Alkaline phosphatase activity in amniotic fluid in pregnancies with fetal disorders

Alkaline phosphatase (ALP) activity was determined in 255 amniotic fluid samples collected by amniocentesis between 15 and 39 weeks of gestation. The samples were originally used for chromosomal analysis and/or alpha-fetoprotein measurements. The mean ALP activity in early amniotic fluid from pregnancies with fetal trisomy 18 and 21 syndromes was half of that found in the controls. Highly elevated ALP activity (over 10 times the median level) was found in 14 samples. Two of these pregnancies had normal outcome. Three samples were from pregnancies with intrauterine fetal death. Fetal disorders, including abdominal wall defect (four cases), Meckel's syndrome (two), hydrops fetalis syndrome (two) and genital anomaly (one), were observed in nine cases. Moderately elevated ALP activity (over three times the median) was found in 10 cases, including five pregnancies with a preterm labour shortly after the sample collection. The results indicate that elevated ALP activity in the third trimester amniotic fluid is often associated with fetal disorders.     

False-positive amniotic fluid acetylcholinesterase analysis in the third trimester

Thirty-two third-trimester amniotic fluid samples were studied according to the indication for amniocentesis, result of acetylcholinesterase (AChE) analysis, and outcome, in order to address the issue of the effectiveness of AChE testing late in gestation. The results indicate that third-trimester AChE analysis is less effective than second trimester in distinguishing open neural tube defects (ONTDs) and ventral wall defects (VWDs) from other abnormalities. False-positive results occurred in cases of isolated hydrocephaly (four of seven cases), polyhydramnios, and intrauterine growth retardation (IUGR). Caution is recommended in interpreting third-trimester AChE tests, particularly when neither an ONTD nor a VWD is observed by ultrasound.     

Determination of maternal serum acetylcholinesterase in pregnancies with fetal neural tube defects

We have investigated the occurrence of acetylcholinesterase (AChE) (E.C.3.1.1.7) in fetal serum, amniotic fluid and maternal serum using an immuno-chemical assay-technique employing both polyclonal and monoclonal antibodies. Fetal serum had increased amounts of AChE, which is due to an increase in the 10.5S form of the enzyme. This form was also found in amniotic fluids of pregnancies with a fetal neural tube defect (NTD), but not in normal amniotic fluid. The increase in amniotic fluid AChE was however, not reflected in the maternal serum.     

The association between ‘faint-positive’ amniotic fluid acetylcholinesterase and fetal malformations

The finding of a ‘faint-positive’ acetylcholinesterase band in amniotic fluid samples of women at 15 weeks' gestation or above is associated with an increased risk of fetal abnormalities, most commonly gastroschisis. This finding warrants a targeted sonographic evaluation, in order to rule out significant fetal malformations.     

Normal second-trimester amniotic fluid alphafetoprotein and acetylcholinesterase associated with fetal sacrococcygeal teratoma

Amniocentesis was performed at 19 weeks' gestation on a patient with two sequential serum alphafetoprotein values above 2 times median. Ultrasound examination suggested a possible sacrococcygeal teratoma. However, both amniotic fluid alphafetoprotein and acetylchol-inesterase were normal, and the patient elected to continue her pregnancy. At 24 weeks fetal demise was confirmed, and prostaglandin induction of labour produced a macerated female fetus with a large sacrococcygeal teratoma.     

Glial fibrillary acidic protein in amniotic fluids from pregnancies with fetal neural tube defects

The glial fibrillary acidic protein (GFAP) is the subunit protein of intermediate filaments in astrocytes and closely related cell types. By means of an enzyme immunoassay we have determined the concentration of GFAP in amniotic fluids from normal pregnancies and from pregnancies complicated by various fetal malformations. The group of 20 cases of fetal anencephaly had a significantly higher mean amniotic fluid GFAP concentration (115 μg/1±133.6 (S.D.), range 6–378 μg/1) than the control group of 117 normal pregnancies (13 μg/1k±5.5 (S.D.), range 0–31 μg/1), (P<0.001). Two cases of fetal encephalocele likewise had very high amniotic fluid GFAP concentrations. None of the other cases of fetal malformations investigated, including 12 cases of spina bifida, had increased amniotic fluid GFAP concentrations. We conclude that determination of the amniotic fluid GFAP concentration may give additional information in the prenatal diagnosis of fetal nervous system malformations.     

Sacrococcygeal teratoma: Prenatal diagnosis with elevated alphafetoprotein and acetylcholinesterase in amniotic fluid

A sacrococcygeal teratoma was suspected by ultrasound examination at 24 weeks gestation. The amniotic fluid alphafetoprotein was markedly elevated, as was maternal serum AFP. Gel electrophoresis of amniotic fluid showed an acetylcholinesterase band. Labour began at 25 weeks gestation and the chromosomally normal male fetus was found to have a sacrococcygeal teratoma equal to three-quarters of the weight of the fetus.     

Discriminant analysis for assessing the value of amniotic fluid microvillar enzymes in the prenatal diagnosis of cystic fibrosis

We have analysed the sensitivity, specificity, and reliability of biochemical diagnosis based on microvillar membrane enzyme assay and using discriminant analysis in amniotic fluid samples obtained from 54 pregnancies at high risk for cystic fibrosis and 125 normal pregnancies. Our results show that amniotic fluid trehalase, alkaline phosphatase, alkaline phosphatase isoenzymes and gamma-glutamyltransferase enzyme activities measured during 16–20 gestational weeks, in spite of their non-specificity for cystic fibrosis, have a very good predictive value for fetal cystic fibrosis or exclude the possibility of the disease. Overall enzyme activity analysis provided over 90 per cent reliability of the method.     

The synaptic membrane D2-protein in amniotic fluid from pregnancies with fetal neural tube defects

The D2-protein is a neuronal membrane protein which has an immunochemically detectable soluble derivative in cerebrospinal fluid. We used rocket-on-line immunoelectrophoresis with an antiserum against rat synaptosomal membranes for demonstration of the human D2-protein in fetal cerebrospinal fluid and in amniotic fluids from pregnancies with fetal neural tube defects. D2 was neither found in normal amniotic fluids nor in cases of amniotic fluids from pregnancies with other malformations. Analysis of D2 in amniotic fluids may thus have a future role in the antenatal diagnosis of fetal neural tube defects.     

Prenatal diagnosis of citrullinemia: Elevated levels of citrulline in the amniotic fluid in the three affected pregnancies

In three pregnancies at risk for citrullinemia affected fetuses were predicted both by strongly increased levels of citrulline in the amniotic fluid and by the reduced incorporation of ¹⁴C-citrulline into TCA-precipitable material in cultured amniotic fluid cells. The prenatal diagnoses of affected fetuses were confirmed after termination of the pregnancies by direct and indirect assays of argininosuccinate synthetase in the fetal livers and fibroblasts respectively. Measurement of the citrulline concentration in amniotic fluid appears to be a valuable adjunct in the prenatal diagnosis of citrullinemia.     

Prenatal diagnosis of the fragile X syndrome using fetal blood and amniotic fluid

Nineteen pregnancies at risk for the Martin–Bell syndrome have been monitored during the second trimester for the presence of the fragile Xq27. Of the 19 potential carrier mothers, 14 showed the presence of the fragile X in their lymphocytes at a level of 4 per cent or above. As one was a twin pregnancy, fetal blood was obtained at fetoscopy from 20 fetuses and amniotic fluid obtained simultaneously from 19 of them. Of the 20 fetuses, 18 were males (including both of the twins) and two were females. Of these 18 males, seven were found to carry the fragile Xq27 in lymphocytes and subsequently six of the seven were terminated. The diagnosis was confirmed in five of the six terminated fetuses (the sixth case was a patient whose pregnancy was terminated abroad) and also in a full-term male baby. Five of the seven males without the marker X who came to term had their karyotypes confirmed post natally. Of the two female fetuses one was found to be a carrier of the fragile X and the other was not. Both babies had full-term deliveries and both had their karyotypes confirmed post natally. In some cases the diagnosis made in fetal lymphocytes was confirmed later in amniocytes.     

False-negative amniotic fluid acetylcholinesterase in a case of meningo-encephalocele

We describe a patient with a significantly elevated serum alphafetoprotein (AFP) concentration at 17 weeks of gestation, who showed only a marginally increased amniotic fluid AFP and lacked the second rapidly migrating band of acetylcholinesterase electrophoresis. Ultrasound examination revealed an encephalocele and ventriculomegaly. Autopsy showed that the encephalocele was not covered by skin.