Amniotic Fluid Acetylcholinesterase Research Articles

Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test. The basic screening methodology was described in the late 1970s and screening programs were active a few years later. By identifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% of anencephaly can be identified as early as 16 weeks gestation. The interpretation of msAFP levels is complicated by the need to consider multiple factors such as gestational age, maternal weight, maternal race, multiple gestations, and more. Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification of the lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosis is made, options include termination, surgery after delivery, or in utero surgery, depending on factors such as location and size of the defect, and the presence of any additional anomalies. Screening for ONTD should be performed as part of a comprehensive program linking primary obstetrical care providers, laboratorians, and high-risk clinicians.

Current Selection Criteria and Perioperative Therapy Used for Fetal Myelomeningocele Surgery.

To determine the current maternal and fetal selection criteria and operative approaches used at centers performing fetal myelomeningocele surgery. The 17 principal investigators participating in the Fetal Myelomeningocele Consortium were asked to participate in an anonymous online survey regarding the current practice of maternal-fetal surgery for neural tube defect repair and results were tabulated. The 35-question survey related to diagnostic testing, inclusion and exclusion criteria, and clinical management. Sixty-five percent (11/17) of principal investigators responded to the survey and not all centers responded to all 35 questions. All centers continue to use magnetic resonance imaging in their preoperative evaluation. Diagnostic testing from amniocentesis is varied: 5 of 11 (45%) require amniotic fluid α-fetoprotein, 4 of 10 (40%) amniotic fluid acetylcholinesterase, and 8 of 11 (73%) DNA microarray. There is also variation from the Management of Myelomeningocele Study with regard to body mass index (BMI) (1/11; 9% would offer surgery with BMIs higher than 35), maternal medical risk factors (surgery would be offered for controlled pregestational diabetes [3/10 (30%)]), hepatitis C with negative viral load (4/11 [36%]), and human immunodeficiency virus with an undetectable viral load (1/10 [10%] or an obstetric history [3/11 (27%)] would offer surgery with a history of preterm delivery on progesterone). Ten of 11 (91%) centers did not consider ventriculomegaly of 18 mm and 9 of 11 (82%) centers did not consider lack of leg movement as an exclusion criteria. Nuances in the perioperative and intraoperative management were also reported, including 5 of 11 (45%) use intraoperative echocardiography and alterations in postoperative tocolytics. Variation in practice patterns for offering and performing maternal-fetal surgery for myelomeningocele repair exists among centers. Ongoing evaluation of inclusion and exclusion criteria as well as operative techniques is warranted to ensure continued safety, effectiveness, and beneficence.

Neural Tube Defects Cannot Be Diagnosed Prenatally by Electrophoresis of Amniotic Fluid Transferrin Isoforms

Prenatal diagnosis of neural tube defects (NTDs) is based on ultrasonography; but uncertainty exists in a few cases, and biochemical analysis of amniotic fluid (AF) is required. Electrophoresis of AF acetylcholinesterase is a specific and sensitive method for diagnosis of myelomeningocele (1)(2). Although false-positive results are rare, another biochemical technique would be of great value. Adult and infant cerebrospinal fluid (CSF) is characterized by a specific marker, asialotransferrin or β2-transferrin, because it migrates more slowly in electrophoresis than β1-tetrasialotransferrin, the main isoform in all biological fluids (3). The specific behavior of β2-transferrin is used for the detection of CSF leakage from the subarachnoid space into the nasal or aural cavity (4)(5). Assuming that CSF would leak from a myelomeningocele-affected fetus into the AF, we screened AF …

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories *

Prevention of Neural Tube Defects by Periconceptional Use of Folic Acid

Prevention of Neural Tube Defects by Periconceptional Use of Folic Acid

Amniotic fluid alpha-fetoprotein determination at the time of genetic amniocentesis: has it outlived its usefulness?

The purpose of this retrospective study was to evaluate the utility of routine measurement of amniotic fluid alpha-fetoprotein levels at the time of second trimester genetic amniocentesis (mean gestational age, 17.3 weeks +/- 2.5 weeks standard deviation; median, 16.8 weeks; range, 15 to 22 weeks). During the study period 7174 patients underwent second trimester genetic amniocentesis. Outcome data were available in all cases. In 79 (1.1%) cases the amniotic fluid alpha-fetoprotein level was > or = 2.0 multiples of the median. Thirty-three of the 79 (42%) patients had normal ultrasonograms, and in 31 of 33 (94%) the amniotic fluid alpha-fetoprotein level was between 2.0 and 3.0 multiples of the median. Forty-six of the 79 (58%) patients had abnormal ultrasonographic findings, and of these, 82% were neural tube defects, abdominal wall defects, or cystic hygromas. Acetylcholinesterase was positive in 37 cases, all of which had abnormal ultrasonographic findings. None of the fetuses with negative findings on sonographic screening had detectable abnormalities at birth. In this study, with over 7000 patients, amniotic fluid alpha-fetoprotein and acetylcholinesterase levels did not increase the detection of fetal abnormalities. On the basis of these results, routine measurement of amniotic fluid alpha-fetoprotein level at the time of routine genetic amniocentesis (15 to 22 weeks) does not appear justified.

Faint and positive amniotic fluid acetylcholinesterase with a normal sonogram

OBJECTIVE: Both faint and positive amniotic fluid acetylcholinesterase determinations have been associated with fetal abnormalities. We evaluated the effect of a normal sonogram and positive or faint acetylcholinesterase level on the risk for anomalies. STUDY DESIGN: Between Jan. 1, 1989, and Feb. 1, 1995, 4859 amniocenteses were performed. Twenty-three cases of abnormal acetylcholinesterase determinations combined with normal sonograms were identified, and pregnancy outcomes were determined. RESULTS: One abnormal karyotype was identified (45,X/47,XXX mosaic). No neural tube defects were seen in infants with an abnormal acetylcholinesterase determination and normal sonogram. One fetus of a twin pregnancy had a ventral wall defect that was not detected on ultrasonography. Seventy-three percent of infants were normal at birth, but 27% of the pregnancies had abnormal outcomes. CONCLUSIONS: Advances in ultrasonography have led to improved detection of fetal abnormalities. With a normal karyotype, repeat invasive testing may not be necessary. (Am J Obstet Gynecol 1996;175:1000-3.)

Are routine alpha-fetoprotein and acetylcholinesterase determinations still necessary at second-trimester amniocentesis? Impact of high-resolution ultrasonography

To audit routine measurement of alpha-fetoprotein (AFP) and acetylcholinesterase in amniotic fluid (AF) samples obtained at second-trimester amniocentesis. We reviewed retrospectively 1737 consecutive AF specimens obtained for cytogenetic evaluation over a 4-year period and routinely assayed for AFP and acetylcholinesterase. In all instances, high-resolution ultrasonography was performed before amniocentesis. Details of pregnancy outcome of all cases with AF AFP levels greater than 2.0 multiples of the median and a positive or faint acetylcholinesterase band were obtained. There were 31 abnormal results (1.8%, 1 of 56). Of these, 25 cases had elevated AF AFP and/or positive acetylcholinesterase. Ultrasonography correctly identified all 18 fetuses with anomalies associated with abnormal levels of these biochemical markers, including open neural tube defects and/or anterior abdominal wall defects (17 cases) and fetal hydrops (one). In the remaining seven, no fetal anomalies were detected, and all neonates were structurally normal after birth. In addition, six pregnancies with faint acetylcholinesterase and normal AF AFP showed no fetal abnormalities at ultrasonographic examination and post-delivery. High-resolution ultrasonography was more accurate than AF biochemistry in the detection of congenital anomalies associated with elevated AFP levels and acetylcholinesterase in the AF. Routine measurement of these biochemical markers in AF samples obtained for cytogenetic analysis appears to have a very low yield and would therefore not be cost-effective in practices where high-resolution ultrasonography is performed before amniocentesis.

Scanning Gel Densitometry of Amniotic Fluid Acetylcholinesterase and Butyrylcholinesterase: Quantification of ‘Faint-Positive’ Bands in Fetal Malformations

The quantification of 'faint-positive' cholinesterases in amniotic fluid was performed in 40 patients with positive acetylcholinesterase (AchE) tests. Fetuses with anencephaly and open spina bifida presented an AchE/butyrylcholinesterase (A/B) ratio of more than 0.3 with clearly dense bands. Fetuses with gastroschisis showed a 'faint-positive' AchE band (A/B < 0.3). In 5 fetuses (1 teratoma, 3 open spina bifida, 1 unaffected) we found faint AchE and butyrylcholinesterase bands.

The psychiatric patient: a challenge for a TIS service

This chapter describes the prenatal diagnosis of open neural tube defects (NTD). Spina bifida and anencephaly, which collectively account for nearly all NTD, are serious fetal malformations resulting from incomplete closure of the neural tube during embryogenesis. The two occur in approximately a 1:1 ratio, and roughly 20% of spina bifida lesions are skin-covered. Mean alpha-fetoprotein (AFP) concentrations in amniotic fluid fall steadily throughout the second trimester, emphasizing the need to document gestational age before interpreting test results. AFP is the major fetal serum protein during the early weeks of pregnancy, occurring in concentrations as high as 300 mg/100 ml at the twelfth week of gestation. It is found that about 40% of anencephalic and 20% of open spina bifida pregnancies are associated with bloodstaining. Brown samples also appear on occasion. These latter rarely have intact red cells but may have detectable hemoglobin F. Rather than being procedure-related, these brown samples are felt to indicate an earlier spontaneous hemorrhage. A report indicates that identification of a specific molecular form of acetylcholinesterase (AChE) in amniotic fluid can be useful both in diagnosing neural tube defects and in identifying false-positive AFP results.

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.

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.

Amniocentesis and chorionic villus sampling

Amniocentesis performed at 16 to 18 weeks' gestation has been the gold standard approach for prenatal cytogenetic diagnosis. Over the past few years, large collaborative studies on chorionic villus sampling have confirmed the safety and efficacy of chorionic villus sampling as a viable alternative for women seeking prenatal diagnosis. While the expanding experience with chorionic villus sampling has answered questions regarding the safety of the transabdominal approach, it has also raised questions concerning possible associations with limb abnormalities, its usefulness in multiple gestations, and the clinical significance of confined placental mosaicism. These issues, as well as the technical and gestational age limitations of chorionic villus sampling, have led many investigators to study the technical feasibility, safety, and accuracy of amniocentesis performed in the first trimester or early second trimester. While this approach appears both safe and efficacious, there are concerns regarding orthopedic abnormalities and the reliability of first-trimester amniotic fluid acetylcholinesterase and alpha-fetoprotein levels in the diagnosis of neural tube defects.

Amniotic fluid acetylcholinesterase is found in gastroschisis but not omphalocele.

Amniotic fluid acetylcholinesterase (ACHE) has been used to evaluate neutral tube defects. It has also been detected in ventral wall defects. However, the role of ACHE to differentiate between omphalocele and gastroschisis has not been established. We examined amniotic fluid ACHE in 16 pregnancies complicated by gastroschisis and 8 by omphalocele. One ruptured omphalocele was excluded. ACHE was negative in all 7 omphaloceles and either positive or suspicious in all gastroschises (chi 2 = 17.3, p < 0.0001). Amniotic fluid ACHE may be useful to differentiate between omphalocele and gastroschisis.

Prenatal biochemical screening for Downʼs syndrome and neural tube defects

Antenatal serum screening for Down's syndrome is now becoming established in many centers throughout the world. The screening method is based on the measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between 15 and 22 weeks of pregnancy. These measurements, used in conjunction with a woman's age, provide risk estimates of having a pregnancy with Down's syndrome for every woman screened. By identifying the 5% of women with highest risk and offering them an amniocentesis, about 60% of Down's syndrome pregnancies can be identified. If an ultrasound scan examination is used routinely to estimate gestational age, the detection rate can be increased by 5% to 10%. Recent information on the distribution of the three serum markers in twin pregnancies and pregnancies with insulin-dependent diabetes mellitus now means that screening can be carried out in such pregnancies. Various other serum markers of Down's syndrome have been reported, but at present they do not have a place in routine antenatal screening for Down's syndrome. The role of amniotic fluid acetylcholinesterase measurement, alone and in combination with amniotic fluid alpha-fetoprotein measurement, in the antenatal diagnosis of open neural tube defects has recently been clarified. The best policy is to perform an amniotic fluid alpha-fetoprotein measurement as the primary test and an acetylcholinesterase determination for those women who have an amniotic fluid alpha-fetoprotein measurement of two times the normal median or greater. The acetylcholinesterase can be measured either by the standard method (gel electrophoresis) or by a new quantitative monoclonal antibody method.

Preparing a positive control for qualitative gel electrophoresis analysis for acetylcholinesterase in amniotic fluid

Preparing a positive control for qualitative gel electrophoresis analysis for acetylcholinesterase in amniotic fluid

Cholinesterases exhibiting aryl acylamidase activity in human amniotic fluid

Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) in human amniotic fluid were estimated in the presence of selective inhibitors. Amniotic fluid cholinesterases (mixture of acetylcholinesterase and butyrylcholinesterase) purified by procainamide-Sepharose affinity chromatography exhibited aryl acylamidase activity which was sensitive to serotonin inhibition (a property of aryl acylamidases associated with both acetyl- and butyrylcholinesterases) and tyramine activation (shown exclusively by aryl acylamidase associated with butyrylcholinesterase). Tyramine activation was unaffected in the presence of the selective acetylcholinesterase inhibitor BW284C51 whereas it was abolished in the presence of the selective butyrylcholinesterase inhibitor ethopropazine, suggesting the presence of both types of aryl acylamidases in amniotic fluid, one associated with acetylcholinesterase and the other associated with butyrylcholinesterase. Butyrylcholinesterase and the associated aryl acylamidase activity in the affinity purified enzyme was selectively immunoprecipitated by a polyclonal antibody raised against human serum butyrylcholinesterase. Estimation of the activity ratio of acetylcholinesterase to butyrylcholinesterase in a few samples of amniotic fluid showed that this could vary depending on the butyrylcholinesterase arising from contaminating blood in the samples. Gel electrophoresis under non-denaturing conditions and enzyme staining showed that butyrylcholinesterase band was detectable on the gel in all the samples whereas acetylcholinesterase band was below detectable levels in normal samples but visible in samples from pregnancies of neural tube defect fetuses. It is suggested that the use of selective cholinesterase inhibitors along with gel electrophoresis and immunoprecipitation studies may be useful in the assessment of cholinesterase activities in human amniotic fluid.

Rapid and sensitive discriminating determination of acetylcholinesterase activity in amniotic fluid with a choline sensor

A simple method for the separate determination of acetylcholinesterase and butyrylcholinesterase activities in amniotic fluid is reported. This determination is performed with an enzyme electrode involving an immobilized choline oxidase membrane associated with the amperometric detection of hydrogen peroxide. Acetylcholine or butyrylcholine, in the presence of samples containing acetylcholinesterase or butyrylcholinesterase are specifically hydrolyzed, the formation of choline being detected vs time by the sensor with no need for a selective inhibitor. The dynamic linear ranges for acetylcholinesterase and butyrylcholinesterase are respectively 100 μU to 10 mU and 30 μU to 3 mU per ml sample.

Ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities

International Journal of Gynecology & ObstetricsVolume 36, Issue 4 p. 347-347 Citations from the literature pregnancy and delivery Ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities AG Rasmussen Loft, AG Rasmussen LoftSearch for more papers by this authorV Mortensen, V MortensenSearch for more papers by this authorJ Hangaard, J HangaardSearch for more papers by this authorB Norgaard-Pedersen, B Norgaard-PedersenSearch for more papers by this author AG Rasmussen Loft, AG Rasmussen LoftSearch for more papers by this authorV Mortensen, V MortensenSearch for more papers by this authorJ Hangaard, J HangaardSearch for more papers by this authorB Norgaard-Pedersen, B Norgaard-PedersenSearch for more papers by this author First published: December 1991 https://doi.org/10.1016/0020-7292(91)90501-UAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume36, Issue4December 1991Pages 347-347 RelatedInformation

Alpha‐fetoprotein and acetylcholinesterase are not predictive of fetal junctional epidermolysis bullosa, Herlitz variant

Junctional epidermolysis bullosa, Herlitz variant (junctional EB-Herlitz) is a lethal autosomal recessive skin disorder currently amenable to prenatal diagnosis only by direct analysis of fetal skin. However, elevated levels of alpha-fetoprotein, as well as the presence of acetylcholinesterase in amniotic fluid, have been associated with other severe fetal genodermatoses. Fetal skin samplings were performed in ten pregnancies at risk for fetal junctional EB-Herlitz, with three fetuses affected on the basis of electron microscopic detection of blisters within the lamina lucida and abnormal hemidesmosomes. In neither affected nor unaffected pregnancies were maternal serum or amniotic fluid alpha-fetoprotein levels elevated. Moreover, alpha-fetoprotein levels in both maternal serum and amniotic fluid were not statistically different comparing affected and unaffected fetuses. Acetylcholinesterase was not present in the amniotic fluid samples of the three affected pregnancies. Unlike other severe fetal genodermatoses, neither alpha-fetoprotein nor acetylcholinesterase was predictive of junctional EB-Herlitz.