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Transfusion. Author manuscript; available in PMC 2018 January 01.
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Published in final edited form as:

Transfusion. 2017 January ; 57(1): 36–44. doi:10.1111/trf.13815.

Patterns and Predictors of Severe Postpartum Anemia after

Cesarean Section
Alexander. J. Butwick, MBBS, FRCA, MS1, Eileen. M. Walsh, RN, MPH2, Michael
Kuzniewicz, MD, MPH2, Sherian.X. Li, MS2, and Gabriel.J. Escobar, MD2
1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of
Medicine, Stanford, California
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2Division of Research, Kaiser Permanente Northern California, Oakland, California

Abstract
Background—Postpartum anemia is associated with maternal and perinatal morbidity.
Population-level data may inform guideline development for postpartum anemia screening. Our
objectives were to evaluate the associations between potential predictors (predelivery anemia and
postpartum hemorrhage (PPH)) with severe postpartum anemia after cesarean section.

Study Design and Methods—Data were collected from 70,939 hospitalizations for cesarean
section performed at Kaiser Permanente Northern California facilities between 2005 and 2013.
Severe postpartum anemia was defined as a hemoglobin < 8 g/dl before hospital discharge. Using
multivariable logistic regression, we assessed the associations between predelivery anemia and
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PPH with severe postpartum anemia. Distributions of these characteristics among women with
severe postpartum anemia were evaluated.

Results—The overall rate of severe postpartum anemia was 7.3%; 95% confidence interval (CI)
= 7.1 – 7.4. Severe postpartum anemia was strongly associated with a predelivery hemoglobin
between 10 and 10.9 g/dl (adjusted odds ratio (aOR) 5.4; 95% CI = 4.89– 5.91), predelivery
hemoglobin <10 g/dl (aOR 30.6; 95% CI = 27.21– 34.6, and PPH (aOR 8.45; 95% CI = 7.8–9.16).
The proportions of women with severe postpartum anemia were highest for those experiencing
PPH but no predelivery anemia (12.2%; 95% CI = 11.0 – 13.6), and those who did not incur PPH
nor predelivery anemia (10.7%; 95% CI = 9.6 – 12.0).

Conclusions—Our findings suggest that PPH and predelivery anemia are strong independent
risk factors for severe postpartum anemia. Optimization of patients’ hemoglobin prior to delivery
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may reduce the incidence of severe anemia after cesarean section.

Keywords
Cesarean Section; Anemia; Hemorrhage

Correspondence Address: Dr. Alexander Butwick, Department of Anesthesiology, Perioperative and Pain Medicine (MC: 5640),
Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, TEL: 510-648-5115 (US), Fax: 650-725-8544
(US), ajbut@[Link].
Conflicts of Interest:
No authors have any conflicts of interest to declare.
 Butwick et al. Page 2

INTRODUCTION
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In the United States, the prevalence of anemia during pregnancy has been reported to be as
high as 241 per 1000 pregnant women.1 To address this issue, The American College of
Obstetricians and Gynecologists (ACOG) have published recommendations for managing
anemia during pregnancy.2 These include: screening all pregnant women for anemia during
pregnancy, and iron supplementation for women with iron deficiency anemia. By
comparison, postpartum anemia has received less attention and is an underappreciated
women’s health issue. Morbidities linked to postpartum anemia include: depression,3,4
fatigue,5 and impaired cognition6. These patient-centric outcomes can have important
negative impacts on maternal-child bonding and the mother’s ability to provide newborn
care.7

Because symptoms of maternal anemia are non-specific,8 anemia can only be detected by
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measuring the hemoglobin level. If postpartum anemia goes unrecognized, mothers may face
a greater degree of physical or emotional hardship than non-anemic mothers. Therefore, to
limit the likelihood of anemia-related morbidity, population-level data are needed to inform
guideline development for postpartum anemia screening.

Predelivery anemia and PPH are presumed to confer the greatest risks to women for
postpartum anemia.8 Women who undergo cesarean section may be particularly susceptible
to postpartum anemia because their risk of PPH is higher than women undergoing vaginal
delivery.9,10 However, there is a dearth of studies examining the frequency of anemia after
cesarean section and the relations between predelivery anemia and PPH with postpartum
anemia. These studies will be important in advancing clinical knowledge and providing key
epidemiologic data for guiding discussions about optimizing Patient Blood Management in
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obstetrics.

The main objectives of this analysis were to describe the incidence of severe postpartum
anemia, assess the relationships between severe postpartum anemia with blood loss at
delivery and predelivery anemia, and to estimate the frequencies of these characteristics
among women with severe postpartum anemia. In our secondary analyses, we calculated
rates of postpartum anemia testing after cesarean section and examined characteristics of
women who did not undergo postpartum hemoglobin testing. For these analyses, we
employed data from Kaiser Permanente Northern California (KPNC), a pre-paid integrated
healthcare delivery system in the United States.

MATERIALS AND METHODS

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This study was approved by the KPNC and Stanford University institutional review boards,
and the Committee for the Protection of Human Subjects of the California Health and
Human Services Agency.

Data Source and Study Cohorts

We used the existing research infrastructure of an integrated health care delivery system
(KPNC) in California, United States. All KPNC hospitals and clinics use information

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 Butwick et al. Page 3

systems that are linked by a common medical record number. For this study, data were
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obtained from linked electronic databases within KPNC, cleaned and processed using
methods previously described.11–13 A flow diagram depicts the cohorts used for our primary,
subgroup, and secondary analyses (Figure 1). For our primary analysis, the study cohort
comprised of 70,939 women with a measured postpartum hemoglobin value who underwent
cesarean section at a KPNC obstetric center between January 1, 2005 and December 31,
2013. We excluded women who were aged <15 years at the time of delivery. Because EBL
data were available from the KPNC electronic medical records (EMRs) from 2010 onwards,
we performed a subgroup analysis using a cohort comprised of 38,086 women who
underwent cesarean section between January 1, 2010 and December 31, 2013. For our
secondary analyses, we assessed characteristics of 13,086 women who delivered between
2005 and 2013 with no recorded postpartum hemoglobin value.

Variables
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For our primary analysis, the outcome of interest was severe postpartum anemia, defined by
World Health Organization (WHO) criteria 14 as a postpartum hemoglobin <8 g/dl,
measured closest to the day of hospital discharge. To further substantiate this cutpoint, PPH
guidelines published by several national societies (The Royal College of Obstetricians and
Gynecologists and an interdisciplinary consensus group from Germany, Austria, and
Switzerland [DACH]) indicate that a hemoglobin of 8 g/dl or more should be a therapeutic
goal.15,16

The main independent variables of interest were: predelivery anemia and PPH. Predelivery
anemia was determined using the antenatal hemoglobin level closest to the day of cesarean
section. During pregnancy, the WHO define mild, moderate, and severe anemia as a
hemoglobin between 10–10.9 g/dl, 7–9.9 g/dl, and <7 g/dl, respectively.14 As only 11
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women in our study cohort had a predelivery hemoglobin <7 g/dl, we reclassified
predelivery anemia as follows: ‘mild’ for hemoglobin values between 10–10.9 g/dl, and
‘moderate-severe’ for hemoglobin values <10 g/dl. We identified PPH using International
Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) diagnosis codes for
PPH (see Table 1 in the Supplementary Appendix).

For our subgroup (n=38,086) who delivered between 2010 and 2013 (Figure 1: flow
diagram), instead of the ICD-9 code for PPH, we used EBL data from the EMR to classify
grades of blood loss severity at delivery. Descriptions of the methods of EBL measurement
or estimation were not available in KPNC databases. Based on literature review,9,17–19 we
classified normal blood loss, non-severe PPH, and severe PPH based on the following EBL
criteria: <1000 ml, 1000 – 1499 ml and ≥1500 ml respectively. Due to uncertainties about
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the accuracy of very low EBL values, we classified any EBL<100 ml as missing data
(n=345).

Other covariates in our analyses included patient and clinical characteristics, specified a
priori, as potential confounders between the main independent variables and severe
postpartum anemia. These were determined according to clinical relevance and prior
literature review.8,20 Demographic characteristics included: age, race or ethnic group, and
year of delivery. Medical characteristics included: hereditary or acquired coagulation

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disorders and thrombocytopenia. Obstetric and peripartum characteristics included:

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gestational age at delivery, grand multiparity, number of prior cesarean deliveries, obesity,
labour, maternal hypertensive disease, placenta previa, antepartum hemorrhage, and
transfusion. Maternal age, number of prior cesarean deliveries, gestational age at delivery,
and year of delivery were extracted from linked KPNC databases. Data on mothers’ self-
reported race and ethnicities were obtained from the State of California Birth Certificate
Database. We used ICD-9 codes to identify diagnoses and procedures associated with each
delivery hospitalization (Table S1 in the Supplemental Appendix).

STATISTICAL ANALYSIS
We calculated the number of days between predelivery hemoglobin measurement and
cesarean section, discharge hemoglobin measurement and cesarean section, and the
postpartum length of stay. Overall rates of anemia were calculated, and Wilson’s method
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was used to derive 95% confidence intervals.21 To evaluate temporal trends, we calculated
annual rates of severe postpartum anemia at discharge. We also calculated annual rates of
severe postpartum anemia for deliveries that were accompanied with ICD-9 codes for PPH
or transfusion. Temporal trends were assessed using the χ2 test for linear trend in
proportions.

We performed bivariate analyses to compare the distribution of patient and obstetric

characteristics between women with vs. without severe postpartum anemia. We used
multivariable logistic regression to assess the associations between the predelivery
hemoglobin categories and PPH with severe postpartum anemia. We created separate logistic
models to account for the influence of patient and obstetric characteristics, and year of
delivery. Sequential models were constructed with increasing levels of adjustment for the
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following sets of covariates: model 1 = only predelivery hemoglobin categories and PPH;
model 2 = covariates in model 1 + year of birth; model 3 = covariates in model 2 + patient
demographics (including: maternal age, race/ethnicity); model 4 = covariates in model 3 +
medical/obstetric characteristics (including: obesity, grand multiparity, hereditary or
acquired coagulation disorders, thrombocytopenia, gestational age, number of prior cesarean
deliveries, hypertensive disorders of pregnancy, labor or induction of labor, placenta previa,
and antepartum hemorrhage). Individual hospitals were accounted for as random effects in
each model. For each model, we calculated odds ratios for severe postpartum anemia at
discharge as a function of the key variables of interest. To estimate the proportion of women
with severe postpartum anemia that would have been eliminated if one of the main
exposures (predelivery anemia or PPH) had been eliminated, we calculated population
attributable fractions (based on adjusted odds ratios from non-hierarchical multivariable
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logistic models). Using full models, we also added interaction terms to investigate whether
effect modification occurred between transfusion with PPH and predelivery anemia,
respectively.

For our subgroup analyses, we examined data from 38,086 cesarean sections that occurred
between 2010 and 2013 (see Figure 1: flow diagram). We calculated absolute rates of severe
postpartum anemia according to the presence or absence of PPH (based on available EBL
data) and predelivery anemia. We also analyzed data from 35,614 cesarean sections where

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EBL data were not missing (see Figure 1: flow diagram) to examine the relations between
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pre-delivery anemia and PPH (using EBL categories) with severe postpartum anemia.

Lastly, in our secondary analyses, we performed multivariable logistic regression to identify

characteristics that may explain why 13,086 women who underwent cesarean section
between 2005 and 2013 did not undergo testing for postpartum anemia (see Figure 1: flow
diagram).

All analyses were conducted using SAS version 9.2 (SAS Institute Inc., Cary, NC) and
STATA version 12 (Stata Corp., College Station, TX).

RESULTS
Between 2005 and 2013, we identified 84,025 hospitalizations for cesarean delivery. The
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median postpartum length of stay was 3 days (interquartile range (IQR) = 2– 3); data were
missing for 187 hospitalizations. Pre-delivery and post-delivery hemoglobin values were
available for 48,439 (57.6%) and 70,939 (84.4%) hospitalizations respectively (Figure 1:
flow diagram). The median time period between the predelivery hemoglobin level and
cesarean section was 0 days (IQR = 0 – 1), and the median time period between cesarean
section and the discharge hemoglobin level was 1 day (IQR = 1 – 2).

Among women with a recorded postpartum hemoglobin value, the rate of severe postpartum
anemia was 7.3% (95% confidence interval [CI] = 7.1 – 7.4). Between 2005 and 2013, a
modest increase occurred in the rate of severe postpartum anemia (P for trend=0.04; Figure
S1 in Supplemental Appendix).

Characteristics of Women with Severe Postpartum Anemia

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Maternal and obstetric characteristics of women with and without severe postpartum anemia
at discharge are presented in Table 1. (The proportions of women with severe postpartum
anemia for each maternal/obstetric characteristic (row percentages) are presented in Table S2
in Supplementary Appendix). On univariate analyses, women with mild or moderate-severe
predelivery anemia and those with PPH were more likely to have severe postpartum anemia.
Table 2 shows the crude and adjusted logistic regression models between predelivery anemia
and PPH with postpartum anemia. For each predictor, the odds of severe postpartum anemia
was relatively unchanged after adjustment for birth year, medical, and obstetric
characteristics; in model 4, the adjusted odds ratio was 5.4 among women with mild
predelivery anemia (95% CI=4.89– 5.91); 30.6 among those with moderate-severe
predelivery anemia (95% CI=27.21– 34.6), and 8.45 among those with PPH (95% CI=7.8–
9.16). (Point estimates for all covariates in model 4 are presented in Table S2 in
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Supplementary Appendix). The proportions of severe postpartum anemia that could be

attributed to PPH was 13.7% (95% CI=12.6–14.8%) and predelivery anemia (Hb<11 g/dl)
was 30.6% (95% CI=28.7–32.4%).

Interactions according to transfusion were significant, therefore we performed stratified

analyses to account for the presence/absence of transfusion (Table S3 in the Supplementary
Appendix). In the non-transfused cohort, PPH, mild predelivery anemia, and moderate-

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severe anemia remained independently associated with severe postpartum anemia. In

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contrast, in the transfused cohort, the adjusted odds ratio was 2.12 (95% CI=1.37– 3.26)
among those with mild predelivery anemia; 1.77 (95% CI=1.11– 2.81) among those with
moderate-severe predelivery anemia; and 0.64 (95% CI=0.49 – 0.84) among those with PPH.

Subgroup Analyses
In our subgroup analyses, we examined data from 38,086 women who underwent cesarean
section between 2010 and 2013 (Figure 1: flow diagram). Where available, EBL data were
extracted from the EMR, and PPH was classified according to EBL severity. We calculated
proportions for severe postpartum anemia according to the presence or absence of the
following key factors: predelivery anemia ± PPH ± transfusion (Table 3). Of those with
severe postpartum anemia, 12.2% (95% CI=11.0 – 13.6) women had PPH but did not incur
predelivery anemia nor transfusion, and 10.7% (95% CI=11.0 – 13.6) women had a normal
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EBL, no predelivery anemia and did not receive transfusion.

For 35,614 women with a recorded EBL≥100 ml,(see Figure 1: flow diagram), we
performed multivariate logistic regression to assess the relationships between predelivery
hemoglobin and PPH (using EBL categories) with severe postpartum anemia. The results are
presented in Table S4 in the Supplementary Appendix. Compared to women with an
EBL<1000 ml, women who experienced moderate PPH (EBL=1000 – 1499 ml) or severe
PPH (EBL≥1500 ml) had a 3.9 and 13.4 fold increased odds of severe postpartum anemia
respectively.

Secondary Analyses
For our secondary analyses, we examined 13,086 women who underwent cesarean section
who did not have a recorded postpartum hemoglobin (see Figure 1; flow diagram).
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Characteristics of women with no recorded postpartum hemoglobin value are presented in

Table S5 in the Supplemental Appendix. Women who delivered <37 weeks’ gestational age
had the highest odds of not undergoing postpartum hemoglobin testing (aOR=156.9).
Women of unknown ethnicity and those without a predelivery hemoglobin value had a 3-fold
increased odds of not getting tested. In contrast, the odds of not getting tested were lowest
for women who underwent one or at least two prior cesareans compared to women who
underwent primary cesarean section.

Within our full subgroup (n=38,086), we calculated proportions for women with missing
hemoglobin values at discharge (Table S6 in Supplementary Appendix); those with missing
predelivery hemoglobin values who experienced normal blood loss and no transfusion
accounted for the highest proportion (56.7%; 95% CI=55.4 – 58.0).
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DISCUSSION
With anemia management and blood loss minimization approaches being central tenets of
good Patient Blood Management practice for surgical and medical patients,22–24 our
findings that predelivery anemia and PPH are strong risk factors for severe postpartum
anemia are timely and topical. Because predelivery anemia is a modifiable risk factor, our
findings should prompt key stakeholders, including transfusion medicine specialists,

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obstetricians, and anesthesiologists, to examine ways to better detect and treat anemia prior
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to cesarean section. Until Patient Blood Management guidelines that are applicable to
obstetrics are published, we recommend that anemia screening after cesarean section be
considered for patients with predelivery anemia, no recorded predelivery hemoglobin level,
or those who experience PPH.

In our analyses, predelivery anemia and PPH were identified as strong risk factors for severe
postpartum anemia after cesarean section. After accounting for potential maternal and
obstetric covariates in our sequential models, the magnitude of these associations remained
relatively unchanged. These findings have important clinical relevance for several reasons.
Firstly, predelivery anemia and PPH are not infrequent; predelivery anemia affects 25% of
pregnant women 1 and the rate of PPH during cesarean section is approximately 9%25.
Secondly, there is underappreciation of the negative health burden associated with
postpartum anemia. Postpartum anemia may precipitate or worsen depressive symptoms,
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cognitive function, fatigue, reduced work performance, and maternal-infant bonding.3–8

Thirdly, few recommendations exist for detecting severe anemia after cesarean section. The
Centers for Disease Control recommend targeted screening for anemia between four to six
weeks postpartum.26 However, the value of this guidance is uncertain as acute or subacute
postpartum anemia can develop much earlier (at 24–48 hr postpartum).8,20 Therefore, if
severe anemia goes unrecognized after cesarean section, these women may face greater
emotional or physical hardship than non-anemic mothers after hospital discharge. Fourthly,
because predelivery anemia is a modifiable antepartum risk factor, the early identification
and treatment of predelivery anemia may reduce the incidence of severe postpartum anemia
after cesarean section. In the non-obstetric surgical setting, similar approaches have been
recommended for the management of preoperative anemia by experts in Patient Blood
Management.22,27
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Although predelivery anemia and PPH were important risk factors, a high proportion of
women with severe postpartum anemia (10.7%) had a ‘normal’ EBL and no predelivery
anemia. Even with quantitative data for blood loss, clinicians are prone to underestimating
blood loss as the volume of actual blood loss increases.28,29 As a consequence, screening for
postpartum anemia during the early postpartum period may be helpful for early diagnosis
and initiation of therapy,8 especially for those with predelivery anemia or who experience
PPH.30 Of note, specific recommendations for detecting and treating women with iron
deficiency anemia among pregnant and non-pregnant women have been published by an
expert multidisciplinary group, sponsored by the Society for the Advancement of Blood
Management.31 These recommendations may serve as an important foundation for formally
establishing Patient Blood Management guidelines in obstetrics.
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We acknowledge that others have also observed an association between PPH and early
postpartum anemia.20,32–34 However, the majority of these studies focused on women who
underwent vaginal delivery, and data on the prevalence of severe postpartum anemia after
cesarean delivery is more limited. Horowitz et al. reported that the incidence of severe
anemia (hemoglobin<8 g/dl) after elective cesarean delivery is 0.5%.35 However, this small
cohort was sourced from a single obstetric center and did not include intrapartum cesarean
sections, thus study generalizability is limited.

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In our study, transfusion modified the associations between PPH and predelivery anemia
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with severe postpartum anemia. Because we relied upon ICD-9 codes to identify women
who received transfusions, we cannot determine the context, triggers, timing or
appropriateness of transfusion. This has clinical relevance because transfusion is recognized
to be an important indicator of maternal morbidity.36 Less is known about the use of
transfusion therapy for treating postpartum anemia in non-bleeding patients who are
intravascularly replete. Medical and transfusion societies, such as the AABB and the
American College of Critical Care Medicine, recommend that transfusion is not beneficial if
the hemoglobin level is greater than 10 g/dl, but may have benefit when the hemoglobin
level is less than 6–8 g/dl.37,38 In the setting of PPH, a hemoglobin level >8 g/dl is
recommended as a therapeutic goal by several obstetric societies.15,16 However, maternal
outcomes associated with moderate or severe anemia among women managed with a
restrictive approach are not well understood. Among women with acute postpartum anemia
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(hemoglobin levels between 4.8 – 7.9 g/dl), Prick et al. observed that maternal fatigue, upto
6 weeks postpartum, is only marginally improved with transfusion compared to a non-
transfusion based approach.39 In a separate study, Van der Woude et al. observed that
maternal health status and fatigue were not different, upto 5 weeks postpartum, between
women with vs. without postpartum anemia (hemoglobin <10.5 g/dl vs. hemoglobin ≥10.5
g/dl).40 Further research is needed to investigate long-term cognitive, functional, and
psychological outcomes of women with moderate or severe postpartum anemia in the
absence of transfusion.

Based on our analysis, the proportion of women with severe postpartum anemia who did not
undergo predelivery hemoglobin testing and who did not experience PPH or transfusion was
relatively high (9.9%). Therefore, it is unclear whether these women had unrecognized
predelivery anemia and/or underestimated blood loss. Furthermore, 16% women in our
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cohort did not undergo postpartum hemoglobin testing. Women undergoing preterm
cesarean delivery had the highest odds of not getting tested (aOR=261), whereas the odds
were lowest for women with at least one prior cesarean. These findings emphasize the need
for formal guidelines or protocols to standardize anemia screening approaches after cesarean
section.

The main strengths of our study are that we obtained postpartum hemoglobin levels for
70,939 cesarean sections, with recorded clinical data on blood loss available for over 50% of
our cohort. However, our study has several limitations. For our main analysis, we identified
PPH using ICD-9 codes, therefore misclassification is a potential concern. Non-differential
misclassification can typically bias results towards the null. Using EBL data to classify PPH,
we still observed a strong associations between PPH and severe postpartum anemia in our
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follow-up analysis. Nonetheless, we acknowledge that the true exposure effect of blood loss
severity on our primary outcome may have been underestimated. We could not account for
all potential confounders in our logistic models, such as labor augmentation with oxytocin,
type and volume of iv fluids administered prior to delivery, and body mass index. However,
the point estimates for PPH and chronic anemia remained relatively unchanged in our
sequential models, thus these associations are unlikely to be markedly affected by residual
confounders. We did not assess whether women received medication, such as oral or
intravenous iron, to prevent or treat postpartum anemia. Stabilization of maternal

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hemoglobin values occurs between 5–7 days postpartum.8 As the median length of
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postpartum stay was 3 days, postpartum hemoglobin levels may not have completely
stabilized by the time of hospital discharge. Due to the observational nature of our study
design, we could not examine factors that influence physicians’ decision to transfuse or
screen for anemia before or after cesarean section. Although obstetric agencies are focusing
attention on initiatives to reduce major maternal morbidity,41,42 future studies are needed to
determine whether improvements in anemia screening and the use of non-RBC based
therapies can improve patient-centric outcomes, including debilitating maternal quality of
life disorders, such as fatigue and depression.

Using a contemporary obstetric cohort, our results provide insight into the epidemiology of
severe postpartum anemia after cesarean section. With anemia detection, diagnosis and
treatment recognized as key facets of Patient Blood Management, we encourage transfusion
medicine and other health specialists to consider strategies to potentially reduce the
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incidence of severe postpartum anemia. Until national guidelines are updated, hospitals and
providers may need to consider anemia screening after cesarean section for women with at
least one of the following: predelivery anemia, no predelivery hemoglobin level, and PPH.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

Acknowledgments
Source of work: Secondary analyses of data sourced from databases based at the Division of Research at Kaiser
Permanente Northern California, Oakland, California.

Financial Support: This study was supported and funded internally by the Department of Anesthesiology,
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Perioperative and Pain Medicine, Stanford University School of Medicine and the Division of Research at Kaiser
Permanente Northern California, Oakland, California. This work received funding support from the Eunice
Kennedy Shriver National Institute of Child Health and Human Development (grant number: K23HD070972). Dr.
Butwick is supported by an award from the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (K23HD070972).

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Figure 1.
Flow Chart.
EBL = estimated blood loss; EMR = electronic medical record; Hb = hemoglobin; PPH =
postpartum hemorrhage
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Table 1

Patient Characteristics of Women with and without Severe Postpartum Anemia who underwent Cesarean
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Section between 2005 and 2013.

Patient Characteristics No Severe Anemia (n=65,796) Severe Anemia (n=5,143) P value

Maternal age (y): <0.001

<20 1475 (2.2%) 232 (4.5%)

20–34 44,439 (67.6%) 3492 (67.9%)

≥35 19,882 (30.2%) 1419 (27.6%)

Race/ethnicity: <0.001

White 26,606 (39.8%) 1564 (30.4%)

Black 5618 (8.5%) 512 (10%)

Hispanic 16,064 (24.4%) 1453 (28.2%)

Asian 15,399 (23.4%) 1442 (28.1%)

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Other 1866 (2.9%) 134 (2.6%)

Unknown 643 (1.0%) 38 (0.7%)

Prepartum Hb level (g/dl): <0.001

≥11 g/dl 40,597 (61.7%) 2264 (44%)

10 – 10.9 g/dl 3,267 (5%) 857 (16.7%)

<10 g/dl 661 (1%) 793 (15.4%)

Hb missing 21,271 (32.3%) 1229 (23.9%)

Hereditary or acquired coagulation disorder† 91 (0.1%) 93 (1.8%) <0.001

Gestational age at delivery: <0.001

<37 weeks 1378 (2.1%) 119 (2.3%)

37–41 weeks 60,736 (92.3%) 4615 (89.7%)

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>41 weeks 3682 (5.6%) 409 (8%)

Grand multiparity† 163 (0.3%) 32 (0.6%) <0.001

Number of prior CSs: <0.001

0 54,711 (83.2%) 4460 (86.7%)

1 10,267 (15.6%) 620 (12.1%)

≥2 818 (1.2%) 63 (1.2%)

Obesity† 10,323 (15.7%) 709 (13.8%) <0.001

Thrombocytopenia† 1258 (1.9%) 163 (3.2%) <0.001

Preeclampsia† 3445 (5.2%) 466 (9.1%) <0.001

Labor† 30,716 (46.7%) 3145 (61.2%) <0.001

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Placenta previa† 1131 (1.7%) 173 (3.4%) <0.001

Antepartum hemorrhage † 1191 (1.8%) 236 (4.6%) <0.001

Postpartum hemorrhage † 3144 (4.8%) 1466 (28.5%) <0.001

RBC transfusion† 364 (0.6%) 1183 (23%) <0.001

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Data presented as n (%). Column percentages are presented in each cell.

†
Variables identified according to diagnosis or procedure codes in the International Classification of Diseases, 9th Revision, Clinical Modification.

CS = Cesarean section; Hb = hemoglobin; RBC = red blood cell

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Table 2

Associations between Severe Postpartum Anemia with Predelivery Hemoglobin and Postpartum Hemorrhage*
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Model 1a Model 2b Model 3c Model 4d

OR (95% CI) aOR (95% CI) aOR (95% CI) aOR (95% CI)

PPH 9.57 (8.85 – 10.34) 9.82 (9.08 – 10.62) 9.57 (8.85 – 10.36) 8.45 (7.8 – 9.16)

Prepartum Hb level (g/dl):

> 11 Reference Reference Reference Reference

10 –10.9 5.05 (4.61 – 5.54) 5.06 (4.61 – 5.54) 5.10 (4.65 – 5.60) 5.38 (4.89 – 5.91)

< 10 26.7 (23.75 – 30.0) 26.9 (23.92 – 30.23) 27.06 (24.03 – 30.46) 30.6 (27.1 – 34.6)

Missing Hb 1.16 (1.08 – 1.25) 1.16 (1.07 – 1.25) 1.19 (1.10 – 1.28) 1.54 (1.42 – 1.67)

*
Denominator consists of 70,939 patients (Figure 1); dependent variable is severe postpartum anemia (N = 5,143)
a
unadjusted model
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b
adjusted for year of birth as a fixed effect, and individual hospital as a random effect.
c
adjusted for year of birth, maternal age, and race/ethnicity as fixed effects, and individual hospital as a random effect.
d
adjusted for year of birth, maternal age, race/ethnicity, grand multiparity, hereditary or acquired coagulation disorders, gestational age at delivery,
number of prior cesarean deliveries, obesity, thrombocytopenia, pre-eclampsia, labor, placenta previa, antepartum hemorrhage as fixed effects, and
individual hospital as a random effect.

aOR = adjusted odds ratio; CI = confidence interval; Hb = hemoglobin; PPH = postpartum hemorrhage
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Table 3

Characteristics of 2,376 Women with Severe Postpartum Anemia who underwent Cesarean Section between
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2010 and 2013.

Patients with Severe Postpartum Anemiaa

N %

No Predelivery Anemia
No PPH:

Not Transfused 255 10.73

Transfused 68 2.86

PPH:

Not Transfused 290 12.21

Transfused 62 2.61

Severe PPH:
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Not Transfused 141 5.93

Transfused 136 5.72

No Documented EBL:

Not Transfused 50 2.1

Transfused 21 0.88

Mild Predelivery Anemia

No PPH:

Not Transfused 171 7.2

Transfused 19 0.8

PPH:

Not Transfused 101 4.25

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Transfused 24 1.01

Severe PPH:

Not Transfused 25 1.05

Transfused 35 1.47
No Documented EBL:

Not Transfused 17 0.72

Transfused 5 0.21

Severe Predelivery Anemia

No PPH:

Not Transfused 215 9.05

Transfused 20 0.84
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PPH:

Not Transfused 62 2.61

Transfused 21 0.88

Severe PPH:

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Patients with Severe Postpartum Anemiaa

N %
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Not Transfused 13 0.55

Transfused 17 0.72

No Documented EBL:

Not Transfused 16 0.67

Transfused 5 0.21

No Predelivery Hb
No PPH:

Not Transfused 234 9.85

Transfused 43 1.81
PPH:

Not Transfused 135 5.68

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Transfused 33 1.39

Severe PPH:

Not Transfused 43 1.81

Transfused 53 2.23

No Documented EBL:

Not Transfused 37 1.56

Transfused 9 0.38

a
This cohort consists of 2,376 women among the 38,086 women who underwent cesarean section between 2010 and 2013 (see Figure 1); this
subset developed severe postpartum anemia. Column percentages are presented.

EBL = estimated blood loss; Hb = hemoglobin; PPH = postpartum hemorrhage

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