Umbilical artery velocity waveforms before and after chorionic villus sampling.

Because a vascular aetiology has been suggested for the limb and oromandibular defects described after chorionic villus sampling (CVS), to determine whether transabdominal (TA) CVS causes noticeable changes in umbilical artery velocity waveforms in first-trimester pregnancies, the pulsatility index (PI) of the umbilical artery was evaluated before and after TA-CVS in 175 pregnancies sampled between 10.0 and 13.0 weeks' gestation. In 139 uncomplicated pregnancies, the mean PI values (with 95 per cent confidence interval) were before TA-CVS 2.751 (2.692-2.809), after 10 min 2.723 (2.697-2.809), and after 1 h 2.781 (2.722-2.840). There were no significant changes in PI relative to the CVS procedure either in pregnancies with an abnormal result or in those ending in spontaneous abortion. Our data do not support any statistically significant change in umbilical artery PI relative to TA-CVS in first-trimester pregnancies. This procedure, despite its invasive character, does not appear to affect the feto-placental circulation.

Psychological implications and acceptability of preimplantation diagnosis.

The aim of this study was to ascertain the degree of acceptability of preimplantation diagnosis with blastocentesis in 180 women at risk for beta-thalassaemia awaiting chorionic villus sampling (CVS). The women were asked to fill in a questionnaire some days before sampling. All women who had had previous therapeutic abortion found blastocentesis acceptable. Only 30% of women who had not had previous therapeutic abortion chose blastocentesis, whilst 25% of primigravid women opted for blastocentesis. From these preliminary data it seems that obstetric experience is an important factor in the reproductive choice of women at high genetic risk.

Early transabdominal chorionic villus sampling in couples at high genetic risk.

OBJECTIVE: The purpose of the study was to evaluate the feasibility and safety of transabdominal chorionic villus sampling before 9 weeks' gestation. STUDY DESIGN: Two hundred pregnancies at risk for beta-thalassemia (n = 198) or Duchenne muscular dystrophy (n = 2) underwent transabdominal CVS at 6 through 8 weeks. Sampling success and fetal loss are expressed in percentages. RESULTS: Sampling was successful in all cases (100%). Forty-eight fetuses were affected by beta-thalassemia and one by Duchenne muscular dystrophy. The percentage of fetal loss, expressed as a proportion of continuing pregnancies, was 4.0%. All women (n = 144) have been delivered, and no misdiagnoses have occurred. We observed one anencephalus and one mild limb defect consisting of absence of distal phalanges of index and little fingers of both hands and distal phalanges of both little toes. CONCLUSION: Transabdominal CVS before 9 weeks is a reliable and relatively safe method for prenatal diagnosis in patients at high risk for genetic diseases. However, further studies are necessary to assess the risk to the fetus.

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 per cent (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.

Early antenatal sonographic diagnosis of conjoined syncephalus-craniothoraco-omphalopagus twins. Case report.

The paper describes the prenatal ultrasonographic diagnosis of conjoined syncephalus-craniothoraco-omphalopagus twins at 13 weeks' gestation. The mother, after genetic counseling, decided to interrupt the pregnancy. The fetal karyotype, the maternal serum and amniotic fluid alpha-fetoprotein levels were normal. The diagnosis was confirmed by pathologic examination of the fetus after termination of pregnancy.

Antenatal diagnosis of beta-thalassemia in Sardinia.

This paper reviews the characteristics and the results of 15 years of experience with a preventive program, based on carrier screening and prenatal diagnosis, designed to control thalassemia major in the Sardinian population. The education of the population about thalassemia and the modalities for its prevention was accomplished via the mass media. Carrier screening was carried out voluntarily on couples of child-bearing age. Prenatal diagnosis was initially carried out by fetal blood analysis; since 1983, it has been done by DNA analysis on non-amplified or amplified DNA. Different chorionic villous sampling procedures have been used. Nowadays, we have adopted the transabdominal approach because, in our experience, it seems to be associated with a low risk (2%) of fetal mortality. At the present time, the beta-thalassemia mutations are detected directly by dot-blot analysis of amplified DNA with 32P- or horseradish peroxidase-labeled allele-specific oligonucleotide probes. Two oligonucleotide probes, one complementary to the codon-39 nonsense mutation, which accounts for 95.7% of the beta-thalassemia chromosomes in the Sardinian population, and the other complementary to the frameshift at codon 6, which is the second most common mutation in our population (2.1%), allow us to make prenatal diagnosis in the large majority of cases. Notwithstanding a careful dissection of maternal decidua from chorionic villi, co-amplification of maternal sequence was detected in 4 out of 425 cases tested by this procedure. In order to avoid this pitfall, the simultaneous amplification of highly polymorphic VNTR (variable number of tandem repeats) segments could be used. On the whole we have so far carried out 2711 prenatal tests: 1130 by fetal blood analysis, 1156 by oligonucleotide hybridization on electrophoretically separated DNA fragments, and 425 by dot-blot analysis on amplified DNA with allele-specific oligonucleotide probes. Two errors occurred by fetal blood analysis and none by DNA analysis. The incidence of thalassemia major declined from 1:250 live births in the absence of prevention to 1:1000 after the establishment of this program, indicating that carrier screening and prenatal diagnosis are effective means for preventing thalassemia major at the population level.

The prevention of thalassemia in Sardinia.

In this paper we review the characteristics and effectiveness of a program aimed at preventing homozygous beta-thalassemia in the Sardinian population. The target population for screening were couples at marriage, conception or early pregnancy. Awareness of the problem and the involvement of the population were achieved via the mass media or by personal approaches through lectures or discussions. Parents' Associations were consulted and have made themselves available to prospective couples in several critical areas. Education on thalassemias was introduced into the school curriculum. Counseling was based on private interviews at which the several options available were discussed with the individual carrier or the couples. Prenatal diagnosis was chosen by the large majority of couples counseled. The introduction of 1st trimester diagnosis resulted in a striking increase of the acceptance rate from 93.2 to 99.1%. Prenatal diagnosis was carried out initially by fetal blood analysis and thereafter by trophoblast or amniocyte DNA analysis. Direct detection of the mutation by oligonucleotide hybridization on agarose gel separated DNA fragments or by dot-blot analysis with allelic specific oligonucleotide probes on enzymatically amplified DNA was used. This program resulted in a decline in thalassemia major births of 90%. The reasons for residual cases were mostly lack of information and, less frequently, misdiagnoses or refusal of fetal diagnosis.

Prenatal diagnosis of beta-thalassaemia by second-trimester chorionic villus sampling.

In this study we evaluated the feasibility of second-trimester transabdominal chorionic villus sampling for prenatal diagnosis of beta-thalassaemia in 80 pregnancies at risk presenting in the second trimester at the Antenatal Service. Sampling was carried out from 13 to 20 weeks and was successful in all cases. The amount of chorionic villi obtained varied from 10 to 40 mg, which was sufficient to make fetal diagnosis by oligonucleotide analysis within 10 days from sampling in all cases. No fetal losses occurred. From these results we conclude that transabdominal chorionic villus sampling is a useful procedure for prenatal diagnosis of beta-thalassaemia in those couples presenting after the first trimester.

Chorionic villus sampling by rigid forceps: experience with 300 cases at risk for thalassemia major.

In this article we report the results of chorionic villus sampling by a biopsy forceps inserted via the cervix under ultrasonic guidance in 300 pregnancies at risk for thalassemia major. A sufficient amount of chorionic villi for deoxyribonucleic acid analysis by oligonucleotide hybridization was obtained in all cases tested but one, with a success rate of 99.7%. The percentage of fetal loss, expressed as proportion of continuing pregnancies, was 4.8%. To verify the results, we carried out amniocyte deoxyribonucleic acid analysis in all the continuing pregnancies for the first 100 cases and in those in which trophoblast deoxyribonucleic acid analysis showed the heterozygous state for beta-thalassemia for the second 200 cases. At the beginning we had two cases of decidual contamination in such an amount to cause misdiagnosis. Successively more careful elimination of decidual tissue from villi avoided avoided this pitfall. These results indicate that chorionic villus sampling by a rigid forceps is a reliable and relatively safe method for fetal diagnosis of genetic diseases by deoxyribonucleic acid analysis.

Control of homozygous beta-thalassemia by carrier screening and antenatal diagnosis in Sardinians.

This paper reports the present results of an ongoing program aimed at preventing homozygous beta-thalassemia by means of heterozygote screening and antenatal diagnosis in the Sardinian population. Screening based on the knowledge of carrier frequency and types of thalassemia prevalent in this population was designed to discover all heterozygotes except the few silent beta-thalassemia carriers. Most of the couples at risk were informed and accepted testing. Information was conveyed by mass media, midwives and marriage registry offices. Antenatal diagnosis was accepted by the majority of the couples counselled. The results of antenatal testing were very accurate. There was only one misdiagnosis out of 949 pregnancies tested. This risk of fetal loss was 7.5%. The program was highly effective, as shown by the decline of the incidence of the homozygous state from 1:205 live births in 1976 to 1:557 in 1981.