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This study was undertaken in an attempt to determine the significance of elevated maternal serum human chorionic gonadotropin (MShCG), in the presence of an otherwise normal screen with respect to fetal malformations, chromosomal aberrations, and pregnancy outcome. Targeted ultrasound findings and perinatal outcome of 298 women in whom serum hCG was > or = 2.5 MOM and who were screen-negative for Down syndrome (the study group) were compared with a control group of 229 women in whom serum hCG as well as the other parameters were within the normal range. Genetic amniocentesis was performed in 125 women from the study group. Ultrasonically detected malformations were significantly more frequent among the study group (12 vs. 1, P = 0.01). Pregnancy complications were similar in the two groups, with the exception of pre-eclampsia-toxaemia, which was significantly more frequent in the study group (5 vs. 0, P = 0.02). There was one case of an abnormal karyotype (47,XXY). Although genetic amniocentesis does not appear warranted, isolated elevated MShCG levels during the second trimester screening was associated with an increased risk of fetal anomalies detected by ultrasound and of toxaemia of pregnancy.

Cytogenetic and fluorescent in situ hybridization (FISH) studies were performed on several formalin-fixed tissues obtained from four fetuses diagnosed at amniocentesis as 45,XO-Turner syndrome. Three of the four were phenotypically normal and one had malformations. The three phenotypically normal cases were found to have an additional normal cell line, which may explain their ability to survive, at least to the time of pregnancy termination well into the second trimester. The abnormal 45,XO fetus was not found to be mosaic in all of the tissues examined. In 45,XO cases in which no malformation is detected, the possibility of mosaicism should be raised and thus the counselling should be modified accordingly.

We report the results of screening for Down's syndrome (DS) in older women using published rate schedules based on maternal serum alpha-fetoprotein (MSAFP) and age. Five hundred and seventeen patients aged 35 years and older, who were referred for a mid-trimester genetic amniocentesis, were first tested for MSAFP and then underwent an amniocentesis. Individual risks for DS, combining MSAFP and age, were derived using three different published rate schedules. Theoretical selection for amniocentesis was made using the cut-off level of the average collective risk for a 35-year-old woman (1:380 at live birth or 1:270 at amniocentesis). Six affected pregnancies (five with DS and one with trisomy 18), which were diagnosed prenatally, were all found to be at a higher risk than the specified cut-off. These cases would have been diagnosed in any event, using any of the published rate schedules. According to these rate schedules, between 39 and 45 per cent of the patients would be in the lower risk group and therefore would have been counselled not to undergo amniocentesis. Further studies should be conducted in order to reach conclusive screening policies for DS in older women.

Comparative genomic hybridization (CGH) was applied to samples taken from various sites of placentas originating from complicated pregnancies: 24 with intrauterine growth restriction (IUGR), one with multiple fetal malformation, one with toxemia, one with hydrocephalus and two with undetectable maternal serum alpha-fetoprotein (MSAFP). One of the most common aberrations in the IUGR cases was the addition of a whole or part of the X chromosome. Other aberrations such as additional Y chromosome or of 13(q22) or loss of chromosome 17 also appeared in different cases. In one IUGR case trisomy 8 (in one site) and 47,XXY (in all sites) were detected. In the two cases with undetectable MSAFP monosomy 16 was found. Some of the results were also confirmed by the FISH technique. In all the control cases (six normal and five with aneuploidy) CGH concurred with the known karyotype. Our results demonstrate the usefulness of the CGH technique in the genetic evaluation of fresh and paraffin embedded placentas in problematic pregnancies even when morphology is normal. However, it is very important to take multiple samples from different sites of the placenta.

Objective A study was conducted to evaluate the sensitivity of combining a second trimester triple test and targeted ultrasound in order to detect Down syndrome in women undergoing amniocentesis over 35 years of age. Methods Women over 35 years of age underwent a triple test and an ultrasound examination for chromosomal markers immediately prior to genetic amniocentesis. Results One thousand and six women were examined. Four hundred and thirty seven were triple test-positive and in 195 cases ultrasonographic abnormalities were observed. Thirteen had Down syndrome and eight had other chromosomal abnormalities. All women with Down syndrome babies were triple test-positive and seven also had ultrasonographic markers. Three of eight women who had babies with chromosomal aberrations other then Down syndrome were also triple test-positive. Conclusions The use of the triple test as a screening tool in our population would reduce the number of amniocenteses by 60%, while no cases of Down syndrome would be missed. Ultrasonographic markers have added little to this population. Three non-Down syndrome chromosomal abnormalities and two Down syndrome mosaic cases would be missed by this approach. Copyright © 2002 John Wiley & Sons, Ltd.

Various non-invasive techniques for prenatal diagnosis have been under investigation. We evaluated the success of fetal sexing using a non-invasive technique for obtaining fetal cells, uterine cervix brushing, in combination with FISH. Thirty pregnant women who completed between 6 and 10 weeks of gestation and who were scheduled to undergo pregnancy termination were included in the study. A Pap smear cytobrush was inserted through the external os to a maximum depth of 2 cm and removed while rotating it a full turn. The material that was caught on the brush was spread on four microscope slides. Two-color FISH was used for fetal sexing. Following pregnancy termination, a placental sample was used for full karyotyping. In 29/30 cases FISH diagnosis was confirmed by chromosomal analysis. The only male case in which a Y chromosome was not seen was from a pregnancy of 6 weeks 6 days gestational age. One case was mosaic of 46,XY/47,XXY (25%). In most cases (7/13) the Y chromosome was already identified in the first analyzed slide. With the use of a cytobrush fetal cells can be easily obtained for the purpose of prenatal diagnosis of chromosomal disorders.

We report a case in which mosaicism of trisomy 13 was detected in 4/10 cells (40 per cent) in amniotic fluid cell cultures, followed by a low rate of mosaicism (1/160 cells) detected in a fetal blood sample. This finding presents a dilemma both for the genetic counsellor and for the parents in determining whether or not to terminate the pregnancy.

We investigated the contribution of different screening criteria to the prenatal detection of Down syndrome (DS) as well as other chromosomal anomalies in the Jewish population in Israel during 1990 and 1992. There was a significant decrease (P0.03) in the incidence of DS live-births during 1992 (40:78 442) compared with 1990 (69:73 751) which paralleled a marked increase in total prenatal testing and in DS cases detected prenatally. Private laboratories, which perform amniocenteses mostly for women with a low risk of DS and without genetic counselling, had a significantly lower detection rate (1:917) compared with that of the genetic institutes, which following genetic counselling test both womenor = 37 years of age (1:91) and women younger than 37 years (1:113). The detection of chromosomal anomalies other than DS was less affected by the reason for amniocentesis. Amniocentesis indicated by maternal serum marker screening of women younger than 37 years identified a greater number of chromosomal anomalies other than DS than amniocentesis based on age (or = 37 years) alone (111:9604 versus 94:9810; P0.06). Prenatal detection of DS is most effective when the indication for amniocentesis follows genetic counselling. The increasing use of maternal serum marker screening leads to a significant improvement in the positive detection rate of chromosomal anomalies other than DS in young women.