Trends in Ectopic Pregnancy Mortality in the

United States
1980 2007
Andreea A. Creanga, MD, PhD, Carrie K. Shapiro-Mendoza, PhD, MPH, Connie L. Bish,
Suzanne Zane, DVM, Cynthia J. Berg, MD, MPH, and William M. Callaghan, MD, MPH
OBJECTIVE: To estimate trends in ectopic pregnancy
mortality and examine characteristics of recently hospitalized women who died as a result of ectopic pregnancy
in the United States.
METHODS: We used 1980 2007 national birth and
death certificate data to calculate ectopic pregnancy
mortality ratios (deaths per 100,000 live births) overall
and stratified by maternal age and race. We performed
nonparametric tests for trend to assess changes in ectopic
pregnancy mortality over time and calculated projected
mortality ratios for 20132017. Ectopic pregnancy deaths
among hospitalized women were identified from 1998
2007 Nationwide Inpatient Sample data.
RESULTS: Between 1980 and 2007, 876 deaths were attributed to ectopic pregnancy. The ectopic pregnancy mortality ratio declined by 56.6%, from 1.15 to 0.50 deaths per
100,000 live births between 1980 1984 and 20032007; at
the current average annual rate of decline, this ratio will
further decrease by 28.5% to 0.36 ectopic pregnancy deaths
per 100,000 live births by 20132017. The ectopic pregnancy
mortality ratio was 6.8 times higher for African Americans
than whites and 3.5 times higher for women older than 35
years than those younger than 25 years during 20032007.
See related articles on pages 828, 850, and 948.

From the Epidemic Intelligence Service, Office of Workforce and Career

Development, and the Division of Reproductive Health, Centers for Disease
Control and Prevention, Atlanta, Georgia.
The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease Control and
Prevention.
Corresponding author: Andreea A. Creanga, MD, PhD, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health
Promotion, 4770 Buford Highway, NE, Mail Stop K-23, Atlanta GA
30341-3717; e-mail: acreanga@cdc.gov.
Financial Disclosure
The author did not report any potential conflicts of interest.
2011 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/10

VOL. 117, NO. 4, APRIL 2011

PhD, MPH,

Of the 76 deaths among women hospitalized between 1998

and 2007, 70.5% were tubal pregnancies; salpingectomy
was performed in 80.6% of cases. Excessive hemorrhage,
shock, or renal failure accompanied 67.4% of ectopic pregnancy deaths among hospitalized women.
CONCLUSION: Despite a significant decline in ectopic
pregnancy mortality since the 1980s, age disparities, and especially racial disparities, persist. Strategies to ensure timely
diagnosis and management of ectopic pregnancies can further
reduce related mortality and age and race mortality gaps.
(Obstet Gynecol 2011;117:83743)
DOI: 10.1097/AOG.0b013e3182113c10

n ectopic pregnancy occurs when a fertilized

ovum implants outside the endometrial cavity.
Although only 1% to 2% of all pregnancies in the
United States are ectopic,1,2 this condition has important health consequences and represents an important
cause of morbidity and mortality for women of reproductive age. Specifically, affected women are not only
exposed to complications from the ectopic pregnancy
itself and the related treatment procedures, but are
also at greater risk of another ectopic pregnancy and
future infertility.3,4
Medical and surgical treatment of ectopic pregnancy is currently provided in both inpatient and
outpatient settings. For this reason, obtaining reliable
estimates for the incidence of ectopic pregnancy at the
national level is difficult.3 The latest such estimate of
19.7 ectopic pregnancies per 1,000 pregnancies was
reported for 1990 1992 using inpatient National Hospital Discharge Survey and outpatient National Hospital Ambulatory Medical Care Survey data.5 More
recent attempts to estimate ectopic pregnancy incidence used data from surveys or administrative databases of public and private insurance and managed
care systems.3,6,7 Although not nationally representative, these data suggest that incidence of ectopic

OBSTETRICS & GYNECOLOGY

837

pregnancy has not changed substantially in the

United States since the early 1990s. Complications of
ectopic pregnancy were associated with approximately 13.0% of all maternal deaths between 1970
and 19898 and 6.0% of all pregnancy-related deaths
between 1991 and 1999.1 This decline in proportionate mortality is likely attributable to technological
advances (eg, more sensitive human chorionic gonadotropin assays, improved ultrasound equipment and
techniques) in the diagnosis and treatment of this
condition.4,6,9 Using national vital statistics data from
19911999, Grimes estimated an ectopic pregnancy
mortality rate of 31.9 per 100,000 ectopic pregnancies
and found that relative to a womans risk of dying
after a live birth, a woman with an ectopic pregnancy
was 4.5 times more likely to die.10
This studys objectives were to: 1) estimate trends
in ectopic pregnancy mortality in the United States
between 1980 and 2007; 2) estimate age and racial
disparities in ectopic pregnancy mortality; and 3)
describe sociodemographic and clinical characteristics of recently hospitalized women who died from
ectopic pregnancy complications.

MATERIALS AND METHODS

We used national multiple cause-of-death mortality
and natality data from death and birth certificates in
the National Vital Statistics System to calculate ectopic pregnancy mortality ratios (deaths per 100,000
live births) overall and stratified by maternal age and
race. We identified ectopic pregnancy deaths by
searching the records for all deaths occurring in the
50 states and the District of Columbia: 1) during
1980 1998 that contained International Classification
of Diseases, 9th Revision codes 633.x; and 2) during
1999 2007 that contained International Classification
of Diseases, 10th Revision codes O00.x as a contributing cause of death. Codes for ectopic pregnancy
included: 633.0 and O00.0 (abdominal pregnancy),
633.1 and O00.1 (tubal pregnancy), 633.2 and O00.2
(ovarian pregnancy), 633.8 and O00.8 (other ectopic
pregnancy, ie, cervical, combined, corneal, intraligamentous, mesometric, mural), and 633.9 and O00.9
(unspecified ectopic pregnancy) based on International Classification of Diseases, 9th Revision and
International Classification of Diseases, 10th Revision, respectively. Women were grouped into four
age categories: younger than 25, 2529, 30 34, and
35 years or older; for consistency over the entire study
period, the race-specific analysis was limited to two
race groups: whites and African Americans. Because
age- and race-specific annual mortality ratios based
on small numbers of deaths (20 or fewer) are consid-

838

Creanga et al

Ectopic Pregnancy Mortality Trends

ered unreliable,11 we calculated 5-year moving averages to smooth the data and gain stability with a
minimal loss of information. Cuzick nonparametric
tests for trend across ordered groups were performed
to assess the statistical significance of changes in
mortality ratios over time.12 We used the 5-year
moving averages to calculate the average annual
percent change in ectopic pregnancy mortality ratios
overall and by maternal age and race, and, through
linear extrapolation, to project changes in ectopic
pregnancy mortality ratios over the next 10 years (ie,
by 20132017).
To describe characteristics of hospitalized women
who died from ectopic pregnancy complications, we
used 1998 2007 Nationwide Inpatient Sample hospital discharge data obtained from the Healthcare Cost
and Utilization Project.13 The Nationwide Inpatient
Sample is the largest all-payer inpatient care database
publicly available in the United States. The sampling
universe for the Nationwide Inpatient Sample is
comprised of US hospitals defined as nonfederal
general and specialty hospitals with average lengths of
stay less than 30 days and whose facilities are open to
the public.13 The Nationwide Inpatient Sample sampling frame uses five strata: type of ownership, number of hospital beds, teaching status, urban or rural
location, and country region; all hospital discharges
are retained in all Nationwide Inpatient Sample sampled hospitals. Each year, the Nationwide Inpatient
Sample collects data from a 20% stratified sample of
hospitals in the United States; thus, derived analytic
weights can be used to provide national-level estimates. Hospital discharge diagnoses and clinical procedures in the Nationwide Inpatient Sample data are
classified using the International Classification of Diseases, 9th Revision, Clinical Modification codes.
Using the Nationwide Inpatient Sample data, we
identified all records with an ectopic pregnancy discharge diagnosis (633.xx) and at least one corresponding clinical procedural code for operations on fallopian tubes (66.0x, 66.2x, 66.3x, 66.4, 66.5x, 66.6x,),
removal of extratubal ectopic pregnancy (74.3), or
injection of a cancer chemotherapeutic substance to
account for the use of methotrexate (99.25). Of these,
records from women who died during their hospitalization for an ectopic pregnancy were included in the
analysis. Univariable analyses were conducted to
examine womens age, recorded clinical diagnoses
and treatment procedures, the length of hospital stay,
and the total in-hospital care charges in US dollars.
Both National Vital Statistics System and Nationwide Inpatient Sample data are publicly available and
neither source includes personal identifiers. Thus,

OBSTETRICS & GYNECOLOGY

Ectopic pregnancy mortality ratio*

4.0
All women
White women
Black women

3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
1
80
19

98

1
85
19

98

1
90
19

99

1
95
19

99

institutional review board approval was not required.

All statistical analyses were conducted using STATA
10. The analysis using Nationwide Inpatient Sample
data were adjusted for complex survey design using
Taylors linearization method.

RESULTS
According to death certificate data, 876 deaths in the
United States were attributable to ectopic pregnancy
between 1980 and 2007. The ectopic pregnancy
mortality ratio declined significantly by 56.6% during
the study period (P.001) from 1.15 to 0.50 deaths
per 100,000 live births when comparing 1980 1984
and 20032007, respectively (Fig. 1). Although over
the same period of time ectopic pregnancy mortality
ratio declined by 60.4% (P.001) among white
women, the corresponding decrease was 50.8%
(P.001) among African American women, from 0.65
to 0.26 deaths per 100,000 live births among whites

07
04
20
20
3
0
0
0
20
20

Fig. 1. Trends in ectopic pregnancy

mortality for all women and by race:
United States, 1980 2007. *Each data
point represents a 5-year moving average expressed per 100,000 live births.
X-axis labels are shown for every fifth
data point and for the last data point.
Creanga. Ectopic Pregnancy Mortality
Trends. Obstet Gynecol 2011.

and from 3.57 to 1.75 deaths per 100,000 live births

among African American women. Thus, the ectopic
pregnancy mortality ratio was 5.5 (95% confidence
interval [CI] 5.35.8) times higher for African American compared with white women during 1980 1984
and 6.8 (95% CI 6.57.3) times greater during 2003
2007.
By and large, the ectopic pregnancy mortality
was higher among older than younger women and
declined for women of all ages between 1980 1984
and 20032007 (Fig. 2). The pattern of decline also
varied with maternal age. We observed an overall
continuous decline in mortality resulting from ectopic
pregnancy for women younger than 30 years and a
less consistent, but, nonetheless, important decline for
older women. Of note, women 35 years and older had
the highest reduction in ectopic pregnancy mortality
between the two time periods (68.8%). Specifically,
between 1980 1984 and 20032007, the ectopic

Ectopic pregnancy mortality ratio*

3.5
Less than 25 years
2529 years
3034 years

3.0
2.5

35 years or older

2.0
1.5
1.0
0.5
0.0
1
80
19

98

1
85
19

98

VOL. 117, NO. 4, APRIL 2011

1
90
19

99

1
95
19

99

04
07
20
20
0
3
0
0
20
20

Creanga et al

Fig. 2. Trends in ectopic pregnancy

mortality by age group: United States,
1980 2007. *Each data point represents a 5-year moving average expressed per 100,000 live births. X-axis
labels are shown for every fifth data
point and for the last data point.
Creanga. Ectopic Pregnancy Mortality
Trends. Obstet Gynecol 2011.

Ectopic Pregnancy Mortality Trends

839

pregnancy mortality ratio declined from 0.82 deaths

to 0.30 deaths per 100,000 live births among women
younger than 25 years and from 1.10 deaths to 0.42
deaths per 100,000 live births among women 2529
years of age. Among women 30 34 years, the level of
ectopic pregnancy mortality fluctuated between a
maximum ectopic pregnancy mortality ratio of 1.37
deaths per 100,000 live births in 1980 1984 and a
minimum of 0.50 deaths per 100,000 live births in
20012005, and reached 0.56 deaths per 100,000 live
births in 20032007. Ectopic pregnancy mortality
ratios varied even more among the oldest group of
women (35 years and older), from a high 3.33 deaths
per 100,000 live births in 1980 1984 to 1.04 deaths
per 100,000 live births in 20032007. Tests for trend
for all trends described here were statistically significant at a level P.001. Based on the most recent point
estimate (20032007), women 2529, 30 34, and 35
years or older were 1.4 (95% CI 0.8 2.0; this estimate
is not statistically significant but it is clinically important), 1.9 (95% CI 1.32.5), and 3.5 (95% CI 3.0 4.1)
times more likely to die as a result of complications of
ectopic pregnancy than women younger than 25
years.
We calculated the observed (1980 2007) and
projected (20132017) changes in ectopic pregnancy
mortality ratios (Table 1). During the study period,
the estimated average annual percent decrease in the
ectopic pregnancy mortality ratio was 3.3% for all
women, higher for whites (3.5%) than for African
Americans (2.8%) and for women in the highest and
lowest age groups (4.1% and 3.6%, respectively) than
for women 2529 years (3.5%) and 30 34 years of age
(3.1%). If the current average annual rate of decline in
ectopic pregnancy mortality ratio in the United States
continues, the ratio will further decline by 28.5% by
20132017 to 0.36 ectopic pregnancy deaths per
100,000 live births, less so for African Americans
(24.9%) and for women 30 34 years (27.1%) but more
for whites and for women in the other age groups
(29.6 33.9%).

Seventy-six deaths resulting from ectopic pregnancy complications were identified using Nationwide Inpatient Sample hospital discharge data between 1998 and 2007. The median age of the women
was 33 years (range 13 43 years). A majority of
women (81.8%) were admitted to a hospital from the
emergency department. Women were hospitalized
for a median of 1 day, with the length of hospital stay
ranging from 0 to 74 days. Approximately 7 in 10
women (70.5%) had tubal pregnancies, and salpingectomy was performed in 80.6% of hospitalized patients; of note, no identified patient received treatment with methotrexate. More than two thirds
(67.4%) of hospitalized women experienced either
excessive hemorrhage, shock, or renal failure.

DISCUSSION
Using the most recent mortality data available, this
analysis provides national trends in ectopic pregnancy mortality and describes age- and race-specific
mortality patterns for 1980 2007. During this period,
ectopic pregnancy mortality declined significantly to
a 5-year national average ectopic pregnancy mortality
ratio of 0.50 per 100,000 live births and an average of
approximately 21 ectopic pregnancy deaths annually
between 2003 and 2007. Technologic changes including widespread use of progressively more sensitive
pregnancy tests, ultrasound examination, and laparoscopy have likely contributed to an earlier and more
accurate diagnosis of ectopic pregnancy,1,4,6,9 and, in
turn, to the observed reduction in ectopic pregnancy
mortality. Greater awareness of ectopic pregnancy on
the part of women and physicians, earlier intervention, and less invasive treatment for unruptured ectopic pregnancies may be additional contributing factors to this decline in mortality. To the extent that
efforts to increase awareness of ectopic pregnancy
and knowledge of its risk factors, diagnosis, and
treatment, in tandem with access to care and better
methods of early treatment, contributed to the observed decrease in ectopic pregnancy mortality, this

Table 1. Observed and Projected Changes in Ectopic Pregnancy Mortality Ratios for All Women and by
Race and Age Group: United States
Race
Indicator
Average annual decline in EPMR during
19802007
Overall projected decline in EPMR between
20032007 and 20132017

Age Group (y)

All Women

White

African
American

Younger
Than 25

2529

3034

35 or
Older

3.3

3.5

2.8

3.6

3.5

3.1

4.1

28.5

29.6

24.9

30.9

30.1

27.1

33.9

EPMR, ectopic pregnancy mortality ratio.

Data are %.

840

Creanga et al

Ectopic Pregnancy Mortality Trends

OBSTETRICS & GYNECOLOGY

trend represents a successful integration of public

health and clinical medicine.
Despite the general downward trend in ectopic
pregnancy mortality, age disparities, and especially
racial disparities, persist. Age disparities in ectopic
pregnancy mortality are not surprising given that
incidence of ectopic pregnancy also increases with
age.7,14 Biologic explanations for such variation in
ectopic pregnancy incidence rates are anatomic and
functional age-related changes of the fallopian tubes
as well as repeated pelvic inflammatory disease that
may induce tubal damages and predispose women to
ectopic pregnancy15; use of assisted reproductive technologies16 and tubal ligation17 are also higher among
women older than 35 years. Of note, the identified
age disparity in ectopic pregnancy mortality is consistent with findings from other studies examining allcause pregnancy-related deaths in the United
States.1,18 For example, Chang et al1 report that relative to women in their 20s, those 3539 and older
than 40 years were 2.5 and 5.3 times more likely,
respectively to experience a pregnancy-related death
between 1991 and 1999.
Like previous ectopic pregnancy mortality trend
analyses,8,14 our results indicate that African American women are more likely to die as a result of ectopic
pregnancy complications than white women. Between 2003 and 2007, African American women were
approximately 6.8 times more likely than white
women to die as a consequence of an ectopic pregnancy, whereas the all-cause maternal mortality rate
for the same time period was only 2.73.7 times
higher for African Americans than for whites.19 23
Whether this considerable African Americanwhite
gap in ectopic pregnancy mortality is the result of an
increased ectopic pregnancy incidence or to a higher
case-fatality rate among African Americans than
whites is unknown. Data from 1986 showed that the
risk of ectopic pregnancy among African Americans
was 1.6 times higher than among white women.14 If
this difference did not change greatly over time, then
it appears that African Americans do have a higher
ectopic pregnancy case-fatality rate than whites. Such
a conclusion is in line with findings reported by
Tucker et al24; they used 1988 1999 national data to
calculate prevalence and case-fatality rates for preeclampsia, eclampsia, abruptio placentae, placenta
previa, and postpartum hemorrhage among African
American and white women and found that the
higher pregnancy-related mortality from these causes
among African American women was largely attributable to higher case-fatality rates. Both the higher
ectopic pregnancy mortality and the higher case-

fatality rate among African Americans relative to

whites might be explained by higher rates of late
entry into or no prenatal care,25,26 lower health insurance coverage,27 and lower education attainment28 for
African American women compared with white
women. All these considered, it is unlikely that a
single intervention can eliminate the African Americanwhite gap in ectopic pregnancy mortality, because disparities likely stem from a combination of
causes.
The Nationwide Inpatient Sample data add some
new information to the limited clinical information on
hospitalized women in the United States dying from
ectopic pregnancy. Despite the relatively small number of cases identified, we found that complications
such as hemorrhage, shock, and renal failure accompanied an important proportion of these cases. Overall, the 76 ectopic pregnancy deaths identified in the
1998 2007 Nationwide Inpatient Sample data represent 34.9% of all ectopic pregnancy deaths captured
by national mortality data during the same period.
Thus, almost two thirds of all ectopic pregnancy
deaths in the United States appear to have occurred in
the emergency department, in transit to a hospital, or
outside the hospital. Atrash et al29 examined ectopic
pregnancy deaths in the United States between 1970
and 1983 and found that approximately 59% of the
women dying did so in a hospital; yet, their analysis
preceded the increase in outpatient management of
ectopic pregnancy.30
Our analysis is not without limitations. First,
identification and correct classification of ectopic
pregnancy deaths depends on having complete and
accurate cause of death information on death certificates. Because maternal death in the United States is
a rare event, physicians may not be as familiar with
completion of death certificates for women dying as a
result of maternal causes.31 Thus, if not all ectopic
pregnancy deaths were identified as such (eg, deaths
that occurred without surgical intervention or autopsy
were more likely to be missed), our ectopic pregnancy
mortality ratios represent underestimates of the true
mortality ratios. Comparative analyses using national mortality data and one or more other sources
of data on maternal mortality demonstrate that no
single data source can capture all maternal deaths.32
We compared our data against that compiled for the
Centers for Disease Control and Preventions Pregnancy-Related Mortality Surveillance System for the
period between 1991 and 1999; whereas 237 ectopic
pregnancy deaths were captured through surveillance
by the Centers for Disease Control and Prevention,1
our analysis using multiple cause-of-death data iden-

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Ectopic Pregnancy Mortality Trends

841

tified 257 ectopic pregnancy deaths during the same

period of time; both data sources aim to capture
deaths at the national level. Second, misclassification
of race on death certificates may have resulted in
either under- or overestimates of race-specific ectopic
pregnancy mortality ratios; moreover, as a result of
data limitations, we could not examine ectopic pregnancy mortality among other racial and ethnic groups
over the entire study period.
Research has shown that approximately half of all
women with an ectopic pregnancy diagnosis do not
have any known risk factors.33 Therefore, early detection and treatment of ectopic pregnancies is, therefore, the most effective way to ensure that outcomes
occur at a less severe point along the continuum and
to reduce related hospitalization, morbidity, and mortality. Because most ectopic pregnancies are diagnosed during the first trimester of pregnancy,29 early
prenatal care or contact with a physician is highly
important in preventing ectopic pregnancy deaths
because it provides an opportunity for early diagnosis
and treatment of this condition. This aspect appears to
be especially important for African American women
who tend to have less prenatal care and initiate their
antenatal care visits later.25,26 Thus, measures to educate the public (ie, through media, health education in
schools, during patient clinician interactions) regarding ectopic pregnancy are needed, particularly targeting women at risk of ectopic pregnancy and ectopic
pregnancy mortality, including African American and
older women of reproductive age. In addition, continued surveillance and studies tracking trends in
ectopic pregnancy incidence and mortality should be
conducted to monitor the burden from ectopic pregnancy, identify risk factors, and develop strategies to
prevent women with ectopic pregnancy from dying.

6. Van Den Eeden SK, Shan J, Bruce C, Glasser M. Ectopic

pregnancy rate and treatment utilization in a large managed
care organization. Obstet Gynecol 2005;105:10527.
7. Hoover KW, Tao G, Kent CK. Trends in the diagnosis and
treatment of ectopic pregnancy in the United States. Obstet
Gynecol 2010;115:495502.
8. Goldner TE, Lawson HW, Xia Z, Atrash HK. Surveillance for
ectopic pregnancyUnited States, 1970 1989. MMWR CDC
Surveill Summ 1993;42:73 85.
9. Anderson FW, Hogan JG, Ansbacher R. Sudden death: ectopic pregnancy mortality. Obstet Gynecol 2004;103:1218 23.
10. Grimes DA. Estimation of pregnancy-related mortality risk by
pregnancy outcome, United States, 1991 to 1999. Am J Obstet
Gynecol 2006;194:92 4.
11. Hoyert DL. Maternal mortality and related concepts. Vital
Health Stat 3 2007;33:113. Available at: www.cdc.gov/nchs/
data/series/sr_03/sr03_033.pdf.
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(MD): Agency for Healthcare Research and Quality; 2010.
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cdc.gov/nchs/data/nvsr/nvsr56/nvsr56_10.pdf.

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