The impact of prenatal diagnosis on the occurrence of chromosome abnormalities

From the public health point of view, several formal attempts have been made to measure the impact of prenatal diagnosis (PND) on the incidence of Down's Syndrome (DS), but the results have varied widely. The impact of PND (reduction in the birth rate of chromosomally abnormal neonates) is related to utilization rates but quantitative estimates of this have not been established. In a three-year (1981–1983) total population study from Queensland, Australia, we present results to measure the impact of a voluntary PND programme on the birth incidence of DS, and also other chromosomally abnormal births. Utilization rates for the PND service were 15·5 per cent in that population of mothers 35 years and over. Numbers and rates of all cases of chromosomal abnormalities are presented, subclassified by type of diagnosis–-either by PND or by clinical diagnosis after birth. For the total population, 7·3 per cent of cases of DS were detected prenatally, and 15·4 per cent of all chromosome abnormalities. (A method for measuring the impact of PND is described.) Using this in conjunction with our demographic data, we estimate that with a 15 per cent utilization rate of PND by older mothers, 14 per cent of DS births can be prevented in this age group, or a 5 per cent overall reduction can be achieved if mothers of all ages are considered. One index–-the ratio of the percentage of DS births which are preventable compared with the population utilization rates of PND–-has potential for widespread use. Queensland data for this ratio is 0·34, a figure consistent with that from other studies. Thus a 3·5 per cent drop in the overall DS birth rate may be expected for each 10 per cent increase in the utilization rates of PND for mothers of 35 years and over. A diagram is presented which may serve as a model for improved data collection and better impact estimates in the future.     

Placental biopsy in the third trimester of pregnancy

Forty-two women with abnormal ultrasound findings after 27 weeks' gestation underwent a placental biopsy. In 39 cases, a karyotype was obtained from a direct preparation within 48 h, five abnormal karyotypes being detected (four trisomies and a triploidy). One confirmed placental mosaic was also detected. In one case, a small terminal deletion of chromosome 7 was not detected at the time due to the quality of the preparation. A karyotype can be obtained from a direct preparation in the third trimester in over 90 per cent of cases, the quality of the preparation allowing the reliable detection of abnormalities of chromosome number. We believe that this technique may be usefully, reliably, and safely employed in the third trimester of pregnancy by those with an interest in antenatal ultrasound diagnosis who do not have immediate access to a cytogenetics laboratory and who feel that cordocentesis is inappropriate for their situation.     

Prenatal and presymptomatic diagnosis of the marfan syndrome using fluorescence pcr and an automated sequencer

The Marfan syndrome (MFS) is a heritable connective tissue disorder characterized by skeletal, ocular, and cardiovascular abnormalities. Defects in fibrillin, an elastin-associated microfibrillar protein, are now known to cause MFS. Since the discovery of fibrillin as the gene responsible for MFS, requests for prenatal and presymptomatic diagnosis have become common-place. Here we report the use of the polymerase chain reaction (PCR), using fluorescence labelled primers and an automated sequencer, to establish linkage data for “molecular diagnosis”. The mistaken clinical diagnosis of MFS based on the appearance of a common cardiovascular manifestation, mitral valve prolapse, and a positive family history is also discussed.     

Missed prenatal diagnosis of fragile-X syndrome

An account is given of a pregnancy in an obligatory carrier of the fragile-X syndrome, in whom examination of chorionic villus cells and fetal blood cells showed the presence of a male fetus who lacked the fragile-X chromosome. However, at 3 months of age he had 14 per cent of fragile-X cells in his blood. Reasons are suggested for this error in diagnosis. The empirical risk for an error of this sort is 3 per cent.     

The influence of obstetricians on the utilization of amniocentesis

A study of 173 Western New York State obstetricians was undertaken to study referral patterns for second-trimester amniocentesis in 1974–1978. Referral patterns were analysed in relation to obstetrician age, religion, board certification, hospital affiliation and practice location. Forty-seven per cent of the obstetricians had never referred a patient for amniocentesis. Those referring were overall younger than those not referring and were significantly more often board certified. Obstetrician religion was significantly related to referral with fewer Catholic obstetricians referring. Hospital affiliation (teaching versus non-teaching) and obstetrician practice location (urban versus rural) were not important factors after controlling for religion and board certification. Obstetrician factors account for a small but important part of the variability in referral, and other factors, such as cost and access to laboratory and obstetric care need further investigation.     

Prenatal diagnosis of the fragile X syndrome using fetal blood and amniotic fluid

Nineteen pregnancies at risk for the Martin–Bell syndrome have been monitored during the second trimester for the presence of the fragile Xq27. Of the 19 potential carrier mothers, 14 showed the presence of the fragile X in their lymphocytes at a level of 4 per cent or above. As one was a twin pregnancy, fetal blood was obtained at fetoscopy from 20 fetuses and amniotic fluid obtained simultaneously from 19 of them. Of the 20 fetuses, 18 were males (including both of the twins) and two were females. Of these 18 males, seven were found to carry the fragile Xq27 in lymphocytes and subsequently six of the seven were terminated. The diagnosis was confirmed in five of the six terminated fetuses (the sixth case was a patient whose pregnancy was terminated abroad) and also in a full-term male baby. Five of the seven males without the marker X who came to term had their karyotypes confirmed post natally. Of the two female fetuses one was found to be a carrier of the fragile X and the other was not. Both babies had full-term deliveries and both had their karyotypes confirmed post natally. In some cases the diagnosis made in fetal lymphocytes was confirmed later in amniocytes.     

Prenatal diagnosis of the pterygium syndrome

We report two second trimester pregnancy terminations in the same woman following intrauterine ultrasonic findings of hydrops fetalis, polyhydramnios, lack of fetal movements, and short, fixed malformed limbs. One fetus also showed a cystic mass at the back of the head. Radiographic and anatomic studies of the fetuses demonstrated multiple pterygia, flexion contracture of multiple joints, abnormal facial appearance, cleft palate, pulmonary hypoplasia, and gracile bones. The cystic mass of the back of the head was found to be a cystic hygroma. These findings are consistent with the lethal variant of multiple pterygium syndrome. Early prenatal diagnosis of this condition is possible using ultrasonography.     

Prenatal cytogenetic diagnosis after transabdominal chorionic villus sampling in the first trimester

First trimester prenatal cytogenetic diagnosis was attempted in 350 pregnancies after trans-abdominal chorionic villus sampling. The cytogenetic investigation was performed using both a short-term method (24 h incubation) and cell culture. Adequate samples were obtained in 99·1 per cent and in all these cases the fetal karyotype was established. A chromosome abnormality was found in 2·0 per cent of cases. A discrepancy between the karyotype obtained after 24 h incubation and the karyotype in cell culture was observed in 2·3 per cent. Maternal cell contamination in the cultures was confirmed in 13 of 181 cases where the 24 h incubation revealed a male karyotype. Studies of culture morphology showed that colonies of convoluted cells may serve as a marker for contamination with maternal cells in culture. For the present, we recommend using a short-term method as well as cell culture for cytogenetic investigation until the problems with karyotype discrepancy and maternal cell contamination have been further clarified.     

Ultrasound diagnosis of the pena shokeir phenotype at 14 weeks of pregnancy

This report describes the early prenatal diagnosis of the Pena Shokeir phenotype in an at-risk patient at 14 weeks' gestation. The diagnosis was based on an abnormal fetal movement profile, in association with an abnormal position of the fetal limbs. Pena Shokeir phenotype describes an inherited condition characterized by arthrogryposis and dysmorphic features as a result of fetal akinesia. It is a lethal abnormality and early diagnosis allows safer surgical methods of termination.     

Prenatal transvaginal diagnosis of the ectrodactyly,ectodermal dysplasia,cleft palate (EEC) syndrome

Transvaginal ultrasonography performed at 14 weeks' gestation demonstrated a bilateral cleft lip and lobster-claw deformities of the hands and feet, in keeping with the diagnosis of EEC syndrome (ectrodactyly or lobster-claw deformity, ectodermal dysplasia, and cleft lip and palate). The fetus was aborted and the diagnosis of EEC syndrome was confirmed.     

Prenatal diagnosis of giant cystic hygroma: Prognosis,counselling, and management; case presentation and review of the recent literature

Cystic hygromas have historically been associated with a grim prognosis when discovered during prenatal sonographic study of the fetus. This same grim prognosis is not observed by the paediatric surgeon who evaluates the neonate or paediatric patient. We present a fetal patient with a massive anterior cystic hygroma discovered in the third trimester prior to 30 weeks. This case and a review of the literature suggest tailoring the prognosis by category when counselling patients: (1) first trimester, normal karyotype-good; (2) first trimester, abnormal karyotype-poor; (3) second trimester and early third-poor to guarded; and (4) mid to late third trimester-good.     

Progression of exencephaly to anencephaly in the human fetus—an ultrasound perspective

Exencephaly as a precursor of anencephaly is well delineated in animal studies. In humans, a similar though unproven embryologic sequence is postulated. In the case reported, serial ultrasound studies allowed us to identify a 16-week human exencephalic fetus and observe the cephalic changes during its progression to a classic anencephalic appearance.     

Ultrasound diagnosis of structural abnormalities in the first trimester

The advances in ultrasound technology have made it possible to identify fetal structural abnormalities and genetic syndromes in the first trimester. First trimester prenatal diagnosis of fetal central nervous system, renal, gastrointestinal, cardiac, and skeletal abnormalities is reviewed. Copyright © 2002 John Wiley & Sons, Ltd.