care settings in the US and Canada.

Data from 62,685 women were analyzed, excluding those with prior knowledge of hemochromatosis or iron overload diagnoses. Participants provided written informed consent, and data on age, sex, race, ethnicity, TS, and SF were collected.

Pregnancy was self-reported. Blood samples were analyzed for TS and SF using standardized methods. ID was defined using three criteria: HEIRS (TS < 10% and SF < 15 ng/mL), WHO (SF < 15 ng/mL), and IDE (SF < 25 ng/mL).

Statistical analysis compared ID prevalence across age, pregnancy status, and racial/ethnic groups using variance, χ2 tests, t-tests, and linear models. Relative increases in ID prevalence were calculated with 95% confidence intervals from 100,000 random samples.

Findings

The study analyzed data from 62,685 women with an average age of 49.58. ID prevalence varied significantly based on the definition used: 3.12% based on the definition used by HEIRS, 7.43% by the definition used by WHO, and 15.33% based on the definition of IDE.

Among women aged 25-54 years, 4.46% had ID based on HEIRS, 10.57% by WHO, and 21.23% by IDE. ID prevalence also varied across ethnic and racial groups, with the highest rates among Hispanic and Native American women.

Among women aged 25-44 years who reported being pregnant, ID prevalence was 5.44% by HEIRS, 18.05% by WHO, and 36.10% by IDE. The overall relative prevalence of ID increased 2.4-fold by WHO and 4.9-fold by IDE compared to HEIRS.

White women showed the highest relative increases (3.0-fold by WHO and 6.9-fold by IDE), while Black and Native American women had the lowest relative increases.

These findings underscore the impact of definition criteria on ID prevalence estimates.

Conclusions

The study found that ID prevalence among women varied significantly depending on the definition used, with these differences appearing to be observed regardless of age, pregnancy status, and racial and ethnic groups.

The study included a large cohort of over 62,000 women from diverse racial and ethnic backgrounds and utilized advanced technology for measuring TS and SF.

The three ID definitions—HEIRS, WHO, and IDE—corresponded to increasing prevalence and decreasing severity of ID. Previous research showed similar trends, with higher SF thresholds correlating with higher ID prevalences.

The study's strengths include its large, diverse sample size and robust methodology. However, limitations include the lack of data on hemoglobin levels, socioeconomic factors, and the reliance on self-reported pregnancy status.

The study was also geographically limited to Canada and the United States and included only women aged 25 and older.

Future research should address these limitations by including more diverse populations and additional variables like socioeconomic status and dietary iron intake. It should also validate the IDE definition in different age groups and clinical settings.

The study underscores the need for unified international ID definitions, especially during pregnancy, to improve diagnosis and treatment outcomes and reduce related morbidity.

Specifically, using SF thresholds to identify ID cases could lead to higher diagnosis rates and, thus, better-quality treatment, which could reduce the burden of illness caused by ID.

Journal reference:
Priyanjana Pramanik

Written by

Priyanjana Pramanik

Priyanjana Pramanik is a writer based in Kolkata, India, with an academic background in Wildlife Biology and economics. She has experience in teaching, science writing, and mangrove ecology. Priyanjana holds Masters in Wildlife Biology and Conservation (National Centre of Biological Sciences, 2022) and Economics (Tufts University, 2018). In between master's degrees, she was a researcher in the field of public health policy, focusing on improving maternal and child health outcomes in South Asia. She is passionate about science communication and enabling biodiversity to thrive alongside people. The fieldwork for her second master's was in the mangrove forests of Eastern India, where she studied the complex relationships between humans, mangrove fauna, and seedling growth.

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