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tational age at the time of assessment. In addition, the relationship between gestational age and radius was different for white and black subjects (i.e., a lO-day difference in gestational age assessment was noted in the third trimester). In this respect, we agree with Thompson's findings. We did not include this type of analysis in the more recent study because our focus was on comparison of overall regression equations across the full spectrum of gestational ages. Lyndon M. Hill, MD, and David S. Cuzick, MD, PhD Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Forbes Ave. and Halhet St., Pittsburgh, PA 15213

REFERENCES 1. Guzick DS, Lowe TW, Santos-Ramos R, Leveneo K], Nel-

son SD. Ultrasound prediction of fetal weight in prolonged pregnancy. AM] OSSTET GYNECOL 1985;151:783-6. 2. Hill LM, Guzick D, Thomas ML, Fries]K. Fetal radius length: a critical evaluation of race as a factor in gestational age assessment. AM] OSSTET GYNECOL 1989; 161: 193-9.

Role of 17p-estradiol and tamoxifen in induction of endometrial carcinoma in experimental animal model: Nude mice To the Editors: I read with great interest the article by

Sakakibara et al. (Sakakibara K, Kan NC, Satyaswaroop PG. Both 17j3-estradiol and tamoxifen induce c10s messenger ribonucleic acid expression in human endometrial carcinoma grown in nude mice. AM J OBSTET GYNECOL 1992; 166:206-12) on the modulation of protooncogene expression by 17j3-estradiol and tamoxifen in human endometrial carcinomas. They reported that EnCa-138 tumor was chosen as a negative control because its growth was unaffected by E2 and tamoxifen and that they monitored the growth rate of the tumor weekly over a lO-week period; it would have been interesting to see data regarding the growth of the tumor over an extended period to evaluate the pattern of growth in the control, E 2, and the tamoxifen groups. I am surprised that E2 and tamoxifen showed rapid and transient induction of c10s messenger ribonucleic acid in EnCa-138 tumor, and I wonder if these findings were reprod ucible. The clinical significance of the oncogenic effect of tamoxifen has been reported.,·2 It has been shown that adenosis-like lesions were found in the upper vagina, (and including the cervical region of ICR mice) as early as 1 day after five daily injections of 200 ,...g tamoxifen starting the day of birth'; in another study an adverse effect on the ovary was noted. It is worth noting that the increased incidence of endometrial cancer and adenosis may limit the usefulness of tamoxifen for benign conditions and as adjuvant treatment of early breast cancer. Samir A. Farghaly, MD, PhD Ullmann Medical Research Building, Albert Einstein College of Medicine, 1300 Morris Park Ave., New York, NY

REFERENCES 1. Fornander T, Rutovist LE, Wilkins N. Effects oftamoxifen on the female genital tract. Ann N Y Acad Sci 1991 ;622:469-76.

October 1992 Am J Obstet Gynecol

2. Gusberg SR. Tamoxifen for breast cancer: associated endometrial cancer. Cancer 1990;65: 1463-4. 3. Touchi T, Tguchi I, Todoroki R, Yamaguchi S, Takashgi N. Changes in the uterus and vagina of mice treated neonatally with antiestrogens. Acta Anal (Basel) 1989; 136(2): 146-54.

Reply

To the Editors: We appreciate Farghaly's comments. The transient messenger ribonucleic acid expression for c[os in response to estradiol and tamoxifen in EnCa-138 tumor was repeatedly observed in three separate experiments. As indicated in the article, these results were quite intriguing because EnCa-138 was devoid of steroid receptors and insensitive to E2 or tamoxifen with regard to growth in the nude mouse. A similar effect ofE2on c10s expression in a steroid receptor-negative, estrogen-nonresponsive endometrial cancer cell line, AN3CA in vitro, was recently reported by Wu and Wan.' Lack of effect of E2 or tamoxifen on EnCa-138 growth in nude mice was a consistent observation. EnCa-138 grows rapidly under all conditions and reaches a geometric mean diameter of 1 to 1.5 cm by 4 to 6 weeks. The duration of observation for EnCa138 was 9 weeks, the results of which were presented in Fig. 1 in our article. Because tumors larger than 1 cm in geometric mean diameter (-1 gm) invariably develop necrosis at the center, tumor growth was rarely monitored beyond this point. P.C. Satyaswaroop, PhD Department of Obstetrics and Gynecology, The Milton S. Hershey Medical Center, Hershey, PA 17033

REFERENCE 1. Wu T-C], Wan Y-]Y. Estrogen regulates c10s gene expression in human endometrial cancer cell lines [Abstract 443]. In: Proceedings of the Thirty-eighth Annual Meeting of the Society for Gynecologic Investigation, San Antonio, Texas, March 20-23, 1991. Anticardiolipin tests in healthy pregnant women To the Editors: We read with interest the article by Harris

and Spinnato (Harris EN, Spinnato JA. Should anticardiolipin tests be performed in otherwise healthy pregnant women? AM J OBSTET GYNECOL 1991; 165:1272-7). We agree that the predictive value of low cardiolipin antibody titers is poor and that screening is at present unjustified. However, in the described study >90% of the population was tested at term when a successful pregnancy outcome was virtually guaranteed. The sample of women whose test results for anticardiolipin antibodies were positive at term are likely to be those in whom the presence of antibodies is not associated with a pathologic condition. Women with spontaneous abortion, the most common pathologic condition associated with the presence of anticardiolipin antibodies, were excluded by the study design. Harris and Spinnato conclude that aggressive treatment for women with a history of recurrent spontaneous abortion and low positive immunoglobulin G antibody titers (5 to 20 immunoglobulin G phospholipid units) may not be justified. Although this may be, their

Letters

Volume 167 Number 4, Part 1

study design does not provide evidence for this conclusion. In our recurrent miscarriage clinic 33 (41 %) of 81 women with a history of three or more first trimester abortions have a positive immunoglobulin G anticardiolipin test (14.9 ± 7.6 immunoglobulin G phospholipid units). This is a strong association. There is conflicting evidence on the value of treatment with either low-dose aspirin or corticosteroids." 2 We await the results of randomized, controlled studies currently underway before any conclusions can be drawn. NS. Pattison, MD, and M.A. Birdsall, MB, ChB Department of Obstetrics and Gynecology, National Women's Hospital, University of Auckland, Claude Road, Auckland 3, New Zealand

REFERENCES I. Lubbe WF, Butler WS, Palmer SJ, Liggins GC. Fetal sur-

vival after prednisone suppression of maternal lupus anticoagulant. Lancet 1983;1:1361-3. 2. Lockshin MD, Druzin ML, Qamar T. Prednisone does not prevent recurrent fetal death in women with anti phospholipid antibody. AM J OBST£T GYN£COL 1989; 160:439-43. Reply To the Editors: We agree with Pattison and Birdsall that our study of the predictive value of anticardiolipin tests in healthy pregnant women may have excluded a group with early miscarriages. However, about 10% of the women we studied had complications of pregnancy normally associated with anticardiolipin antibodies, but these antibodies were no more frequent in this group than in women with uncomplicated pregnancies. We do note with interest that in the clinic of Pattison and Birdsall 41 % of the women with a history of three or more first-trimester abortions had primarily low positive anticardiolipin tests. Given the well-known interest of Pattison et al. in the anti phospholipid syndrome, we wonder whether their numbers may be biased because patients with these problems are referred to their clinic. The thrust of our paper was not that women with recurrent miscarriages and low positive anticardiolipin test results should not be treated. It was that this test result was usually negative or low positive in otherwise healthy pregnant women and, at these low levels, had poor predictive value for pregnancy loss. Hence there seems little to be gained by ordering this test in a healthy pregnant woman unless the woman had a history suggestive of the antiphospholipid syndrome or systemic lupus erythematosus. In the appropriate clinical setting (multiple miscarriages, history of thrombosis), an obstetrician may well elect to treat a woman with low positive anticardiolipin tests during pregnancy. E. Nigel Harris, MD, and]. A. Spinnato, MD Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292

Oral magnesium chloride for the prevention of recurrent preterm labor

To the Editors: Ricci et al. (Ricci JM, Hariharan S, Helfgott A, Reed K, O'Sullivan MJ. Oral Tocolysis with magnesium chloride: a randomized controlled prospective clinical trial. AM J OBSTET GVNECOL

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1991; 165:603-10) conclude that orally administered magnesium chloride (3.2 gm/ day) is as effective as ritodrine (120 mg/day) both in prolonging pregnancy in women with preterm labor and in preventing recurrent preterm labor. However, neither agent was more effective in preventing recurrent preterm labor or preterm delivery than no treatment. The described study design was apparently intended to test two hypotheses: first, that oral maintenance therapy with either ritodrine or magnesium chloride would prolong pregnancy to a greater degree than no treatment in women who had been successfully treated for an episode of preterm labor; and second, that the efficacy and safety of magnesium chloride was equal to or superior to that of ritodrine. Unfortunately, neither hypothesis was adequately tested. The sample size (n = 25 in each group) was far too small to evaluate the absolute or relative effectiveness of any of the three treatment modalities. The incidence of the adverse outcome variable (preterm delivery) was 52% in the no-treatment group. To have a power of 0.80 ([3 = 0.2, ex = 0.05), a 30% reduction in pre term delivery resulting from treatment would require a sample size of 170 in each group; a 50% reduction in the rate of preterm delivery would require a sample size of 55 in each group. Further, in comparing magnesium chloride and ritodrine Ricci et al. used an inadequate dosage of ritodrine. Although they used the dose of ritodrine recommended by the manufacturers (i.e., 120 mg/day), this dosage has been shown to be less effective than 30 mg of terbutaline in preventing recurrent preterm labor.' This dose of ritodrine results in low plasma concentrations that are clearly inadequate to prevent recurrent preterm labor.2.3 Orally administered ritodrine at a dosage of 120 mg / day is therefore not a standard against which any new therapy should be judged. In summary, we disagree with the conclusion of Ricci et al. that their study indicates that oral magnesium chloride should be viewed as an acceptable option for prevention of recurrent preterm labor and delivery. We do agree with Ricci et al. that additional clinical trials are necessary to determine whether oral maintenance therapy is useful in preventing recurrent preterm labor and delivery. Steve N Caritis, MD University of Pittsburgh School of Medicine, Magee-Womens Hospital, Forbes Ave. and Halket St., Pittsburgh, PA 15213

REFERENCES I. Caritis SN, Toig G, Heddinger LA, Ashmead G. A double-

blind study comparing ritodrine and terbutaline in the treatment of preterm labor. AM J OBST£T GYN£COL

1984;150:7-14. 2. Caritis SN, Venkataramanan R, Cotroneo M, Chiao JP.

Pharmacokinetics of orally administered ritodrine. AM J OBST£T GYN£COL 1989;161:32-25. 3. Smit DA, Essed GGM, de HaanJ. Serum levels ofritodrine during oral maintenance therapy. Gynecol Obstet Invest 1984;18:105-12.

Reply To the Editors: We thank Caritis for his comments regarding our study. He is correct in his description of the hypotheses we intended to test. The dose of rito-