The psychological effects of false-positive results in prenatal screening for fetal abnormality: A prospective study

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points—prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.     

Detection of fetal cells in maternal blood

We report the detection of fetal cells in the maternal circulation by enzymatic amplification of a single copy gene sequence that was fetal-specific. Fetal HLA-A2-positive cells were sorted from maternal HLA-A2-negative cells by flow cytometry and confirmed by demonstration of a fetal-specific HLA-DR4 sequence. However, this sequence could not be detected in unenriched maternal DNA prepared at 28 and 32 weeks' gestation. The sensitivity of detection was 1 HLA-DR4-positive cell in 10⁵ HLA-DR4-negative cells. We conclude that prenatal diagnosis of paternally inherited autosomal-dominant genetic defects may be possible by selective gene amplification of maternal peripheral blood. However, preliminary enrichment for fetal cells may be necessary.     

Prenatal diagnosis of trisomy for the distal two-thirds of the long arm of chromosome 14 (q21→qter)

A de novo case of ‘pure’ trisomy 14q21 → qter is described which was detected at amniocentesis following an abnormal ultrasound scan of a 25–year-old woman. This is apparently the largest distal 14q duplication reported in a case surviving beyond the first trimester. The infant apipeared to have an association of clinical abnormalities previously observed in distal 14q trisomy and proximal 14q trisomy/mosaic trisomy 14.     

Prenatal detection of an Arg→Ter mutation at codon 111 of the pah gene using DNA amplification

A CGA→TGA mutation at codon 111 in exon 3 of the phenylalanine hydroxylase (PAH) gene was recently identified in a Chinese phenylketonuria (PKU) patient. This paper reports the prenatal diagnosis of a Chinese fetus at risk for PKU using DNA amplification with PCR and oligonucleotide hybridization. RFLP analysis revealed that the fetus had inherited a PKU gene from his mother, but his paternal PAH gene was uninformative. PCR amplification of 300 bp which included exon 3 plus the flanking intronic sequences of the PAH gene was performed. The amplified DNA was hybridized with a pair of allele-specific oligonucleotide probes. The results indicated that the fetal DNA carried a PAH 111 Arg→Ter mutant gene inherited from his father. Thus, the fetus was predicted to be affected with PKU.     

Non-immunological hydrops fetalis and intrapericardial teratoma: Case report and review

A large intrapericardial teratoma was found at necropsy in a 38−week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an ehogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.     

Prenatal diagnosis of pyruvate dehydrogenase E1α subunit deficiency

Pyruvate dehydrogenase (PDH) E1α subunit deficiency is an X-linked inborn error of metabolism affecting males and females with equal frequency. The diagnosis is usually based on determination of enzyme activity, although this may present difficulties in some females because of X-inactivation patterns favouring expression of the normal X chromosome. This is a particular problem for prenatal diagnosis using chorionic villus cells where normal enzyme assay results do not necessarily exclude the diagnosis and confirmatory X-inactivation analysis may be complicated by variable methylation of active and inactive X chromosomes. We describe prenatal diagnosis in two pregnancies in a family following diagnosis of a PDH E1α deficient male. The first prenatal diagnosis was performed by enzyme assay, but by the time of the subsequent pregnancy, the underlying mutation in the affected male had been identified and direct gene analysis was possible. This study highlights the limitations of diagnosis of PDH E1α deficiency based on measurement of the gene product and illustrates the need for mutation analysis in affected individuals.     

Prenatal diagnosis and carrier detection in mucopolysaccharidosis type II by mutation analysis. A 47,xxy male heterozygous for a missense point mutation

Identification of iduronate-2-sulphatase (IDS) gene mutations in patients with mucopolysaccharidosis type II (MPS II, Hunter syndrome) allows fast and reliable carrier detection and prenatal diagnosis. We describe here three cases of prenatal diagnosis by direct detection of the gene mutation. In addition to two affected male fetuses from two different families, a 47,XXY fetus carrying both the normal and the mutant allele was diagnosed in a third family. The latter pregnancy was carried to term and the child is obviously not affected by MPS II.     

Intrauterine mediastinal teratoma associated with non-immune hydrops fetalis

We describe a rare case of non-immune hydrops fetalis caused by mediastinal teratoma. The sonographic appearance was that of a mixed cystic and solid mass in the antero-superior mediastinum. The teratoma, on post mortem, extended cranially to the upper part of the thyroid, exerting pressure and causing deviation of the trachea, oesophagus, and aortic arch. The pathogenesis of non-immune hydrops fetalis suggests obstruction of venous return caused by this tumour.     

Temporal changes in Ohio amniocentesis utilization during the first twelve years (1972–1983), and frequency of chromosome abnormalities observed

The history of amniocentesis utilization in the seventh largest state of the United States is documented from its inception in 1972 through the first half of 1984. Amniocentesis utilization ratios for Ohio residents aged ⩾35 have increased from 0.21 per cent (19/9091) in 1972 to 23.4 per cent (1655/7531) in 1983, representing an average annual growth rate of 43.1 per cent. Of the amniocenteses performed from January 1, 1978–July 1, 1984, 71 per cent were referred for advanced maternal age (⩾35), 15 per cent for maternal anxiety (30–34), 10 per cent for family history or previous child with a genetic defect, and 4 per cent for other reasons. Between 1978-1983 utilization by women 45 years of age was only 20 per cent higher than women 35 even though their risk of giving birth to a Down syndrome child was about one order of magnitude higher. In addition, various factors were tested as to whether they affected utilization of amniocentesis by women ⩾35 during 1978 1983. A strong correlation of +0.89 existed between county population size and utilization ratios. No difference in utilization was found between whites and nonwhites, regardless of county population size. When utilization ratios were compared separately between Protestants, Catholics and other religions in Ohio's most populated county, no statistical differences were found. From 1978–July 1, 1984, the frequency of all cytogenetically abnormal chromosome results observed in Ohio amniocenteses to women ⩾35 was 2.48 per cent (187/7536). Of these, 2.15 per cent (162/7536) had unbalanced karyotypes. Future maximum amniocentesis utilization for women ⩾35 is estimated at 60–70 per cent.     

Polymerase chain reaction analysis of the cystic fibrosis ΔF508 mutation in human blastomeres following oocyte injection of a single sperm from a carrier

The efficiency of the polymerase chain reaction (PCR) in detecting the cystic fibrosis (CF) ΔF508 mutation (which is the most common mutation of CF) was assessed in single human blastomeres. Twenty-one human immature oocytes (germinal-vesicle-stage oocytes) that had been donated for research were matured in vitro and a single spermatozoon from a carrier of the CF ΔF508 mutation was injected into the ooplasm. Fourteen embryos were obtained after intracytoplasmic sperm injection (ICSI). PCR analysis was carried out on 70 single blastomeres isolated from these 14 embryos. The results showed that the efficiency of DNA amplification by PCR in single nucleate blastomeres was 94 per cent (59/63). There were no false-positive results since none of the blank samples or the blastomeres without a nucleus showed an amplified signal. We found that nine embryos were homozygous for the unaffected genotype and that four embryos were heterozygous since they contained both the unaffected and the ΔF508 genotype. In a four-cell embryo, we observed the homozygous unaffected genotype in one blastomere and a heterozygous ΔF508/unaffected genotype in the other three blastomeres.