Cystic Adenomatoid malformation of the lung: Prenatal diagnosis and outcome

During an 8-year period (1984–1992), we made the ultrasonographic diagnosis of cystic adenomatoid malformation (CAM) of the lung in 58 fetuses at 17–39 weeks' gestation. We reviewed the records of these fetuses and combined the data from 74 cases reported in the literature to determine the incidence of the different types of CAM, associated malformations, and outcome. The lesions were macrocystic in 78 (59 per cent) and microcystic in 54 (41 per cent) of the cases. CAM was left-sided in 51 per cent, right-sided in 35 per cent, and bilateral in 14 per cent of the fetuses. In 15 (11 per cent) of the fetuses there were additional malformations and 57 (43 per cent) were hydropic. The pregnancy was electively terminated in 44 (33 per cent) of the cases, including all those with bilateral CAM. There were six (5 per cent) intrauterine deaths, five in association with hydrops, and one with growth retardation and heart defect. Of the 82 (62 per cent) infants that were liveborn, 21 (26 per cent) died in the neonatal period, 15 before and six after surgery. Of the 61 survivors, 16 (26 per cent) did not require surgery. In the 88 cases where the pregnancy was not terminated, survival was better if the CAM was macrocystic (74 per cent versus 58 per cent for microcystic), if there was no hydrops (92 per cent versus 21 per cent for hydrops), and if the amniotic fluid volume was normal or decreased (82 per cent versus 53 per cent for polyhydramnios).     

Tertiary centre referral of small-for-gestational age pregnancies: A 10-year retrospective analysis

Between 1981 and 1991, 461 pregnant women between 15 and 40 weeks of gestation (mean 30 weeks) with completed follow-up were referred to our centre for prenatal diagnosis because of a small-for-gestational age (SGA) fetus or combined SGA and structural abnormality. The referral diagnosis was based either on biparietal diameter measurements or on measurement of the upper-abdominal circumference. SGA in our centre was defined as a fetal upper-abdominal circumference below the tenth centile. SGA was confirmed by ultrasound in 75 per cent of the fetuses, whilst combined SGA and fetal structural abnormality was substantiated in only 16 per cent of the fetuses. However, in our centre structural abnormality was detected in 34 fetuses who were referred because of SGA alone. Nearly half of the structurally normal SGA fetuses displayed a normal head-to-abdomen (H/A), ratio, whereas an increased H/A ratio was found in 13/15 fetuses with an abnormal karyotype. An abnormal karyotype was present in 20 fetuses, which is 7 per cent of the total SGA population. Nearly 50 per cent represented triploidy associated with oligohydramnios. SGA was confirmed by a birth weight below the tenth centile in 89 per cent, below the fifth centile in 77 per cent, and below the 2·3rd centile in 55 per cent of infants. Structural abnormality was confirmed in 65 per cent of infants, whereas in 19 per cent of infants the abnormality was missed or a misclassification was made. Perinatal mortality was 31 per cent for all SGA fetuses, 27 per cent for SGA fetuses without anomalies, and 64 per cent for SGA fetuses with structural abnormality.     

Prenatal evaluation and outcome of fetal obstructive uropathies

Between January 1982 and January 1986, 76 pregnant women between 15 and 40 weeks of gestation were referred because of suspected fetal obstructive urinary tract pathology. A total of 14 high-level (ureter) and 17 low-level (urethral) obstructions were diagnosed. High-level obstructions were at the uretero-pelvic level in 11 and at the uretero-vesical level in 3 cases. Increased amniotic fluid volume was observed in 28 per cent. The survival rate was 86 per cent. In the 17 cases of urethral obstruction, oligohydramnios was present in 70 per cent, associated structural defects in 30 per cent, and an abnormal karyotype in 6 per cent. Pregnancy was terminated because of progressive massive hydronephrosis in 41 per cent; intrauterine or neonatal death occurred in 47 per cent, resulting in a survival rate of only 12 per cent.     

Prenatal diagnosis and management of anterior abdominal wall defects in the West of Scotland

An attempt was made to identify all the cases of abdominal wall defects occurring in the West of Scotland over a 7-year period to determine the current incidence, prenatal diagnosis, management, and prognosis for fetuses and neonates with abdominal wall defects. Cases were identified because they presented either for prenatal diagnosis, or to the Department of Pathology following termination or spontaneous pregnancy loss, or as neonates to the Neonatal Surgical Department. The incidence of abdominal wall defects was found to be 1 in 2500 births. Exomphalos was diagnosed before birth in 66 per cent of cases, and in 30 per cent of cases it was associated with another major abnormality. There was a 20 per cent intact survival in the cases diagnosed prenatally who had no fetal anomaly and who opted to continue with the pregnancy. Gastroschisis was diagnosed before delivery in 70 per cent of cases, and in the group who continued with the pregnancy there was an intact survival of 77 per cent. Body stalk anomalies were all diagnosed prenatally and terminated. Maternal serum alpha-fetoprotein was elevated in 89 per cent of the cases with exomphalos and in 100 per cent of the cases with gastroschisis and body stalk anomalies in which it was tested.     

Amniotic fluid acetylcholinesterase measurement in the prenatal diagnosis of open neural tube defects. Second report of the collaborative acetylcholinesterase study

Seventeen centres from Australia, Britain, France, and the United States collaborated in a study to compare amniotic fluid acetylcholinesterase (AChE) determination by gel electrophoresis and amniotic fluid alpha-fetoprotein (AFP) measurement as diagnostic tests for open neural tube defects. The study was based on 32 642 women with singleton pregnancies (including 428 with open spina bifida and 238 with anencephaly) who had an amniocentesis at 13–24 weeks' gestation. The AChE test yielded a detection rate for open spina bifida of 99 per cent (95 per cent confidence interval 98–100 per cent), 98 per cent for anencephaly (95 per cent confidence interval 96–100 per cent), and a false-positive rate of 0.34 per cent (95 per cent confidence interval 0.28–0.40 per cent) excluding miscarriages, intrauterine death, and serious fetal abnormalities. The false-positive rate was 0.30 per cent among the 13 centres that used a specific AChE inhibitor in the test. Comparable rates for the AFP test were less favourable. (For example, the open spina bifida detection rate was 90 per cent and the false-positive rate was 0.46 per cent using the cut-off levels specified in the U.K. Collaborative AFP Study.) The AChE false-positive rate was lower in samples that were not bloodstained (0.16 per cent) than in those that were (2.4 per cent). It was higher in women who had an amniocentesis on account of a raised maternal serum AFP level (0.56 per cent) than in those who had one for other reasons (0.29 per cent). The best results were obtained by a combination of the two tests, an effective and economical policy being to perform the AFP measurement on all amniotic fluid samples and an AChE test on samples with AFP levels greater than or equal to 2.0 multiples of the normal median (about 5 per cent of all samples). Using this policy, the open spina bifida detection rate was 96 per cent and the false-positive rate was 0.14 per cent (0.06 per cent for samples that were not bloodstained and 1.2 per cent for those that were; 0.40 per cent for women with raised serum AFP levels and 0.09 per cent for other women). This policy offers a useful improvement to the prenatal diagnosis of open spina bifida.     

Chromosomal prenatal diagnosis: Study of 936 cases of intrauterine abnormalities after ultrasound assessment

Nine hundred and thirty-six prenatal chromosomal analyses were performed by four cytogenetic centres after ultrasound diagnosis of fetal abnormalities, amniotic fluid disorders, fetal growth retardation, and fetal or placental abnormalities. During the same period, 6515 fetal karyotypes were analysed because of maternal age. Frequencies of chromosomal aberrations in each case were respectively 4·4, 6·7 and 15·8 per cent, compared with 3·18 per cent when the fetal karyotype was performed because of maternal age. High rates of chromosomal aberrations are observed in cases of cervical hygroma, limb abnormalities, omphaloceles, duodenal stenosis, hydrocephalus, and facial abnormalities. In the case of polymalformations, this rate was 29·2 per cent. When malformations were seen together with an amniotic fluid disorder or growth retardation, 21·5 per cent chromosomal aberrations were observed. This frequency was 10·4 per cent when growth retardation was associated with an amniotic fluid disorder. Trisomy 13, 18, 21 and monosomy X accounted for 4/5 of all abnormalities in which we observed a high rate of triploidies (4·9 per cent) and balanced (3·3 per cent) or unbalanced (9·8 per cent) non-Robertsonian structural abnormalities. Sonographic ascertainment of these aberrations and prenatal characteristics of major anomalies are discussed.     

Prenatal cystic fibrosis carrier screening: Factors in a woman's decision to decline testing

Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per cent) answered a questionnaire soliciting their reasons for not participating. The main factor was opposition to termination of pregnancy, with 43 per cent being against termination for any reason and another 11 per cent against termination of a CF fetus. Other reasons given were partner's disapproval or non-participation (10 per cent), perceived risk of a CF child being low (7 per cent), the error rate of the test (6 per cent), and the generation of unacceptable levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not wish to be tested during pregnancy, but only six of these would have accepted screening at another time.     

Chorionic villus sampling by biopsy forceps. Results of 1580 procedures from a single centre

The results of a prospective series of 1580 chorionic villus sampling (CVS) procedures using biopsy forceps are presented. Most of the procedures (1442), including 11 sets of twins, were performed by the transcervical approach (TC-CVS), using a curved-shank thin forceps, and 138 by the transabdominal approach (TA-CVS), using a trocar-guided straight thin forceps. The mean gestational age for TC-CVS was 10.9 weeks, and in 233 cases (16 per cent) the procedure was carried out between the 12th and 14th weeks. The mean gestational age for TA-CVS was 16.7 weeks. The major indication for CVS was advanced maternal age (92.7 per cent in the TC and 91.8 per cent in the TA approach), and indications for abnormal ultrasound findings were more common in the TA approach (4.5 per cent) than in TC-CVS (0.07 per cent). Although sampling was apparently accomplished in all the procedures, in 3.1 per cent of the TC-CVS and 2.2 per cent of TA-CVS procedures, the samples were less than 1 mg after dissection. A cytogenic report was obtained in 96.1 per cent of the TC-CVS and 90.6 per cent of the TA-CVS. Maternal serum alpha-fetoprotein (MSAFP) was measured before and after TC-CVS and the post-CVS MSAFP was positively correlated with the sample weight. Second-trimester amniocentesis following CVS was required in 5.2 per cent (TC-CVS) and 6.5 per cent (TA-CVS), due to the failure to obtain a cytogenetic report or diagnostic confirmation. The follow-up to the 20th week was 100 per cent by ultrasound scan, and 88.6 per cent from the 21st week to 1 week after delivery. Fetal loss rates within 2 weeks of the procedure were 1.7 per cent (TC-CVS) and 0.8 per cent (TA-CVS) and total fetal loss accumulated to 1 week after delivery was 4.6 per cent (TC-CVS) and 5.9 per cent (TA-CVS). Factors found to increase significantly fetal loss in the TC-CVS series were maternal age and the collection of very small samples, but not the number of forceps insertions.     

Karyotype abnormalities in fetuses diagnosed as abnormal on ultrasound before 20 weeks' gestational age

This study examined rates of karyotype abnormalities in fetuses diagnosed by ultrasound as abnormal before 20 weeks' gestational age and which prompted a follow-up amniocentesis or chorionic villus sampling. Those diagnosed before 20 weeks were compared with those diagnosed at or after 20 weeks. A retrospective study identified ultrasonographically abnormal fetuses in whom karyotyping had been undertaken, 306 fetuses before 20 weeks' gestational age and 241 after. Isolated malformations before 20 weeks had, on average, an 18 per cent risk of karyotype abnormality, compared with 20 per cent later. Specific rates were calculated; for example, heart abnormality was associated with karyotype abnormality in 7 per cent of cases before 20 weeks and in 14 per cent later. Multiple malformations and karyotype abnormalities were found together in 28 per cent of fetuses prior to 20 weeks and in 33 per cent of the older fetuses. Specific associations included nuchal oedema and trisomy 21 in 21 per cent of fetuses before 20 weeks. No karyotype abnormalities were found in fetuses diagnosed with choroid plexus cysts. An overview of trisomies in Victoria, in 1991, showed that 50 per cent of trisomy 18, 42 per cent of trisomy 13, and 9·5 per cent of trisomy 21 cases were identified by ultrasound in women less than 37 years of age. Another 28·6 per cent of trisomy 21 fetuses were detected in women of advanced maternal age who underwent amniocentesis or chorionic villus sampling, making a total of 38·1 per cent of trisomy 21 that were detected prenatally. The importance of early karyotyping specifically relates to the ongoing management of the pregnancy if the chromosomes are normal, and facilitates decision-making regarding termination of pregnancy if the chromosomes are abnormal.     

Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities

The alpha subunit of human chorionic gonadotropin (alpha-hCG), human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were measured in the serum of 25 women with chromosomally abnormal fetuses between 18 and 25 weeks of gestation and in 74 normal pregnancies. AFP levels less than 0.5 multiples of the median (MoM) or greater than 2.5 MoM were observed in 24 per cent of the abnormal pregnancies and in 6.76 per cent of the normal pregnancies. A low concentration of hCG (< 0.25 MoM) was observed in 8 per cent of abnormals and in 2.7 per cent of normals while an elevated concentration of hCG (>2.5 MoM) was observed in 56 per cent of abnormals and in 1.35 per cent of normals. Elevated hCG-alpha (>2.5 MoM) was observed in 28 per cent of abnormals and in none of the normals. Determination of elevated levels of hCG-alpha or hCG resulted in detection of 68 per cent of pregnancies with chromosomally abnormal fetuses with a false positive rate of 1.35 per cent. Determination of both elevated and depressed gonadotropin levels resulted in detection of 76 per cent of abnormal pregnancies with a false positive rate of 4.05 per cent. Measurement of hCG and hCG-alpha in maternal serum samples can be used as a screening procedure for detecting pregnancies at risk for fetal chromosome abnormalities.     

Prenatal screening and diagnosis of neural tube defects in England and Wales in 1985

A survey was carried out to determine the effect of prenatal screening and therapeutic abortion on births in 1985 with anencephaly and spina bifida in England and Wales. Maternal serum alpha-fetoprotein tests were done on 399 288 women (60 per cent of pregnant women): 4 per cent were reported as being screen-positive and 1 per cent had an amniocentesis. An estimated 534 pregnancies associated with anencephaly were terminated and an estimated 445 pregnancies associated with spina bifida (but without anencephaly) were terminated. Most (63 per cent) of the anencephalic pregnancies were first suspected from an ultrasound examination; 57 per cent of the spina bifida pregnancies were first suspected from a positive maternal serum alpha-fetoprotein test, 35 per cent by ultrasound, and the remaining 8 per cent by other means. The birth prevalence of anencephaly declined by 94 per cent between 1964–1972 and 1985, but when the terminations of pregnancy on account of having a fetus with anencephaly are added to the births the decline in prevalence was only 50 per cent. The birth prevalence of spina bifida declined by 68 per cent over the same period but when the terminations were added to the births the decline in prevalence was only 32 per cent. Among births with anencephaly 66 per cent had had no screening or diagnostic tests in early pregnancy, but in those that did nearly all were positive–usually in twin pregnancies where one fetus was affected but not the other. Among births with spina bifida, 48 per cent had no tests and in those that did the results were mainly negative. We conclude that in order to monitor adequately the national screening programme for anencephaly and spina bifida a special neural tube defects register should be formed.     

Transabdominal chorionic villus sampling: Fetal loss rate in relation to maternal and gestational age

In this paper we report the fetal loss rate in relation to both maternal and gestational age in 1764 pregnant women who underwent transabdominal chorionic villus sampling (TA-CVS) between January 1986 and August 1990. The fetal loss rate, considered as a proportion of continuing pregnancies, decreased with advancing gestational age at sampling from 4.3 per cent before 9 weeks to 0.4 per cent at or after 13 weeks, the difference being statistically significant (p <0.025). The fetal loss rate increased from 1.6 per cent in women under 30 to 2.4 per cent in women of 40 years or over, but the difference was not statistically significant. Considering that the total fetal loss rate before 28 weeks' gestation was on average 1.91 percent (1.3 per cent under 35 years and 2.8 per cent in women of 35 or over), we believe that TA-CVS is a safe and effective technique for prenatal diagnosis of genetic diseases.     

Prospective maternal serum human chorionic gonadotropin screening for the risk of fetal chromosome anomalies and of subsequent fetal and neonatal deaths

A prospective study of maternal serum human chorionic gonadotrophin (hCG) measurement for the selection of pregnancies with an increased risk of fetal trisomy 21 was undertaken in 24 000 pregnancies from 1 January 1989 to 31 December 1990. Maternal serum was sampled at 15-18 weeks of gestation. hCG was measured in one laboratory, with one technique. This ‘hCG high level’ technique was developed for this screening. Amniocentesis was offered to each woman with a maternal serum hCG level above the cut-off. The follow-up of the pregnancies is known in 92 per cent of cases. The combination of hCG values and maternal age gave a detection efficiency of 63 per cent for trisomy 21 with rates of amniocentesis of 30 per cent for patients aged 37 years, 20 per cent for patients aged 35 or 36 years, and 5 per cent for patients under 35 years of age. Based on this prospective study, an individual risk was calculated combining the serum hCG value and maternal age. Seventy-four per cent of trisomy 13, trisomy 18, triploidy, and 5p- deletion were detected either in the same selected group of women or in combination with ultrasonography performed when hCG values were very low. The follow-up study showed that women who had high or low hCG values represented a group at high risk for fetal or perinatal death.     

Patient care before and after termination of pregnancy for neural tube defects

A retrospective study was designed to examine the perception of care in women who had experienced a second-trimester termination of pregnancy (TOP) for a neural tube defect. Women were identified over a 3-year period, 1983–1985. After appropriate consent, 166 women were visited at home between 4 weeks and 7 months post-TOP and interviewed by one experienced interviewer using a structured questionnaire with open and closed questions. The majority (137, 82 per cent) felt satisfied with the care received during screening, prenatal diagnosis, and during the TOP (126, 76 per cent). Patients were less satisfied (63, 38 per cent) with post-TOP care in hospital. On leaving hospital, the post-termination sequelae were mentioned to only 25 (15 per cent) patients, which left 135 (81 per cent) confused and bewildered by the post-partum reactions of their bodies, and by their strong emotions. After-care was perceived as unsatisfactory by 113 (68 per cent). One-quarter (42, 25 per cent) did not have, and were not invited for, a post-termination appointment and thus did not have an opportunity to ask questions or to discuss the fetus. Eighty-six (51-8 per cent) had no visit from any member of the primary health-care team, yet most would have appreciated such a visit. Suggestions for improved management are presented.     

Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: Their characterization and delineation of defects in pregnancies at risk

During a follow-up study of 19 790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty-two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.     

United states survey on chromosome mosaicism and pseudomosaicism in prenatal diagnosis

The survey of the incidence of chromosome mosaicism and pseudomosaicism detected in prenatal diagnosis included data from approximately 60 000 genetic amniocenteses in the United States. There were 59 participating cytogenetic laboratories nationwide. The overall incidence of chromosome mosaicism was 0.25 per cent (range of 0–0.89 per cent). The average frequency of pseudomosaicism involving multiple cells or clones was 0.7 per cent (range of 0–11.21 per cent). The frequency of single cell or clone pseudomosaicism was 2.47 per cent (range of 0–11.49 per cent). In cases of pseudomosaicism with trisomy, the most frequently involved chromosome was number 2; occurrence rates of trisomies 7,X,9,17 and 20 were also relatively high. In cases of pseudomosaicism with structural abnormalities, this survey showed an association between relative chromosome size and the frequency of involvement in structural rearrangement. Data on a total of 185 cases of chromosome mosaicism collected in this survey as well as from other documented sources showed 89 cases involved an autosome, 13 cases a sex chromosome, and 23 a marker chromosome. The frequency of noticeable phenotypic abnormalities was highest (37.8 per cent) in the autosomal mosaics and lowest (10.5 per cent) in the sex chromosome mosaics. The average rate for cytogenetic confirmation was 70 per cent.     

Evaluation of transcervical chorionic villus sampling with a completed follow-up of 1550 consecutive pregnancies

Data from 1550 consecutive pregnancies after first-trimester prenatal diagnosis by transcervical chorionic villus sampling (TC-CVS) are presented. The sampling efficacy was 97.8 per cent; the mean amount of collected villus tissue was 23 mg (range 5–100 mg). There were 97 affected fetuses, mainly (73.2 per cent) with a chromosomal abnormality or a male karyotype in carriers of X-linked disease. Pregnancy termination in these and four other women for social reasons resulted in 1449 continuing pregnancies. In these pregnancies, the fetal loss rate up to 28 weeks of gestation was 5.1 per cent with the highest loss rate (3.9 per cent) before 16 weeks. When relating this fetal loss rate to maternal age, this was 6.1 per cent in the advanced maternal age group (⩾36 years) against 3.1 per cent in the younger age group. In 1376 pregnancies continuing beyond 28 weeks, the perinatal mortality rate was 1.1 per cent; the percentage of non-genetic congenital anomalies was 0.9 per cent. The reproductive pattern of women at high genetic risk after CVS followed by pregnancy termination was evaluated. Within 12 months after the first CVS followed by pregnancy termination, 70 percent of women again requested CVS in a subsequent pregnancy.     

The value of sonographic diagnosis of fetal malformations: Different results between indication-based and screening-based investigations

The advantages of a routine screening or indication-based ultrasound investigation during pregnancy are still under debate. This is the first study where both methods are compared in two different time periods. More malformations were diagnosed before the 24th week of gestation by means of screening-based than indication-based investigation (18 per cent vs. 5 per cent, P<0·005), and before 28 weeks in 26 per cent compared with 15 per cent respectively (P<0·01). Twenty-six per cent of all malformations were detected by means of screening-based investigations as opposed to 15 per cent by means of indication-based scans. Primary fetal malformations were also diagnosed much earlier (25 weeks vs. 30 weeks). Except for the fetal head, the detection rate of malformations was higher in nearly all other body regions of the fetus in the screening-based investigation. The most important advantage of a screening-based ultrasound investigation during pregnancy is to detect the malformations early enough in pregnancy for possible intrauterine treatment or to offer safe termination of pregnancy for the woman, at least for those anomalies that are lethal or significantly handicapping.     

Ultrasonography in pregnancy and fetal abnormalities: Screening or diagnostic test? IPIMC 1986–1990 register data

The aim of the present study was to assess the sensitivity of ultrasound diagnosis used as a screening test in detecting major congenital anomalies in the prenatal period in a large nation-based multicentre setting. Data from the IPIMC register were collected in the period 1986–1990. One hundred and thirty-five hospitals, located in 17 out of the 20 regions in Italy, participated in the register. Study cases were 3479 infants with major congenital anomalies diagnosed at birth or in the first week of life. Subjects with chromosomal anomalies or multiple defects were excluded. The sensitivity of ultrasound prenatal diagnosis was 49.5 per cent for central nervous system anomalies, 3.8 per cent for congenital heart diseases, 17.1 per cent for gastrointestinal tract defects, 46.6 per cent for abdominal wall defects, 74.8 per cent for urinary tract anomalies, and 22.9 per cent for skeletal abnormalities. The detection rate for diaphragmatic hernia was 24.2 per cent. Overall, only 18 per cent of the defects diagnosed in utero were detected before 24 weeks' gestation. The sensitivity of prenatal diagnosis was 30.1 and 19.0 per cent in the northern, central, and southern regions, respectively. In light of its low sensitivity, ultrasonography as a screening test in the general population should be abandoned, although some improvement in its performance should be expected following adequate training of the ultrasound staff and the use of good technical equipment.     

Comparison of transabdominal and transcervical CVS and amniocentesis: Sampling success and risk

A total of 2931 women randomized to either transabdominal CVS, transceirvical CVS, or amniocentesis were studied. Unless intended or unintended abortion had occurred, they had completed up to 28 weeks of pregnancy. No significant difference was seen between total fetal loss in the transabdominal CVS group and the amniocentesis group (6.5 and 6.8 per cent, respectively, SE difference = 0.92 per cent, p = 0.01). The total fetal loss in the transcervical CVS group was 10.1 per cent. After pooling our data with data from the Canadian randomized study and the American non-randomized study, the difference in risk between trans-cervical CVS and amniocentesis was 1.8 per cent (SE difference = 0.64 per cent, p = 0.8). When the number of failed procedures and those cases evaluated as infeasible for the assigned method-for anatomical reasons-are compared, the overall sampling efficacy is poorer transcervically than transabdominally.