Szabó M

Prenatal diagnosis of cystic fibrosis by trehalase enzyme assay in amniotic fluid

Amniocentesis and amniotic fluid trehalase enzyme assay were offered to 14 pregnant women at a 1 in 4 risk for a child with cystic fibrosis. Twelve of these pregnancies were screened at the 18th week of gestation; ten proceeded to term, seven following the finding of a normal trehalase activity and three despite the low enzyme level in amniotic fluid. In all ten cases prenatal diagnosis proved to be correct. In two cases with low enzyme activity parents opted for termination at the 19th week, and with PAS‐Alcian Blue staining some slight histochemical lesions characteristic of cystic fibrosis were seen in the exocrine glands, including the pancreas and intestinal mucosa, of both fetuses. The total protein content in the meconium of these fetuses was significantly higher than in the controls.

Early prenatal diagnosis of cystic fibrosis by ultrasound.

Sirs, We have recently shown that trehalase assay in the amniotic fluid is a potential prenatal test for cystic fibrosis (Szabo et al. 1984, 1985) and that in fetuses with cystic fibrosis slight deviations can be observed on histochemical and biochemical study as early as the 17th week of gestation (Szab6 et al. 1985, Szeifert et al. 1985). We have also demonstrated fetal meconium ileus by ultrasound at the 28th week of gestation by dilated intestinal lumens and unusual intensive echogenic abdominal mass which was associated with cystic fibrosis detected by low trehalase activity in amniotic fluid at the 18th week (Szabo et al. 1985). When we realized that meconium ileus was detectable by ultrasonography, we decided to perform careful real-time scanning of the fetal abdomen at the time of the amniocentesis performed in pregnancies at a 1 in 4 risk of cystic fibrosis. Until now five pregnancies have been monitored by ultrasound in addition to the amniotic fluid enzyme assay. In four cases both enzyme activities and ultrasound findings were normal, and these pregnancies proceeded to term. All resulted in children not affected with cystic fibrosis. However, in a pregnancy at a 1 in 4 risk of cystic fibrosis, ultrasound examination (Picker LS 2000) showed an echo-rich unusual mass in the fetal abdomen at the 15th gestational week. The trehalase enzyme activity in the amniotic fluid sample taken by transabdominal amniocentesis was low (0.443 U/g). The amniotic fluid was unusually viscous and of greenish colour. Two weeks later the dense echogenic area was more evident by ultrasound (Fig. 1). The couple refused a further amniocentesis and requested termination. Abortion was induced and the female fetus weight, 170 g, was autopsied two hours after delivery. The large intestine of the fetus contained inspissated meconium closely attached to the mucosa and this caused wide dilation of the crypts and flattening of the lining epithelial cells (Szeifert et al. 1985). More recently we also scanned a case of fetal meconium peritonitis. A 24-year-old patient was referred to our genetic counselling clinic because of polyhydramnios at the 24th week of her first pregnancy. The scan-

Maternal Age-Dependent and Sex-Related Changes of Gestational Serum Alpha-Fetoprotein

Maternal serum alpha-fetoprotein (MSAFP) concentration values were measured in relation to maternal age and fetal sex in the 16th to 20th gestational weeks in samples taken from 9,556 pregnancies with the outcome of live, mature and healthy infants. Our results show positive significance between MSAFP concentration and maternal age (p < 0.001); we also found significantly higher AFP values in male fetuses than in female fetuses (p < 0.001). This specificity is by all probability due to the change in the physiologic AFP concentration of the pregnant woman. Considering maternal age and the new percentile AFP values, cut-off concentration values can be corrected, thus the quality of routine AFP screening can be improved. At the same time, with the application of the above parameters, a more effective selection of pregnancies at high risk for Down syndrome can be achieved.

Ventriculomegaly with radial and renal defects: Prenatal diagnosis in two consecutive sibs

We describe two consecutive mid-trimester fetuses of different sexes with identical anomalies of the upper limbs and the kidneys in association with severe ventriculomegaly. We compare this apparently autosomal recessive syndrome to VACTERL-H association, Fanconi anemia, and two other, so far unparalleled syndromes. Taking into account the absence of chromosome breaks, the associated changes of the amniotic fluid, and the renal histology, we conclude that we are dealing with a different entity.

Morphology of cystic fibrosis at 17 weeks of gestation

Sirs, We have recently shown that some histological and biochemical abnormalities can be observed in fetuses with cystic fibrosis at 19 weeks of gestation (Szabo et al. 1985). More recently we diagnosed a case of fetal cystic fibrosis by low amniotic fluid trehalase enzyme activity and by ultrasound at an even earlier stage of gestation (Papp et al. 1985), and we present here the morphological changes found in the fetus. In a pregnancy at a 1 in 4 risk of cystic fibrosis, ultrasound at the 15th gestational week showed an echo-rich unusual mass in the fetal abdomen. The trehalase enzyme activity in the amniotic fluid sample taken by transabdominal amniocentesis was low (0.443 U/g) (Szabo et al. 1984, 1985). The amniotic fluid was unusually viscous and of greenish colour. Two weeks later the dense echogenic area was more evident by ultrasound. The couple refused a further amniocentesis and requested termination. The abortion was induced using 100 ml of 0.1 % Rivanol solution injected transcervically into the extra-amnia1 area, with an oxytocin drip infusion the following day. The female fetus weighed 170 g and was autopsied two hours after delivery. Dissected samples from various tissues were fixed in 8% formaldehyde-ethanol solution for 48 h, dehydrated in graded alcohols, and embedded in paraffin. The 5 pm sections were stained with Alcian blue-PAS (pH 2.9). The most obvious alterations were found in the intestinal tract. There was intensive goblet cell hyperplasia with strongly alcianophilic mucinous material in the lumen, and the bulging goblet cells seemed to crowd out the intervening columnar epithelium in some places (Fig. l a and lb). Otherwise the small intestinal villous and microvillous architecture seemed to be normal. The large intestine was inspissated with dense meconium closely attached to the mucosa and this caused wide dilatation of the crypts and flattening of the lining epithelial cells (Fig.

Amniotic fluid microvillar enzyme activity in fetal malformations

Prenatal diagnosis of cystic fibrosis based on amniotic fluid microvillar enzyme activity assay has become routine practice in the past few years. Normal (median) values of these enzymes were determined in 177 normal healthy pregnancies between 15–20 gestational weeks and were related to enzyme values measured in 50 pregnancies complicated with congenital malformations, 6 monogenic inherited diseases and 4 chromosomal aberrations. It is concluded that increased trehalase activity has diagnostic importance in detecting fetal kidney diseases, and radial‐renal syndrome (with elevated GGT activity), while low enzyme activities may indicate chromosomal aberrations (with no signs of intestinal obstruction). With the collection of further data, the analysis of these enzymes might provide an opportunity to set up diagnostic procedures for the detection of other, non‐CF‐related cases.