Received: 29 October 2023 Revised: 3 April 2024 Accepted: 15 April 2024

DOI: 10.1002/ajh.27352

RESEARCH ARTICLE

High prevalence of iron deficiency and socioeconomic

disparities in laboratory screening of non-pregnant
females of reproductive age: A retrospective cohort study

Sophia Wen 1 | Rosane Nisenbaum 2 | Angela C. Weyand 3 | Grace H. Tang 4 |

Michael Auerbach 5 | Michelle Sholzberg 6

1
Department of Medicine, Temerty Faculty of
Medicine, University of Toronto, Toronto, Abstract
Ontario, Canada
Iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID) are highly
2
Division of Biostatistics, Applied Health
Research Centre, MAP Centre for Urban
prevalent among non-pregnant females of reproductive age. Canada has no national
Health Solutions, Li Ka Shing Knowledge screening guidelines for this population. Screening, when performed, is often with a
Institute, St Michael's Hospital, Dalla Lana
School of Public Health, University of Toronto,
complete blood count alone without ferritin or iron indices. The primary objective
Toronto, Ontario, Canada was to determine the prevalence of screening for NAID and IDA over a 3-year period
3
Division of Hematology/Oncology, in non-pregnant females of reproductive age who had tests performed at outpatient
Department of Pediatrics, University of
Michigan Medical School, Ann Arbor, laboratories in Ontario, Canada. Retrospective cohort study of non-pregnant females
Michigan, USA ages 15–54 in Ontario, from 2017 to 2019. NAID was defined as ferritin <30 μg/L,
4
Division of Hematology-Oncology,
St. Michael's Hospital, University of Toronto,
anemia as hemoglobin <120 g/L, and IDA as ferritin <30 μg/L and hemoglobin
Toronto, Ontario, Canada <120 g/L. Annual household income was estimated using patient postal codes. A total
5
Department of Medicine, Georgetown of 784 132 non-pregnant females were included. The 82.1% were screened for iron
University School of Medicine, Washington,
DC, USA deficiency, 38.3% had NAID and 13.1% had IDA; 55.6% with IDA had normal mean
6
Coagulation Laboratory, Division of corpuscular volumes. The median household income was $89454.80 compared with a
Hematology-Oncology, Hematology-Oncology
provincial median of $65285.00. Patients in the lowest income quintile had the highest
Clinical Research Group, St. Michael's Hospital,
Li Ka Shing Knowledge Institute, University of odds of being anemic, and the lowest odds of having a ferritin checked. A large propor-
Toronto, Toronto, Ontario, Canada
tion of non-pregnant females of reproductive age in this cohort were screened for iron
Correspondence deficiency. In this relatively privileged cohort, NAID affected nearly 40%, and IDA 13%.
Sophia Wen, Department of Medicine,
Most patients with IDA did not have microcytosis. Low household income was associ-
Temerty Faculty of Medicine, University of
Toronto, Toronto, ON, Canada. ated with the greatest odds of anemia and the lowest odds of being screened, highlight-
Email: sophia.wen@gmail.com
ing inequitable access to screening for IDA in Ontario, Canada.

1 | I N T RO DU CT I O N range from 9% to 40%, while 2%–17.2% have IDA.4–6 Compared with

Iron deficiency anemia (IDA) is one of the most prevalent medical
1
conditions in the world. Globally, approximately 29% of females of
reproductive age are anemic, with 50% of cases attributed to iron defi-
ciency.2,3 Non-anemic iron deficiency (NAID) is even more prevalent. In
the United States, older estimates of NAID in non-pregnant females
white patients of higher socioeconomic status (SES), the risk of IDA dou-
bles in females of self-identified minority race/ethnicity, or lower SES.4
Previous statistics for the prevalence of NAID and IDA are likely under-
estimates due to lack of consistent screening, heterogeneity in guidelines
for diagnosis of NAID, and growing evidence that current laboratory fer-
ritin thresholds for iron deficiency are inappropriately low.7–11

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any
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© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.

Am J Hematol. 2024;1–8. wileyonlinelibrary.com/journal/ajh 1


2 WEN ET AL.
Iron is a fundamental component of hemoglobin, but also essen-
tial to cellular mechanisms including DNA synthesis, mitochondrial
energy generation, and various enzymatic functions.12 Anemia is only
one indicator of end-organ damage from iron deficiency, and the
health consequences of both NAID and IDA are important and well-
described. In pregnancy, IDA is associated with preterm labor, low
birth weight, increased risk of maternal blood transfusion, and mater-
nal death.13–16 In non-pregnant females, NAID is associated with
decreased exercise tolerance and physical and cognitive perfor-
mance.17,18 Importantly, iron supplementation corrects anemia and its
17–20
negative sequelae.
Oral iron supplementation is inexpensive, readily available, and
effective for treating NAID. There are few adverse effects,
although gastrointestinal side effects may limit adherence in some
patients. 20
However, NAID and overt IDA are often not diagnosed
nor treated.9,10 Moreover, lower SES is associated with a lower
likelihood of appropriate laboratory testing.4,21,22 Thus, those most
in need of testing and treatment are the least likely to receive
appropriate care.
Laboratory screening recommendations for IDA in non-pregnant
female patients are heterogeneous or non-existent.7 In the
United States, the Centers for Disease Control and Prevention recom-
mends screening non-pregnant patients every 5–10 years for anemia,
using hemoglobin along with clinical evaluation for risk factors.23 Con-
versely, the US Preventive Services Task Force does not address
screening in this population. The United Kingdom has screening
guidelines for IDA in pregnancy, but not in non-pregnant females.
Existing UK guidelines also use hemoglobin as screening in preg-
nancy.24 However, low hemoglobin is neither sensitive nor specific
for iron deficiency; testing hemoglobin rather than laboratory indica-
tors of iron status can be confounded by other causes of anemia and
overlooks patients with NAID. In contrast, laboratory screening using
serum ferritin has been recommended as an accurate indicator as a
ferritin threshold less than 30 μg/L has a sensitivity of 92% and
specificity of 98% for NAID. 25–28
Of note, serum ferritin testing is
inexpensive and widely available.29,30
In Canada, a high-resource country with a publicly-funded health
services system, there are no national recommendations for NAID or
IDA screening in non-pregnant females of reproductive age despite its
high prevalence, negative health impacts, and availability of inexpen-
sive tests and treatments. In the absence of guidelines, practices are
variable and may lead to inequitable or inappropriate management.31
Previous Canadian studies in pregnant patients have shown lower
rates of screening for NAID and higher rates of both NAID and
anemia in patients from lower-income households, however, there is
currently a paucity of studies on the impact of this care gap on non-
11,32
pregnant female patients.
Considering these observations, we sought to quantify the gap in
care by determining the prevalence of testing for NAID and IDA over
a 3-year period among non-pregnant female outpatients of reproduc-
tive age in Ontario, Canada. We also sought to determine patient
demographic and provider characteristics that influence the likelihood
of screening.
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2 | METHODS
2.1 | Study design
This was a retrospective cohort study of non-pregnant female patients
aged 15–54 years who had outpatient laboratory testing between January
1, 2017 to December 31, 2019 in Ontario, Canada. Anonymized labora-
tory data were obtained from Dynacare, the second-largest private labora-
tory enterprise in Ontario, which performs approximately one-third of
non-hospital laboratory testing annually. Data were obtained from Dyna-
care at no cost and without research restrictions and variables included
laboratory test results and dates, patient age, sex, postal code, and order-
ing provider specialty. Dynacare was not involved in study design, data
analysis, or in manuscript preparation. In this study, the terminology
“female patients” refers to biological sex, encompassing patients who have
the capacity to menstruate and become pregnant and does not refer to
gender, a social construct. Study approval was granted by the research
ethics board at St. Michael's Hospital (reference number 21-158). The
study was conducted in accordance with the Declaration of Helsinki.
2.2 | Objectives
The primary objective was to determine the prevalence of testing for
NAID and IDA from January 1, 2017 to December 31, 2019 among
non-pregnant female outpatients of reproductive age who had labora-
tory studies performed at Dynacare laboratories in Ontario, Canada.
Secondary objectives were to determine the prevalence and severity
of NAID, factors influencing follow-up after diagnosis of NAID or IDA,
and patient demographics and provider characteristics that influence
the likelihood of screening in this patient population.
2.3 | Study cohort
Patients within the ages of 15–54 years were included. The median age of
menopause in Canadian women is around 51 years, whereas international
studies have described the median age of menopause up to 53 years.33,34
This age range was chosen to be inclusive of the upper estimated median
age of menopause, and to align with Statistics Canada census reporting,
which frequently groups the population into 5-year age intervals.
As this was a study of non-pregnant females, laboratory evidence
of pregnancy was excluded. Patients who ever had a beta-HCG value
of 5 IU/L or greater or any antenatal laboratory tests (consisting of pre-
natal hepatitis B antigen, HIV, syphilis, or rubella) within the study
period were excluded. As patients may not have received beta-HCG or
antenatal testing at Dynacare to confirm pregnancies, pregnancy was
also defined using a previously validated laboratory definition based on
Ontario antenatal screening guidelines; pregnancy was inferred from
the co-occurrence of a Rubella and ABO/Rh test (the “index date”), fol-
lowed by a Group B Streptococcus swab at least 4 months and no more
than 8 months after the index date. Those meeting laboratory criteria
for pregnancy were excluded from the analysis.22

WEN ET AL.
2.4 | Iron deficiency and anemia definitions
NAID was defined as a serum ferritin less than 30 μg/L. A serum ferri-
tin of less than 30 μg/L has been shown to be both highly sensitive
and specific for NAID.28,35–38 Anemia in non-pregnant female patients
was defined as a hemoglobin less than 120 g/L.39 IDA was defined as
both ferritin less than 30 μg/L and hemoglobin less than 120 g/L
tested within 90 days of each other.
2.5 | Income determination
The Environics Analytics DemoStats data set was used to determine
income. Postal codes from laboratory test requisitions were linked to the
associated dissemination area using the Statistics Canada Postal Code
Conversion File and the average annual household income for that dis-
semination area was then applied. For patients with multiple ferritin tests
during the study period, each with discrepant postal codes, the mean
income across all ferritin testing dates was used. For patients who did
not have a ferritin measured, income associated with hemoglobin tests
was used, while for patients without either ferritin or hemoglobin tested,
the mean income associated with other laboratory tests was used.
Annual household income quintiles were derived from Ontario's Statis-
tics Canada 2016 census tables and applied to the cohort.40 The lowest
income quintile (Q1) represented annual household income less than
$60000CAD, Q2 $60000–89999CAD, Q3 $90000–124999CAD, Q4
$125000–149999CAD, and Q5 greater than $150000CAD.
2.6 | Statistical analysis
Counts and percentages, mean and standard deviation (SD), or median
and interquartile range (IQR) were calculated to characterize the sample
according to different outcomes during specified time periods. The
prevalence of ferritin or hemoglobin testing during an interval was cal-
culated by dividing the number of patients who ever had the specified
test by the total number of eligible patients in the cohort. Logistic
regression models estimated odds ratios and 95% confidence intervals
(CI) for the association between income and any ferritin or hemoglobin
check, and the association between age and every IDA screening. Odds
ratios by income quintiles were age-adjusted categorically. All analyses
were performed using SAS 9.4 (SAS Institute Inc., Cary, NC).
3 | RESULTS
3.1 | Patients
A total of 6 652 487 laboratory tests of female patients aged 15–54 years
performed between January 1, 2017 and December 31, 2019 were
retrieved from the Dynacare database. After exclusions based on eligi-
bility criteria, or duplicates, 4 623 284 records representing 784 132
patients remained (Figure 1). Median age was 37 years (IQR 27–46).
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3
The median number of laboratory service testing dates per patient was
2 (IQR 1–3). Only 5% of patients had more than 5 service dates within
the study period.
3.2 | Screening for iron deficiency
Of the 784 132 patients in our cohort, 644 066 (82.1%) had a ferritin
checked at least once during the study period for a total of 1 053 367
tests. Mean ferritin was 60.7 μg/L (SD 86.9 μg/L) and median 41.0
(IQR 21.0–74.0). Of 642 588 patients who had any test results avail-
able over the study period, 38.3% were ever iron deficient with ferri-
tin less than 30 μg/L.
Table 1 presents data for the first ferritin check by ferritin level.
The proportion of patients with NAID at their first ferritin check was
34.7%. Most ferritins were ordered by family physicians or general
practitioners (74.1% of tests), with 7.2% of tests ordered by
obstetrician-gynecologists or internists and internal medicine subspe-
cialists, 2.4% by other specialties and 16.3% did not have specialty
information. Of the patients who ever had a ferritin check, only
10 670 (1.66%) did not have a hemoglobin check within 90 days of
the ferritin test.
3.3 | Screening for anemia
A total of 709 434 (90.5%) had a CBC checked at least once. Among
1 509 926 tests, the mean hemoglobin was 130.1 g/L (SD 12.9 g/L)
and the median was 132.0 (IQR 124.0–138.0). The distribution of ane-
mia tests by severity level is presented in Table 2.
Of 708 337 who had a CBC result, 134 265 (19%) were anemic
at least once. To determine the proportion ever screened for IDA, we
looked at patients who had both a CBC and ferritin checked within
90 days. A total of 633 396 (80.8%) in our cohort were screened for
IDA, with test results available for 631 721 patients, and 82 655
(13.1%) met the criteria for a diagnosis of IDA.
Of the 633 396 screened for IDA, 631 786 had mean corpuscular
volume (MCV) results with 89.5% having an MCV while only 8.9%
had a low MCV. Of the 82 655 who met the criteria for IDA diagnosis,
the majority had a normal MCV (Table S3).
3.4 | Income, screening, and iron deficiency
The median after-tax household income was CAD$89454.80 (IQR
CAD$69359.50–106620.50). Most were in Q2 and Q3 of household
income, representing 41.6% and 44.3%, respectively. Only 9.0% of
patients were in Q1 (household income less than CAD$60 000), while
4.7% in Q4 ($125 000–149 999) and 0.3% in Q5 (greater than
$150 000). The frequency distributions by income quintile are pre-
sented in supplemental materials Figure S3.
The odds of ever being diagnosed with IDA or all-cause anemia
were generally lower in higher income quintiles compared with the
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4 WEN ET AL.

FIGURE 1 STROBE flow diagram of participants screened for eligibility for the final cohort.

T A B L E 1 Proportion of patients with iron deficiency by ferritin There does not appear to be a clear gradient effect between iron
level, at their first ferritin check. insufficiency or severe iron deficiency and income (Figure S6).

Number of patients
Ferritin (μg/L) (% of all patients)
>150 (above the upper limit of normal) 41 425 (6.5%) 3.5 | Follow-up investigations following a
45–150 (normal) 263 497 (41.1%)
diagnosis of iron deficiency or iron deficiency anemia
30–44.9 (iron insufficient) 114 572 (17.9%)
Of those who had a CBC checked, severe anemia was associated with
15–29.9 (iron deficiency) 130 182 (20.3%)
an increased frequency of subsequent ferritin checks (Table S4). Of
<14.9 (severe iron deficiency) 92 292 (14.4%)
the 82 655 who met the criteria for IDA, 21.1% (17 432 patients)
Missing results at first ferritin check 2098
had follow-up testing with hemoglobin and ferritin within 180 days of
initial diagnosis, with a median of 98 days (IQR 58–135). Of those
with IDA, lower initial hemoglobin was associated with increased odds
lowest income quintile (Figure 2A,B). This gradient effect is not of follow-up testing with hemoglobin and ferritin checked within
entirely preserved for odds of NAID (Figure 2C). Higher-income 180 days of initial diagnosis (Figure S4).
quintiles had greater odds of being screened for NAID and all-cause Of patients who had a ferritin test, 36.9% (237 771) had
anemia compared with the lowest-income quintile (Figure 2D,E). at least one subsequent ferritin check during the study period.

WEN ET AL.
T A B L E 2 Proportion of hemoglobin tests by anemia severity
categories among patients who ever had a hemoglobin check with
results (N = 708 337).
Number of tests
Hemoglobin level (g/L) (% of all hemoglobin tests)
>120 (normal hemoglobin) 1 264 766 (83.8)
110–119 147 533 (9.8)
100–109 57 047 (3.8)
90–99 23 638 (1.6)
80–89 10 382 (0.7)
70–79 4449 (0.3)
<70 2111 (0.1)
Note: A total of 1 509 926 hemoglobin tests representing 708 337
patients were ordered. A total of 1097 patients had hemoglobin tests
ordered but were missing test results.
Of those with multiple ferritin tests, 92 302 patients had NAID
(ferritin <30 μg/L) at their first test. The 69.4% (64 081) of these
initially iron deficient patients remained iron deficient at their last
ferritin check in the study period, whereas 30.6% had a ferritin
>30 μg/L at their last ferritin check.
3.6 | Age and iron deficiency
The youngest age category (15–24 years) had the lowest prevalence
of IDA at 9.5%. The 35–44 years age category had the highest preva-
lence of IDA, at 14.1% (Table S5). However, those in the oldest age
category (45–54 years) had the highest odds of being screened for
IDA compared to every other age category (Figure S5).
4 | DISCUSSION
We evaluated the prevalence of screening for NAID and IDA in a
large cohort of non-pregnant female patients of reproductive age.
We report a high proportion of patients were screened for NAID
(82.1%) at least once during the 3-year study period. Of those
screened, a high prevalence had NAID (38.3%) and 13.1% had IDA.
These estimates are higher than previous studies in similar popula-
tions in the United States, which reported 9%–21.3% prevalence
4,5
of NAID and 2%–7.5% of IDA. However, previous studies
used extremely low ferritin cut-offs (<12 μg/L) which underesti-
mated the prevalence of NAID.4,5 The under-diagnosis of NAID
represents a systematic missed opportunity for treatment before
the development of anemia, which appears to disproportionately
affect low-income or marginalized patients.22,32
Most ferritin tests (74.1%) were ordered by family physicians and
general practitioners. This shows that family medicine and general
practitioners are the ideal stakeholder group for knowledge transla-
tion interventions designed to better diagnose and treat NAID and
IDA in non-pregnant females. Additionally, most diagnosed with IDA
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5
had a normal MCV, providing further support that microcytosis is
not sensitive to IDA. Overall, a CBC tested alone is inadequate to
screen for IDA.41
There is a higher prevalence and severity of NAID and IDA in
socioeconomically disadvantaged patients.4 Our sampled population
is relatively affluent; this cohort had a relatively high average annual
household income, with a median of CAD$89454.80 compared to the
provincial median of CAD$65285.00 in 2016.42 This may account for
the high proportion who were adequately screened for NAID due to
enhanced access to care.43,44 However, despite this socioeconomic
advantage, our cohort still had a high prevalence of NAID and IDA,
which suggests that these conditions are likely further underdiag-
nosed, thus undertreated, in disadvantaged Ontarian females. Nota-
bly, a large proportion of patients with severe anemia did not have
subsequent ferritin checks (Table S4). Given the limitations of this
study design, we are unable to determine whether patients received
treatment such as oral iron, IV iron, blood transfusions, or had subse-
quent testing done in other laboratories. However, the overall low
follow-up rates of testing for CBC suggest the need for enhanced
follow-up and monitoring of response to treatment.
Our findings also reveal socioeconomic disparities in screening
for NAID; patients from the lowest income households (annual
income <CAD$60000) had the lowest likelihood of being screened for
NAID, as well as lower rates of screening for anemia compared with
higher income quintiles (Figure 2C). Patients in the highest income
quintile Q5 did not have significantly different odds of anemia screen-
ing compared with the lowest quintile (Figure 2E); however, there
were relatively few patients in Q5 (0.3% of patients were in Q5, as
shown in Figure S3) which may have impacted this finding. These
results emulate findings from our previous work examining screening
for NAID in pregnant patients in Ontario, which also found those
from lower-income households were less likely to be screened.22
Other work has shown that pregnant patients living in low-income
neighborhoods in Canada have lower ferritins and a higher frequency
of anemia at delivery.32
Older age categories were more likely to be screened for anemia
and ID compared to the youngest age category (Figure S5). This may
reflect increased utilization of healthcare or improved self-advocacy
with increased age. The 35–44 age group had the highest proportions
of both IDA and NAID (Tables S5 and S6), which may reflect the
impacts of repeated menstruation and pregnancies by this age.
This was a large retrospective cohort study using real-world data
that reflects current clinical practice in Ontario, Canada. However,
there are important limitations to this study. First, in using data from
an outpatient laboratory system, bloodwork performed within hospi-
tals or other laboratory companies are not captured. Patient baseline
variables such as medical history or comorbidities are also unavail-
able. Second, the use of average annual household income derived
from postal code does not account for significant income variation
between households in each area. However, the use of neighbor-
hood income quintiles has been used as a surrogate for socioeco-
nomic status in previous population-based studies.22 Third, the
laboratory definition of pregnancy follows Ontario guidelines for
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6 WEN ET AL.

F I G U R E 2 The odds ratios by income

quintile of (A) ever having IDA (ferritin
<30 μg/L and Hb<120 g/L within 90 days),
(B) ever having anemia (Hb < 120 g/L),
(C) ever having NAID (ferritin <30 μg/L),
(D) ever having a ferritin checked, and E)
ever having a hemoglobin checked within
the study period. All odds ratios were age-
adjusted. The lowest quintile
(Q1) representing an annual household
income of <CAD$60000 is the reference
group. Annual household income was
estimated using the patient's postal code.
Income quintiles were derived from
Statistics Canada provincial census data.

routine pre-partum care; however, this method may not have results for tests. It is a limitation of the study design that we are
excluded those who did not receive routine prenatal care. Fourth, unable to assess the reasons for missing results; these patients were
there is a small number of patients in the cohort who were missing excluded from further analysis.

WEN ET AL.
Lastly, our results may not be generalizable to the entire province
of Ontario. The 2016 Statistics Canada census reported a total of
3 629 930 females in Ontario between the ages of 15 and 54.40 Our
cohort of 784 132 patients, represents only 21.5% of the population.
This cohort, which is relatively affluent as demonstrated by its high
annual household income, inherently represents a subset of the popu-
lation with access to outpatient medical care and laboratory tests.
Thus, the study may not capture the most marginalized individuals
whom we know are more likely to suffer from NAID and IDA, and
likely attenuates the findings of this study. The high proportion of
screening for NAID in this cohort may reflect the ability to access
healthcare and cannot necessarily be extrapolated to the general
population of Ontario.
In conclusion, 38% of non-pregnant female patients of reproduc-
tive age tested at an outpatient laboratory in Ontario, Canada were
iron deficient and 13% had IDA. There were generally low follow-up
testing rates after diagnosis of IDA. Low household income was signif-
icantly associated with higher rates of anemia but lower rates of ferri-
tin testing. This highlights a care gap in screening for NAID and IDA,
with persistent socioeconomically driven health disparities despite
Canada's publicly-funded health services system. There is an urgent
need for properly developed knowledge translation interventions that
consider individual and contextual variables that may lead to intersec-
tional socio-medical vulnerability related to iron deficiency.
CONF LICT OF IN TE RE ST ST AT E MENT
Dr Auerbach receives research support for data management only
from Covis Pharma for studies on restless leg syndrome and bariatrics.
Dr Auerbach provides educational and non-promotional programs for
Pharmacosmos. Dr. Sholzberg has unrestricted research funding and
honoraria from Pfizer.
DATA AVAI LAB ILITY S TATEMENT
Data available on request from the authors.
PATIENT C ONSENT STATEMENT
This study utilized anonymized patient data obtained from Dynacare
Medical Laboratories. Patients provided Dynacare with consent for
the use of their anonymized data for research purposes. Data were
stripped of identifiable information, such as names, addresses, and
contact details.
ORCID
Sophia Wen https://orcid.org/0009-0008-6964-2331
Angela C. Weyand https://orcid.org/0000-0003-2595-8541
Michael Auerbach https://orcid.org/0000-0003-0707-8647
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How to cite this article: Wen S, Nisenbaum R, Weyand AC,
Tang GH, Auerbach M, Sholzberg M. High prevalence of iron
deficiency and socioeconomic disparities in laboratory
screening of non-pregnant females of reproductive age: A
retrospective cohort study. Am J Hematol. 2024;1‐8. doi:10.
1002/ajh.27352