ArticlePDF Available

An evidence-based definition of anemia for singleton, uncomplicated pregnancies

PLOS
PLOS One
Authors:

Abstract and Figures

Background The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970’s to 1980’s. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed. Objective To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients. Materials and methods Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student’s t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant. Results In the public and private populations, 777 and 785 women presented in the first trimester while 223 and 215 presented in the second. The women at the private hospital were more likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth percentile was compared between the women in the private and public hospitals and were clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester, and 10.0 g/dL/30.2% pre-delivery. Conclusions Fifth percentile determinations were made from a combined cohort of normal, uncomplicated pregnancies to define anemia in pregnancy. Comparison of two different cohorts confirms that the same definition for anemia is appropriate regardless of demographics or patient mix.
This content is subject to copyright.
RESEARCH ARTICLE
An evidence-based definition of anemia for
singleton, uncomplicated pregnancies
Amanda C. ZofkieID
1,2
*, W. Holt GarnerID
1‡
, Rachel C. Schell
1‡
, Alexandra
S. RagsdaleID
1‡
, Donald D. McIntireID
1‡
, Scott W. Roberts
1
, Catherine Y. Spong
1
1Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, University of Texas
Southwestern Medical Center, Parkland Health and Hospital System, Dallas, Texas, United States of
America, 2Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Washington
University School of Medicine in St. Louis, St. Louis, Missouri, United States of America
These authors contributed equally to this work.
WHG, RCS, ASR and DDM also contributed equally to this work.
*azofkie@gmail.com,zofkie@wustl.edu
Abstract
Background
The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the
1970’s to 1980’s. To identity women at risk of blood transfusion, a common cause of Severe
Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy
United States cohort is needed.
Objective
To define anemia in pregnancy in a United States population including a large county vs. pri-
vate hospital population using uncomplicated patients.
Materials and methods
Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion
criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval preg-
nancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron for-
tification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-
delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients
were included, 1000 from the public county hospital and 1000 from the private hospital.
Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were com-
pared for differences in the fifth percentile for each antepartum epoch. Student’s t-test and
chi-squared statistical tests were used for analysis, p-value of 0.05 was considered
significant.
Results
In the public and private populations, 777 and 785 women presented in the first trimester
while 223 and 215 presented in the second. The women at the private hospital were more
likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth
PLOS ONE
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 1 / 8
a1111111111
a1111111111
a1111111111
a1111111111
a1111111111
OPEN ACCESS
Citation: Zofkie AC, Garner WH, Schell RC,
Ragsdale AS, McIntire DD, Roberts SW, et al.
(2022) An evidence-based definition of anemia for
singleton, uncomplicated pregnancies. PLoS ONE
17(1): e0262436. https://doi.org/10.1371/journal.
pone.0262436
Editor: Mohamed A Yassin, Qatar University,
QATAR
Received: August 10, 2021
Accepted: December 23, 2021
Published: January 13, 2022
Copyright: ©2022 Zofkie et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: The de-identified data
set underlying this study is available in a
Supporting information file.
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
percentile was compared between the women in the private and public hospitals and were
clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/
hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester,
and 10.0 g/dL/30.2% pre-delivery.
Conclusions
Fifth percentile determinations were made from a combined cohort of normal, uncompli-
cated pregnancies to define anemia in pregnancy. Comparison of two different cohorts con-
firms that the same definition for anemia is appropriate regardless of demographics or
patient mix.
Introduction
Maternal mortality complicated 20.1 per 100,00 live births in 2019 in the United States, a
higher rate than other medically developed countries [1]. As a proxy to mortality, Severe
Maternal Morbidity (SMM) is a set of risk metrics measured to identify these adverse out-
comes, which are often preventable. While the potential morbidities in pregnancy are numer-
ous, the Centers for Disease Control (CDC) has specifically identified the need for blood
transfusion as a leading cause of SMM, an adverse outcome which has increased significantly
in the last two decades [2,3]. As a necessary predictor for the risk of transfusion, and those
women at risk for evaluation and treatment of anemia, an evidence-based definition of anemia
in pregnancy is of paramount importance.
Anemia has been traditionally defined by the CDC and World Health Organization
(WHO) as hemoglobin or hematocrit values less than the fifth percentile of the population in
pregnant and nonpregnant populations [4,5]. In pregnancy, this translates to a hemoglobin of
less than 11 g/dL or a hematocrit less than 33% in the first and third trimesters and a hemoglo-
bin of less than 10.5 g/dL or hematocrit less than 32% in the second trimester, accounting for
the expanded plasma volume of pregnant women [3]. These definitions were originally defined
in 1989 and reaffirmed in 1998 [4,6]. These fifth percentile population values were derived
from four small European studies in pregnant women from the late 1970’s to the 1980’s [7
10]. These studies examined a total of 427 pregnant women between the four studies. The
American College of Obstetricians and Gynecologists has also supported this definition of ane-
mia in pregnancy [11]. To date, there have been no studies to determine if they are valid in a
modern United States pregnant population.
The normal hematologic changes of pregnancy include an expansion of plasma volume
that exceeds the pregnancy-related increase in red blood cell mass which creates a “physio-
logic anemic state.” This physiologic anemia predisposes women to lower hemoglobin and
hematocrit values during pregnancy. Iron deficiency affects 30–38% of women of childbear-
ing age [12]. Several factors can affect hematocrit values in pregnant women, such as short
interval pregnancy, preeclampsia, race, socioeconomic status, and pre-existing maternal
comorbidities. We sought to define anemia in normal, uncomplicated pregnancies. We gath-
ered data from two cohorts of pregnant women: one cohort at a public county hospital and
another at a private hospital and compared these cohorts to identify if there was a difference
between the fifth percentiles. We hypothesized that there would be no statistical or clinical
difference between the cohorts, and thus combined a definition of anemia in pregnancy
could be established.
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 2 / 8
Materials and methods
To evaluate a time-independent, representative normal, uncomplicated cohort, the first 250
women in 2011, 2013, 2015 and 2018 to deliver at a large inner-city county hospital (Parkland
Health and Hospital Systems) and a private University-Practice hospital (Clements University
Hospital) that met inclusion criteria were studied for a total of 2000 women. Women were
included if they presented to prenatal care before 20 weeks of gestation. Exclusion criteria
included preterm birth (less than 37-weeks gestation), preeclampsia, hypertension, diabetes,
short interval pregnancy (less than 18 months from delivery to conception), multiple gestation,
placental abruption, pyelonephritis during the pregnancy, maternal sickle cell disease, mater-
nal hemoglobinopathies, placenta previa, placenta accreta spectrum, fetal demise, and patients
requiring parenteral iron infusions during the antepartum period. Gestational age at presenta-
tion to care and delivery were obtained on all women. All women had iron fortification with
ferrous sulfate 325 mg daily recommended throughout pregnancy. Presentation to care hemo-
globin/hematocrit, and pre-delivery values were obtained. If hemoglobin (g/dL) levels were
not available, they were derived from the hematocrit levels drawn [13,14]. The fifth percentile
for both hemoglobin and hematocrit was determined from the cohorts and the fifth percentile
was determined for presentation to care, first trimester, second trimester, and pre-delivery.
The cohorts were compared in demographics, hemoglobin/hematocrit values, and their fifth
percentiles. The primary outcome was the difference between fifth percentile values at each
antepartum epoch between the public and private hospital cohorts. This study was deemed
exempt by the Institutional Review Board (IRB) at the University of Texas Southwestern Medi-
cal Center (STU 2020–0200) and the IRB waived the requirement for informed consent. The
data set was not fully anonymized before it was accessed but was anonymized before data
analysis.
After comparison of the cohorts was completed, the two cohorts were combined to create
a diverse patient mixed cohort to use for the definition of anemia in normal, uncomplicated
pregnancies. The fifth percentile of the combined cohort (n = 2000) as a whole was calculated
for each antepartum epoch.
Statistical analysis
Maternal demographics were compared using the student’s t-test or chi-squared test where
appropriate. Fifth percentile values of each antepartum epoch were compared between the
cohorts by estimating the fifth percentiles through the empirical distribution (ordered data
points) by locating the first point in the ordered distribution which is 5% of the way through
the distribution. Estimates of the difference in the fifth percentile between the public and pri-
vate hospital cohorts were estimated using quantile regression with an indicator variable of
hospital location. The estimate of the coefficient was then the estimate of the fifth percentile.
Confidence intervals were presented using the Student’s t-distribution for this estimate. The
null hypothesis of the test is that the coefficient of the indicator variable is equal to zero. This
was then evaluated with the student’s t-test.
Results
Of the 2000 women, there were 1000 from the public and 1000 from the private hospital. Each
cohort of 1000 patients were comprised of the first 250 patients to deliver at each institution in
2011, 2013, 2015, and 2018 that met criteria for inclusion in order to identify women without
complications. To identify a normal, uncomplicated cohort of 1000 women in each cohort,
3567 women were screened with 842 excluded in the public hospital cohort and 725 in the pri-
vate hospital cohort, as per the exclusion criteria (Fig 1). In the public cohort this included 197
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 3 / 8
women in 2011, 182 women in 2013, 208 women in 2015, and 255 women in 2018 in the pub-
lic cohort. The private cohort excluded 388 women in 2011, 72 women in 2013, 116 women in
2015 and 149 women in 2018. Maternal demographics and outcomes of each normal, uncom-
plicated cohort are depicted and compared in Table 1. Those patients in the private hospital
cohort were significantly older, more likely to be nulliparous, and had a higher percentage of
White women when compared to the public hospital cohort, which had a higher percentage of
Hispanic women.
The hematologic indices in each cohort and antepartum epoch are presented and compared
in Table 2. Seven hundred and seventy-seven patients presented in the first trimester (less than
14 weeks gestation) in the public hospital cohort, with 785 in the private cohort. When com-
pared by student’s t-test, the hemoglobin mean in each antepartum epoch and the hematocrit
mean in the second trimester and third trimester/predelivery were statistically different
between the cohorts. The estimates of the fifth percentiles of each antepartum epoch are com-
pared between the public hospital cohort and the private hospital cohort in Table 3. The pre-
delivery hemoglobin and hematocrit fifth percentile estimates were statistically different
between the cohorts.
Fig 1. Flow diagram of anemia cohort distribution.
https://doi.org/10.1371/journal.pone.0262436.g001
Table 1. Maternal demographics and obstetric outcomes.
Characteristic Public Hospital Cohort (n = 1000) Private Hospital Cohort (n = 1000) p-value
Age (years) 27.4±6.2 29.6±5.6 <0.001
Race/Ethnicity <0.001
Hispanic 850 (85) 121 (12)
Black 99 (10) 196 (20)
White 21 (2) 405 (40)
Other 30 (3) 161 (16)
Unknown 0 (0) 117 (12)
Nulliparous 322 (32) 509 (51) <0.001
Gestational Age at Presentation to Care (weeks) 10.4±3.7 10.8±3.4 0.01
Delivery mode 0.46
Vaginal Delivery 692 (69) 707 (71)
Cesarean Section 308 (31) 293 (29)
Data expressed as n (%) or mean ±standard deviation as appropriate. Student’s t-test and Chi-squared tests used where appropriate.
https://doi.org/10.1371/journal.pone.0262436.t001
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 4 / 8
The combined cohort of normal, uncomplicated pregnancies fifth percentiles of each ante-
partum epoch are detailed in Table 4, which can be used to define anemia at each timepoint in
pregnancy.
Conclusions
By comparing the hematologic indices of normal, uncomplicated diverse populations of
obstetric patients at each antepartum epoch, we demonstrate that the definition of maternal
anemia is consistent. Using this combined uncomplicated, normal pregnancy cohort, we iden-
tified normal fifth percentile cutoff values to define anemia in pregnancy. The fifth percentile
hematocrit and hemoglobin cutoff values of 10.7 g/dL or 32.1% at presentation to care, 11.0 g/
dL or 32.8% in the first trimester, 10.3 g/dL or 30.6% in the second trimester, and 10.0 g/dL or
30.2% pre-delivery can be used for normal, uncomplicated pregnancies.
Table 2. Average hemoglobin/hematocrit per antepartum epoch.
Antepartum Epoch Public Hospital Cohort (n = 1000) Private Hospital Cohort (n = 1000) p-value
Presentation to Care N = 1000 N = 1000
Hemoglobin (g/dL) 12.3±0.9 12.4±1.1 0.03
Hematocrit (%) 36.9±2.7 37.0±3.0 0.43
First Trimester N = 777 N = 785
Hemoglobin g/dL) 12.4±0.9 12.6±1.0 <0.001
Hematocrit (%) 37.4±2.6 37.3±2.9 0.47
Second Trimester N = 223 N = 215
Hemoglobin (g/dL) 11.8±0.9 12.1±1.1 0.002
Hematocrit (%) 35.3±2.7 35.9±3.1 0.03
Pre-Delivery N = 1000 N = 1000
Hemoglobin (g/dL) 12.1±1.1 11.9±1.3 <0.001
Hematocrit (%) 36.2±3.2 35.9±3.4 0.04
Data expressed as mean ±standard deviation.
https://doi.org/10.1371/journal.pone.0262436.t002
Table 3. Comparison of fifth percentile estimates between cohorts by antepartum epoch.
Antepartum Epoch Public Hospital Cohort Fifth Percentile Estimate Private Hospital Cohort Fifth Percentile Estimate p-value
Presentation to Care N = 1000 N = 1000
Hemoglobin (g/dL) 10.7 (10.6, 10.9) 10.7 (10.6, 10.9) 0.78
Hematocrit (%) 32.2 (31.8, 32.7) 32.2 (31.4, 32.4) 1.00
First Trimester N = 777 N = 785
Hemoglobin (g/dL) 11.0 (10.9, 11.1) 11.0 (10.8, 11.1) 1.00
Hematocrit (%) 33.0 (32.7, 33.4) 32.5 (32.2, 33.0) 0.09
Second Trimester N = 223 N = 215
Hemoglobin (g/dL) 10.2 (9.7, 10.5) 10.4 (9.6, 10.6) 0.55
Hematocrit (%) 30.6 (29.1, 31.4) 30.8 (28.7, 31.6) 0.83
Pre-Delivery/Third Trimester N = 1000 N = 1000
Hemoglobin (g/dL) 10.2 (10.0, 10.4) 9.6 (9.3, 9.8) <0.001
Hematocrit (%) 30.7 (30.1, 31.1) 29.9 (29.3, 30.4) 0.02
Data presented as Fifth Percentile Estimate (95% Confidence Interval).
https://doi.org/10.1371/journal.pone.0262436.t003
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 5 / 8
The European studies from the 1970’s and 1980’s used iron fortified pregnant women to
obtain their mean and fifth percentile hemoglobin and hematocrits [68,15]. In turn, the
CDC adopted these measures as there were no comparable population-based studies in the
United States for normal pregnant women. Our pre-delivery hematocrit in term pregnancies
of 30.2% in our selected “normal” population is less than the recognized 33% from the Centers
for Disease Control. However, the United States population is different and more diverse than
that of Scandinavia, and there have been significant changes in obstetric and medical care
within the past 35 years.
In our data set, there were statistical differences between the hemoglobin mean in each
antepartum epoch and the hematocrit mean in the second trimester and third trimester/prede-
livery between the cohorts. However, it could be argued that these differences are clinically
irrelevant as these differences are within the standard of error.
Anemia can have many different causes and contributing factors to its development and
pathophysiology. To be able to define cutoff values, it is critical to use a normal, healthy and
uncomplicated obstetric population. By defining anemia in pregnancy, we are able to identify
women at risk of severe maternal morbidity and mortality and circumvent the need for blood
transfusion postpartum. Furthermore, this will translate into the timing of interventions such
as iron fortification and other measures to increase hematocrit in pregnancy prior to delivery,
such as parenteral iron or erythropoietin derivatives [16].
Determining women at the highest risk for blood transfusion, a marker for severe maternal
morbidity, is imperative when determining when to intervene in the events surrounding deliv-
ery. Defining a hemoglobin cutoff of 10.0 g/dL and hemoglobin cutoff of 30.2% at delivery to
be the fifth percentile cutoff values will assist labor and delivery clinicians in determining
which patients may be at highest risk for a blood transfusion or severe maternal morbidity sur-
rounding delivery and allow them to prepare by alerting the blood bank or having postpartum
hemorrhage treatments readily available at delivery.
This study determines fifth percentile values to define anemia from a modern, United States
pregnant cohort. Future studies can focus on defining anemia by maternal outcomes, specifi-
cally Severe Maternal Morbidity outcomes and determine if patients who had poor outcomes
had differing values than fifth percentile values from a normal, uncomplicated population.
Future studies also need to focus on interventions that can prevent SMM in anemic popula-
tions prior to delivery.
A strength of our study is that we provide data from a modern United States cohort to
define normative values for anemia. Current recommendations are based on small studies that
were performed in European countries over 35 years ago. In addition, consistent with studies
defining anemia in non-pregnant individuals, we used a normal, healthy population, control-
ling for obstetric and medical complications that could impact the hematologic values at deliv-
ery, which has not been previously described.
One of the main limitations of our study were that our cohort was representative of a
majority white-Hispanic population. Only a minority of our combined population (n = 295 or
15%) was African American, a population in which anemia in pregnancy is prevalent. There is
Table 4. Anemia defined, fifth percentile values of a normal, uncomplicated population.
Antepartum Epoch Hemoglobin (g/dL) Hematocrit (%)
Presentation to Care 10.7 32.1
First Trimester 11.0 32.8
Second Trimester 10.3 30.6
Pre-Delivery/Third Trimester 10.0 30.2
https://doi.org/10.1371/journal.pone.0262436.t004
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 6 / 8
support, however, for equivalent iron stores (higher ferritin levels in African American men
and women) between Caucasian and African American women [17,18]. At our public hospital
system, we primarily utilize hematocrits because of the nature of our hospital and prenatal
care clinic system. Hematocrits, not complete blood counts, are often obtained in our prenatal
clinicals and labor and delivery area due to this reason. However, hematocrit and hemoglobin
are equivalent measures in most patients, and the equivalent values can be estimated from
each other with clinical accuracy [13,14]. It is also acknowledged that some women in our
overall cohort may have underlying iron deficiency anemia or an unknown diagnosis of thalas-
semia that may skew the results. This could not be clarified in our data set as not all women
had iron, ferritin, or mean corpuscular volume drawn during their routine pregnancy labora-
tory studies. Finally, while iron fortification was recommended for all women, compliance
remains a limitation. we were not able to evaluate if each patient was compliant with the
recommendation.
These data provide guidance for practitioners defining anemia in a United States popula-
tion as hematocrit and hemoglobin values of 32.1% or 10.7 g/dL at presentation to care, 32.8%
or 11.0 g/dL in the first trimester, 30.6% or 10.3 g/dL second trimester, and 30.2% or 10.0 g/dL
pre-delivery. These data will be essential for risk stratification for postpartum hemorrhage,
blood transfusion, and understanding severe maternal mortality indicators. With a standard,
contemporary definition, an approach to mitigate anemia at delivery and improve pregnancy
outcomes is possible.
Supporting information
S1 Data.
(XLSX)
Acknowledgments
We thank the obstetric patients at Parkland Health and Hospital Systems and Clements Uni-
versity Hospital.
Author Contributions
Conceptualization: Amanda C. Zofkie, Scott W. Roberts, Catherine Y. Spong.
Data curation: Amanda C. Zofkie, W. Holt Garner, Rachel C. Schell, Alexandra S. Ragsdale,
Donald D. McIntire, Scott W. Roberts, Catherine Y. Spong.
Formal analysis: Amanda C. Zofkie, Donald D. McIntire, Scott W. Roberts, Catherine Y.
Spong.
Investigation: Amanda C. Zofkie, Scott W. Roberts, Catherine Y. Spong.
Methodology: Amanda C. Zofkie.
Project administration: Amanda C. Zofkie, Catherine Y. Spong.
Resources: Catherine Y. Spong.
Supervision: Amanda C. Zofkie, Scott W. Roberts, Catherine Y. Spong.
Validation: Amanda C. Zofkie, Scott W. Roberts, Catherine Y. Spong.
Writing original draft: Amanda C. Zofkie, W. Holt Garner, Rachel C. Schell, Alexandra S.
Ragsdale, Scott W. Roberts, Catherine Y. Spong.
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 7 / 8
Writing review & editing: Amanda C. Zofkie, W. Holt Garner, Rachel C. Schell, Alexandra
S. Ragsdale, Scott W. Roberts, Catherine Y. Spong.
References
1. Hoyert DL. Maternal mortality rates in the United States, 2019. NCHS Health E-Stats [Internet]. 2021
Apr [cited 2021 Jul 22]; [about 5 p.] https://www.cdc.gov/nchs/data/hestat/maternal-mortality-2021/E-
Stat-Maternal-Mortality-Rates-H.pdf.
2. Kilpatrick SK, Ecker JL. Severe maternal morbidity: screening and review. Am J Obstet Gynecol. 2016;
215(3):B17–22. https://doi.org/10.1016/j.ajog.2016.07.050 PMID: 27560600
3. Callaghan WM, Creanga AA, Kuklina EV. Severe maternal morbidity among delivery and postpartum
hospitalizations in the United States. Obstet Gynecol. 2012; 120(5):1029–1036. https://doi.org/10.
1097/aog.0b013e31826d60c5 PMID: 23090519
4. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Con-
trol and Prevention. MMWR Recomm Rep. 1998; 47(Rr-3):1–29. PMID: 9563847
5. WHO Guidelines Approved by the Guidelines Review Committee. In: WHO Recommendations on Ante-
natal Care for a Positive Pregnancy Experience. Geneva: World Health Organization 2016.; 2016.
6. CDC criteria for anemia in children and childbearing-aged women. MMWR Morb Mortal Wkly Rep.
1989; 38(22):400–404. PMID: 2542755
7. Svanberg B, Arvidsson B, Norrby A, Rybo G, Solvell L. Absorption of supplemental iron during preg-
nancy—a longitudinal study with repeated bone-marrow studies and absorption measurements. Acta
Obstet Gynecol Scand Suppl. 1975; 48:87–108. https://doi.org/10.3109/00016347509156332 PMID:
1062910
8. Sjostedt JE, Manner P, Nummi S, Ekenved G. Oral Iron Prophylaxis During Pregnancy–A Comparative
Study on Different Dosage Regimens. Acta Obstet Gynecol Scand. 1977; 56(S60):3–9. https://doi.org/
10.1111/aogs.1977.56.s60.3 PMID: 29120032
9. Puolakka J, Janne O, Pakarinen A, Jarvinen PA, Vihko R. Serum ferritin as a measure of iron stores
during and after normal pregnancy with and without iron supplements. Acta Obstet Gynecol Scand
Suppl. 1980; 95:43–51. https://doi.org/10.3109/00016348009156379 PMID: 6935911
10. Taylor DJ, Mallen C, McDougall N, Lind T. Effect of iron supplementation on serum ferritin levels during
and after pregnancy. Br J Obstet Gynaecol. 1982; 89(12):1011–1017. https://doi.org/10.1111/j.1471-
0528.1982.tb04656.x PMID: 7171510
11. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008; 112(1):201–207. https://
doi.org/10.1097/AOG.0b013e3181809c0d PMID: 18591330
12. Camaschella C. Iron-deficiencyanemia, N Engl J Med. 2015; 372(19):1832–1843. https://doi.org/10.
1056/NEJMra1401038 PMID: 25946282
13. Weatherall MS, Sherry KM. An evaluation of the Spuncrit infra-red analyser for measurement of haema-
tocrit. Clin Lab Haematol. 1997; 19(3):183–186. PMID: 9352142
14. Nijboer JMM, van der Horst ICC, Hendriks HGD, ten Duis HJ, Mifsten MWN. Myth or reality: hematocrit
and hemoglobin differ in trauma. J Trauma. 2007; 62(5):1310–2. https://doi.org/10.1097/TA.
0b013e3180341f54 PMID: 17495743
15. World Health Organization. (2001). The Clinical use of blood in medicine, obstetrics, paediatrics, sur-
gery and anaesthesia, trauma and burns. Geneva: World Health Organization, Blood Transfusion
Safety. https://apps.who.int/iris/handle/10665/42397.
16. Sienas L, Wong T, Collins R, Smith J. Contemporary uses of erythropoietin in pregnancy: a literature
review. Obstet Gynecol Surv. 2013; 68(8):594–602. https://doi.org/10.1097/OGX.0b013e3182a2d51c
PMID: 23921673
17. Johnson_Spear MA, Yip R. Hemoglobin difference between black and white women comparable iron
status: justification for race-specific anemia criteria. Am J Clin Nutr 1994; 60:117–21. https://doi.org/10.
1093/ajcn/60.1.117 PMID: 8017324
18. Perry GS, Byers T, Yip R, Margen S. Iron nutrition does not account for the hemoglobin differences
between blacks and whites. J Nutr 1992; 122:1417–24. https://doi.org/10.1093/jn/122.7.1417 PMID:
1619469
PLOS ONE
Defining anemia in pregnancy
PLOS ONE | https://doi.org/10.1371/journal.pone.0262436 January 13, 2022 8 / 8
... Anemia was de ned as a hemoglobin value of less than 11 g/dL [10]. ...
Preprint
Full-text available
Background Iron-folate (IFA) supplementation is a well-established strategy for reducing anemia in pregnant women. Studies on the extent to which it reduces maternal anemia, its effect on leukocytes and platelet count are limited and require further investigation. Objective This study aimed to assess effect of iron folate supplementation on maternal hematological parameters among pregnant women in public hospitals in Addis Ababa, Ethiopia. Methods An institution-based prospective follow-up study was conducted in public hospitals in Addis Ababa from May 1, 2023, to March 30, 2024, with 410 participants selected through systematic random sampling. Data collection involved interviews, medical record reviews, and laboratory tests. Statistical analysis was performed using SPSS Version 27, including Shapiro-Wilk test, descriptive statistics, paired sample t-tests, and Wilcoxon signed-rank tests. A p-value of less than 0.05 was considered significant. Results The RBC count significantly increased in both sets of respondents. In non-anemic individuals, it rose from a baseline of 4.51 ± 0.43 to 4.70 ± 0.54 million cells per microliter (P < 0.001), while in anemic respondents, it increased from 4.05 ± 0.37 to 4.23 ± 0.39 million cells per microliter (P < 0.001). Similarly, the platelet count decreased across both groups. In anemic participants, it dropped from 293.3 ± 37.01 to 285.4 ± 37.83 thousand per microliter (P < 0.01), and in non-anemic pregnant women, it declined from 274.9 ± 56.3 to 254.29 ± 59.07 thousand per microliter (P < 0.001). After supplementation, no significant change in leukocyte count was observed in both anemic and non-anemic pregnant women (p = 0.065 and p < 0.059) respectively. Conclusion Iron-folate supplementation significantly increased RBC counts in both anemic and non-anemic pregnant women, with a slight decrease in platelet counts and no change in leukocyte levels. Further research on the effect of iron folate intake on hematological indices is recommended.
... Anemia was de ned as a hemoglobin value of less than 11 g/dL [9]. Hemoglobin responses to IFA supplementation were categorized as either adequate or inadequate [5,10]. ...
Preprint
Full-text available
Background Iron-folate supplementation is a common recommended strategy for reducing the incidence of anemia in pregnant women. However, studies on the hemoglobin response to iron folate supplementation and factors associated with the effectiveness of the intervention in developing countries, including Ethiopia, are limited. Objective This study aimed to assess the hemoglobin response to iron folate supplementation and associated factors among pregnant women attending public hospitals in Addis Ababa, Ethiopia. Methods A prospective follow-up study was conducted in public hospitals in Addis Ababa between May 1, 2023, and March 30, 2024. A total of 410 participants were selected via systematic random sampling. The data collection methods included participant interviews, medical record reviews, laboratory tests, and anthropometric assessments. Statistical analyses were carried out via SPSS Version 27. Descriptive statistics were used to describe the profile of the study participants. A p value of less than 0.05 was considered statistically significant. Logistic regression analysis was performed, and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated to identify significant associations. Results A total of 59.7% of pregnant women exhibited an inadequate hemoglobin response to iron-folate supplementation, and 17% remained anemic despite supplementation. Early ANC booking (AOR = 3.9, 95% CI: 2.4–4.2), iron-folate intake for more than two months (AOR = 2.6, 95% CI: 1.6–4.2), adequate dietary diversity (OR = 3.4, 95% CI: 2.1–5.6), and primiparity (OR = 2.4, 95% CI: 1.4–4.2) were significantly associated with an adequate hemoglobin response. Conclusion The response of hemoglobin to iron-folate supplementation is low. Promoting early antenatal care, prolonged iron-folate supplementation, and ensuring adequate dietary diversity are crucial to improve the hemoglobin response in pregnant women. Efforts to increase awareness and accessibility to these key factors can help reduce the burden of anemia during pregnancy and improve maternal and fetal health outcomes.
... g/dL), moderate (Hb 7-9.9 g/dL) and severe (Hb <7 g/dL) (WHO, 2011). The Center of Disease Control (CDC) defined in detail that Hb level lower than 11 g/dL or Hct level lower than 33% in the first and third trimester of pregnancy and Hb level lower than 10.5 g/dL or Hct level lower than 32% in the second trimester of pregnancy us due to the physiological changes during pregnancy (CDC, 1989;Zofkie et al., 2022). ...
Article
Full-text available
Background: Iron deficiency anemia in pregnant women is a crucial global health problem. Iron deficiency anemia is impacted on health during antenatal, labor and postpartum period. Although the national policy provides the preventive and solving the maternal anemia, the statistics of maternal anemia are still high. Purpose: The aim of the study is to develop a health promotion program that is suitable for maternal anemia. Methods: Qualitative research was used to develop the health promotion program on maternal anemia through in-depth interviews. Ten pregnant women who had hematocrit less than 33 volume percentages or hemoglobin less than 11 g/dl and five healthcare professionals were selected by purposive sampling. A total of fifteen participants were interviewed based on the semi-structured questionnaire for 30-45 minutes per case at the antenatal care clinic, Watbot hospital, Phitsanulok, Thailand. The period of the study was six months from the first of August 2022 until the end of January 2023. Results: Thematic analysis was used to analyze the data and identified three main themes: 1) encouragement the attitude of self-care during pregnancy; 2) accessibility of the program ; and 3) practical use of the program and integrating the program based on the context of pregnant women and healthcare professionals. Conclusion: The health promotion program was developed suitable for maternal anemia. The tailored program should be tested in terms of feasibility, accessibility, and practical use. It will support pregnant women with anemia, develop a key performance index of maternal and child health, decrease risks and complications, and promote maternal and child health based on the various contexts.
... Based on Riskesdas data in 2013, the prevalence of anemia in young women was 23% and it had increased in 2018 by 32%, meaning that 3-4 out of 10 adolescents suffer from anemia. The government's program to administer Blood Supplement Tablets (TTD) to young women aims to reduce the prevalence of anemia which is still high in young women (Zhu et al., 2020;Zofkie et al., 2022). This activity is in the form of giving blood-supplemented tablets for 4 months to young women which must be consumed according to the rules so that young women do not experience iron nutritional anemia. ...
Article
Full-text available
Anemia is a nutritional problem in young women that needs to be prevented and addressed because it will impact the First 1000 Days of Life (HPK) period. Creating functional food products in the form of contemporary drinks that are nutritious and liked by teenagers is very important as an alternative to preventing anemia. Delays in early treatment of anemia have an impact on women experiencing pregnancy, which can cause bleeding complications during childbirth, giving birth to babies with low body weight and stunting. This condition must be treated as early as possible, because anemia in young women can indirectly affect the quality of human resources in the future. The purpose of this study was to find out how the Formulation and Analysis of the Nutritional Content of Millenia (Anti-Anemia Jelly Drink) to Increase Hemoglobin Levels in Young Girls. This type of research is experimental research, using a completely randomized study design consisting of three factors, in this case the researchers used three treatments, namely red guava juice with the addition of moringa leaf jelly and beet jelly using the symbols A1, A2 and A3. In treatment A1, red guava fruit juice, honey, moringa leaf jelly, and beetroot jelly were added at the respective doses of 200 ml, 20 gr, 10 gr, 20 gr. This drink is expected to be a drink that is rich in iron and other nutrients that can increase hemoglobin levels in the blood and is liked by teenagers because it is made like a contemporary drink that is currently a trend
Article
Full-text available
Importance Postpartum transfusion is the most common indicator of severe maternal morbidity in the US. Higher rates of anemia are associated with a higher blood transfusion rate. Objective To determine if providing, rather than recommending, supplements with iron at prenatal visits in a medically underserved community is associated with improved hematologic indices and reduced blood transfusion. Design, Setting, and Participants In this quality improvement study, patients who delivered between May 13 and December 13, 2020, and thus were provided a prenatal supplement with iron throughout pregnancy were compared with those who delivered between January 1 and August 1, 2019, before supplements were dispensed. The study was conducted at Parkland Health, a safety net hospital in Dallas, Texas, with a 95% Medicaid-funded or self-pay population and included all patients who delivered at our institution during the study period with available hematologic data. Exposures In the earlier cohort, all patients were recommended to obtain and take iron supplements. In the later cohort, prenatal supplements with iron were dispensed via clinic pharmacy to all patients during prenatal visits. Main Outcomes and Measures Maternal hematocrit levels (28-32 weeks, delivery admission, and discharge), rates of anemia (hematocrit <30%), and postpartum transfusion for acute blood loss anemia were compared using χ ² and analysis of variance methods with P < .05 considered significant. The analysis took place in July of 2022. Results Overall, 13 910 patients (98%) met inclusion criteria (mean age [SD], 27.9 [6.5] and 27.6 [6.5] years, mean [SD] body mass index at first visit, 29.2 [6.6] and 29.3 [6.6]). Mosty of the patients in both cohorts were of Hispanic ethnicity (76%). Providing iron-containing prenatal supplements was associated with higher average hematocrit levels at all time points including a mean difference of 1.27% (95% CI, 1.13%-1.42%) on admission for delivery, when compared with those who were not directly dispensed iron. Among patients prior to providing supplements, 18% had anemia on admission compared with 11% with iron-containing supplements dispensed (risk ratio [RR], 0.61; 95% CI, 0.56-0.66). Postpartum transfusion for acute blood loss anemia was reduced by one-third in patients after program implementation from 10 per 1000 to 6.6 per 1000 (RR, 0.62; 95% CI, 0.43-0.91). Conclusions and Relevance In this quality improvement study, providing supplements with iron to patients at prenatal visits was associated with improved hematocrit levels, rates of anemia, and reduced transfusions unrelated to obstetric catastrophes among a predominantly Medicaid population.
Article
Background: Few normative longitudinal hemoglobin data are available to estimate the prevalence and risk factors for anemia among a multiethnic United States pregnant population. Objectives: The aim of this study was to characterize hemoglobin distributions and prevalence of anemia in a pregnant population receiving care at a large urban medical center. Methods: A retrospective medical chart review was undertaken in 41,226 uncomplicated pregnancies of 30,603 pregnant individuals who received prenatal care between 2011 and 2020. Mean hemoglobin concentrations and anemia prevalence in each trimester and incidence of anemia during pregnancy in a subset of 4821 women with data in each trimester were evaluated in relation to self-reported race and ethnicity and other possible risk factors. Risk ratios (RRs) of anemia were determined using generalized linear mixed-effects models. Smoothed curves describing changes in hemoglobin across pregnancy were created using generalized additive models. Results: The overall prevalence of anemia was 26.7%. The observed fifth percentiles of the hemoglobin distributions were significantly lower than the United States CDC anemia cutoffs in the second and third trimesters (T3). The RR (95% CI) of anemia were 3.23 (3.03, 3.45), 6.18 (5.09, 7.52), and 2.59 (2.48, 2.70) times higher in Black women than that in White women in each trimester, respectively. Asian women recorded the lowest risk of anemia compared with other racial groups in T3 (compared with White womenRR: 0.84; 95% CI: 0.74, 0.96). Hispanic women presented a higher risk of anemia in T3 than non-Hispanic women (RR: 1.36; 95% CI: 1.28, 1.45). In addition, adolescents, individuals with higher parity, and those carrying multiple fetuses experienced a higher risk of developing anemia in late gestation. Conclusions: Anemia was evident in more than one-quarter of a multiethnic United States pregnant population despite current universal prenatal iron supplementation recommendations. Prevalence of anemia was higher among Black women and lowest among Asian and White women.
Article
Full-text available
Many researchers have reported lower hemoglobin concentrations in blacks than in whites, but the reason for this difference is unknown. Data for 2515 persons (in 3-12 y and 18-45 y age groups) from the Second National Health and Nutrition Examination Survey (NHANES II) were evaluated to investigate the roles of iron intake and biochemical iron status indicators in explaining black and white differences in hemoglobin concentration. Dietary iron intake was estimated from one 24-h food recall, and hemoglobin, serum ferritin, transferrin saturation and erythrocyte protoporphyrin were measured by standard laboratory methods. Hemoglobin levels were substantially lower in black children (120.3 g/L) than in white children (126.8 g/L). Hemoglobin concentrations were also lower in black women (128.4 g/L) than in white women (133.9 g/L), and in black men (144.8 g/L) than in white men (153.2 g/L). Blacks had lower hemoglobin concentration than whites at most levels of dietary iron intake, serum ferritin, transferrin saturation and erythrocyte protoporphyrin. Despite their lower hemoglobin levels, blacks had higher serum ferritin levels than whites. These results suggest that the difference in hemoglobin concentrations between blacks and whites in the United States is the result of factors other than iron intake and iron status. More specific investigations of both the genetic and environmental determinants of iron utilization in blacks are needed.
Article
This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review. © 2016 American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Article
The effect of oral iron prophylaxis on haemoglobin concentration (Hb) and haematocrit (Hct) has been studied in 300 pregnant women. From the 3rd to 4th month of pregnancy and until term the women were randomly treated with 100 mg or 200 mg ferrous iron daily respectively as sustained‐release tablets (Duroferon ® Duretter ® ) or 200 mg ferrous iron as rapidly disintegrating tablets. All three treatments gave the same effect on Hb and Hct. This was true irrespective of the initial Hb. It was concluded that even the 100 mg dose was sufficient to cover the increased iron demands during pregnancy and to give an increase in Hb in anemic patients. The frequency of side‐effects was lower in the two groups receiving the sustained‐release tablets. The changes in Hb with time during pregnancy in relation to the initial iron status are discussed and some practical conclusions concerning the interpretation of the effect of iron supplementation during pregnancy are drawn.
Article
Objective: The objectives of this study were to survey the current research and provide an update on the uses and benefits of erythropoietin (EPO) in pregnancy and the postpartum period. Data sources: A review of MEDLINE (1947 to present) was performed. Search terms included "erythropoietin," "pregnan*," with subheadings of "administration & dosage," "pharmacokinetics," "therapeutic use," "fetus," "fertility." Method of study selection: We reviewed relevant articles published from 2002 to 2012. Case reports, observational studies, case-control studies, randomized controlled trials, retrospective analyses, animal studies, and review articles were included. Articles were selected if they discussed a use of EPO in pregnancy or the immediate postpartum period, as well as use of EPO in the neonate. Tabulation, integration, and results: Authors independently reviewed and extracted data. Of the 65 articles reviewed, 45 were included. Erythropoietin was used in the treatment of maternal anemia. Because of the molecule's large size, recombinant EPO does not appear to cross the placenta. No fetal morbidity or mortality was noted. Therefore, this is a safe therapy that can be used in pregnancy. Use of EPO may be especially important for women who decline blood products. Neonatal uses of EPO show benefit in the treatment of anemia due to blood type incompatibility. Conclusions: Erythropoietin is gaining popularity as a therapeutic option during pregnancy and the postpartum period. Further investigation is needed to establish a standard dosage and dosing interval. New studies reviewing its use in the neonate for perinatal-hypoxic injury and anemia due to blood type incompatibility provide exciting opportunities for further therapeutic use. Target audience: Obstetricians and gynecologists, family physicians. Learning objectives: After completing this CME activity, physicians should be better able to treat anemia in pregnancy, including causes and interventions; assess renal disease in pregnancy, targets of hemoglobin, precautions, and treatment considerations; and evaluate erythropoietin use in neonates and fetuses, including benefits, complications, and areas for upcoming research/uses.
Article
: To propose a new standard for monitoring severe maternal morbidity, update previous estimates of severe maternal morbidity during both delivery and postpartum hospitalizations, and estimate trends in these events in the United States between 1998 and 2009. : Delivery and postpartum hospitalizations were identified in the Nationwide Inpatient Sample for the period 1998-2009. International Classification of Diseases, 9 Revision codes indicating severe complications were used to identify hospitalizations with severe maternal morbidity and related in-hospital mortality. Trends were reported using 2-year increments of data. : Severe morbidity rates for delivery and postpartum hospitalizations for the 2008-2009 period were 129 and 29, respectively, for every 10,000 delivery hospitalizations. Compared with the 1998-1999 period, severe maternal morbidity increased by 75% and 114% for delivery and postpartum hospitalizations, respectively. We found increasing rates of blood transfusion, acute renal failure, shock, acute myocardial infarction, respiratory distress syndrome, aneurysms, and cardiac surgery during delivery hospitalizations. Moreover, during the study period, rates of postpartum hospitalization with 13 of the 25 severe complications examined more than doubled, and the overall mortality during postpartum hospitalizations increased by 66% (P<.05). : Severe maternal morbidity currently affects approximately 52,000 women during their delivery hospitalizations and, based on current trends, this burden is expected to increase. Clinical review of identified cases of severe maternal morbidity can provide an opportunity to identify points of intervention for quality improvement in maternal care. : III.
Article
Serum ferritin, total plasma ferritin and haematological indices were determined during and for 6 months after normal pregnancy in 45 healthy women, 21 of whom took oral iron supplements. The physiological effect of pregnancy was to markedly depress serum ferritin concentration. During unsupplemented pregnancy median serum ferritin concentration decreased to approx. 6.0 μg/l by 28 weeks gestation, this concentration was maintained until term and was associated with the appearance of erythrocyte microcytosis during the third trimester. At 6 months postpartum, individual and average serum and total plasma ferritin values showed a deficit compared with the values recorded at the beginning of pregnancy. Oral iron supplementation during pregnancy modified the fall in serum ferritin, median serum ferritin concentrations remained about 14.0μg/I after 28 weeks gestation; normocytic erythropoiesis was maintained throughout the third trimester and no deficit in serum and total plasma ferritin occurred as a result of pregnancy. It is concluded that routine oral iron administration should be recommended during pregnancy, certainly after 28 weeks gestation.
Article
Iron absorption, bone‐marrow smears and haematological parameters were repeatedly studied during pregnancy in 50 women. The same studies were repeated two months after delivery. The material was randomly divided into two groups. Twenty‐four women were treated with 200 mg of ferrous iron daily while 26 were given placebo. The iron absorption was measured from radioiron‐labelled test doses of 100 mg ferrous iron in a whole‐body counter with high sensitivity. In the placebo group the iron absorption increased throughout pregnancy from an average of 6.5 % at the 12th week to 14.3 % at the 35th week of gestation. Two months after delivery the absorption was higher than initially. In the iron‐treated group the absorption increased between the 24th and 35th week of gestation from 6.0 to 8.6 %. After delivery 5.5 % of the test dose was absorbed. The haemosiderin iron in the bone‐marrow was mobilized during pregnancy. In the placebo group no woman had more than trace of haemosiderin in the bone‐marrow smears at the 35th week of gestation. In the iron‐treated group 65 % had the same bone‐marrow findings. The amount of bone‐marrow haemosiderin at term seems not to have the same significance for the diagnosis of iron deficiency in pregnancy as in non‐pregnant subjects. Two months after delivery about 50 % of the women in the placebo group had restored their iron depots. In the iron‐group the haemosiderin content in the bone‐marrow smears was enhanced in most women compared to early pregnancy. In the placebo group haematoLogical data indicated a high frequency of iron deficiency in late pregnancy while in the iron‐treated group iron deficiency was prevented.
Article
To understand better the epidemiology and to describe the causes of maternal death, we reviewed all identified maternal deaths in the United States and Puerto Rico for 1979-1986. The overall maternal mortality ratio for the period was 9.1 deaths per 100,000 live births. The ratios increased with age and were higher among women of black and other minority races than among white women for all age groups. The causes of death varied for different outcomes of pregnancy; pulmonary embolism was the leading cause of death after a live birth. Unmarried women had a higher risk of death than married women. The risk of death increased with increasing live-birth order, except for primiparas. In order to develop strategies to reduce the risk of maternal death in the United States, future studies should include expanded information about each death, which will allow better understanding of factors associated with maternal mortality.