Serum PAPP-A levels are depressed in women with fetal Down syndrome in early pregnancy

The value of maternal serum pregnancy-associated plasma protein (PAPP)-A in screening for Down syndrome in early pregnancy was assessed using stored samples. Seventeen cases of Down syndrome and 66 unaffected control pregnancies were studied. The median PAPP-A level in the cases was 0.42 multiples of the expected value in controls (p <0.0001). Eleven cases (65 per cent) had levels less than half the expected value compared with only six controls (9 per cent). A commercial assay kit is now needed so that prospective screening with this marker can begin.     

Expanding multiple marker screening for Down's syndrome to include Edward'S syndrome

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE₃), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10–12 (67–80 per cent) cases with a false-positive rate of 0.3–0.6 per cent depending on the risk cut-off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE₃ and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false-positive rate.     

Prenatal diagnosis of 21-hydroxylase deficiency by rflp analysis of the 21-hydroxylase,complement C4, and HLA class II genes

In 19 pregnancies at risk for 21-hydroxylase deficiency (21OHD) in 18 families with at lea one affected child, prenatal diagnosis was performed by RFLP analysis using the enzymi Taq I and EcoRI and the DNA probes specific for the 21 OH genes, the closely linke complement C4 genes and the highly polymorphic HLA class II genes DRB, DQB, and DPI For fetal DNA analysis either chorionic villi or cultivated amniotic cells were used. In all 1 cases, a clear prenatal diagnosis was possible either with the 21OH probe alone or in mo cases, by combining the results of the different closely linked loci.     

Determinants of parental decisions to abort for chromosome abnormalities

Parental decisions concerning the continuation of pregnancy following prenatal detection of abnormal chromosomes were evaluated for 80 patients whose diagnosis and prenatal counselling were performed in our centre. Twenty-two anomalies were diagnosed by chorionic villus sampling (CVS) and 58 by amniocentesis. The severity of the chromosome anomaly and associated ultrasound findings in the first vs. second trimester were correlated with patients' decisions. No difference was found in the likelihood of parental decisions to interrupt or continue a pregnancy between CVS and amniocentesis for either the‘severe’ or the‘questionable’ group of chromosome anomalies. Ninety-three per cent of patients with severe prognosis and 27 per cent with questionable prognosis opted for pregnancy termination (p <0·0001). The association of ultrasound anomalies and termination was highly significant (p< 0·001). The severity of the chromosome anomaly, and, to a lesser extent, the visualization of anomalies on ultrasound were the major determinants of parental decisions to terminate the pregnancy. The diagnosis of an anomaly in the first trimester was no more likely ito lead to a termination of pregnancy than in the second trimester.     

Dystrophin protein and rflp analyis for fetal diagnosis and carrier confirmation of duchenne muscular dystrophy

A pregnant woman with indeterminate Duchenne muscular dystrophy (DMD) carrier status, but with DMD diagnosed in her deceased brother (unavailable for study), presented for prenatal diagnosis, intending to continue the pregnancy only if proven unaffected with DMD with near absolute certainty. Creatine kinase (CK) assays to clarify carrier status were inconclusive. Male sex in the fetus was identified, but DNA restriction fragment length polymorphism (RFLP) analysis was not yet available to this centre to investigate the possible transmission of the DMD gene, and the pregnancy was terminated. Tissue histology and dystrophin protein analysis demonstrated the absence of DMD. In a situation with proven maternal carrier status, future fetal inheritance of the opposite maternal X chromosome would indicate the presence of DMD. However, maternal carrier status remained in doubt through a second pregnancy, even with RFLP studies, and was finally established when dystrophin analysis confirmed the presence of DMD in the second fetus. Histologic findings are presented, contrasting features in the two fetuses. The value of dystrophin analysis for establishing the diagnosis of fetal DMD, in this case proving maternal carrier status in a difficult situation, and for demonstrating DMD gene:RFLP haplotype relationships is illustrated.     

Continuous subcutaneous insulin infusion (CSII) in pregnant diabetic patients

The efficacy of the insulin infusion pump (CSII) in pregnancy was examined in 12 diabetic patients and compared with intermittent insulin therapy (IIT). In patients poorly controlled on IIT constant and rapid equilibrium was achieved with CSII (mean of glucose levels: CSII versus IIT=84 versus 137 mg/dl; S.D. = 36 versus 63 mg/dl; mean amplitude of glycemic excursion (MAGE)=65 versus 112 mg/dl. In patients well controlled on IIT, CSII led to a reduction in the variation of glucose excursions (S.D.= 29 versus 36 mg/dl; MAGE=48 versus 76 mg/dl). CSII generally produced a reduction of 20–37 per cent of daily insulin dose (in three cases there was an increase of dose with the achievement of glycemic control). Furthermore in CSII treated-patients amniotic glucose, insulin and C-peptide concentrations werefound tobeinthenormalrange(22.1±10.1 mg/dl; 5.2±2.7μ/ml; 1.25±0.71 ng/ml, respectively). All infants were horn at or near-term, had no macrosomia or neonatal problems. It is concluded that CSII is a highly efficient way to achieve normal glucose levels in pregnancy, not only in type I, hut also in type II or gestational diabetes.     

Prenatal ultrasound diagnosis of fetal scoliosis with termination of the pregnancy: Case report

Gross scoliosis of the fetal thoracic spine was diagnosed at 18 weeks gestation. The pregnancy was terminated and the fetus found to have webbing of the neck and an imperforate anus in addition to vertebral defects.     

Service transformation—managing a shift from business travel to virtual meetings

It has been shown that the potential for environmental, and financial improvements through the increased substitution of in-person meetings by virtual communication is considerable. However, it has also been shown that this potential is not automatically realized by investing in the technology that can enable virtual meetings. This paper describes two case studies that explored the factors that influenced communication and meeting behavior. A number of drivers and barriers for virtual meetings are identified, and, in addition, measures are proposed to improve the utilization of virtual tools for business communication.     

Prenatal diagnosis of β-thalassaemia in Mediterranean populations by dot blot analysis with DNA amplification and allele specific oligonucleotide probes

In this study, we describe a simple strategy to detect β-thalassaemia mutations in prospective parents and to make prenatal diagnosis in pregnancies at risk in the Mediterranean population. Screening of prospective parents is carried out by dot blot analysis on enzymatically amplified DNA with a set of oligonucleotide probes complementary to the most common mutations in this population. Prenatal diagnosis is accomplished by the same procedure on enzymatically amplified amniocyte or trophoblast DNA. The main advantages of this procedure are the simplicity, sensitivity (0.05 μg of DNA), and rapidity (12–24 h). Further simplification is obtained by amplification of the DNA from crude amniotic cell lysate. The very low amount of fetal material necessary for this analysis eliminates the need to culture amniotic fluid cells and may decrease the fetal loss rate associated with trophoblast sampling. The number of specific DNA sequences obtained by the amplification procedure allowed us to use non-radioactive labelled oligonucleotide probes, which have several advantages compared to radioactive probes.     

Prenatal diagnosis of Opitz (BBB) syndrome in the second trimester by ultrasound detection of hypospadias and hypertelorism

Prenatal diagnosis in a kindred with the Opitz (BBB) syndrome is presented. The inheritance is consistent with either autosomal dominant inheritance with sex limited expression or X-linked inheritance. The abnormalities in the kindred consist of hypertelorism, hypospadias, ambiguous genitalia, urocolic fistula, imperforate anus, mental retardation, diaphragmatic hernia, and malrotation with volvulus. A male fetus at 19 weeks was found by ultrasound to have hypertelorism and hypospadias with a small phallus consistent with the syndrome. The diagnosis was confirmed by pathologic examination after pregnancy termination. This is the first report of prenatal diagnosis of Opitz syndrome by ultrasonographic demonstration of hypertelorism and hypospadias in the second trimester.