The value of acetylcholinesterase (AChE) analysis as an adjunctive test to amniotic alpha fetoprotein (amAFP) for the diagnosis of fetal abnormality has been investigated in a series of 3785 amniotic fluid samples. Quantitative analysis of AChE performed retrospectively on a selected group of 541 amniotic fluid samples failed to discriminate between normal and open neural tube defect pregnancies. Qualitative analysis of AChE by polyacrylamide gel (PAG) electrophoresis in the same series of 541 fluids correctly identified 251 of the 255 pregnancies with open neural tube defect and 29 of the 31 pregnancies with false positive amAFP results. The failure of the test to diagnose 4 cases of open neural tube defect was probably attributable to the age and condition of the stored AF samples. Routine diagnostic testing of AChE isoenzymes in a further 3244 AF samples successfully identified all 170 cases of open neural tube defect and 20 cases with other fetal defects. Thirteen fluids gave false positive AChE results (0.4 per cent) compared to 59 of the series in which there were false positive amAFP results (1.8 per cent). Six of the 13 false positive AChE cases had AChE bands of low intensity which would not be regarded as diagnostic of fetal abnormality, and in five the AChE band may have been the result of significant blood contamination. False positive AChE results contributed to the decision to abort three apparently normal fetuses, but a normal AChE result undoubtedly helped to save a number of pregnancies with false positive amAFP results. Our experience suggests that repeating the amniocentesis may help in resolving the rare diagnostic difficulty of a positive AChE result with or without an elevated amAFP in the absence of ultrasound evidence of fetal abnormality, particularly where there is blood contamination of the amniotic fluid sample.

Abdominal Muscles↗

PubMedDate not supplied

Amniotic band disruption syndrome associated with elevated amniotic AFP and normal acetylcholinesterase gel test.

Ultrasonography in an 18 week pregnancy selected for detailed scanning because of a single elevated maternal serum AFP result suggested the presence of anencephaly. Amniocentesis at 19 weeks yielded a clear AF with an elevated AFP result (5.4 MOM) and no evidence of an acetylcholinesterase band of neural origin on PAG electrophoresis. At termination, the fetus had cephalo-amniotic fusion and multiple abnormalities including bilateral cleft lip and palate and digital amputations characteristic of the amniotic band syndrome. The cranial defect was completely sealed by attachment of the amniotic surface of the placenta to the skull.

Acetylcholinesterase↗

PubMedDate not supplied

Microvillar enzyme analysis in amniotic fluid and the prenatal diagnosis of cystic fibrosis.

The activities of two microvillar enzymes, gamma-glutamyltranspeptidase (GGTP) and alkaline phosphatase (ALP) have been determined in amniotic fluid (AF) samples from 39 pregnancies with a 1-in-4 risk of cystic fibrosis. Seventeen of these were investigated prospectively. A reduced proportion of the fetal specific intestinal ALP isoenzyme was found in 7 of a total of 13 pregnancies with cystic fibrosis and in one pregnancy of confirmed normal outcome. Eight of the affected pregnancies were tested for AF GGTP activity and depressed levels were found in 15. None of the 3 liveborn cystic fibrosis cases in the prospective series was identified by the ALP assay although 2 had significantly reduced GGTP activity. There were several amniotic fluid samples from cases of cystic fibrosis, trisomy 18 and normal outcome which had discordant GGTP and ALP results. Four of the 6 cases of cystic fibrosis misclassified by the ALP assay had amniocentesis at 15 or 16 weeks gestation. Evidence is presented which confirms a previous suggestion that amniocentesis after 17 weeks gestation improves the predictability of the ALP isoenzyme assay for the prenatal diagnosis of cystic fibrosis.

Alkaline Phosphatase↗

PubMedDate not supplied

Alphafetoprotein and alphafetoprotein receptor expression in the normal human placenta at term.

Alphafetoprotein (AFP) is detectable in maternal serum from around six weeks of gestation and is synthesised by the yolk sac and the fetal liver. The role of the placenta in the transport and possible synthesis of AFP is uncertain. The aim of this study was to investigate placental expression of AFP and the AFP receptor in uncomplicated pregnancies at term. Immunohistochemistry and Western blotting clearly demonstrated the presence of AFP in villous tissue at term. However, evidence of AFP mRNA expression or synthesis of AFP was not found following reverse transcription polymerase chain reaction of total RNA isolated from villous tissue and trophoblast cell cultures. The presence of a cell surface receptor for AFP in placental villous tissue, identified by immunohistochemistry and Western blotting, suggests a possible receptor-mediated mechanism for placental transport of AFP while the patterns of expression of AFP and its receptor may indicate a possible route by which AFP is transported across the placenta between the fetal and maternal circulations. These findings demonstrate that the placenta does not synthesise AFP at term and that the presence of AFP in the placenta is a reflection of transplacental transport of AFP possibly via a receptor-mediated mechanism.

Adult↗

PubMedDate not supplied

Placental synthesis of oestriol in Down's syndrome pregnancies.

In the second trimester, oestriol is synthesized in the placenta and secreted into the maternal circulation. 16alpha-hydroxy dehydroepiandrosterone sulphate (16alpha-OH-DHEAS) is formed in the fetal liver by hydroxylation of dehydroepiandrosterone sulphate (DHEAS) and transported to the placenta where it undergoes desulphation by steroid sulphatase (STS) and aromatization to oestriol. Maternal serum levels of unconjugated oestriol (UE3) are lower in Down's syndrome pregnancies than in unaffected pregnancies in the second trimester. The underlying cause of this variation was investigated in placenta, fetal liver, maternal serum and amniotic fluid from Down's syndrome pregnancies by measuring the levels of UE3, DHEAS and STS in appropriate tissues and in corresponding samples from unaffected pregnancies. UE3 levels, expressed as multiples of the control median at the appropriate gestation (MOM), were lower in placental tissue (0.52 MOM), maternal serum (0.65 MOM) and amniotic fluid (0.61 MOM) than in unaffected pregnancies. There was a significant correlation between placental and maternal serum levels of UE3 in the Down's syndrome cases. The median STS activity in placental tissue from Down's syndrome pregnancies (1.14 MOM) was not significantly different from that of the control pregnancies (1. 01 MOM), suggesting that placental turnover of the fetal precursor DHEAS is not reduced. However, levels of DHEAS were reduced in maternal serum (0.69 MOM), placental tissue (0.54 MOM) and fetal liver (0.65 MOM) from Down's syndrome pregnancies. Thus, a diminished supply of the fetal precursor DHEAS may be the cause of the decreased placental production of UE3 in Down's syndrome pregnancies in the second trimester.

Arylsulfatases↗

PubMedDate not supplied

Placental and maternal serum inhibin-A and activin-A levels in Down's syndrome pregnancies.

The objective of this study was to analyse the levels of inhibin-A and activin-A in maternal serum and placental tissue from Down's syndrome (DS) pregnancies. Inhibin-A and activin-A levels were determined by specific immunoassays and individual results were expressed as multiples of the control median (MoM) at the appropriate gestation. Immunohistochemistry was used to localize inhibin alpha and beta(A)-subunits in a selection of placental sections. In DS pregnancies, median inhibin-A levels were found to be significantly elevated to 1.46 MoM (P< 0.05) in placental extracts, and 2.06 MoM (P< 0.0001) in maternal serum, when compared with uncomplicated pregnancies. Median activin-A MoMs were also elevated in placental extracts and maternal serum to 1.62 MoM (P< 0.01), and 1.26 MoM (P< 0.05), respectively. Immunohistochemistry revealed that the alpha subunit of inhibin-A and the beta(A)subunit of inhibin-A and activin-A were mainly localized to the trophoblastic layer of placental villi. Semiquantitative studies of staining intensity revealed a trend towards stronger staining of placental trophoblasts and stroma of DS tissues, although this was statistically significant only for beta(A)subunit staining of trophoblasts (P< 0.05). These results support the hypothesis that maternal serum levels of inhibin-A and activin-A are elevated due to increased production in the placenta, and increased immunostaining of trophoblasts suggests that this may be due to increased production in the trophoblasts.

Activins↗