First-trimester prenatal diagnosis in quintuplets: A practical approach using step-by-step embryo reduction

A multiple pregnancy of high rank may occur in a couple at risk for a Mendelian disorder. Prenatal diagnosis is hampered by the difficulty of (1) obtaining chorionic villi from each zygote arid (2) unequivocally relating each sample to the corresponding embryo. The calculation of the genetic risk according to the number of zygotes led us to propose a diagnostic strategy based on embryo reduction, a technique initially designed to improve the perinatal outcome of multiple pregnancies with normal embryos. We report a case in which this approach allowed rational use of first-trimester chorionic villus sampling in a quintuplet pregnancy at risk for non-ketotic hyperglycinaemia, resulting in the selective birth of unaffected twins.     

A fetus with a parvovirus B19 infection and congenital anomalies

A fetus with multiple structural defects was seen at prenatal ultrasound examination. After termination of the pregnancy a bilateral cleft lip, alveolus, and palate; micrognathia; and webbed joints were seen. Fetal tissues showed indications of infection, intranuclear inclusion bodies, chronic stress, haemolysis, arterial wall damage, and profuse haemorrhage. Parvovirus B19 DNA was detected in fetal tissues by dot hybridization after polymerase chain reaction. The possibility of parvovirus B19 infection leading to congenital malformations is discussed.     

Congenital nephrosis in low-risk pregnancies

Congenital nephrosis is an autosomal recessive disorder requiring neonatal renal transplant for survival. The postnatal diagnosis rests upon the electron microscopic evaluation of the epithelial foot processes and basal membrane of the glomeruli. The prenatal diagnosis can be suspected in the presence of a positive family history with an amniotic fluid (AF) alpha-fetoprotein level greater than 5 standard deviations (SD) above the population mean accompanied by a negative AF acetylcholinesterase, absent haemoglobin F, and an unremarkable fetal sonographic examination. We reviewed our series of seven cases of congenital nephrosis fulfilling the above criteria; four cases had negative family histories, and in two cases the diagnosis of congenital nephrosis was further supported by the presence of elevated AF albumin concentrations. We conclude that (1) the prenatal diagnosis of congenital nephrosis is feasible in a low-risk population, and (2) an elevated AF albumin concentration may represent an additional marker for the diagnosis of congenital nephrosis, even though false-negative results have been reported.     

Prenatal diagnosis of spinal muscular atrophy in Russia

Ninety-two families with spinal muscular atrophy (SMA) applied for genetic counselling and further prenatal diagnosis. To minimize expenses, only one tightly linked informative marker was determined in the course of preliminary examination, and non-radioactive allele detection was preferably used. Four prenatal diagnoses of SMA type I, four of SMA type II, and one of SMA type III were made. This trial programme shows the considerable requirements, importance, and potential effectiveness of prenatal prediction of SMA in Russia.     

Prenatal sonographic diagnosis of intracranial haemorrhage: Report of a case with a sinusoidal fetal heart rate tracing,and review of the literature

The sinusoidal fetal heart rate pattern has been described in association with severe fetal anaemia, with fetal hypoxaemia, and with the administration of parenteral narcotics. Here, we report a case of decreased fetal movement in which a sinusoidal tracing was recorded. The sonographic diagnosis of a massive fetal intracranial haemorrhage was made. A non-interventive approach was taken and the fetus died soon after in utero. We review 28 previous cases in which the prenatal sonographic diagnosis of fetal intracranial haemorrhage was made, including the underlying maternal and fetal factors and neonatal outcomes. We propose that the sinusoidal tracing in this case was due to the intracranial bleed and suggest that fetal intracranial haemorrhage be considered in the sonographic evaluation of the fetus with a sinusoidal pattern.     

Prenatal diagnosis in two cases of de novo complex balanced chromosomal rearrangements. Three-year follow-up in one case

We report two cases of apparently balanced complex de novo chromosomal rearrangements (BCCR) detected prenatally at 17 weeks and 10 weeks of gestation, respectively. Chromosomes were studied using GTG-banding and fluorescent in situ hybridization (FISH). In one case four chromosomes and in the other case three chromosomes were involved in the rearrangements. One of the pregnancies was terminated and no external or internal abnormalities were detected at autopsy. The other pregnancy continued to term. Level III ultrasound examination showed no abnormalities. The child is now 3 years old and has neither congenital anomalies nor evidence of delayed psychomotor development.     

Prenatal diagnosis of Freeman–Sheldon syndrome (whistling face)

The diagnosis of Freeman–Sheldon syndrome was made by ultrasonographic evaluation of a 20-week fetus with a positive family history. The ultrasonographic features were abnormalities of the extremities and mouth.     

Early prenatal diagnosis of an infratentorial arachnoid cyst: Association with an unbalanced translocation

Arachnoid cysts are an uncommon central nervous system malformation, representing only 1 per cent of all intracranial masses. We report the second-trimester prenatal diagnosis of a posterior fossa arachnoid cyst, associated with an unbalanced X;9 translocation.     

Attitudes to prenatal screening,diagnosis and research among pregnant women who accept or decline an alpha-fetoprotein test

The aim of the study was to describe the opinion of pregnant women who had accepted or declined an alpha-fetoprotein (AFP) test, not only on AFP screening in general, but also on whether every pregnant woman should be offered amniocentesis (AC)/chorionic villus sampling (CVS) and an ultrasound scan for fetal malformations. An additional aim was to describe pregnant women's attitudes concerning continued research in the prenatal field. The study was performed as a questionnaire study in two regions over a 1-year period from 1 October 1988 to 30 September 1989. Results are based on answers from 3331 women who had taken an AFP test and 336 women who had declined the offer of a test. A total of 79 per cent of the women thought that an AFP test, 70 per cent that an ultrasound scan for fetal malformations, and 26 per cent that AC or CVS should be offered to all pregnant women. Fifty-nine per cent of the women were positive towards continued research in the prenatal field. Women who had had an AFP test were generally much more positive towards screening and research than women who had declined, who were generally against. Women who had left school without a high school degree were on average more positive towards the screening issues than women who had this degree. In conclusion, the results obtained in this study strongly suggest that women's attitudes are very dependent on how the prenatal screening programme is already organized in their local area.     

Flow sorting of fetal erythroblasts using intracytoplasmic anti-fetal haemoglobin: Preliminary observations on maternal samples

Monoclonal antibody to fetal haemoglobin (a₂γy₂) has been proposed as a fetal-specific reagent. We developed an intracellular staining protocol that combines fluorescein isothiocyanate or phycoerythrin conjugated anti-γ with the DNA binding dye Hoechst 33342 to identify and flow sort fetal erythroblasts from maternal blood. Our preliminary observations on anti-γ-positive cells sorted from four different pregnant women are described here, using fluorescence in situ hybridization (FISH) with chromosome-specific probes to identify fetal cells. Our data demonstrate that far fewer candidate fetal cells are sorted with this protocol than by current cell surface staining methods that employ the monoclonal antibody CD71. This results in increased fetal cell sorting purities. With this protocol, standard FISH techniques require modification due to the rigorous fixation with 4 per cent paraformaldehyde. Our initial data indicate the promise of this approach.