1130 Correspondence

the umbilical artery waveforms in the last trimester of pregnancy. Within 5 minutes of exercise on a bicycle ergometer, a mean of 67.4% of submaximal exercise was achieved. The mean systolic/diastolic ratio decreased significantly at 2 and 4 minutes of recovery, respectively, (P < 0.01 and p < 0.001). The maternal uterine artery waveforms were examined in 102 patients. After an initial rise at 2 and 4 minutes, the systolic/ diastolic ratio decreased significantly from 8 minutes to 20, 24, and 30 minutes of recovery (P < 0.05, P < 0.001, p < 0.001), respectively. Smokers had a higher systolic! diastolic ratio before and after exercise than nonsmokers. Nagy M. Rafla, MD Department of Obstetrics and Gynaecology University College Hospital Galway, Ireland REFERENCES 1. Fairlie FM, Walker 11, Lang GD. The relation between fetal heart rate and Doppler velocity waveform AlB ratio. Br] Obstet Gynaecol 1988;95:312-4. 2. Pijpers L, Wladimiroff ]W, McGhie]. Effect of short-term maternal exercise on maternal and fetal cardiovascular dynamics. Br] Obstet GynaecoI1984;91:1081-6.

Reply To the Editors: I welcome the opportunity to respond to the comments by Dr. Rafla. The letter levels several criticisms that I think are unjustified. With regard to the number of participants in our study, this was specifically chosen on the basis of a power analysis to detect changes in the systolic/diastolic ratio of 0.2. We thought that changes smaller than this were of little clinical or physiologic significance. Dr. Rafla appears to have misunderstood the rest period before our study. In fact, each subject was allowed to rest for 15 minutes before the control measurements were commenced; therefore the comment that the systolic/diastolic ratio was measured after 5, 10, or 15 minutes of rest is incorrect. There was no statistical significance between any of the maternal or fetal measurements within the control periods and no significant trend was observed. We are well aware of the effects of heart rate on the systolic! diastolic ratio, and allowing for this, these changes did not affect our interpretation of the data. I. 2 Extending the recovery time for a further 10 minutes would not have altered the conclusions. We agree that smoking may affect the systolic/ diastolic ratio;3 for this reason there were no smokers in the study. We agree that different intensities of exercise may show different effects and we can only comment on the standard exercise challenge that we used. The effect of different exercise challenges is indeed interesting but outside the scope of this study. I decline to comment on the results of the Liverpool study without further information, such as the magnitude of the changes in the systolic/diastolic ratio that

April 1990 Am J Obstet Gynecol

were observed. I do, however, look forward to the publication of this study in full. Robert J. Morrow, MD Department of Midwifery Queen Mother's Hospital University of Glasgow Glasgow, Scotland G3 8SH REFERENCES 1. Gagnon R, Morrow R, Ritchie K, Hunse C, Patrick]. Umbilical and uterine blood flow velocities after vibratory acoustic stimulation. AM] OBSTET GYNECOL 1988; 159: 574-8. 2. Morrow B], Adamson SL, Lewin M, Bull SB, Ritchie]WK. The influence of spontaneous accelerations of fetal heart rate on umbilical artery velocity waveforms. AM] OBSTET GYNECOL 1989;160:995-7. 3. Morrow Rj, Ritchie jWK, Bull SB. Maternal smoking: the effect on umbilical and uterine blood flow velocity. AM] OBSTET GYNECOL 1988; 159: 1069-71.

Causes of the increase in ectopic pregnancy To the Editors: The paper by Makinen et al. (Makinen JI, Erkkola RU, Laippala PJ. Causes of the increase in the incidence of ectopic pregnancy. AM J OBSTET GVNECOL 1989; 160:642-46) addresses an important public health problem. Unfortunately, methodologic flaws in the study preclude its use to draw conclusions regarding the causes of the ectopic pregnancy epidemic. First, and most importantly, presenting information about patients with ectopic pregnancies in the absence of any information on a comparable group of women who do not have ectopic pregnancies leaves us with "dangling numerators." In other words, we lack the ability to determine whether any particular exposures are more common among women with ectopic pregnancies compared with women without ectopic pregnancies. For example, the authors conclude that current use of an intrauterine contraceptive device (IUD) is causing some of the increase in ectopic pregnancies because 28% of the patients were using an IUD at conception. However, if IUD use in the general population has reached 25% to 30%, as stated in the "Comment" section of the paper, current IUD usage rates would not appear to differ between patients and the general population. Therefore, current IUD use should not be seen as a risk factor for ectopic pregnancy, contrary to the paper's conclusions, but consistent with prior studies. I • 2 Similarly, the prevalence of other "risk factors" among patients may not differ substantially from the prevalence of these exposures among women who do not experience ectopic pregnancy. Without comparative information, no conclusions about the cause of ectopic pregnancy can be drawn from these data. Second, with regard to previous pelvic surgery, the actual risk factor for ectopic pregnancy is likely to be the indication for the original operation, rather than the surgery itself. Such indications include infertility, tubal disease, and prior ectopic pregnancy, all of which

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are known to be risk factors for ectopic pregnancy. In any analysis seeking to identify risk factors for ectopic pregnancy, we believe that reasons for prior operation rather than the surgery itself should be investigated as potential risk factors. Finally, information about "known" risk factors was abstracted from medical charts of patients who had ectopic pregnancies over the years. Although we disagree that the factors selected (particulary antecedent induced abortion) are, in fact, well-established risk factors, some have certainly been hypothesized to be risk factors, and some await clarification by more appropriately designed studies. Because these factors have been suspected to be related to ectopic pregnancy risk, hospital personnel may have become more diligent in seeking and documenting information about these exposures. Thus increases in prevalence of such "risk factors" over time in patients' charts may be a result of information bias, rather than a real increase in the existence of these risk factors. Hani K. Atrash, MD, MPH Adele Franks, MD Pregnancy Epidemiology Branch Division of Reproductive Health Center for Chronic Disease Prevention and Health Promotion Centers for Disease Control Atlanta, GA 30333 REFERENCES 1. Chow W-H, Daling JR, Cates W Jr, Greenberg RS. Epidemiology of ectopic pregnancy. Epidemiol Rev 1987;9:7094. 2. Ory HW. The Women's Health Study. Ectopic pregnancy and intrauterine contraceptive devices: new perspectives. Obstet Gynecol 1981;57:137-44.

Reply To the Editors: We appreciate the comments of Drs. Atrash and Franks concerning our article. In response we would like to point out some me thodologie and theoretical issues that seem to need further clarification. Often in studies on epidemics a disorder is observed over time and the only available information is retrospective. Possible factors and factor combinations that are connected with the disease associated with an epidemic are sought. We agree that case-control studies may provide useful information on the cause of ectopic pregnancies. When applying that method two problems emerge. First, it may be very difficult to create a truly wellmatched control group. Second, one problem still remains: interactions of various factors. The advantage of log-linear models lies in the possibility to analyze interactions of several risk factors (e.g., previous pelvic surgery and indication for operation in the case of ectopic pregnancy). In our study this approach revealed



the risk factors that probably have significance in the cause of ectopic pregnancy. Some assumed risk factors proved to be insignificant. This result shows that the method was able to differentiate between various risk factors. It also provided information on the possible changes in the significance of various risk factors in different age groups and cohorts in different time periods of the study. With significant risk factors defined, it is possible to design either case-control or prospective studies to tackle the individual causative factors. Use of IUDs as a causative factor in ectopic pregnancy has been a matter of much discussion and debate. In our study IUD use emerged as a significant risk factor even after exclusion of all other possible factors. As Table IV shows, IUD use as a risk factor is not dependent on the adhesions brought about by previous pelvic inflammatory disease, operation, or other reasons. Unlike, for example, oral contraception, IUD use carries an inherent risk factor for ectopic pregnancies. With 300,000 IUD users in Finland since the early 1970s and with an estimated pregnancy rate of 1.0%, the annual number of pregnancies with IUD use is 3000. The estimations of the rate of ectopic pregnancies approach 9%'; hence the number of ectopic pregnancies with IUD use may vary between 120 and 270 per year. This figure could explain a part but not all of the increase in the number of ectopic pregnancies in Finland; in 1985 there were 1736 ectopic pregnancies in Finland! After we submitted our article a case-control study was published that strongly supports our findings and conclusions.' Among 274 IUD users who were matched with 548 controls, IUD use proved to be the most serious risk factor among 22 recorded factors, carrying a thirteenfold risk for ectopic pregnancies. Probably for the reasons stated above, the possible interactions between various risk factors were not analyzed. We do agree with Drs. Atrash and Franks that our study does not give the final answers of causes for ectopic pregnancy, and it does not give the magnitude of order between various risk factors. Nevertheless, by applying a log-linear method it leads to similar conclusions as the case-control method. 3 In addition, it provides useful information for designing further research projects in this field. Although a prospective, randomized, double-blinded study with placebo-controlled subjects could give the final answers, such a study appears impossible for ethical reasons. Juha I. Makinen, MD Risto U. Erkkola, MD Department of Obstetrics and Gynecology University of Turku Kiinamyllynkatu 4-8 SF-20520 Turku, Finland PekkaJ. Laippala, PhD Department of Public Health University of Tampere Tampere, Finland

Causes of the increase in ectopic pregnancy.

1130 Correspondence the umbilical artery waveforms in the last trimester of pregnancy. Within 5 minutes of exercise on a bicycle ergometer, a mean of...
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