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Time trends in risk factors and clinical outcome of ectopic pregnancy*
FERTILITY AND STERILITY
Vol. 54, No.1, July 1990 Printed on ocid-free paper in U.S.A.
Copyright" 1990 The American Fertility Society
Time trends in risk factors and clinical outcome of ectopic pregnancy·
Susan G. Krantz, Sc.M. t Ronald H. Gray, M.D.t:J: Marian D. Damewood, M.D.§ Edward E. Wallach, M.D.§ The Johns Hopkins University, Baltimore, Maryland
Ectopic pregnancy (EP) admissions at The Johns Hopkins Hospital were reviewed for 160 patients admitted from 1970 to 1974 and 253 patients from 1980 to 1984. Over the decade, average annual admissions for EP increased by 64%, and a higher proportion of cases in 1980 to 1984 were unmarried women with no insurance coverage. There were significant increases in cases with a history of sexually transmitted diseases (from 19.1 % to 31.6%) and in recurrent EPs (7.6% to 19.0%) but declines in EP associated with contraceptive failures. Newer diagnostic techniques such as quantitative serum human chorionic gonadotropin assays, pelvic ultrasound, and laparoscopy were more frequently used in the 1980 to 1984 period, resulting in less severe morbidity on admission, more conservative surgical management, and reduced length of hospitalization. Thus, although admissions for EP have increased, the severity of illness has been reduced by earlier diagnosis and more conservative management. Fertil Steril 54:42, 1990
Ectopic pregnancy (EP) is associated with substantial medical and economic consequences. Delayed diagnosis or treatment can result in more severe morbidity or mortality, and even when the disease is promptly treated, future fertility may be compromised. The incidence of EP in the United States has increased from 4.5 per 1,000 pregnancies in 1970 to 14.3 per 1,000 pregnancies in 1986, and ectopic gestation has now become a leading cause Received October 20, 1989; revised and accepted March 16, 1990. * Supported by grant number NOI-HD-2939 from the National Institute of Child Health and Development, Bethesda, Maryland.. t Department of Population Dynamics, School of Hygiene and Public Health. Reprint requests: Ronald H. Gray, M.D., Department of Population Dynamics, The Johns Hopkins University, School of Hygiene and Public Health, 615 N. Wolfe Street, Baltimore, Maryland 21205. § Department of Obstetrics and Gynecology, School of Medicine.
*
42
Krantz et aI.
Time trends in EP
of maternal mortality.1,2 The annual economic burden ofEP in the United States, including both hospitalization and indirect costs, has been conservatively estimated as over $177 million. 3 Similar increases in EP incidence have also been reported in other populations over the past two decades. 4- 6 Changes in the prevalence of EP risk factors have been associated with this rise in incidence, l whereas concurrent improvements in diagnosis and management may have contributed to reduced severity and long-term sequelae of the disease. 7- 9 A number of risk factors have been implicated in the pathogenesis of EP, including pelvic inflammatory disease, sexually transmitted diseases (STDs), intrauterine contraception, sterilization, previous infertility treatment, pelvic surgery, and in utero exposure to diethylstilbestro1. 1,9,lo This study describes time trends in the epidemiological and clinical features of patients with EP treated at The Johns Hopkins Hospital during two 5-year periods one decade apart (1970 to 1974 and 1980 to 1984).
Fertility and Sterility
MATERIALS AND METHODS
The study was conducted at The Johns Hopkins Hospital, which serves as a primary care center for a poor inner-city population, and as a tertiary care center for a wider but unknown catchment population. A computer listing of all patients with a discharge diagnosis of EP during the years 1970 to 1974 and 1980 to 1984 was obtained, and from this listing, each of the 212 EP cases admitted from 1970 to 1974 and a sample of 309 cases chosen randomly from the 345 EP admissions from 1980 to 1984 comprised the initial study population. Medical records of the selected cases were requested for review through the Medical Record Department. We successfully retrieved the records for 160 of the 212 EP patients admitted from 1970 to 1974 (75.5%) and 253 out of the sample of 309 EP patients admitted from 1980 to 1984 (81.9%). The final study population of 413 cases constitutes 74% of the 557 EP admissions during the years under study. Review of the computerized discharge records showed that the excluded patients, or patients for whom records could not be retrieved, did not differ from the study population with respect to age, race, or payment status. For each patient, information was abstracted on sociodemographic characteristics, medical and obstetrical history, presence of suspected risk factors, clinical investigations, therapy for the EP, and length of hospital stay. The admitting physicians routinely collected information on prior medical conditions such as STDs or EP. If a history of these conditions was noted in the charts (with or without laboratory confirmation), it was interpreted as a positive history. No information or explicit mention of no prior STD or EP were interpreted as indicative of a negative history. Characteristics of the EP cases were compared over the 1970 to 1974 and 1980 to 1984 time periods. x2 and t-tests were used to determine the statistical significance of differences in the independent variables between the two time periods. Data on costs of hospitalization were derived from computerized billing records for the 1980 to 1984 period. RESULTS
Annual admissions for EP at Johns Hopkins Hospital increased by 64%, from an average of 42 per year in 1970 to 1974 to 69 per year in 1980 to 1984, but the ratio of EPs per 1,000 live births was
Vol. 54, No.1, July 1990
Table 1 Sociodemographic and Obstetrical Characteristics of EP Cases by Time Period of Admission Time period Sociodemographic characteristics" Race b Black White Marital status b Single Married Separated/divorced Unknown Payment source b Insurance Medicaid No insurance coverage Self-payment Unknown Agee Median age Paritye Graviditye Obstetrical history of gravid cases b.1 Spontaneous abortion Induced abortion EP
1970 to 1974"
1980 to 1984"
81.9 18.1
79.0 21.0
25.6 49.4 24.4 0.6
53.4 e 32.0e 13.8 e 0.8
32.5 41.2
36.0 34.4
5.0 7.5 13.8 26.3 ±0.44 25 1.7 ± 0.13 2.3 ± 0.16
18.2e 2.4 d 9.1 26.7 ± 0.33 27 1.2 ± 0.08 e 2.2 ± 0.11
30.3 17.4 7.6
26.1 41.7 e 19.0 d
"n = 160 for 1970 to 1974; n = 253 for 1980 to 1984. b Values are percents. e P < 0.01. d P<0.05. e Values are means ± SE. In = 132 for 1970 to 1974; n = 211 for 1980 to 1984.
similar in the two time periods (23.0 and 26.2 per 1,000, respectively). The sociodemographic characteristics of EP patients are presented by time period in Table 1. The racial composition of ectopic admissions remained unchanged, and despite modest increases in the mean age from 26.3 to 26.7 years, the proportion of unmarried women significantly increased from 25.6% between 1970 and 1974 to 53.4% between 1980 and 1984. Although approximately two thirds of the cases possessed either private insurance or Medicaid coverage for their hospitalization expenses, the proportion of cases with no insurance significantly increased from 5% to 18.2%. Thus, our population of ectopic cases consists largely of black women, who in recent years are predominantly single mothers often lacking adequate medical insurance. Table 1 also presents the obstetric history of EP patients. The mean parity of cases significantly decreased from 1.7 between 1970 and 1974 to 1.2 between 1980 and 1984, but the mean number ofpreg-
Krantz et al.
Time trends in EP
43
Table 2
Risk Factors for EP by Time Period of Admission Time period 1970 to 1974a
Risk factors
1980 to 1984a %
History of STD Use of contraception at time of conception IUD d use at time of conception Tubal ligation Oral contraceptive use at time of conception Treatment of infertility
19.1
31.6'
34.3
24.9 b
12.5 5.0
5.1 ' 4.7
5.0 12.0
4.7 16.6
an = 160 for 1970 to 1974; n = 253 for 1980 to 1984. b P<0.05. 'P< 0.01. d IUD, intrauterine device.
nancies (gravidity) of cases remained essentially unchanged, because of the increased frequency of induced abortion. The proportion of multigravida women who had a previous EP significantly increased from 7.6% to 19.0%. Women with recurrent EPs were on average 1 year older than women with first episodes, and this factor in large part accounts for the rise in the median age of patients overtime. The prevalence of suspected etiological factors among EP patients between 1970 and 1974 and between 1980 and 1984 was assessed (Table 2). The proportion of patients with a history of STD recorded on their charts increased significantly from 19.1 % between 1970 and 1974 to 31.6% between 1980 and 1984. The proportion of EP cases using contraception at the time of conception declined, and use of intrauterine devices (IUDs) at the time of conception decreased from 12.5% between 1970 and 1974 to 5.1% between 1980 and 1984. There was no change in the frequency of either tuballigation or oral contraceptive use, and the proportion of cases with a history of infertility was constant overtime. Presenting symptoms of EP patients and their condition on admission are shown in Table 3. There were significant declines in patients presenting with abdominal pain, shoulder tip pain, spotting, bleeding, shock, and fever between the 1970 to 1974 period and the 1980 to 1984 period, whereas the mean hematocrit on admission was significantly higher between 1980 and 1984. These observations suggest a reduction in the severity of illness on presentation.
44
Krantz et aI.
Time trends in EP
Table 3 also shows the methods of diagnosis. The use of culdocentesis significantly decreased over time, and a greater proportion of culdocentesis tests produced dry taps suggesting a reduction in intraperitoneal hemorrhage (5.6% dry taps between 1970 and 1974 and 14.6% dry taps between 1980 and 1984). Use of qualitative and quantitative human chorionic gonadotropin (hCG) assays became routine over the decade; quantitative serum hCG assays increased from 4.4% to 53.0%. Pelvic ultrasonography was also more frequent (5.7% of cases between 1970 and 1974 and 46.2% of cases between 1980 and 1984), and serum hCG was combined with sonography for only 1.9% of diagnoses between 1970 and 1974 compared with 31.6% between 1980 and 1984. Similarly, 21.4% of cases had diagnostic laparoscopy between 1970 and 1974 compared with 51.4% between 1980 and 1984. Despite evidence suggestive of less severe illness on admission, the mean recorded length of gestation remained unchanged (8.36 weeks between 1970 and 1974 and 8.69 weeks between 1980 and 1984), but the data on the last menstrual period in the records from the earlier period were incomplete and unreliable. However, palpable uterine enlargement was noted in 42.9% of cases between 1970 and Table 3 Clinical Presentation and Diagnosis of EP Cases by Time Period of Admission Time period 1970 to 1974
1980 to 1984 %
Presenting symptoms and characteristics on admission Abdominal pain Shoulder tip pain Spotting Bleeding Shock Fever HCT' on admission d Diagnostic methods Culdocentesis Endometrial biopsy Biopsy of D & C curettings UrinehCG SerumhCG Sonogram Sonogram and serum hCG Diagnostic laparoscopy
94.4 18.5 37.6 47.1 17.8 11.5 33.1 ± 0.45
86.2a 7.9 b 28.1 a 37.2a 4.4 b 5.9 a 34.3 ± 0.31 a
80.4 13.1 16.9 39.5 4.4 5.7 1.9 21.4
62.8 b 0.8 b 24.5 65.3 b 53.0 b 46.2b 31.6 b 51.4 b
P<0.05. < 0.001. 'HCT, hematocrit. d Values are means ± SE. a
bP
Fertility and Sterility
Table 4 Surgical Management and Clinical Outcome of EP Cases by Time Period of Admission Time period 1970 to 1974"
1980 to 1984" %
Surgical management b Salpingectomy Salpingectomy and oophorectomy Abdominal hysterectomy Cornual resection Partial salpingectomy Salpingotomy Manual expression Other Concomitant tubal sterilization Clinicaloutcome e Duration of surgery in minutes Estimated blood loss (cc) Units of blood transfused Duration hospital stay (d) "n = 160 for 1970 to 1974; n b Values are percents. 'P < 0.001. d P<0.05. e Values are means ± SE.
42.5
68.4 c
34.4 10.6 1.2 5.0 1.9 1.9 2.5
5.9 c
1.6" 2.0 14.2d 4.0 0.8 3.2
15.6
1.2 c
103 ± 939 ± 1.46 ± 7.68 ± =
6.5 65.4 0.15 0.30
122 ± 5.7 d 603 ± 43.6' 1.13 ± 0.12 5.97 ± 0.15'
253 for 1980 to 1984.
time of EP surgery decreased substantially from 15.6% between 1970 and 1974 to 1.2% between 1980 and 1984. The mean duration of surgery for EP significantly increased from 103 minutes to 122 minutes. However, the mean estimated blood loss at surgery significantly decreased from 939 cc between 1970 and 1974 to 603 cc between 1980 and 1984, and there was a corresponding decline in the mean units of blood transfused from 1.46 to 1.13. The mean duration of hospital stay also significantly decreased from 7.68 days between 1970 and 1974 to 5.97 days between 1980 and 1984. Comparable reductions in length of hospitalization were evident regardless of whether cases were first or recurrent episodes or whether there was tubal rupture. Computerized billing data on hospital costs were available for the 1980 to 1984 period, and the average daily cost of hospitalization (including operating room costs and physicians' fees) was $520. The mean length of stay (5.97 days) translates into an average total hospitalization cost of approximately $3,107 per ectopic admission between 1980 and 1984. DISCUSSION
1974 and only 17.7% of cases between 1980 and 1984, suggesting a shorter duration of pregnancy in the later time period. Tubal rupture was observed in 41.9% of cases between 1970 and 1974 and 37.7% between 1980 and 1984, indicating only a slight decrease in this complication. A preponderance of right-sided EPs was noted in both time periods, but the proportion of cases with an absent contralateral tube significantly increased from 8.8% between 1970 and 1974 to 17.4% between 1980 and 1984, reflecting the rising proportion of women reporting recurrent disease (Table 1). The surgical management of patients with EP is tabulated in Table 4. Salpingectomy was the most common surgical procedure, performed for 42.5% ofEP patients between 1970 and 1974 and 68.4% of patients between 1980 and 1984, but more radical surgical procedures such as combined salpingectomy/oophorectomy and hysterectomy declined markedly. There was a significant increase over time in the use of conservative surgical procedures (partial salpingectomy, salpingotomy, and manual expression) from 8.8% between 1970 and 1974 to 19.0% between 1980 and 1984. The proportion of patients with tubal sterilization performed at the
Vol. 54, No.1, July 1990
Although this study was conducted in one innercity hospital with a predominantly black population, time trends with regard to risk factors, diagnostic methods, disease severity, and surgical management probably reflect more widespread changes in the epidemiology and clinical outcome of EP over the past two decades. The three main risk factors examined in this study are a history of STD, contraceptive use, and recurrent EP. In our series, the proportion of women with a recorded history of STD was increased in the second time period studied, and almost one third of charts for women admitted between 1980 and 1984 reported a STD history. This observation is consistent with findings of other investigators and trends in national statistics. 1,8-11 It is unlikely that accidental pregnancies during contraception contributed to the rise in ectopic admissions in our population, because the proportion of women who reported using contraception at the time the EP was established declined over the decade. Also, use of contraceptive methods that have been associated with EP, such as the IUD,l,12 declined from 12.5% to 5.1% between the 1970 to 1974 and the 1980 to 1984 periods. The proportion
Krantz et al.
Time trends in EP
45
of sterilized patients remained unchanged at around 5%. These changes in IUD use mirror nationally reported trendsP However, it is well established that a prior EP increases the risk of a subsequent ectopic gestation. 1,6,12 Thus, recurrent ectopic gestation in the contralateral tube may have become an important factor in the rising morbidity from this disease. Our data show that recurrent ectopics among women who had ever been pregnant increased from 7.6% to 19.0%, a change similar to that reported in another hospital-based study.11 Recurrent disease also probably accounts for the slight increase over time in the median age of our patients. The early diagnosis of EP is of importance, both for the reduction of acute morbidity and mortality, and the maintenance of future fertility.8 Between 1970 and 1974 and 1980 and 1984 there was a major reduction in the severity of symptoms and signs at time of admission, particularly with regard to signs of intraperitoneal hemorrhage such as shoulder tip pain, shock, and fever (Table 3). This reduced severity of illness was largely due to the application of new diagnostic protocols, employing a combination of repeat quantitative hCG tests, pelvic ultrasound, and diagnostic laparoscopy. The decreased severity and early diagnosis were accompanied by more conservative surgical management, and in the 1980 to 1984 period the majority of patients were treated by salpingectomy (68.4%) or by measures designed to preserve reproductive function such as partial salpingectomy, salpingotomy, or manual expression (Table 4). Similar trends have been reported by other authors. 7- 9 ,l1 Concurrent oophorectomy, hysterectomy, and surgical sterilization, although common in the 1970s, were seldom performed in the 1980 to 1984 period. This shift to conservative surgery also resulted in significant reductions of blood loss and may contribute to shorter length of hospitalization. However, we cannot determine from our data whether the conservative surgical management improved subsequent reproductive function or contributed to the risk of recurrent ectopic gestation as has been suggested by another investigator.9 Washington et al. 14 indirectly estimated the average cost of hospitalization for EP to be $4,115 in 1984. Our data derived directly from computerized
46
Krantz et al.
Time trends in EP
billing records for that year gave a total cost of $3,329, which suggests that The Johns Hopkins Hospital costs are somewhat lower than the national average. In summary, this study suggests that increases in STDs and recurrent EPs may have contributed to the rising ectopic admissions at The Johns Hopkins Hospital between the 1970 to 1974 and the 1980 to 1984 periods. Although admissions for EP have increased, the severity of the disease and the risks of sequelae may have been reduced by earlier diagnosis and more conservative management. Acknowledgment. The authors are grateful to Mr. Harold G. Moore for his assistance with data on hospital costs.
REFERENCES 1. Chow WH, Daling JR, Cates W, Greenberg RS: Epidemiology ofectopic pregnancy. Epidemiol Rev 9:70, 1987 2. Lawson HW, Atrash HK, Saftlas AF, Finch EL: Ectopic pregnancy in the United States, 1970-1986. MMWR 38(SS-2):1,1989 3. Washington AE, Arno PS, Brooks MA: The economic cost of pelvic inflammatory disease. JAMA 255:1735, 1986 4. Beral V: An epidemiological study of recent trends in ectopic pregnancy. Br J Obstet Gynaecol82:775, 1975 5. Meirik 0: Ectopic pregnancy during 1961-78 in Uppsala County, Sweden: impact of demographic factors on overall incidence. Acta Obstet Gynecol Scand 60:545, 1981 6. Westrom L, Bengtsson L Ph, Mardh P-A: Incidence, trends, and risks of ectopic pregnancy in a population of women. Br Med J 282:15, 1981 7. Brenner PF, Roy S, Mishell DR: Ectopic pregnancy: a study of 300 consecutive surgically treated cases. JAMA 243:673, 1980 8. Damewood MD, Wallach EE: Ectopic pregnancy: a different disease in the 1980s? Postgrad Obstet Gynecol5:1, 1985 9. Weckstein LH: Current perspective on ectopic pregnancy. Obstet Gynecol Surv 40:259, 1985 10. Westrom L: Influence of sexually transmitted diseases on sterility and ectopic pregnancy. Acta Eur Fertil16:21, 1985 11. Stock RJ: The changing spectrum of ectopic pregnancy. Obstet Gynecol 71:885, 1988 12. World Health Organization Task Force on Intrauterine Devices: A multinational case-control study of ectopic pregnancy. Clin Reprod Fertil3:131, 1985 13. National Center for Health Statistics, Bachrach CA, Mosher WD: Use of contraception in the United States, 1982. Advance Data from Vital and Health Statistics, No. 102. Hyattsville, Maryland, Public Health Service, December 4,1984, DHHS Publications No. (PHS) 85-1250 14. Washington AE, Arno PS, Brooks MA: The economic costs of pelvic inflammatory disease. JAMA 255:1735,1986
Fertility and Sterility
Vol. 54, No.1, July 1990 Printed on ocid-free paper in U.S.A.
Copyright" 1990 The American Fertility Society
Time trends in risk factors and clinical outcome of ectopic pregnancy·
Susan G. Krantz, Sc.M. t Ronald H. Gray, M.D.t:J: Marian D. Damewood, M.D.§ Edward E. Wallach, M.D.§ The Johns Hopkins University, Baltimore, Maryland
Ectopic pregnancy (EP) admissions at The Johns Hopkins Hospital were reviewed for 160 patients admitted from 1970 to 1974 and 253 patients from 1980 to 1984. Over the decade, average annual admissions for EP increased by 64%, and a higher proportion of cases in 1980 to 1984 were unmarried women with no insurance coverage. There were significant increases in cases with a history of sexually transmitted diseases (from 19.1 % to 31.6%) and in recurrent EPs (7.6% to 19.0%) but declines in EP associated with contraceptive failures. Newer diagnostic techniques such as quantitative serum human chorionic gonadotropin assays, pelvic ultrasound, and laparoscopy were more frequently used in the 1980 to 1984 period, resulting in less severe morbidity on admission, more conservative surgical management, and reduced length of hospitalization. Thus, although admissions for EP have increased, the severity of illness has been reduced by earlier diagnosis and more conservative management. Fertil Steril 54:42, 1990
Ectopic pregnancy (EP) is associated with substantial medical and economic consequences. Delayed diagnosis or treatment can result in more severe morbidity or mortality, and even when the disease is promptly treated, future fertility may be compromised. The incidence of EP in the United States has increased from 4.5 per 1,000 pregnancies in 1970 to 14.3 per 1,000 pregnancies in 1986, and ectopic gestation has now become a leading cause Received October 20, 1989; revised and accepted March 16, 1990. * Supported by grant number NOI-HD-2939 from the National Institute of Child Health and Development, Bethesda, Maryland.. t Department of Population Dynamics, School of Hygiene and Public Health. Reprint requests: Ronald H. Gray, M.D., Department of Population Dynamics, The Johns Hopkins University, School of Hygiene and Public Health, 615 N. Wolfe Street, Baltimore, Maryland 21205. § Department of Obstetrics and Gynecology, School of Medicine.
*
42
Krantz et aI.
Time trends in EP
of maternal mortality.1,2 The annual economic burden ofEP in the United States, including both hospitalization and indirect costs, has been conservatively estimated as over $177 million. 3 Similar increases in EP incidence have also been reported in other populations over the past two decades. 4- 6 Changes in the prevalence of EP risk factors have been associated with this rise in incidence, l whereas concurrent improvements in diagnosis and management may have contributed to reduced severity and long-term sequelae of the disease. 7- 9 A number of risk factors have been implicated in the pathogenesis of EP, including pelvic inflammatory disease, sexually transmitted diseases (STDs), intrauterine contraception, sterilization, previous infertility treatment, pelvic surgery, and in utero exposure to diethylstilbestro1. 1,9,lo This study describes time trends in the epidemiological and clinical features of patients with EP treated at The Johns Hopkins Hospital during two 5-year periods one decade apart (1970 to 1974 and 1980 to 1984).
Fertility and Sterility
MATERIALS AND METHODS
The study was conducted at The Johns Hopkins Hospital, which serves as a primary care center for a poor inner-city population, and as a tertiary care center for a wider but unknown catchment population. A computer listing of all patients with a discharge diagnosis of EP during the years 1970 to 1974 and 1980 to 1984 was obtained, and from this listing, each of the 212 EP cases admitted from 1970 to 1974 and a sample of 309 cases chosen randomly from the 345 EP admissions from 1980 to 1984 comprised the initial study population. Medical records of the selected cases were requested for review through the Medical Record Department. We successfully retrieved the records for 160 of the 212 EP patients admitted from 1970 to 1974 (75.5%) and 253 out of the sample of 309 EP patients admitted from 1980 to 1984 (81.9%). The final study population of 413 cases constitutes 74% of the 557 EP admissions during the years under study. Review of the computerized discharge records showed that the excluded patients, or patients for whom records could not be retrieved, did not differ from the study population with respect to age, race, or payment status. For each patient, information was abstracted on sociodemographic characteristics, medical and obstetrical history, presence of suspected risk factors, clinical investigations, therapy for the EP, and length of hospital stay. The admitting physicians routinely collected information on prior medical conditions such as STDs or EP. If a history of these conditions was noted in the charts (with or without laboratory confirmation), it was interpreted as a positive history. No information or explicit mention of no prior STD or EP were interpreted as indicative of a negative history. Characteristics of the EP cases were compared over the 1970 to 1974 and 1980 to 1984 time periods. x2 and t-tests were used to determine the statistical significance of differences in the independent variables between the two time periods. Data on costs of hospitalization were derived from computerized billing records for the 1980 to 1984 period. RESULTS
Annual admissions for EP at Johns Hopkins Hospital increased by 64%, from an average of 42 per year in 1970 to 1974 to 69 per year in 1980 to 1984, but the ratio of EPs per 1,000 live births was
Vol. 54, No.1, July 1990
Table 1 Sociodemographic and Obstetrical Characteristics of EP Cases by Time Period of Admission Time period Sociodemographic characteristics" Race b Black White Marital status b Single Married Separated/divorced Unknown Payment source b Insurance Medicaid No insurance coverage Self-payment Unknown Agee Median age Paritye Graviditye Obstetrical history of gravid cases b.1 Spontaneous abortion Induced abortion EP
1970 to 1974"
1980 to 1984"
81.9 18.1
79.0 21.0
25.6 49.4 24.4 0.6
53.4 e 32.0e 13.8 e 0.8
32.5 41.2
36.0 34.4
5.0 7.5 13.8 26.3 ±0.44 25 1.7 ± 0.13 2.3 ± 0.16
18.2e 2.4 d 9.1 26.7 ± 0.33 27 1.2 ± 0.08 e 2.2 ± 0.11
30.3 17.4 7.6
26.1 41.7 e 19.0 d
"n = 160 for 1970 to 1974; n = 253 for 1980 to 1984. b Values are percents. e P < 0.01. d P<0.05. e Values are means ± SE. In = 132 for 1970 to 1974; n = 211 for 1980 to 1984.
similar in the two time periods (23.0 and 26.2 per 1,000, respectively). The sociodemographic characteristics of EP patients are presented by time period in Table 1. The racial composition of ectopic admissions remained unchanged, and despite modest increases in the mean age from 26.3 to 26.7 years, the proportion of unmarried women significantly increased from 25.6% between 1970 and 1974 to 53.4% between 1980 and 1984. Although approximately two thirds of the cases possessed either private insurance or Medicaid coverage for their hospitalization expenses, the proportion of cases with no insurance significantly increased from 5% to 18.2%. Thus, our population of ectopic cases consists largely of black women, who in recent years are predominantly single mothers often lacking adequate medical insurance. Table 1 also presents the obstetric history of EP patients. The mean parity of cases significantly decreased from 1.7 between 1970 and 1974 to 1.2 between 1980 and 1984, but the mean number ofpreg-
Krantz et al.
Time trends in EP
43
Table 2
Risk Factors for EP by Time Period of Admission Time period 1970 to 1974a
Risk factors
1980 to 1984a %
History of STD Use of contraception at time of conception IUD d use at time of conception Tubal ligation Oral contraceptive use at time of conception Treatment of infertility
19.1
31.6'
34.3
24.9 b
12.5 5.0
5.1 ' 4.7
5.0 12.0
4.7 16.6
an = 160 for 1970 to 1974; n = 253 for 1980 to 1984. b P<0.05. 'P< 0.01. d IUD, intrauterine device.
nancies (gravidity) of cases remained essentially unchanged, because of the increased frequency of induced abortion. The proportion of multigravida women who had a previous EP significantly increased from 7.6% to 19.0%. Women with recurrent EPs were on average 1 year older than women with first episodes, and this factor in large part accounts for the rise in the median age of patients overtime. The prevalence of suspected etiological factors among EP patients between 1970 and 1974 and between 1980 and 1984 was assessed (Table 2). The proportion of patients with a history of STD recorded on their charts increased significantly from 19.1 % between 1970 and 1974 to 31.6% between 1980 and 1984. The proportion of EP cases using contraception at the time of conception declined, and use of intrauterine devices (IUDs) at the time of conception decreased from 12.5% between 1970 and 1974 to 5.1% between 1980 and 1984. There was no change in the frequency of either tuballigation or oral contraceptive use, and the proportion of cases with a history of infertility was constant overtime. Presenting symptoms of EP patients and their condition on admission are shown in Table 3. There were significant declines in patients presenting with abdominal pain, shoulder tip pain, spotting, bleeding, shock, and fever between the 1970 to 1974 period and the 1980 to 1984 period, whereas the mean hematocrit on admission was significantly higher between 1980 and 1984. These observations suggest a reduction in the severity of illness on presentation.
44
Krantz et aI.
Time trends in EP
Table 3 also shows the methods of diagnosis. The use of culdocentesis significantly decreased over time, and a greater proportion of culdocentesis tests produced dry taps suggesting a reduction in intraperitoneal hemorrhage (5.6% dry taps between 1970 and 1974 and 14.6% dry taps between 1980 and 1984). Use of qualitative and quantitative human chorionic gonadotropin (hCG) assays became routine over the decade; quantitative serum hCG assays increased from 4.4% to 53.0%. Pelvic ultrasonography was also more frequent (5.7% of cases between 1970 and 1974 and 46.2% of cases between 1980 and 1984), and serum hCG was combined with sonography for only 1.9% of diagnoses between 1970 and 1974 compared with 31.6% between 1980 and 1984. Similarly, 21.4% of cases had diagnostic laparoscopy between 1970 and 1974 compared with 51.4% between 1980 and 1984. Despite evidence suggestive of less severe illness on admission, the mean recorded length of gestation remained unchanged (8.36 weeks between 1970 and 1974 and 8.69 weeks between 1980 and 1984), but the data on the last menstrual period in the records from the earlier period were incomplete and unreliable. However, palpable uterine enlargement was noted in 42.9% of cases between 1970 and Table 3 Clinical Presentation and Diagnosis of EP Cases by Time Period of Admission Time period 1970 to 1974
1980 to 1984 %
Presenting symptoms and characteristics on admission Abdominal pain Shoulder tip pain Spotting Bleeding Shock Fever HCT' on admission d Diagnostic methods Culdocentesis Endometrial biopsy Biopsy of D & C curettings UrinehCG SerumhCG Sonogram Sonogram and serum hCG Diagnostic laparoscopy
94.4 18.5 37.6 47.1 17.8 11.5 33.1 ± 0.45
86.2a 7.9 b 28.1 a 37.2a 4.4 b 5.9 a 34.3 ± 0.31 a
80.4 13.1 16.9 39.5 4.4 5.7 1.9 21.4
62.8 b 0.8 b 24.5 65.3 b 53.0 b 46.2b 31.6 b 51.4 b
P<0.05. < 0.001. 'HCT, hematocrit. d Values are means ± SE. a
bP
Fertility and Sterility
Table 4 Surgical Management and Clinical Outcome of EP Cases by Time Period of Admission Time period 1970 to 1974"
1980 to 1984" %
Surgical management b Salpingectomy Salpingectomy and oophorectomy Abdominal hysterectomy Cornual resection Partial salpingectomy Salpingotomy Manual expression Other Concomitant tubal sterilization Clinicaloutcome e Duration of surgery in minutes Estimated blood loss (cc) Units of blood transfused Duration hospital stay (d) "n = 160 for 1970 to 1974; n b Values are percents. 'P < 0.001. d P<0.05. e Values are means ± SE.
42.5
68.4 c
34.4 10.6 1.2 5.0 1.9 1.9 2.5
5.9 c
1.6" 2.0 14.2d 4.0 0.8 3.2
15.6
1.2 c
103 ± 939 ± 1.46 ± 7.68 ± =
6.5 65.4 0.15 0.30
122 ± 5.7 d 603 ± 43.6' 1.13 ± 0.12 5.97 ± 0.15'
253 for 1980 to 1984.
time of EP surgery decreased substantially from 15.6% between 1970 and 1974 to 1.2% between 1980 and 1984. The mean duration of surgery for EP significantly increased from 103 minutes to 122 minutes. However, the mean estimated blood loss at surgery significantly decreased from 939 cc between 1970 and 1974 to 603 cc between 1980 and 1984, and there was a corresponding decline in the mean units of blood transfused from 1.46 to 1.13. The mean duration of hospital stay also significantly decreased from 7.68 days between 1970 and 1974 to 5.97 days between 1980 and 1984. Comparable reductions in length of hospitalization were evident regardless of whether cases were first or recurrent episodes or whether there was tubal rupture. Computerized billing data on hospital costs were available for the 1980 to 1984 period, and the average daily cost of hospitalization (including operating room costs and physicians' fees) was $520. The mean length of stay (5.97 days) translates into an average total hospitalization cost of approximately $3,107 per ectopic admission between 1980 and 1984. DISCUSSION
1974 and only 17.7% of cases between 1980 and 1984, suggesting a shorter duration of pregnancy in the later time period. Tubal rupture was observed in 41.9% of cases between 1970 and 1974 and 37.7% between 1980 and 1984, indicating only a slight decrease in this complication. A preponderance of right-sided EPs was noted in both time periods, but the proportion of cases with an absent contralateral tube significantly increased from 8.8% between 1970 and 1974 to 17.4% between 1980 and 1984, reflecting the rising proportion of women reporting recurrent disease (Table 1). The surgical management of patients with EP is tabulated in Table 4. Salpingectomy was the most common surgical procedure, performed for 42.5% ofEP patients between 1970 and 1974 and 68.4% of patients between 1980 and 1984, but more radical surgical procedures such as combined salpingectomy/oophorectomy and hysterectomy declined markedly. There was a significant increase over time in the use of conservative surgical procedures (partial salpingectomy, salpingotomy, and manual expression) from 8.8% between 1970 and 1974 to 19.0% between 1980 and 1984. The proportion of patients with tubal sterilization performed at the
Vol. 54, No.1, July 1990
Although this study was conducted in one innercity hospital with a predominantly black population, time trends with regard to risk factors, diagnostic methods, disease severity, and surgical management probably reflect more widespread changes in the epidemiology and clinical outcome of EP over the past two decades. The three main risk factors examined in this study are a history of STD, contraceptive use, and recurrent EP. In our series, the proportion of women with a recorded history of STD was increased in the second time period studied, and almost one third of charts for women admitted between 1980 and 1984 reported a STD history. This observation is consistent with findings of other investigators and trends in national statistics. 1,8-11 It is unlikely that accidental pregnancies during contraception contributed to the rise in ectopic admissions in our population, because the proportion of women who reported using contraception at the time the EP was established declined over the decade. Also, use of contraceptive methods that have been associated with EP, such as the IUD,l,12 declined from 12.5% to 5.1% between the 1970 to 1974 and the 1980 to 1984 periods. The proportion
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Time trends in EP
45
of sterilized patients remained unchanged at around 5%. These changes in IUD use mirror nationally reported trendsP However, it is well established that a prior EP increases the risk of a subsequent ectopic gestation. 1,6,12 Thus, recurrent ectopic gestation in the contralateral tube may have become an important factor in the rising morbidity from this disease. Our data show that recurrent ectopics among women who had ever been pregnant increased from 7.6% to 19.0%, a change similar to that reported in another hospital-based study.11 Recurrent disease also probably accounts for the slight increase over time in the median age of our patients. The early diagnosis of EP is of importance, both for the reduction of acute morbidity and mortality, and the maintenance of future fertility.8 Between 1970 and 1974 and 1980 and 1984 there was a major reduction in the severity of symptoms and signs at time of admission, particularly with regard to signs of intraperitoneal hemorrhage such as shoulder tip pain, shock, and fever (Table 3). This reduced severity of illness was largely due to the application of new diagnostic protocols, employing a combination of repeat quantitative hCG tests, pelvic ultrasound, and diagnostic laparoscopy. The decreased severity and early diagnosis were accompanied by more conservative surgical management, and in the 1980 to 1984 period the majority of patients were treated by salpingectomy (68.4%) or by measures designed to preserve reproductive function such as partial salpingectomy, salpingotomy, or manual expression (Table 4). Similar trends have been reported by other authors. 7- 9 ,l1 Concurrent oophorectomy, hysterectomy, and surgical sterilization, although common in the 1970s, were seldom performed in the 1980 to 1984 period. This shift to conservative surgery also resulted in significant reductions of blood loss and may contribute to shorter length of hospitalization. However, we cannot determine from our data whether the conservative surgical management improved subsequent reproductive function or contributed to the risk of recurrent ectopic gestation as has been suggested by another investigator.9 Washington et al. 14 indirectly estimated the average cost of hospitalization for EP to be $4,115 in 1984. Our data derived directly from computerized
46
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Time trends in EP
billing records for that year gave a total cost of $3,329, which suggests that The Johns Hopkins Hospital costs are somewhat lower than the national average. In summary, this study suggests that increases in STDs and recurrent EPs may have contributed to the rising ectopic admissions at The Johns Hopkins Hospital between the 1970 to 1974 and the 1980 to 1984 periods. Although admissions for EP have increased, the severity of the disease and the risks of sequelae may have been reduced by earlier diagnosis and more conservative management. Acknowledgment. The authors are grateful to Mr. Harold G. Moore for his assistance with data on hospital costs.
REFERENCES 1. Chow WH, Daling JR, Cates W, Greenberg RS: Epidemiology ofectopic pregnancy. Epidemiol Rev 9:70, 1987 2. Lawson HW, Atrash HK, Saftlas AF, Finch EL: Ectopic pregnancy in the United States, 1970-1986. MMWR 38(SS-2):1,1989 3. Washington AE, Arno PS, Brooks MA: The economic cost of pelvic inflammatory disease. JAMA 255:1735, 1986 4. Beral V: An epidemiological study of recent trends in ectopic pregnancy. Br J Obstet Gynaecol82:775, 1975 5. Meirik 0: Ectopic pregnancy during 1961-78 in Uppsala County, Sweden: impact of demographic factors on overall incidence. Acta Obstet Gynecol Scand 60:545, 1981 6. Westrom L, Bengtsson L Ph, Mardh P-A: Incidence, trends, and risks of ectopic pregnancy in a population of women. Br Med J 282:15, 1981 7. Brenner PF, Roy S, Mishell DR: Ectopic pregnancy: a study of 300 consecutive surgically treated cases. JAMA 243:673, 1980 8. Damewood MD, Wallach EE: Ectopic pregnancy: a different disease in the 1980s? Postgrad Obstet Gynecol5:1, 1985 9. Weckstein LH: Current perspective on ectopic pregnancy. Obstet Gynecol Surv 40:259, 1985 10. Westrom L: Influence of sexually transmitted diseases on sterility and ectopic pregnancy. Acta Eur Fertil16:21, 1985 11. Stock RJ: The changing spectrum of ectopic pregnancy. Obstet Gynecol 71:885, 1988 12. World Health Organization Task Force on Intrauterine Devices: A multinational case-control study of ectopic pregnancy. Clin Reprod Fertil3:131, 1985 13. National Center for Health Statistics, Bachrach CA, Mosher WD: Use of contraception in the United States, 1982. Advance Data from Vital and Health Statistics, No. 102. Hyattsville, Maryland, Public Health Service, December 4,1984, DHHS Publications No. (PHS) 85-1250 14. Washington AE, Arno PS, Brooks MA: The economic costs of pelvic inflammatory disease. JAMA 255:1735,1986
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