Which tissue should be used to obtain a fetal karyotype after second trimester termination of pregnancy?

Abstract

TRIMESTER TERMINATION OF PREGNANCY? GARFIELD CLUNIE, STEVEN J. RALSTON, JANET M. COWAN, KAREN KRAJEWSKI, SABRINA D. CRAIGO, Tufts University, OB/GYN, Boston, Massachusetts, Tufts University, Genetics, Boston, Massachusetts OBJECTIVE: The goal of this study was to determine which fetal tissue (cord, placenta, or skin) would most reliably yield a karyotype following second trimester pregnancy termination. STUDY DESIGN: Patients who were referred for pregnancy termination for fetal anomalies or a fetal demise in the second trimester were approached for participation in the study. At the time of their termination, tissue was obtained from the placenta, umbilical cord, and fetal skin. Tissue culture techniques were then used to grow cells from each of these tissues and a karyotypic analysis was performed when possible. A successful culture was defined as one which yielded enough cells for adequate analysis by routine cytogenetic standards. RESULTS: Thirty-five patients were entered over a 12-month period yielding 102 tissue samples; 14 of these patients had demises and 21 had anomalous fetuses. All 3 tissues were obtained in 32 patients; 2 tissues were obtained in the remaining 3 patients. In the 21 cases where there was a living fetus, the placenta, cord, and skin were equally reliable, yielding a result in 95%, 100%, and 100% of cases respectively (P = .4). However, in the subgroup of patients whose diagnosis was fetal demise, placental tissue was the most reliable with a failure rate of 36% (P= .004). In these patients, the incidence of culture failure was 77% for umbilical cord (RR = 2.8, 95% 1.0-8.1, compared to placenta) and 93% for fetal skin (RR= 9.0, 95% CI 1.3-61.9, compared to placenta). Only 3 patients (9%) had failures in all 3 cell lines; all 3 of these patients had fetal demises (P = .09). In the 102 samples, there were 5 cases of karyotypic mosaicism; all 5 were from placental tissue (P = .006). CONCLUSION: For karyotypic analysis after second trimester termination of pregnancy of a living fetus, fetal cord, skin, and placenta are equally reliable sources of fetal cells. In cases of fetal demise, skin and cord become less reliable and placenta tissue should be obtained to determine the karyotype. However, mosaicism occurs more frequently with placental tissue. 131 SECOND TRIMESTER MATERNAL SERUM SCREENING FOR DOWN SYNDROME: AMNIOCENTESIS RATES AND THE NET NUMBER OF AFFECTED PREGNANCIES IDENTIFIED PETER BENN, JAMES EGAN, University of Connecticut, Genetics and Developmental Biology, Farmington, Connecticut, University of Connecticut, Obstetrics and Gynecology, Farmington, Connecticut OBJECTIVE: Traditionally, the efficacy of screening programs has been measured by the sensitivity and false-positive rate and assumes uniform utilization of amniocentesis among all screen-positive women. We evaluated efficacy from the perspective of the actual numbers of amniocenteses performed and Down syndrome (DS) pregnancies prenatally diagnosed. STUDY DESIGN: We reviewed the sensitivity, false-positive rate, amniocenteses performed, and DS pregnancies diagnosed for 99,762 women with singleton pregnancies receiving second trimester screening through our laboratory from 1991 to 2002. Prior to April 1999, screening was based on MS-AFP, hCG, and uE3. Subsequently, inhibin-A was added. The second trimester cut-off was 1:270 and 12.4% of the women screened were aged 35 or more at delivery. RESULTS: Based on 178 DS pregnancies, the screening had a sensitivity of 73.6%. Of the 131 screen-positive women with affected pregnancies, 92 (70.2%) had an amniocentesis resulting in a net detection rate of 51.7%. The screening had a false-positive rate of 6442/99,584 (6.5%) and 3078 (47.8%) of these screenpositive women underwent amniocentesis resulting in a net amniocentesis rate of 3.1% in women with unaffected pregnancies. The rate of amniocentesis was significantly higher in true-positives compared to false-positives (P ! .001). In women with unaffected pregnancies, there was a significant reduction in the rate of amniocenteses between 1991 (70.3%) and 2002 (37.5%) (P ! .001). This trend was not seen for affected pregnancies. The odds of an affected pregnancy, given a positive screening result, were 1:46. The odds of an affected pregnancy when an amniocentesis was performed were 1:32. CONCLUSION: The higher amniocentesis rate in affected compared to unaffected pregnancies is probably attributable to the higher serum screening risks and abnormal ultrasound findings present in many affected pregnancies. The actual number of DS pregnancies prenatally diagnosed and the number of invasive tests performed should be considered when evaluating the various screening protocols available.