Original Research ajog.

org

OBSTETRICS
Severe placental abruption: clinical definition and
associations with maternal complications
Cande V. Ananth, PhD, MPH; Jessica A. Lavery, MS; Anthony M. Vintzileos, MD; Daniel W. Skupski, MD; Michael Varner, MD;
George Saade, MD; Joseph Biggio, MD; Michelle A. Williams, ScD; Ronald J. Wapner, MD; Jason D. Wright, MD

BACKGROUND: Placental abruption traditionally is defined as the
premature separation of the implanted placenta before the delivery of the
fetus. The existing clinical criteria of severity rely exclusively on fetal (fetal
distress or fetal death) and maternal complications without consideration
of neonatal or preterm delivery-related complications. However, two-thirds
of abruption cases are accompanied by fetal or neonatal complications,
including preterm delivery. A clinically meaningful classification for
abruption therefore should include not only maternal complications but
also adverse fetal and neonatal outcomes that include intrauterine growth
restriction and preterm delivery.
OBJECTIVES: The purpose of this study was to define severe placental
abruption and to compare serious maternal morbidity profiles of such
cases with all other cases of abruption (ie, mild abruption) and non-
abruption cases.
STUDY DESIGN: We performed a retrospective cohort analysis using
the Premier database of hospitalizations that resulted in singleton births in
the United States between 2006 and 2012 (n ¼ 27,796,465). Severe
abruption was defined as abruption accompanied by at least 1 of the
following events: maternal (disseminated intravascular coagulation,
hypovolemic shock, blood transfusion, hysterectomy, renal failure, or in-
hospital death), fetal (nonreassuring fetal status, intrauterine growth re-
striction, or fetal death), or neonatal (neonatal death, preterm delivery or
small for gestational age) complications. Abruption cases that did not
qualify as being severe were classified as mild abruption cases. The
morbidity profile included amniotic fluid embolism, pulmonary edema,
acute respiratory or heart failure, acute myocardial infarction, cardiomy-
opathy, puerperal cerebrovascular disorders, or coma. Associations were
expressed as rate ratios with 95% confidence intervals that were derived
from fitting log-linear Poisson regression models.
RESULTS: The overall prevalence rate of abruption was 9.6 per
1000, of which two-thirds of cases were classified as being severe
(6.5 per 1000). Serious maternal complications occurred in 15.4,
33.3, and 141.7 per 10,000 among nonabruption cases and mild
and severe abruption cases, respectively. In comparison with no
abruption, the rate ratio for serious maternal complications were 1.52
(95% confidence interval, 1.35e1.72) and 4.29 (95% confidence
interval, 4.11e4.47) in women with mild and severe placental
abruption, respectively. Rate ratios for the individual complications
were 2- to 7-fold higher among severe abruption cases. Furthermore,
the rate ratios for serious maternal complications among severe
abruption cases compared with mild abruption cases was 3.47 (95%
confidence interval, 3.05e3.95). This association was considerably
stronger for virtually all maternal complications among cases with
severe abruption compared with mild abruption. Annual rates of mild
and severe abruption were fairly constant during the study period.
Although the maternal complication rate among non-abruption births
was stable from 2006-2012, the rate of complications among mild
abruption cases dropped from 2006-2008 and then leveled off
thereafter. In contrast, the rate of serious complications among severe
abruption cases remained fairly stable from 2006-2010 and increased
sharply thereafter.
CONCLUSIONS: Severe abruption was associated with a distinctively
higher morbidity risk profile compared with the other 2 groups. The clinical
characteristics and morbidity profile of mild abruption were more similar to
those of women without an abruption. These findings suggest that the
definition of severe placental abruption based on the proposed specific
criteria is clinically relevant and may facilitate epidemiologic and genetic
research.
Key words: blood transfusion, disseminated intravascular coagulation,
fetal death, intrauterine growth restriction, maternal complication,
placental abruption, preterm delivery

P lacental abruption traditionally is

defined as the premature separation
of the implanted placenta before the
delivery of the fetus. The existing clinical
criteria of severity rely exclusively on
fetal (fetal distress or fetal death)
Cite this article as: Ananth CV, Lavery JA, Vintzileos AM,
et al. Severe placental abruption: clinical definition and
associations with maternal complications. Am J Obstet
Gynecol 2016;214:272.e1-9.
0002-9378/$36.00
ª 2016 Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.ajog.2015.09.069
and maternal complications without
consideration of neonatal or preterm
delivery-related complications.1 How-
ever, two-thirds of abruption cases are
accompanied by fetal or neonatal com-
plications, which includes preterm
delivery. A clinically meaningful classi-
fication for abruption therefore should
include not only maternal complications
but also adverse fetal and neonatal out-
comes that include intrauterine growth
restriction and preterm delivery.
We hypothesized that the criteria that
were needed to define placental abrup-
tion as “severe” should be clinically
meaningful and should include at least 1
of maternal (disseminated intravascular
coagulation, hypovolemic shock, blood
transfusion, hysterectomy, renal failure,
or in-hospital death), fetal (non-
reassuring fetal status, intrauterine
growth restriction, or fetal death), or
neonatal (neonatal death, preterm de-
livery, or small for gestational age)
complications. The intrinsic motivation
for this hypothesis was that abruption
cases with 1 of the aforementioned
criteria will identify a distinct subset of
women with very high risks of serious
maternal complications, in comparison

272.e1 American Journal of Obstetrics & Gynecology FEBRUARY 2016

ajog.org
with women with mild abruption or no
abruption. We tested this hypothesis in a
large cohort of almost 28 million
singleton pregnancies in the United
States.
Methods
Premier data
We performed a retrospective cohort
analysis of data from the Premier data-
base (www.premierinc.com; Premier,
Inc, Charlotte, NC) to obtain all
maternal hospital records for deliveries
that occurred from 2006-2012. The data
include hospitalizations from in-patient,
ambulatory, and emergency admissions
in approximately 500 hospitals each year
in the United States. These hospitals are
chosen to provide a representation of
hospitalizations across the United States.
The Premier data can be purchased from
Premier, Inc. All diagnosis and proce-
dure codes in the Premier data were
coded based on the International Clas-
sification of Disease, 9th version; the
codes used for conditions in this study
are listed in the Supplemental Table. We
sought and obtained approval from the
Institutional Review Board as an exempt
protocol from Columbia University
Medical Center, NY.
Placental abruption
A diagnosis of placental abruption was
based on clinical symptoms that include
vaginal bleeding accompanied with se-
vere abdominal pain, uterine tenderness,
or tetanic contractions. Severe placental
abruption was defined as a delivery with
an abruption accompanied by 1 of the
following maternal, fetal, or neonatal
complications. Maternal complications
included disseminated intravascular
coagulation, hypovolemic shock, blood
transfusion, hysterectomy, renal failure,
and in-hospital death. Fetal complica-
tions included nonreassuring fetal status,
intrauterine growth restriction, or fetal
death. Neonatal complications included
neonatal death, preterm delivery, and
small-for-gestational-age (SGA) births.
Although the risk of some of the severe
maternal morbidities, such as pulmo-
nary edema or cardiomyopathy, are ex-
pected to be higher among pregnancies
that are complicated by abruption, these
OBSTETRICS
conditions are not the typical compli-
cations after abruption; therefore, we do
not consider these variables in the defi-
nition of severe abruption.2-4 Abruption
cases that did not qualify as being severe
were classified as mild abruptions.
Maternal morbidity profile
The primary endpoint was a composite
morbidity outcome comprised of
serious maternal complications that
included pulmonary edema, acute res-
piratory failure, acute heart failure, acute
myocardial infarction, cardiomyopathy,
puerperal cerebrovascular disorder,
coma, and amniotic fluid embolism. In
addition, we also examined the associa-
tions between abruption and each of
these serious maternal complications.
Clinical characteristics
We examined the rates of mild and se-
vere abruption across patient character-
istics. Maternal sociodemographic and
behavioral characteristics included year
of delivery (2006-2012), maternal age,
single marital status, insurance status,
and tobacco, drug, or alcohol use.
Maternal comorbidities included hy-
pertensive diseases (chronic hyperten-
sion, gestational hypertension, or
preeclampsia/eclampsia), chronic renal
disease, asthma, and congenital cardiac
disease. Intrapartum and labor charac-
teristics included premature rupture of
membranes (at preterm or term gesta-
tions), anemia, intrapartum fever, poly-
hydramnios, oligohydramnios, and
chorioamnionitis. SGA was used as
a proxy for intrauterine growth
restriction.
Statistical analysis
Two sets of log-linear regression models
(with a Poisson distribution and a log-
link function) were fit: the first model
was to evaluate the maternal character-
istics that are associated with mild and
severe placental abruption; the second
model was to estimate the association of
serious maternal complications
(morbidity profile) that are associated
with births with mild and severe
abruptions compared with births with
no abruption and to compare serious
maternal complications between severe
FEBRUARY 2016 American Journal of Obstetrics & Gynecology
Original Research
vs mild (reference) abruptions. For
evaluating risk factors for mild and se-
vere abruptions, we first estimated the
unadjusted rate ratio (RR) and 95%
confidence interval (CI). From this
analysis, we chose risk factors that had
RRs either >1.2 or <0.8 for mild and
severe abruption; risk factors that met
this criterion were entered in the final
multivariable log linear Poisson regres-
sion models from which we evaluated
the associations.
RRs and 95% CIs were calculated for
the composite serious maternal
morbidity profile and for each severe
maternal outcome individually. In this
analysis, we adjusted for all maternal
characteristics as potential confounding
factors. All analyses were weighted based
on the weights provided in Premier to
generate national estimates.
Cohort composition
From 28,504,661 (weighted) singleton
deliveries that were identified in the
Perspectives database, records identified
as male (n ¼ 1308; unweighted, 236),
twins and higher-order multiple births
(n ¼ 530,065; unweighted, 79,594) and
women <15 or >59 years old were
sequentially excluded (n ¼ 32,688; un-
weighted, 5187). We additionally
excluded women who received a diag-
nosis of placenta previa (n ¼ 144,135;
unweighted, 21,241). After all exclu-
sions, the analysis cohort was composed
of 27,796,465 (3,961,031 unweighted)
women.
Results
In this cohort of 27,796,465 singleton
births, the prevalence rates of mild and
severe abruption were 3.1 and 6.5 per
1000, respectively (overall prevalence
rate, 9.6 per 1000). The distribution of
clinical characteristics among the 3
groups of nonabruption, mild abrup-
tion, and severe abruption is shown in
Table 1. Maternal age 35 years old,
black race, cigarette smoking status, and
the use of drugs or alcohol were associ-
ated with increased rates of abruption.
Compared with nonabruption births,
the prevalence rates of hypertensive
disorders were increased among
women with mild abruption but were
272.e2
Original Research OBSTETRICS ajog.org

substantially higher among women with

TABLE 1
severe abruption. Similarly, rates of
Distribution of clinical characteristics based on mild
premature rupture of membranes, pol-
and severe placental abruptiona
yhydramnios, and oligohydramnios
No abruption, Mild abruption, Severe were also relatively higher among severe
Variable % % abruption, % abruption.
Maternal age, yb The associations between the clinical
<20 9.0 7.1 10.6
characteristics and mild and severe
placental abruption are shown in
20-24 23.5 22.5 24.3 Table 2. Several differences were found
25-29 28.6 28.1 26.3 between mild vs severe abruption. For
30-34 24.3 25.0 22.4 instance, compared with women 25-29
35-39 12.9 14.8 14.0 years (reference), maternal age 45
years showed stronger associations with
40-44 1.5 2.3 2.0
mild abruption, whereas the risk among
45 0.1 0.2 0.3 women 45 years old was higher among
Maternal race women with severe abruption. RRs were
White 51.3 53.0 47.1
higher for severe rather than mild
abruption for black race, single marital
Black 12.6 13.0 19.7 status, and tobacco use. The risk of se-
Hispanic 9.9 8.6 8.3 vere abruption was substantially higher
Other 26.2 25.4 24.8 than mild abruption in relation to
chronic hypertension (RR, 1.64 vs 1.35),
Marital status
mild preeclampsia (RR, 2.06 vs 1.69),
Married 49.7 48.7 41.3 and severe preeclampsia (RR, 4.21 vs
Single 37.6 39.3 46.6 2.00). In contrast, the RRs of mild
Unknown 12.7 12.1 12.1 abruption were higher compared with
severe abruption among women with
Tobacco use 4.7 7.6 10.2
gestational hypertension (RR, 1.47 vs
Alcohol use 0.1 0.3 0.4 1.21). The RRs for severe abruption were
Drug use 0.2 0.7 1.0 higher than mild abruption in relation to
Insurance premature rupture of membranes, ane-
mia, polyhydramnios, oligohydramnios,
Commercial 52.1 48.7 43.7
and chorioamnionitis.
Medicare 0.6 0.7 0.8 The morbidity profile and the rates of
Medicaid 41.2 43.6 47.8 individual maternal complications in
Uninsured 2.5 3.1 3.4 mild and severe abruption and the
adjusted RRs for these complications are
Unknown 3.6 3.9 4.2
shown in Table 3. Serious maternal
Hypertension status complications occurred in 15.4 per
Normotensive 91.4 86.7 82.2 10,000 for nonabruption and in 33.3 and
Chronic hypertension 1.8 2.5 3.2 141.7 per 10,000 in women for mild and
severe abruption. After adjustment for
Gestational hypertension 3.2 4.5 3.5
confounders, compared with women
Mild preeclampsia 1.8 2.9 3.5 without abruption, the RRs for maternal
Severe preeclampsia 1.8 3.4 7.6 complications were 1.52 (95% CI,
Chronic renal disease 0.2 0.2 0.5 1.35e1.72) in women with mild abrup-
tion and 4.29 (95% CI, 4.11e4.47) in
Asthma 2.9 3.5 3.9
women with severe abruption. RRs for
Anemia 9.8 15.1 23.9 many of the individual complications
Congenital cardiac disease 0.1 0.0 0.1 were increased moderately in women
Premature rupture of membranes 3.5 4.5 8.8
with mild abruption but were 2- to
7-fold higher among severe abruptions.
Intrapartum fever 0.1 0.1 0.1 In fact, the RR of the composite serious
Ananth et al. Severe placental abruption. Am J Obstet Gynecol 2016. (continued) maternal complications in relation to
severe abruption was 4.29 (95% CI,

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TABLE 1
Distribution of clinical characteristics based on mild
and severe placental abruptiona (continued)
Variable
Chorioamnionitis
Polyhydramnios
Oligohydramnios
a
Number (abruption rate per 1000): no abruption, 27,528,415; mild abruption, 86,917 (3.1); severe abruption, 181,133 (6.5);
b
Mean  standard deviation: no abruption, 27.7  6.0; mild abruption, 28.3  6.1; severe abruption, 27.7  6.4.
Ananth et al. Severe placental abruption. Am J Obstet Gynecol 2016.
4.11e4.47; Table 3). Similarly, the RRs
for pulmonary edema (RR, 2.97; 95%
CI, 2.68e3.29), acute heart failure (RR,
3.05; 95% CI, 2.78e3.36), and acute
respiratory failure (RR, 7.00; 95% CI,
6.62e7.39) were all considerably higher
in women with severe abruptions.
The RRs for serious maternal compli-
cations among severe abruption
compared with mild abruption was 3.47
(95% CI, 3.05e3.95). The associations
were considerably stronger for virtually
all maternal complications for severe
abruption rather than for mild abruption.
Rates of mild and severe abruption
between 2006 and 2012 and the corre-
sponding rates of serious maternal
complications in relations to abruption
are shown in the Figure. Rates of mild
and severe abruption were fairly constant
during the study period. Although the
maternal complication rate among
births with no abruption was stable be-
tween 2006 and 2012, the rate of com-
plications for mild abruption dropped
between 2006 and 2008 and then leveled
off thereafter. In contrast, the rate of
serious complications for severe abrup-
tion remained fairly stable between 2006
and 2010, and increased sharply
thereafter.
Comment
Placental abruption is a serious and often
a life-threatening condition to the fetus
and, to a lesser extent, to the woman.5-13
We show that the clinical characteristics
for abruption differ substantially be-
tween mild and severe forms of the
condition and with varying strengths of
associations. The choices of maternal
No abruption, Mild abruption,
% %
1.4 2.2
0.8 1.0
2.6 2.5
conditions that constitute a diagnosis of
severe abruption were not different than
those previously reported in the obstet-
rics literature. The maternal morbidity
profile that we chose includes extreme
maternal conditions that typically are
not seen with abruption and typically are
not included in the definition of abrup-
tion. Under maternal morbidity profile,
we included cardiomyopathy, myocar-
dial infarction, and respiratory failure,
which are conditions that are associated
with severe, prolonged hypoxia. Amni-
otic fluid embolism was also included in
the maternal morbidity profile because it
is not typical for the diagnosis, but its
association with abruption has been
well-documented.2-4,14 These conditions
are extremely serious but not typical of
abruption; for this reason, we included
them in the maternal morbidity profile
rather than in the definition of severe
abruption.
The morbidity profile and rates of
serious maternal complications are pro-
foundly different between mild and se-
vere abruptions, with the rates being
substantially higher between severe
(141.7 per 10,000) rather than mild (33.3
per 10,000) abruptions. Importantly,
severe abruptions comprise two-thirds
of all abruptions mainly because pre-
term delivery and SGA were included in
the definition of severe abruption even in
the absence of severe maternal symp-
toms. Taken together, these findings
suggest that severe abruptions are the
distinct group of really ill patients and
that combining mild and severe forms of
the disease may introduce substantial
heterogeneity in clinical research.
FEBRUARY 2016 American Journal of Obstetrics & Gynecology
OBSTETRICS Original Research
In this study, the diagnosis of placental
abruption was based on clinical criteria
rather than placental pathology reports
(which were unavailable). However, in
Severe our view, pathology reports may not be
abruption, % necessary for 3 reasons: (1) epidemio-
4.1 logic databases very rarely, if ever, have
data regarding pathology reports;
1.2
(2) there are very few experts in placental
3.9 diseases, so any definition that use reli-
able placental pathology information
may affect generalizability; and (3) the
prevalence rate of abruption of 9.6 per
1000 in this study is within the range that
has been reported in other population-
based studies.5,15-17 This suggests that
we have not missed a significant number
of cases because of a lack of placental
pathology data. However, the data
allowed for distinguishing preterm from
term births, despite the lack of data on
the individual gestational age.
Limitations of the data
Despite the interesting observations, the
findings must be interpreted with some
caution. Primarily, the Premier data in-
cludes data on a large number of de-
liveries, but data on few socioeconomic
and behavioral characteristics (such as
maternal education, prepregnancy body
mass index, and weight gain during
pregnancy) are lacking, so the possibility
of the associations being affected by
unmeasured confounders remain. There
is also some possibility of misclassifica-
tion of abruption cases. However, we
believe that such misclassification, if
present, is likely more common for the
milder forms of the condition. Women
with severe abruption are the really ill
patients with >1 serious complication,
and it is very unlikely that abruption
status would be misclassified in this
group.
Strengths of the study
The strengths of the study include the
large study size with data from hospi-
talizations that are associated with over
27 million singleton deliveries from 441
hospitals over a 7-year period (2006-
2012) in the United States. All analyses
were weighted by the sampling weights
of deliveries, which permitted general-
izability of the findings. The associations
272.e4
Original Research OBSTETRICS ajog.org

that we report were adjusted for a variety

TABLE 2
of confounding factors.
Association between clinical characteristics and risks
of mild and severe placental abruptiona
Interpretation of findings
Adjusted rate ratio (95% confidence More than 4 decades ago, Pritchard
interval)b et al18 proposed that severe abruptions
Risk factors Mild abruption Severe abruption are those that are accompanied by 1
of short umbilical cord, external
Maternal age, y
trauma, sudden uterine decomposition,
<20 0.70 (0.68, 0.72) 0.97 (0.95, 0.99) uterine anomaly or tumor, occlusion of
20-24 0.89 (0.87, 0.91) 0.95 (0.94, 0.97) the inferior vena cava, maternal folate
25-29 1.00 (Reference) 1.00 (Reference) deficiency, maternal vascular disease,
high parity, and previous abruption. A
30-34 1.10 (1.08, 1.13) 1.11 (1.09, 1.12)
second classification was based on a
35-39 1.23 (1.21, 1.26) 1.28 (1.26, 1.30) system that assigns a score that ranges
40-44 1.58 (1.51, 1.65) 1.47 (1.42, 1.52) from 0-3, with 0 indicating asymp-
45 0.70 (0.68, 0.72) 0.97 (0.95, 0.99) tomatic women with evidence of small
retroplacental clots on the placental
Maternal race
surface on pathologic examination
White 1.00 (Reference) 1.00 (Reference) after delivery, 1 denoting those women
Black 0.92 (0.90, 0.94) 1.31 (1.29, 1.33) with bleeding and uterine tenderness
Hispanic 0.83 (0.81, 0.86) 0.89 (0.88, 0.91) or tetanic contractions, 2 denoting
bleeding with fetal distress (but no
Other 0.94 (0.92, 0.96) 1.01 (1.00, 1.02)
signs of maternal shock), and 3 denot-
Single marital status 1.06 (1.04, 1.08) 1.20 (1.19, 1.22) ing bleeding with uterine tetany,
Tobacco use 1.49 (1.45, 1.53) 1.90 (1.87, 1.93) persistent abdominal pain, maternal
Alcohol use 1.86 (1.63, 2.13) 1.78 (1.65, 1.92) shock, and fetal death.19
The classification for severe placental
Drug use 2.08 (1.91, 2.26) 2.32 (2.21, 2.44)
abruption that we propose is broad and
Insurance encompasses more objective criteria of
Commercial 1.00 (Reference) 1.00 (Reference) clinically meaningful abruption. In fact,
Medicare 1.14 (1.05, 1.24) 1.10 (1.04, 1.16) the conditions that were used to
define severe abruption were based on
Medicaid 1.21 (1.19, 1.23) 1.19 (1.18, 1.21)
serious co-occurring maternal, fetal,
Uninsured 1.43 (1.37, 1.49) 1.56 (1.52, 1.60) and neonatal clinical complications.
Hypertension status The grading system to classify abrup-
Normotensive 1.00 (Reference) 1.00 (Reference) tion severity19 is restrictive, because
even the grade 0 abruption that results
Chronic hypertension 1.35 (1.29, 1.41) 1.64 (1.60, 1.69)
in preterm delivery will be deemed as
Gestational hypertension 1.47 (1.42, 1.52) 1.21 (1.18, 1.24) being “severe” based on this classifica-
Mild preeclampsia 1.69 (1.63, 1.77) 2.06 (2.01, 2.12) tion system. Based on this definition,
Severe preeclampsia 2.00 (1.92, 2.08) 4.21 (4.13, 4.29) two-thirds of all clinically diagnosed
abruption cases were classified as being
Chronic renal disease 0.73 (0.62, 0.86) 1.35 (1.26, 1.45)
severe. Furthermore, fetal growth re-
Asthma 1.13 (1.09, 1.17) 1.04 (1.02, 1.07) striction and abruption are both largely
Anemia 1.59 (1.56, 1.63) 2.45 (2.42, 2.47) a chronic process that share strong
similarities and are driven by uteropla-
Premature rupture of membranes 1.27 (1.23, 1.32) 2.52 (2.48, 2.56)
cental ischemia,20,21 which provides
Intrapartum fever 2.13 (1.76, 2.57) 1.34 (1.16, 1.55) further support that both preterm de-
Polyhydramnios 1.15 (1.07, 1.23) 1.39 (1.33, 1.45) livery and fetal growth restriction
Oligohydramnios 0.96 (0.91, 1.00) 1.45 (1.42, 1.49) should be considered in the definition
of severe abruptions. This classification
Chorioamnionitis 1.50 (1.43, 1.58) 2.42 (2.36, 2.48)
a
not only identifies women with severe
Associations for all factors listed in the Table 1 were adjusted with the use of the log-linear Poisson regression model; b Rate
ratios for mild and severe abruption are each compared with the nonabruption group.
abruption with substantially higher
Ananth et al. Severe placental abruption. Am J Obstet Gynecol 2016. risk of serious morbidity but also ac-
knowledges that women with severe

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ajog.org OBSTETRICS Original Research

TABLE 3
Ratea and rate ratio of serious maternal complications in relation to mild and severe placental abruptionb
Severe placental
Nonabruption Mild placental abruption abruption Severe vs mild
(n ¼ 27,528,415) (n ¼ 86,917) (n ¼ 181,133) abruption
Adjusted rate ratio Adjusted rate ratio Adjusted rate ratio
(95% confidence (95% confidence (95% confidence
Variable Rate Rate interval) Rate interval) interval)
Composite maternal 15.4 33.3 1.52 (1.35e1.72) 141.7 4.29 (4.11e4.47) 3.47 (3.05e3.95)
outcome
Pulmonary edema 2.8 7.2 1.60 (1.24e2.08) 23.4 2.97 (2.68e3.29) 2.40 (1.82e3.17)
Puerperal cerebrovascular 2.9 9.8 2.46 (1.97e3.08) 16.5 2.72 (2.41e3.07) 1.20 (0.92e1.55)
disorders
Acute heart failure 4.1 5.7 0.93 (0.69e1.25) 27.5 3.05 (2.78e3.36) 4.20 (3.08e5.74)
Acute myocardial infarction 0.2 — — 2.7 7.56 (5.51e10.38) —
Cardiomyopathy 3.4 7.4 1.48 (1.13e1.92) 15.2 2.12 (1.87e2.41) 1.68 (1.26e2.26)
Acute respiratory failure 5.7 13.0 1.62 (1.33e1.96) 88.9 7.00 (6.62e7.39) 5.47 (4.48e6.68)
Amniotic fluid embolism 0.4 — — 5.1 10.56 (8.42e13.24) —
Coma 0.1 — — 1.9 7.04 (4.83e10.25) —
a
Rates are expressed per 10,000; b Associations were adjusted for the factors listed in Table 1 with the use of the log-linear Poisson regression model.
Ananth et al. Severe placental abruption. Am J Obstet Gynecol 2016.

abruption are distinctly different than

those with milder forms of the
FIGURE complication.
Changes in the rates of mild and severe placental abruption between Virtually all studies on placental
2006 and 2012 and that of composite outcome among women with mild
abruption have focused exclusively on
and severe abruption
assessing risks in the perinatal period
and during infancy,22-26 and evaluations
of maternal risks that are associated with
this condition are sparse. Furthermore,
we are unaware of any study that has
attempted to separate mild from severe
forms of abruption. In fact, the inclusion
of neonatal complications (preterm de-
livery and SGA) in the definition of se-
vere abruption results in two-thirds of all
abruptions being classified as severe.
Risk factors for severe abruption
appear driven largely by inflammation
and, to a lesser extent, infection-related
pathways.27 That tobacco and drug
use are stronger risk factors for severe,
rather than mild, abruptions suggest
that chronic hypoxia that leads to
uteroplacental under-perfusion as a
Although the maternal complication rate among births with no abruption was stable between 2006
result of tobacco smoke11,28-30 appears
and 2012, the rate of complications for mild abruption dropped between 2006 and 2008 and then
leveled off thereafter. In contrast, the rate of serious complications for severe abruption remained
to shape the risk of severe abruption.
fairly stable between 2006 and 2010, and increased sharply thereafter. Other pathologic chronic conditions
Ananth et al. Severe placental abruption. Am J Obstet Gynecol 2016.
that include chronic hypertension,12,31-33
preeclampsia,34,35 premature rupture

FEBRUARY 2016 American Journal of Obstetrics & Gynecology 272.e6

Original Research OBSTETRICS
of membranes,36 anemia,37 oligohy-
dramnios,38 and infection-related con-
ditions such as chorioamnionitis38,39 are
stronger risk factors for severe, rather
than mild, abruptions. Interestingly,
asthma and intrapartum fever showed
stronger associations with mild than
with severe abruptions.
The long-term risk of death and
morbidity from premature cardiovascular
disease are approximately 2- to 6-fold
higher among women with abruption
compared with otherwise normal preg-
nancies.40-43 In addition, this study sug-
gests that the risks of serious maternal
cardiovascular complications also remain
substantially higher among women with
severe, rather than mild, abruptions.
Acute complications such as myocardial
infarction and respiratory failure are
approximately 7-fold higher among
women with severe abruption. These
findings provide support to available data
that show that ischemic conditions during
pregnancy such as preeclampsia,44,45 fetal
growth restriction,46,47 preterm de-
livery48,49 and placental abruption40,41,43
may be linked to future cardiovascular
disease in women later in life. One of the
intriguing and unexpected findings is the
temporal increase in the rate of serious
maternal complications among women
with severe abruption since 2010 (Figure),
but this increase remains clinically
insignificant.
Conclusion
This large population-based study sug-
gests that the frequency of maternal
clinical risk factors is different with mild
vs severe abruptions. Furthermore, the
associated serious morbidity profile of
women who receive a diagnosis of severe
abruption is considerably worse than in
those with mild abruption. These find-
ings underscore a substantial heteroge-
neity in both risk factor profile and
serious adverse maternal complications.
Importantly, the definition of severe that
we propose is based on objective data
that include maternal, fetal, and
neonatal complications. Although this
proposed definition is not one that can
be used prospectively, because it
includes outcome data in the definition
of severe abruption, these observations
272.e7 American Journal of Obstetrics & Gynecology FEBRUARY 2016
underscore that future studies on
placental abruption should attempt to
separate mild from severe forms, when
feasible. This recommendation will be
particularly helpful for studies that seek
to understand the genetic imprints and
gene-environment interactions on
abruption risk. Research to unravel the
causes may also benefit from separating
mild from severe placental abruption. n
References
1. Oyelese Y, Ananth CV. Placental abruption.
Obstet Gynecol 2006;108:1005-16.
2. Abenhaim HA, Azoulay L, Kramer MS,
Leduc L. Incidence and risk factors of amniotic
fluid embolisms: a population-based study on 3
million births in the United States. Am J Obstet
Gynecol 2008;199:49.e1-8.
3. Conde-Agudelo A, Romero R. Amniotic fluid
embolism: an evidence-based review. Am J
Obstet Gynecol 2009;201:445.e1-13.
4. Spiliopoulos M, Puri I, Jain NJ, Kruse L,
Mastrogiannis D, Dandolu V. Amniotic fluid
embolism-risk factors, maternal and neonatal
outcomes. J Matern Fetal Neonatal Med
2009;22:439-44.
5. Parker SE, Werler MM, Gissler M, Tikkanen M,
Ananth CV. Placental abruption and subsequent
risk of pre-eclampsia: a population-based case-
control study. Paediatr Perinat Epidemiol
2015;29:211-9.
6. Ananth CV, Kinzler WL. Placental abruption:
clinical features and diagnosis. In:
Lockwood CJ, ed. UpToDate. Philadelphia:
Wolters Kluwer Health; 2014.
7. Sanchez SE, Pacora PN, Farfan JH, et al. Risk
factors of abruptio placentae among Peruvian
women. Am J Obstet Gynecol 2006;194:
225-30.
8. Broers T, King WD, Arbuckle TE, Liu S. The
occurrence of abruptio placentae in Canada:
1990 to 1997. Chronic Dis Can 2004;25:16-20.
9. Sheiner E, Shoham-Vardi I, Hadar A,
Hallak M, Hackmon R, Mazor M. Incidence,
obstetric risk factors and pregnancy outcome of
preterm placental abruption: a retrospective
analysis. J Matern Fetal Neonatal Med 2002;11:
34-9.
10. Rasmussen S, Irgens LM, Dalaker K.
A history of placental dysfunction and risk of
placental abruption. Paediatr Perinat Epidemiol
1999;13:9-21.
11. Kramer MS, Usher RH, Pollack R, Boyd M,
Usher S. Etiologic determinants of abruptio
placentae. Obstet Gynecol 1997;89:221-6.
12. Williams MA, Lieberman E, Mittendorf R,
Monson RR, Schoenbaum SC. Risk factors for
abruptio placentae. Am J Epidemiol 1991;134:
965-72.
13. Ananth CV, Oyelese Y, Yeo L, Pradhan A,
Vintzileos AM. Placental abruption in the United
States, 1979 through 2001: temporal trends and
potential determinants. Am J Obstet Gynecol
2005;192:191-8.
ajog.org
14. Hogberg U, Joelsson I. Amniotic fluid em-
bolism in Sweden, 1951-1980. Gynecol Obstet
Invest 1985;20:130-7.
15. Ananth CV, Keyes KM, Hamilton A, et al. An
international contrast of rates of placental
abruption: an age-period-cohort analysis. PLoS
One 2015;10:e0125246.
16. Pariente G, Wiznitzer A, Sergienko R,
Mazor M, Holcberg G, Sheiner E. Placental
abruption: critical analysis of risk factors and
perinatal outcomes. J Matern Fetal Neonatal
Med 2011;24:698-702.
17. Ruiter L, Ravelli AC, de Graaf IM, Mol BW,
Pajkrt E. Incidence and recurrence rate of
placental abruption: a longitudinal linked national
cohort study in the Netherlands. Am J Obstet
Gynecol 2015;213:573.e1-8.
18. Pritchard JA, Mason R, Corley M,
Pritchard S. Genesis of severe placental abrup-
tion. Am J Obstet Gynecol 1970;108:22-7.
19. Sher G, Statland BE. Abruptio placentae
with coagulopathy: a rational basis for
management. Clin Obstet Gynecol 1985;28:
15-23.
20. Ananth CV, Vintzileos AM. Maternal-fetal
conditions necessitating a medical intervention
resulting in preterm birth. Am J Obstet Gynecol
2006;195:1557-63.
21. Ananth CV, Vintzileos AM. Epidemiology of
preterm birth and its clinical subtypes. J Matern
Fetal Neonatal Med 2006;19:773-82.
22. Kyrklund-Blomberg NB, Gennser G,
Cnattingius S. Placental abruption and perinatal
death. Paediatr Perinat Epidemiol 2001;15:
290-7.
23. Rasmussen S, Irgens LM, Bergsjo P,
Dalaker K. Perinatal mortality and case fatality
after placental abruption in Norway 1967-1991.
Acta Obstet Gynecol Scand 1996;75:229-34.
24. Ananth CV, Berkowitz GS, Savitz DA,
Lapinski RH. Placental abruption and adverse
perinatal outcomes. JAMA 1999;282:1646-51.
25. Ananth CV, Wilcox AJ. Placental abruption
and perinatal mortality in the United States. Am J
Epidemiol 2001;153:332-7.
26. Tikkanen M, Luukkaala T, Gissler M, et al.
Decreasing perinatal mortality in placental
abruption. Acta Obstet Gynecol Scand
2013;92:298-305.
27. Ananth CV, Getahun D, Peltier MR,
Smulian JC. Placental abruption in term and
preterm gestations: evidence for heterogeneity
in clinical pathways. Obstet Gynecol 2006;107:
785-92.
28. Christianson RE. Gross differences
observed in the placentas of smokers and non-
smokers. Am J Epidemiol 1979;110:178-87.
29. Ananth CV, Savitz DA, Luther ER.
Maternal cigarette smoking as a risk factor for
placental abruption, placenta previa, and
uterine bleeding in pregnancy. Am J Epidemiol
1996;144:881-9.
30. Cnattingius S. Maternal age modifies the
effect of maternal smoking on intrauterine
growth retardation but not on late fetal death and
placental abruption. Am J Epidemiol 1997;145:
319-23.
ajog.org
31. Williams MA, Mittendorf R, Monson RR.
Chronic hypertension, cigarette smoking, and
abruptio placentae. Epidemiology 1991;2:
450-3.
32. Ananth CV, Peltier MR, Kinzler WL,
Smulian JC, Vintzileos AM. Chronic hyperten-
sion and risk of placental abruption: Is the as-
sociation modified by ischemic placental
disease? Am J Obstet Gynecol 2007;197:273.
e1-7.
33. Misra DP, Ananth CV. Risk factor profiles of
placental abruption in first and second preg-
nancies: heterogeneous etiologies. J Clin Epi-
demiol 1999;52:453-61.
34. Ananth CV, Peltier MR, Chavez MR,
Kirby RS, Getahun D, Vintzileos AM. Recurrence
of ischemic placental disease. Obstet Gynecol
2007;110:128-33.
35. Cnattingius S, Mills JL, Yuen J, Eriksson O,
Salonen H. The paradoxical effect of smoking in
preeclamptic pregnancies: smoking reduces the
incidence but increases the rates of perinatal
mortality, abruptio placentae, and intrauterine
growth restriction. Am J Obstet Gynecol
1997;177:156-61.
36. Vintzileos AM, Campbell WA,
Nochimson DJ, Weinbaum PJ. Preterm pre-
mature rupture of the membranes: a risk factor
for the development of abruptio placentae. Am J
Obstet Gynecol 1987;156:1235-8.
37. Hibbard BM. The role of folic acid in preg-
nancy; with particular reference to anaemia,
abruption and abortion. J Obstet Gynaecol Br
Commonw 1964;71:529-42.
38. Ananth CV, Oyelese Y, Srinivas N, Yeo L,
Vintzileos AM. Preterm premature rupture of
membranes, intrauterine infection, and oligohy-
dramnios: risk factors for placental abruption.
Obstet Gynecol 2004;104:71-7.
OBSTETRICS
39. Darby MJ, Caritis SN, Shen-Schwarz S.
Placental abruption in the preterm gestation: an
association with chorioamnionitis. Obstet
Gynecol 1989;74:88-92.
40. Pariente G, Shoham-Vardi I, Kessous R,
Sherf M, Sheiner E. Placental abruption as a
significant risk factor for long-term cardiovas-
cular mortality in a follow-up period of more than
a decade. Paediatr Perinat Epidemiol 2014;28:
32-8.
41. Ray JG, Vermeulen MJ, Schull MJ,
Redelmeier DA. Cardiovascular health after
maternal placental syndromes (CHAMPS):
population-based retrospective cohort study.
Lancet 2005;366:1797-803.
42. Veerbeek JH, Smit JG, Koster MP, et al.
Maternal cardiovascular risk profile after
placental abruption. Hypertension 2013;61:
1297-301.
43. DeRoo L, Skjaerven R, Wilcox A, et al.
Placental abruption and long-term maternal
cardiovascular disease mortality:
population-based registry study in Norway
and Sweden. Eur J Epidemiol 2015. Epub
ahead of print.
44. Irgens HU, Reisaeter L, Irgens LM, Lie RT.
Long term mortality of mothers and fathers after
pre-eclampsia: population based cohort study.
BMJ 2001;323:1213-7.
45. Lykke JA, Langhoff-Roos J, Sibai BM,
Funai EF, Triche EW, Paidas MJ. Hypertensive
pregnancy disorders and subsequent cardio-
vascular morbidity and type 2 diabetes
mellitus in the mother. Hypertension 2009;53:
944-51.
46. Lykke JA, Paidas MJ, Triche EW, Langhoff-
Roos J. Fetal growth and later maternal death,
cardiovascular disease and diabetes. Acta
Obstet Gynecol Scand 2012;91:503-10.
FEBRUARY 2016 American Journal of Obstetrics & Gynecology
Original Research
47. Smith GD, Whitley E, Gissler M, Hemminki E.
Birth dimensions of offspring, premature birth,
and the mortality of mothers. Lancet 2000;356:
2066-7.
48. Catov JM, Wu CS, Olsen J, Sutton-Tyrrell K,
Li J, Nohr EA. Early or recurrent preterm birth
and maternal cardiovascular disease risk. Ann
Epidemiol 2010;20:604-9.
49. Rich-Edwards JW, Klungsoyr K, Wilcox AJ,
Skjaerven R. Duration of pregnancy, even at
term, predicts long-term risk of coronary heart
disease and stroke mortality in women: a
population-based study. Am J Obstet Gynecol
2015.
Author and article information
From the Department of Obstetrics and Gynecology (Drs
Ananth, Wapner, and Wright and Ms Lavery) and the
Biostatistics Coordinating Center (Dr Ananth and Ms
Lavery), College of Physicians and Surgeons, and the
a Department of Epidemiology, Joseph L. Mailman School
of Public Health (Dr Ananth), Columbia University, New
York, NY; the Department of Obstetrics and Gynecology,
Winthrop-University Hospital, Mineola, NY (Dr Vintzileos);
the Department of Obstetrics and Gynecology, Weill
Medical College of Cornell University, New York, NY (Dr
Skupski); the Department of Obstetrics and Gynecology,
University of Utah, Salt Lake City, UT (Dr Varner); the
Department of Obstetrics and Gynecology, University of
Texas, Galveston, TX (Dr Saade); the Department of
Obstetrics and Gynecology, University of Alabama, Bir-
mingham, AL (Dr Biggio); the Department of Epidemi-
ology, T.H. Chan School of Public Health, Harvard
University, Boston, MA (Dr Williams).
Received Aug. 31, 2015; accepted Sept. 14, 2015.
The authors report no conflict of interest.
Corresponding author: Cande V. Ananth, PhD, MPH.
cande.ananth@columbia.edu
272.e8
Original Research OBSTETRICS ajog.org

SUPPLEMENTAL TABLE
International Classification of Diseases, 9th edition, clinical modification codes for variables in this study
Condition International Classification of Diseases, 9th edition, clinical modification code
Delivery V27.0-V27.9
Singleton birth Multiple births (V272-V277, 654.x) excluded
Placental abruption 641.2
Infant outcomes
Stillbirth 656.4x, V27.1x
Neonatal death 768.x, 798.x
Preterm delivery 644.2x
Fetal growth restriction 656.5x, 764x
Nonreassuring fetal status 656.3x, 659.7x
Covariates
Hypertensive disorders
Chronic hypertension 642.00-642.24
Gestational hypertension 642.30-642.34
Mild preeclampsia 642.40-642.49
Severe preeclampsia 642.50-642.54
Superimposed preeclampsia 642.70-642.74
Tobacco use 305.1.x, 649.0x
Alcohol use 291.xx, 303.xx, 305.0x
Drug abuse 304.x, 305.2x-305.9x, 648.3x
Chronic renal disease 646.2x, 581.x, 582.x, 583.x, 585.x, 587, 588.x
Asthma 493, 493.0, 493.00, 493.02, 493.1, 493.10, 493.12, 493.2, 493.20, 493.22, 493.81,
493.82, 493.9, 493.90, 493.92
Outcomes/procedures
Maternal death 761.6
Puerperal cerebrovascular disorders 671.5, 671.50, 671.51, 671.52, 671.53, 671.54, 674.0, 674.00, 674.01, 674.02, 674.03,
674.04, 430, 431, 432, 432.0, 432.1, 432.9, 436, 997.01, 997.02, 433.01, 433.11, 433.21,
433.31, 433.81, 433.91, 434.01, 434.11, 434.91, 325, 348.1, 348.3, 348.30, 348.31,
348.39, 348.5, 437.1, 437.2, 437.6, 346.6, 346.60, 346.61, 346.62, 346.63
Pulmonary edema 514, 518.4, 428.1
Amniotic fluid embolism 673.1x
Disseminated intravascular coagulation 666.3x, 286.6, 286.7, 286.9, 287.4, 287.41, 287.49
Acute renal failure 584, 584.5, 584.6, 584.7, 584.8, 584.9, 669.3, 669.30, 669.32, 669.34
Acute heart failure 415, 415.0, 427.5, 428.0, 428.1, 428.21, 428.31, 428.41, 997.1, 428.23, 428.33,
428.43, 428.9
Acute myocardial infarction 410.x
Cardiomyopathy 674.5x, 425x
Acute liver failure 570, 646.7, 646.70, 646.71, 646.73
Acute respiratory failure 518.81, 518.82, 518.84, 518.5, 518.51, 518.52, 518.53, 799.1, 518.7
Blood transfusion V58.2, 99.0, 99.01-99.07
Hysterectomy 68.3, 68.31, 68.39, 68.4, 68.41, 68.49, 68.6, 68.69, 68.9
Coma 780.01, 780.03, 572.2, 250.2x, 250.3x, 251.0x
Shock 669.1x, 785.5x, 998.0x, 995.4, 995.0, 995.94, 99.4x
Ananth et al. Severe placental abruption. Am J Obstet Gynecol 2016.

272.e9 American Journal of Obstetrics & Gynecology FEBRUARY 2016