Ectopic Pregnancy Surveillance, United States, 1970-1987

Kees P. Nederlof, M.D. Herschel W. Lawson, M.D. Audrey F. Saftlas, Ph.D., M.P.H. Hani K. Atrash, M.D., M.P.H. Evelyn L. Finch Division of Reproductive Health Center for Chronic Disease Prevention and Health Promotion

Summary In 1987, both the rate of hospitalizations due to ectopic pregnancy and the number of women hospitalized increased from those reported in 1986. Although ectopic pregnancy represented 1.7% of all pregnancies in 1987, complications of this condition accounted for 12% of all maternal deaths in that year. The case-fatality rate was 3.4 deaths per 10,000 ectopic pregnancies, a decline of 30% from the rate of 4.9 deaths reported in 1986, and a 90% decline from the 35.5 deaths per 10,000 ectopic pregnancies reported in 1970.

Although the racial gap decreased slightly in 1987, the risk of ectopic pregnancy remained 1.4 times higher for women of black and other minority races than for white women. The risk of death from this condition remained 1.8 times higher for women of black and other minority races. INTRODUCTION

Ectopic pregnancy continues to be a major public health problem in the United States. This condition results when a fertilized ovum implants at a site other than the endometrial lining of the uterus and results in considerable maternal morbidity and fetal loss (1). The number of workdays lost by these otherwise healthy women and the costs of hospital care continue to increase. In addition, ectopic pregnancy is one of the leading causes of maternal death in the United States, and is the leading cause of maternal death in the first trimester (2).

This surveillance report includes data for 1987 and updates data on ectopic pregnancy reported by CDC for the period 1970-1986 (2-4). METHODS

The numbers of ectopic pregnancies reported here are estimated from data collected by the National Center for Health Statistics (NCHS), CDC, as part of the ongoing National Hospital Discharge Survey (NHDS). This annually conducted survey samples medical records from approximately 400 nonfederal, short-stay hospitals representing all 50 states and the District of Columbia. Demographic data, final diagnoses, and surgical procedures are abstracted from a sample of medical records from each designated hospital. The greater than 180,000 medical records included in the 1987 sample were weighted to represent greater than 33 million hospital admissions (5).

For the period 1970-1978, the diagnosis of ectopic pregnancy was based on hospital discharge records with the diagnosis code 631 according to the International Classification of Diseases, eighth revision, adapted for use in the United States (ICDA-8) (6). For the period 1979-1987, the diagnosis of ectopic pregnancy was based on records with the diagnosis code 633 according to the International Classification of Diseases, ninth revision (ICD-9) (7).

The number of deaths resulting from ectopic pregnancy was based on U.S. vital statistics collected by NCHS. Ectopic pregnancy rates were calculated by dividing the estimated number of ectopic pregnancies by the total number of reported pregnancies. The term "reported pregnancies" was defined as the sum of live births, legally induced abortions, and ectopic pregnancies. Data for live births were obtained from NCHS natality statistics (8), and data for induced abortions, from CDC's abortion surveillance system. Ectopic pregnancy rates were reported per 1,000 pregnancies. Case-fatality rates were calculated by dividing the number of deaths resulting from ectopic pregnancy by the estimated number of ectopic pregnancies. These rates were then reported as deaths per 10,000 cases. Total "person-days hospitalized" was calculated for each year by multiplying the estimated number of ectopic pregnancies by the average length of stay.

The four U.S. geographic regions defined by the U.S. Department of Commerce, Bureau of Census (Northeast, Midwest, South, and West) were used (9). For the calculation of ectopic pregnancy rates, women were grouped into three age categories: 15-24, 25-34, and 35-44 years of age. For the analysis of deaths resulting from ectopic pregnancy, women were grouped into six age categories: 15-19, 20-24, 25-29, 30-34, 35-39, and 40-44 years of age. Race-specific rates for the categories "white" and "black and other" were used. The numbers of ectopic pregnancies and related deaths of women of unknown race were redistributed according to the racial distribution of cases for which race was recorded. For the assessment of the risk of ectopic pregnancy over time, the numbers of ectopic pregnancies and related deaths were grouped into three 6-year periods: 1970-1975, 1976-1981, and 1982-1987. Estimates of the number of ectopic pregnancies were rounded to the nearest hundred. The rounding and redistribution of cases with unknown race sometimes cause the sum of numbers to differ from the total. Rates, however, were calculated from the unrounded estimates. RESULTS

In 1987, the number and rate of ectopic pregnancies increased over the figures reported in 1985 and 1986 (Table 1, Figure 1) (4). Of the approximately 88,000 hospitalizations for ectopic pregnancy reported in 1987, 61% occurred among women 25-34 years of age. When analyzed by race, the rate of ectopic pregnancies increased 24% for white women, from 12.4 per 1,000 pregnancies in 1986 to 15.4 in 1987; the rate increased 3% for women of black and other minority races, from 20.3 per 1,000 pregnancies to 21.0. The risk of ectopic pregnancy for women of black and other minority races decreased to 1.4 times the risk for white women, down from the 1.6 figure reported in 1985 and 1986 (3,4).

For 1970-1987, approximately 877,400 ectopic pregnancies were reported among U.S. women ages 15-44 years; the overall rate was 10.7 per 1,000 pregnancies (Table 1). Over time, the number of ectopic pregnancies has increased fivefold, from an estimated 17,800 in 1970 to 88,000 in 1987. The rate for all women combined increased from 4.5 in 1970 to 16.8 in 1987. By race, the rate increased almost fourfold for white women (from 4.0 in 1970 to 15.4 in 1987) and almost threefold for women of black and other minority races (from 7.2 in 1970 to 21.0 in 1987).

When numbers of ectopic pregnancies were combined into three 6-year periods (1970-1975, 1976-1981, and 1982-1987) and analyzed by race, the rates for both racial groups increased twofold from the first period (1970-1975) to the last (1982-1987) (Figure 2). The risk of ectopic pregnancy increased with age in both racial groups and was highest for women 35-44 years old (Table 2). White women ages 35-44 were three times more likely than white women ages 15-24 to have ectopic pregnancies (rates = 17.5 versus 5.8), whereas black and other minority women ages 35-44 were almost four times more likely to have ectopic pregnancies than their counterparts ages 15-24 (rates = 29.4 versus 7.7).

Few differences were noted in rates of ectopic pregnancies in the four geographic regions for 1970-1987. As in previous years, race- and region-specific rates varied somewhat. For white women, the rate was highest in the West and, for women of black and other minority races, the rate was highest in the Midwest (Table 3).

The average length of hospital stay for women who had ectopic pregnancies decreased 8%, from 4.1 days in 1986 to 3.8 days in 1987, continuing a previous trend (3,4). In 1987, ectopic pregnancies accounted for 334,400 person-days of hospitalization, a 10% increase from the total reported in 1986. The average length of hospital stay for the period 1970-1987 was 5.3 days, and person-days of hospitalization during that period was 4,655,658.

In 1987, 30 maternal deaths (12% of all maternal deaths) resulted from complications of ectopic pregnancy (10). The case-fatality rate decreased 30%, to 3.4 per 10,000 ectopic pregnancies from the 4.9 reported in 1986 (Table 4). In 1987, the case-fatality rate for women of black and other minority races was 1.8 times higher than that for white women; in 1986, the rate was 2.3 times higher (4).

Between 1970 and 1987, 782 women died as a result of ectopic pregnancies. Overall, the case-fatality rate decreased 95%, from 35.5 per 10,000 ectopic pregnancies in 1970 to 3.4 per 10,000 in 1987. For the 18-year period, the risk of death for women of black and other minority races was 3.3 times higher than that for white women. For the periods 1970-1975, 1976-1981, and 1982-1987, the risk of death was consistently higher for women of black and other minority races than for white women (Figure 3). However, during the period 1982-1987, the racial gap narrowed. During 1970-1987, teenagers of all races had the highest mortality rates, but the rate for teenagers of black and other minority races was almost five times higher than that for white teenagers (Figure 4). During 1987, however, no deaths were reported among teenagers of black and other minority races. DISCUSSION

In 1987, the number and rate of ectopic pregnancies reached the highest level ever reported in the United States; the rate was a fourfold increase from figures reported in 1970. Similar increases have been reported in other countries (11-13). Hypotheses for the reported increases, which affected all racial groups, include a) a higher prevalence of risk factors for ectopic pregnancy, a lower prevalence of protective factors, or both, b) heightened awareness of the condition among women of reproductive age and their health-care providers, c) earlier diagnosis due to the use of advanced technology in pregnancy confirmation (hormone assays) and more sensitive ultrasound imaging, and d) a tendency for recurrence among an estimated 15% of the women who have had one or more previous ectopic pregnancies (14-18).

Although the cause of ectopic pregnancy is unknown, it has been attributed to several maternal factors, including alteration in tubal motility, hormonal release, and anatomical changes such as scarring. Scarring may be caused by acute and chronic salpingitis, resulting from a variety of suspected infectious agents. Ectopic pregnancy is estimated to occur 5-10 times more frequently among women with a prior history of salpingitis (19,20). However, in recent years rates of salpingitis in the United States have remained stable or have decreased slightly, not paralleling the increases in ectopic pregnancy rates (CDC, unpublished data).

The risk of ectopic pregnancy continues to be higher for women of black and other minority races. This higher risk may be partially explained by the higher rates of salpingitis and pelvic inflammatory disease (PID) among these women (21). However, further studies are needed to identify the risk factors that may explain this difference and to determine if those risk factors are amenable to preventive interventions.

In the past, studies estimated that 20% to 70% of women who had ectopic pregnancies were unable to conceive again (22,23); however, new diagnostic and therapeutic measures may improve the outlook for these women. Although the numbers are small and the procedures are still considered investigational, the conservative, nonsurgical management of early-diagnosed, unruptured ectopic pregnancies continues to increase. Diagnostic laparoscopy and conservative, nonsurgical management with or without the use of methotrexate, and the use of serial, quantitative, pregnancy-hormone assays may prevent the extensive tubal damage that results in lessened fertility. A recent study of the use of methotrexate for 36 patients with unruptured ectopic pregnancy showed 94% resolution without operative intervention (24).

The case-fatality rates for ectopic pregnancy continued to decline in 1987. However, a study of maternal mortality in the United States from 1979 to 1986, which used multiple sources for case finding, identified 10% more deaths from complications of ectopic pregnancy than did national vital statistics, which used only death certificate data for the same period (CDC, unpublished data). This finding suggests that all deaths due to ectopic pregnancy complications are not so classified on the death certificate.

Although women of black and other minority races continued to have a higher risk of death associated with ectopic pregnancy than did white women, the racial gap diminished over time. The continued elevation in case-fatality rates among women of black and other minority races may be explained by poorer access to and lower utilization of prenatal care during the first trimester (25).

Increases in rates of ectopic pregnancy in the United States suggest that further study is needed to prevent this condition and its sequelae. However, until risk factors that lead to ectopic pregnancy are well understood, early detection will be the most effective means of reducing morbidity and mortality caused by this condition. All women should be aware of the signs and symptoms of ectopic pregnancy so that they can enter the prenatal care system as early as possible. Emergency room and other primary health-care providers should consider and rule out ectopic pregnancy when treating women of reproductive age who present with pelvic and abdominal pain and amenorrhea with vaginal spotting or bleeding.

References

1. Cunningham FA, MacDonald PC, Gant NF. Williams obstetrics.

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2. CDC. Ectopic Pregnancy in the United States, 1970-1983. MMWR 1986;35(SS-2):29-37.

3. CDC. Ectopic pregnancy surveillance, United States, 1970-1985. MMWR 1988;37(SS-5):9-18.

4. CDC. Ectopic pregnancy surveillance, United States, 1970-1986. MMWR 1989;38(SS-2):1-10.

5. National Center for Health Statistics, Graves EJ. Utilization of short- stay hospitals, United States: 1987 annual summary. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, 1989; DHHS publication no. (PHS)89-1760. (Vital and health statistics; series 13, no. 99).

6. National Center for Health Statistics. International classification of diseases, adapted for use in the United States, eighth revision. Washington, DC: US Department of Health and Human Services, Public Health Service, 1968; PHS publication no. 1693.

7. The Commission on Professional and Hospital Activities. International classification of diseases, ninth revision, clinical modification. Ann Arbor, Michigan: US Department of Health and Human Services, Public Health Service, 1978.

8. National Center for Health Statistics. Advance report of final natality statistics, 1987. Monthly Vital Statistics Report. Hyattsville, Maryland: U.S. Department of Health and Human Services, Public Health Service, 1989:38(Suppl 3).

9. US Department of Commerce, Bureau of Census. Geographic Identification Code Scheme;1980 Census of Population and Housing: 3,10; PHC80-R5; April 1983. 10. National Center for Health Statistics. Advance Report of Final Mortality Statistics, 1987. Monthly Vital Statistics Report. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, 1989:38(Suppl 5). 11. Beral V. An epidemiological study of recent trends in ectopic pregnancy. Br J Obstet Gynaecol 1975;82:775-82. 12. Meirik O. Ectopic pregnancy during 1961-1978 in Uppsala County, Sweden. Acta Obstet Gynecol Scand (Suppl) 1981;60:545-8. 13. Hockin JC, Jessamine AG. Trends in ectopic pregnancy in Canada. Can Med Assoc J 1984;131:737-40. 14. Chow WH, Daling JR, Cates W Jr, Greenberg RS. Epidemiology of ectopic pregnancy. Epidemiol Rev 1987;9:70-94. 15. Vermesh M. Conservative management of ectopic gestation. Fertil Steril 1989;51:559-67. 16. Kojima E, Abe Y, Morita M, et al. The treatment of unruptured tubal pregnancy with intratubal methotrexate injection under laparoscopic control. Obstet Gynecol 1990;75:723-5. 17. Stabile I, Grudzinskas J. Ectopic pregnancy: a review of incidence, etiology and diagnostic aspects. Obstet Gynecol Surv 1990;45:335-47. 18. Hallatt JG. Repeat ectopic pregnancy: a study of 123 consecutive cases. Am J Obstet Gynecol 1975;122:520-4 . 19. Westrom L. Effect of acute pelvic inflammatory disease on fertility. Am J Obstet Gynecol 1975;121:707-13. 20. Westrom L. Influence of sexually transmitted diseases on sterility and ectopic pregnancy. Acta Eur Fertil 1985;16:21-4. 21. Washington AE, Cates WJ, Zaidi AK. Hospitalizations for pelvic inflammatory disease: epidemiology and trends in the United States, 1975 to 1981. JAMA 1984;251:25-9. 22. Mueller BA, Daling JR, Weiss NS, et al. Tubal pregnancy and the risk of subsequent infertility. Obstet Gynecol 1987;69:722-6. 23. Mitchell DE, McSwain HF, Peterson HB. Fertility after ectopic pregnancy. Am J Obstet Gynecol 1989;161:576-80. 24. Stovall TG, Ling WF, Buster J. Outpatient chemotherapy of unruptured ectopic pregnancy. Fertil Steril 1989;51:435-8. 25. National Center for Health Statistics. Health, United States, 1989. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, 1989; DHHS publication no. (PHS)90-1232.

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