Exclusion of citrullinaemia in the first trimester of pregnancy by direct assay of argininosuccinate synthetase in chorionic villi

Citrullinaemia was presumed to be excluded in a fetus at risk by the direct assay of argininosuccinate synthetase in chorionic villi. The diagnosis was confirmed after amniocentesis by normal argininosuccinate synthetase activity in the cultured amniotic fluid cells and by a normal citrulline concentration in the amniotic fluid. The prediction of a normal fetus was confirmed at term by the birth of a non-citrullinaemic boy.     

Maternal age specific rates for chromosome aberrations and factors influencing them: Report of a collaborative european study on 52 965 amniocenteses

Maternal age specific rates for all major chromosome aberrations have been determined in 52 965 pregnancies in mothers 35 years of age and over at the time of amniocentesis. Rates increase exponentially with advancing maternal age for trisomies 21, 18 and 13, and for the XXX and XXY syndromes, but in the autosomal trisomies this rise appears to be followed by a levelling off at the upper end of the age range. A significant inverse relationship with maternal age is found for 45,X cases. It is postulated that these various patterns are the result of the interaction of three principal factors: a maternal age effect acting particularly on first meiotic nondisjunction: a higher spontaneous abortion rate with advancing maternal age for aneuploid as compared to euploid conceptions; and an increased probability of spontaneous abortion before the time of amniocentesis for conceptions with more extensive chromosome imbalance. A stepwise logistic regression analysis of 13 299 pregnancies in which both parental ages are known shows that the father's age does not influence these maternal age specific rates, with the possible exception of the 47,XXY syndrome.     

Adult-onset GM2 gangliosidosis diagnosed in a fetus

Amniocentesis and subsequent tests are reported on a fetus conceived of a rare mating type: its mother has an intermediate level of β hexosaminidase A (HEX A), characteristic of carriers of Tay-Sachs disease (TSD), while the father suffers from an adult-onset GM₂ ganglio-sidosis (AOG) with severe HEX A deficiency. Activity of HEX A in the cultured fetal cells was very low when measured by the heat-inactivation method, thus showing the typical biochemical phenotype of TSD fetuses. However, upon separation of HEX isozymes by ion exchange chromatography, residual HEX A (17 per cent of total HEX) was demonstrated. Also in contrast to TSD fetuses, this fetus' fibroblasts were able to synthesize the precursor of a chains of HEX, and ultrastructural examination of its brain revealed few atypical lamellar bodies, unlike those found in TSD fetuses of the same gestational age. It is therefore concluded that the fetus was not affected with TSD, but rather with AOG.     

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.     

First-trimester diagnosis of duodenal stenosis associated with oesophageal atresia

Duodenal stenosis associated with oesophageal atresia was diagnosed by ultrasound at 12 weeks' gestation. The diagnosis was made by recognition of a double bubble sign which was more pronounced when a vaginal transducer was used. Post-abortion autopsy confirmed the diagnosis. Oesophageal and duodenal obstruction in this case had no effect on the amount of amniotic fluid or the alpha-fetoprotein concentration since swallowing and subsequent utilization of amniotic fluid do not occur before 12 weeks of gestation.     

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.     

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.     

First-trimester prenatal diagnosis of aspartylglucosaminuria

Fetal aspartylglucosaminuria (AGU) was studied during the first trimester of pregnancy in six at-risk pregnancies using chorionic villus samples. The activity of aspartylglucosaminidase (AGA) was high in five cases, indicating an unaffected fetus. This was confirmed through delivery of healthy newborns with a normal pattern of urinary oligosaccharides. Low enzyme activity in an uncultured biopsy specimen and in cultured amniotic fluid cells in one case demonstrated that the fetus was affected. The pregnancy was terminated and the prenatal diagnosis was confirmed by showing reduced AGA activity in cultured fibroblasts of the fetus.