Volume 16:1 Number 2

screening followed by elective abortion rather than improved maternal diabetic control. The outcome of all diabetic pregnancies (deliveries and abortions) in our hospital has been registered consecutively in the entire study period, especially with regard to malformations. As described in our article the abortion rate has been nearly constant over the years; in fact, a significant decrease in induced abortion from 12.8% to 5.6% was observed from the period 1977 through 1981 to 1982 through 1986 in White Classes D and F. Since 1978 antenatal screening for malformations has been done in our department by ultrasound and amniotic fluid u-fetoprotein determination, and since 1982 serum u-fetoprotein determination also has been included. Only one single diabetic pregnancy since 1978 has been terminated because of a malformation diagnosed by second-trimester screening. This was a case of anencephaly diagnosed by ultrasonography and u-fetoprotein; the pregnancy was terminated in the seventeenth week of gestation. The mother was in White Class F with diabetic nephropathy and proliferative retinopathy; preconceptionally she had been strongly advised against pregnancy. This one case will obviously not change the message of the study, namely, that a significant decrease in congenital malformations in newborn infants of mothers with insulin-dependent diabetes has occurred in the period 1982 to 1986 in comparison with the previous 5-year periods. The cause for this decrease in congenital malformation is as previously argued in our article and is probably multifactorial. Our data indicate that the decline in congenital malformations only to a minor degree is caused by improved antenatal screening. We therefore still believe that the decline in congenital malformations is mainly the result of the following two factors: a high frequency of planned pregnancy, which is essential in women with diabetes to reduce the frequency of congenital malformations in the outcome of pregnancy and overall improved diabetes care and metabolic control in young women with diabetes in Denmark during the 1980s. Peter Damm, MD, and Lars M¢fsted-Pedersen, MD Diabetes Center, Department of Obstetrics and Gynecology, Rigshospitalet, Blegdamsveij 9, DK-2JOO Copenhagen 0, Denmark

Rapid determination of fetal sex To the Editors: I would like to comment on the article by Pinckert et al. (Pinckert TL, Lebo RV, Golbus MS. Rapid determination of fetal sex by deoxyribonucleic acid amplification of Y chromosome-specific sequences. AM J OBSTET GYNECOL 1989; 161 :693-8). I disagree with the conclusion that this technique-technology "appears to be a reliable method to rapidly determine fetal sex that also can be used diagnostically to identify translocated Y-chromosomal material." With three false-positive "male" results in 35 fetal sex determinations and approximately a 10% error rate, this is hardly accurate enough for "screening." Quite clearly the problems arise in relying solely on deoxyribonucleic acid study results and not deoxyribonucleic

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acid in conjunction with "some other sex determination technique." It has been documented that visualization of the fetal external genitalia in early pregnancy by Fetal Anatomic Sex Assignment (Fetal Anatomic Sex Assignment is a Service Mark of John D. Stephens, MD, and is registered in U.S. Patent and Trademark Office, July 1990) is essentially 100% accurate and even has the capability of "correcting" laboratory errors. [ It has also been subsequently shown (and I believe that the case of the 15p + de novo Y translocation has previously been "published"2). In this case ultrasound revealed female external genitalia followed by amniocytes, which showed 46,XX,15p+. Q and C banding indicates that this abnormal 15 chromosome is possibly a t(Y; 15). Both parents were shown to have normal karyotypes. A repeat ultrasonogram at 20 weeks again showed female external genitalia. This implied de novo Y;15 translocation with only Yq, mainly heterochromatic area involvement. The couple elected to continue the pregnancy. After delivery skin biopsy showed a positive deoxyribonucleic acid Y-chromosome-specific probe in an otherwise "normal" female infant. This was also repeated and confirmed at The University of Gainesville in Florida (personal communication). The other two cases (cases I and 3) merit discussion because in those cases "reliance" on the deoxyribonucleic acid Y probe as a screening test would have been incorrect in case 3 and probably would have correctly diagnosed male sex but would have missed the 45,X cell line. In case 3 the patient was 41 years old at the time of amniocentesis, which revealed female external genitalia. The amniocytes showed 46,XY. The infant was subsequently born and was confirmed to have testicular feminization syndrome. In case 1 ultrasonography revealed male external genitalia and the amniocytes showed 45,XO/46,XY; although all such information of normal male external genitalia was given during counseling, the couple terminated the pregnancy. The mosaic karyotype was confirmed in fetal skin. The most recent "experience" with confirmation of ultrasonography, chromosomes, and deoxyribonucleic acid Y probe (performed at The University of California Medical Center, San Francisco) was a case of 45,X/46,X dicentric Y chromosome; the fetus had female external genitalia on the ultrasonogram and a positive deoxyribonucleic acid Y probe. The couple elected to terminate the pregnancy. Pathologic study confirmed female external genitalia, and mosaic karyotype was also subsequently reconfirmed. Therefore I disagree with the conclusions made by Pinckert et al.: "These characteristics make polymerase chain reaction sex testing an ideal tool for prenatal studies." The only value of this technology would be in cases in which the chromosome studies have already been performed and there is sex chromosome mosaicism; the value lies in investigating and identifying translocated Y-chromosomal material. The major usefulness in such cases would be for discussion regarding the recommendation that gonads be removed in phenotypic females with Y-chromosomal material.

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Visualization of the fetal external genitalia in early pregnancy, which can be achieved at 12 weeks for males and 14 weeks for females, is more reliable and is the more "ideal" tool for prenatal studies, particularly as a noninvasive tool for genetic counseling when there is a family history of X-linked conditions and when the couple wishes to avoid invasive techniques. John D. Stephens, MD California Prenatal Diagnosis Institute, 1390 S. Winchester Blvd., SanJose, CA 95128

REFERENCES 1. Stephens JD. Determination of fetal sex by ultrasound. N Engl J Med [Letter]. 1983 :984. 2. StephensJD, Wyu C. The value of diagnostic ultrasoundvisualization of fetal external genitalia in a prenatal diagnosis program [Abstract]. In : Proceedings ofthe American Society of Human Genetics. American Society of Human Genetics, 1984.

Reply To the Editors: Dr. Stephens' letter contains a few points that require a response. First, the three false-positive results were obtained with the dot blot method and not the polymerase chain reaction method; that was the point of the article. Second, the Y; 15 translocation reported in our article is not Dr. Stephens' case, although we have studied such a case for him. Third, the two paragraphs regarding his reported abstract are not pertinent; if he wishes to have his work reviewed, he should submit it for peer review. Fourth, the recent case described by Dr. Stephens does serve to remind the reader that the test is designed to determine the presence or absence of a deoxyribonucleic acid fragment and not the genital sex. The fetal genital sex was determined by ultrasonography and we assume Dr. Stephens approves of this . Finally, the remaining sections of the letter are advertisements for Dr. Stephens' patented ultrasonographic determinations of fetal sex and do not require a response. Thomas L. Pinckert, MD, Roger V . Lebo, PhD, and Mitchell S. Golbus, MD University of California, San Francisco, School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Genetics Unit, Room U-262 , San Francisco, CA 94143-0720

Use of the T·ACE questions to detect risk-drinking

To the Editors: Sokol et al. (Sokol Rj, Martier SS, Ager jW. The T-ACE questions : practical prenatal detection of risk-drinking. AM J OBSTET GYNECOL 1989;160: 863-70) studied a technique to identify pregnant "riskdrinkers" for whom targeting unique interventions might be appropriate. However, we do not think their instrument succeeds as a screening tool. Two issues are relevant to screening for maternal alcohol use. The first is whether any alcohol consumption during pregnancy is acceptable. The threshold for adverse outcomes from maternal alcohol consumption is not known. A linear rather than threshold model of toxicity best explains behavior abnormalities caused by prenatal alcohol exposure.' The entire maternal intake

August 1990 Am.l Obstel Gynecol

range before pregnancy was correlated with both Apgar score and rate of spontaneous abortion! Although some adverse outcomes may require high prenatal exposures, lower levels also may have detrimental consequences. The authors used a history of ~ 1 ounce of absolute alcohol per day as their threshold for risk drinking. The T-ACE questions may be insensitive to lower, but clinically important, levels of drinking. A second issue is underreporting of alcohol consumption during pregnancy.3 The methods used by the authors to quantify alcohol consumption are susceptible to this bias. The item in the T -ACE instrument that had the strongest association with alcohol consumption was the question about tolerance. Patients who reported tolerance may be those who discount the importance of alcohol use. They may be a group more likely to report their intake accurately and are less prone to the underreporting bias. Thus the T-ACE instrument may be less sensitive than this study suggested for detecting those women who underreport risk-drinking. A score of 2 or more on the T-ACE questions suggested a high level of alcohol consumption. A lower score should not be interpreted as an indication that counseling and follow-up about alcohol use are not indicated. Rather than a "Papanicolaou smear," as the authors suggest, the questions are more analogous to an electrocardiogram. A "normal" test does not exclude significant problems. Diane L. Elliot, MD, and David H . Hickam, MD Oregon Health Sciences University, 3181 S.w. Sam Jackson Park Road, L 475, Portland, OR 97201-3098

REFERENCES 1. Streissguth AP, Barr HM, Martin DC. Alcohol exposure in utero and functional deficits in children during the first four years of life. In : Mechanisms of alcohol damage in utero. London: Pitman, 1983:176-96; CIBA Foundation symposium no. 105. 2. Russell M, Skinner JB. Early measures of maternal alcohol misuse as predictors of adverse pregnancy outcomes. Alcoholism 1988; 12:824-30. 3. Emhart CB, Morrow-T lucak M, Sokol RJ , Martier S. Underreporting of alcohol use in pregnancy. Alcohol Clin Exp Res 1988;12 :506-11.

Reply To the Editor: The utility of our T-ACE questions as a simple screening device to identify women who drink enough alcohol to potentially damage their unborn offspring is questioned in the above letter on two bases. First, it is speculated that the T-ACE questions may be insensitive to low, but clinically important, levels of drinking. However, screening for "an y use" with TACE is not the issue. Rather, we recommend asking all patients whether they ever drink any alcoholic beverages. Heavy drinkers rarely have a level of denial leading to a negative answer to this question and occasionalto-moderate drinkers uniformly answer positively. The T-ACE questions are then asked of all drinkers, and drinking patterns are explored fully in those who are T-ACE positive. Finally, we recommend abstinence during pregnancy to all women who do drink, although we interpret the literature to indicate no detectable clin-

Rapid determination of fetal sex.

Volume 16:1 Number 2 screening followed by elective abortion rather than improved maternal diabetic control. The outcome of all diabetic pregnancies...
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