Ectopic Pregnancy in the United States, 1970-1986

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

In 1986, both the rate of hospitalizations due to ectopic pregnancy and the number of hospitalizations decreased from those reported in the previous year, although the decreases were not statistically significant. If this leveling off of previous yearly increases becomes a continuing trend, possible explanatory hypotheses include a leveling off of disease occurrence, and an increasing use of outpatient management. The case-fatality rate rose slightly in 1986, to 4.9 deaths per 10,000 ectopic pregnancies, although this rate still represents an 86% decline from the 35.5 deaths per 10,000 ectopic pregnancies reported in 1970. In 1986, ectopic pregnancy accounted for only 1.4% of all pregnancies but was associated with over 13% of maternal deaths. Compared with white women, women of black and other minority races had a 1.6 times greater risk of ectopic pregnancy. Ectopic pregnancy remains one of the leading causes of maternal death in the United States and continues to be an important public health problem. INTRODUCTION

In 1986, an estimated 73,700 women were hospitalized in the United States as a result of an ectopic pregnancy, bringing the number of women hospitalized for this condition since 1970 to almost 800,000. The condition occurs when a fertilized ovum implants anywhere other than the endometrial lining of the uterus (1). In addition to the fetal loss associated with ectopic pregnancy, the lost productivity of young women who are otherwise healthy, and the ever increasing cost of caring for these women, ectopic pregnancy has become one of the leading causes of maternal mortality and is the leading cause of maternal death during the first trimester (2). Ectopic pregnancies accounted for 13.2% of all maternal deaths in 1986 while representing only 1.4% of all pregnancies during that period. CDC has previously reported data on ectopic pregnancy for 1970-1985 (3). This surveillance report includes data for 1986 and updates previously reported data on ectopic pregnancy. METHODS

The numbers of ectopic pregnancies presented in this report are estimated from data collected by the National Center for Health Statistics (NCHS), CDC, as part of the ongoing National Hospital Discharge Survey (NHDS). In 1986, in the NHDS, which is conducted each year, greater than 400 nonfederal, short-stay hospitals that represented all 50 states and the District of Columbia were sampled. Demographic data, final diagnoses, and surgical procedures were abstracted from a sample of medical records from each designated hospital. Medical records ( greater than 190,000) included in the 1986 sample were weighted to represent greater than 34 million hospital admissions (4).  The diagnosis of ectopic pregnancy is 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) for 1970-1978 (5), and on abstracts with the diagnosis code 633 according to the ninth revision (ICD-9) for 1979-1986 (6). The number of deaths resulting from ectopic pregnancy is based on U.S. vital statistics collected by NCHS. Rates for ectopic pregnancy were calculated by dividing the estimated number of ectopic pregnancies by the total number of pregnancies. "Total pregnancies" is defined as the sum of live births, legally induced abortions, and ectopic pregnancies. Data for live births were obtained from NCHS natality statistics (7) and data for induced abortions from CDC's abortion surveillance data system. Because 1986 abortion data were not available, 1985 abortion data were used for calculating rates. Ninety-five percent confidence intervals (CI), using the relative standard error provided by NCHS, were calculated to determine whether statistically significant differences existed between the numbers of ectopic pregnancies in 1985 and 1986 (8,9). The presence of overlapping CIs indicated no statistically significant changes. Case-fatality rates were calculated by dividing the number of deaths caused by ectopic pregnancy by the estimated number of ectopic pregnancies. These rates were then reported as deaths per 10,000 cases (3). Total "person-days hospitalized" was calculated for each year by multiplying the estimated number of ectopic pregnancies by the average length of stay.

The U.S. Department of Commerce, Bureau of Census, has defined the four geographic regions of the United States used in this report (Northeast, Midwest, South, West). 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. Race-specific rates for the categories "white" and "black and other" were used. If race was not included in the medical records, the numbers of ectopic pregnancies were redistributed according to the racial distribution of cases for which race was recorded. The same method was used to redistribute deaths with unknown race. Estimates of the number of ectopic pregnancies have been 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 1986, the numbers and rates of ectopic pregnancies decreased, reversing the previous trend, although the decrease was not statistically significant (Table 1, Figure 1) (3). Sixty-three percent of the ectopic pregnancies in 1986 occurred among 25- through 34-year-olds. The rate of ectopic pregnancies for white women decreased from 13.3 per 1,000 pregnancies in 1985 to 12.4 in 1986; the rate of ectopic pregnancy among women of black and other minority races also decreased, from 21.3 in 1985 to 20.1 per 1,000 pregnancies in 1986. The risk of ectopic pregnancies among women of black and other minority races remained 1.6 times higher than that among white women in 1986, the same as that reported in 1985 (3).

For the period 1970-1986, approximately 790,500 ectopic pregnancies occurred among women ages 15-44 years in the United States; the overall rate was 10.3 per 1,000 reported pregnancies. From 1970 through 1986, the number of ectopicpregnancies increased more than fourfold, from an estimated 17,800 in 1970 to 73,700 in 1986. The rate for all women combined increased more than threefold, from 4.5 in 1970 to 14.3 in 1986. When stratified by race, the rates increased more than threefold for white women (from 4.0 in 1970 to 12.4 in 1986) and slightly less than threefold for women of black and other minority races (from 7.1 in 1970 to 20.1 in 1986). When numbers of ectopic pregnancies were combined into four periods (1970-1973, 1974-1977, 1978-1981, and 1982-1986) and analyzed by race, the rates for each racial group had increased from the earliest years (1970-1973) to the latest years (1982-1986) by the following factors: 2.5-fold for all races combined, 2.7-fold for white women, and almost twofold for women of black and other minority races (Table 2). The risk of ectopic pregnancy increased with age and was highest for women 35-44 years old (Table 3, Figure 2) (1,3). White women 35-44 years of age had almost three times the risk of ectopic pregnancy as white women 15-24 years of age, whereas women of black and other minority races ages 35-44 had four times the risk as their counterparts ages 15-24.

Overall, during the period 1970-1986, the rates of ectopic pregnancies for the four geographic regions were similar; the highest rates occurred in the Midwest and West (Table 4). As in previous years, some variations in the race- and region-specific rates occurred. For white women, the rate was highest in the West; for women of black and other races, the rate was highest in the Midwest.

The average length of hospital stay for women who had ectopic pregnancies decreased from 4.5 days in 1985 to 4.1 days in 1986, continuing a previous trend (3). Ectopic pregnancy accounted for 302,200 person-days of hospitalization. This total represents both a 14% decrease from that reported in 1985 and a 10% decrease in the average length of hospital stay. The average length of stay for the period 1970-1986 was 5.5 days, and the total person-days of hospitalization during that period was 4,321,300.

In 1986, 36 maternal deaths (13.2% of all such deaths) were related to ectopic pregnancy (Table 5). The case-fatality rate increased to 4.9, up from the 4.2 reported in 1985 (Figure 3). In 1986, women of black and other minority races had a case-fatality rate 2.3 times higher than that for white women.  Between 1970 and 1986, a total of 752 women died as a result of an ectopic pregnancy. Overall, the case-fatality rate has decreased greater than 86% since the first reporting period in 1970. Women of black and other minority races continue to have a higher rate of death related to ectopic pregnancy. For the 17-year reporting period, the case-fatality rate for these women was 3.4 times higher than that for white women (Table 6). Teenagers of black and other minority races continue to have the highest rate of death associated with ectopic pregnancy. The rate for that group was almost six times higher than that reported for white teenagers (Figure 4). DISCUSSION

In 1986, for the first time since 1982, the total number of hospitalizations for ectopic pregnancy in the United States decreased, although the decrease was not statistically significant. With few exceptions, the trend over the previous 17 years has been for the numbers and rates of hospitalizations for ectopic pregnancy to increase steadily. Suggested reasons for these increases include 1) higher prevalence of risk factors for this condition, lower prevalence of protective factors, or both (10); 2) improved diagnosis of the condition as a result of (a) heightened awareness among health-care providers of this condition and of the symptoms and signs that may occur among women of childbearing age, and (b) technologic advances such as sensitive and rapid assays of serum progesterone, improved ultrasound techniques, and laparoscopy; and 3) the recent trend of women postponing childbearing until the period of life in which the risk of ectopic pregnancy is highest (11). Advancing technology has certainly facilitated early diagnosis and accurate monitoring of ectopic pregnancy (12).

First described in the 10th century, ectopic pregnancy has been linked to multiple maternal and embryonic factors (1,13,14). Maternal factors include physiologic changes such as alteration in tubal motility, ovum transport, hormonal release, and anatomic changes such as tubal damage or displacement as a result of scarring conditions (e.g., endometriosis, chronic salpingitis (pelvic inflammatory disease), and tubal ligation) (10,13). Embryonic factors primarily include chromosomal abnormalities (13). The prevalence of salpingitis in relation to ectopic pregnancies has been shown to vary widely (20%-92%) (2,10) but is the cause most commonly agreed upon. The increase in salpingitis over the past two decades has certainly contributed, to some degree, to the reported increases in ectopic pregnancies (2,15).

The lack of a continued increase in hospitalizations related to ectopic pregnancy may represent a temporary fluctuation in the data, as occurred in 1982 (Table 1, Figure 1); a leveling off of increases in disease occurrence; or the impact of new techniques for outpatient management. In recent years, the technologic advances allowing for earlier diagnosis have enabled public health personnel to add new goals to that of preventing mortality: to preserve fertility and to reduce morbidity (12). A study involving 141 women showed that nonrupture of an ectopic pregnancy had a statistically significant, positive association with future fertility (16). Considerable importance is thus placed on carefully controlled and conservative management of women diagnosed very early with unruptured ectopic pregnancies. Medical management for this group of women may include the use of serial pregnancy tests, serum progesterone assays, and ultrasound examinations, with or without the use of methotrexate, known for its effectiveness against trophoblastic disease and sometimes used on an outpatient basis (17-20). Several studies in which methotrexate has been used have shown effective resolution of ectopic pregnancies, without hospitalization or operation, in 95% of cases (12,18); however, the number of women so treated was less than 100, and this regimen is still regarded as experimental. Another recent innovation is laparoscopic management of unruptured ectopic pregnancy, which results in lower morbidity, shorter hospitalization, and lower cost to the patient (21). The laparoscope is used either for removing a segment of affected fallopian tube or for opening up the tube and removing the products of conception (12,22). These innovations may contribute to an increasing number of ectopic pregnancies managed on an outpatient basis.

In 1986, the risk of ectopic pregnancy among women of black and other minority races remained 1.6 times higher than that among white women (3). The risk of death associated with ectopic pregnancy increased for white women, whereas it decreased for women of black and other minority races. Nonetheless, teenagers of black and other minority races continued to have the highest death rate related to ectopic pregnancy (5.7 times higher than that of white teenagers). Factors such as timing and quality of prenatal care are often related to deaths associated with ectopic pregnancy. Even though new technology may be reducing the number of deaths caused by ectopic pregnancies, women of black and other minority races and younger women, who tend to have less and later prenatal care, benefit less from this technology than other women (23,24).

References

1. Pritchard JA, MacDonald PC, Gant NF. Williams obstetrics. 17th ed.

Norwalk, Connecticut: Appleton-Century Croft, 1985:423-38.

2. Centers for Disease Control. Ectopic pregnancy in the United States, 1970-1983. In: CDC surveillance summaries, August 1986. MMWR 1986;35(no. 2SS):29SS-37SS.

3. Centers for Disease Control. Ectopic pregnancy surveillance, United States, 1970-1985. In: CDC surveillance summaries, December 1988;37(no. SS-5):9SS-18SS.

4. National Center for Health Statistics, Graves EJ. Utilization of short-stay hospitals, United States: 1986 annual summary. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, 1988:55; DHHS publication no. (PHS)88-1757. (Vital and health statistics; series 13, no. 96).  5. National Center for Health Statistics. International classification of diseases, adapted for use in the United States, eighth revision. Washington, DC: USDHEW, PHS, 1968; PHS publication no. 1693.

6. The Commission on Professional and Hospital Activities. International classification of diseases, ninth revision, clinical modification. Ann Arbor, Michigan: USDHHS, PHS, 1978.

7. National Center for Health Statistics. Vital statistics of the United States, 1986. Vol 1, Natality. Washington, DC: Public Health Service, 1988:1,87,89.

8. National Center for Health Statistics, Graves EJ. Utilization of short-stay hospitals, United States, 1985. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, 1987:55; DHHS publication no. (PHS)87-1752. (Vital and health statistics; series 13, no. 91).

9. National Center for Health Statistics, Graves EJ. Utilization of short-stay hospitals, United States: 1986 annual summary. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, 1988:55; DHHS publication no. (PHS)88-1757. (Vital and health statistics; series 13, no. 96). 10. Chow WH, Daling JR, Cates W Jr, Greenberg RS. Epidemiology of ectopic pregnancy. Epidemiol Rev 1987;9:70-94. 11. Pebley AR. Changing attitudes toward the timing of first births. Fam Plann Perspect 1981; 13:171-5. 12. Vermesh M. Conservative management of ectopic gestation. Fertil Steril 1989;51:559-67. 13. Weckstein LN. Current perspective on ectopic pregnancy. Obstet Gynecol Surv 1985;40:259-72. 14. Barnes AB, Wennberg CN, Barnes BA. Ectopic pregnancy: incidence and review of determinant factors. Obstet Gynecol Surv 1983;38:345-56. 15. Washington A, Cates W, Zaidi A. Hospitalizations for pelvic inflammatory disease: epidemiology and trends in the United States, 1975 to 1981. JAMA 1984;251:2529-33. 16. Ectopic pregnancy. In: Droegemueller W, Herbst A, Mishell D Jr, Stenchever M, eds. Comprehensive gynecology. St. Louis: CV Mosby, 1987:406. 17. Carson S, Stovall T, Umstot E, Andersen R, Ling F, Buster J. Rising human chorionic somatomammotroppin predicts ectopic pregnancy rupture following methotrexate chemotherapy. Fertil Steril 1989;51:593-7. 18. Stovall G, Ling F, Buster J. Outpatient chemotherapy of unruptured ectopic pregnancy. Fertil Steril 1989;51:435-8. 19. Garcia A, Aubert J, Sama J, Josimovich J. Expectant management of presumed ectopic pregnancies. Fertil Steril 1987;48:395-400. 20. Matthews C, Coulson P, Wild R. Serum progesterone levels as an aid in the diagnosis of ectopic pregnancy. Obstet Gynecol 1986;68:390-4. 21. Brumsted J, Kessler C, Gibson C, Nakamija S, Riddick D, Gibson M. A comparison of laparoscopy and laparotomy for the treatment of ectopic pregnancy. Obstet Gynecol 1989;71:889-92. 22. Silva P. A laparoscopic approach can be applied to most cases of ectopic pregnancy. Obstet Gynecol 1988;72:944-7. 23. National Center for Health Statistics. Health, United States, 1984. DHHS publication no. (PHS)85-1232. Washington, DC: Public Health Service, December 1984:10-1. 24. National Center for Health Statistics: Health, United States, 1986. DHHS publication no. (PHS)87-1232. Washington, DC: Public Health Service, December 1986:25.

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