Amniotic-Fluid Acetylcholinesterase and Neural-Tube Defects

Dale, Gordon; Bonham, James R.; Lowdon, P.; Roberts, D. F.

doi:10.1016/s0140-6736(79)91300-x

Cited by 22 publications

(8 citation statements)

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“…Milunsky et a1 (1979) argued in favour of the measurement of total cholinesterase and suggested a radio-chemical method. We agree that total cholinesterase, the sum of AChE and nonspecific cholinesterase ('pseudocholinesterase'), will separate the majority of normal pregnancies from those affected by NTD (Dale et al, 1979); unfortunately, blood contamination can considerably affect the results because the nonspecific cholinesterase activity of plasma is very high. Since something like one-third of amniotic fluid samples are contaminated with blood (Davies et al, 1979), a more specific assay for AChE is needed.…”

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confidence: 71%

“…It effectively separates normal pregnancies from those with open NTD. A preliminary report (Dale et al, 1979) showed that elevated levels of AChE were associated with NTD pregnancies and that maternal blood did not appear to affect the assay materially. However, some of the samples examined had been stored for long periods at -20°C and it was thought desirable to compile a normal reference range based on fresh samples and to examine a variety of abnormal pregnancies.…”

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confidence: 99%

“…THE measurement of amniotic fluid acetylcholinesterase (AChE) as a means of antenatal detection of open neural tube defect (NTD) has much to commend it. The enzyme is characteristically associated with nervous tissue and, as might be expected, its activity is increased in the amniotic fluid of pregnancies affected by open NTD (Smith el al, 1979;Dale et al, 1979). The assay should be considered as a possible alternative to the measurement of alpha-fetoprotein (AFP).…”

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confidence: 99%

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Diagnosis of Neural Tube Defects by Estimation of Amniotic Fluid Acetylcholinesterase

Dale

Archibald

Bonham

et al. 1981

BJOG

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Summary Acetylcholinesterase (AChE) activity in amniotic fluid was assayed directly by a reaction rate method at 30°C using acetylthiocholine iodide as substrate and ethopropazine as a safe ‘pseudo’ cholinesterase inhibitor. Fresh samples from 101 normal pregnancies of 14–24 weeks gestation had a mean AChE activity of 2.56 u/1 (SD 1.10). Elevated levels of AChE were found in association with open spina bifida (5.5–20.4 u/1), anencephaly (10‐2‐19‐5 u/1), exomphalos (2.7–15.6 u/1), intrauterine death (30.2–59.3 u/1) and Turner's syndrome (36.4 u/1) but not with closed spina bifida or rhesus isoimmunisation. When AChE activity was expressed as a percentage of the total cholinesterase activity (‘percentage AChE’), there was a good correlation between AChE activity and‘percentage AChE’in normal pregnancies and the values associated with the 37 pregnancies affected by open neural tube defects (NTD) fell outside the 99.9 per cent confidence limits of the normal group. Qualitative differences in cholinesterase activity could be demonstrated between the groups with exomphalos and open NTD. It is suggested that the assay might be used satisfactorily to demonstrate the presence of open NTD in affected pregnancies.

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confidence: 71%

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confidence: 99%

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confidence: 99%

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Diagnosis of Neural Tube Defects by Estimation of Amniotic Fluid Acetylcholinesterase

Dale

Archibald

Bonham

et al. 1981

BJOG

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“…Subsequent studies have confirmed this raised AChE activity in aganglionic versus ganglionated bowel [13,66], and quantitative AChE assay has been shown to correspond with the histological increase in AChE staining [6,8,12,19,82], suggesting its possible diagnostic use. Wells and Addison [102] suggested that at a level greater than 10 RU, AChE was of significant predictive value in rectal suction biopsy material.…”

Section: Cholinesterase Activity In Aganglionic Tissuementioning

confidence: 90%

“…Possibly more significant was the proportion of AChE increase relative to the BChE activity (the AChE:BChE ratio) in affected intestinal segments [9,12,66]. Our own studies [66] showed that the expression of AChE activity as a percentage of the nonspecific cholinesterase activity (47.15% and 78.75% in normally innervated and aganglionic tissue, respectively; Fig.…”

Section: Cholinesterase Activity In Aganglionic Tissuementioning

confidence: 99%

Acetylcholinesterase in Hirschsprung?s disease

Moore

Johnson

2005

Ped Surgery Int

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The association between the congenital absence of colonic ganglion cells and an increased acetylcholinesterase (AChE) expression in the affected tissue is of diagnostic importance in Hirschsprung's disease (HSCR). Investigation of AChE's function in development may also help unravel some of the complex pathophysiology in HSCR. Normal nerves do not stain for AChE, but increased AChE expression is associated with the hypertrophied extrinsic nerve fibres of the aganglionic segment in HSCR. Although a high degree of histochemical diagnostic accuracy exists, results are not always uniform, and false positives and false negatives are reported. False negative results are primarily related to age, and an absence of AChE reaction does not exclude HSCR in neonates within the first 3 weeks after birth. AChE staining results may lack uniformity, resulting in a number of technical modifications that have been made to improve standardization of AChE staining. At least two distinct histological patterns are described, types A and B. The interpretation of increased AChE staining patterns in ganglionated bowel at the time of surgical pull-through remains a problem in patients with HSCR. The development of rapid staining techniques has helped to identify normal ganglionated bowel with greater certainty. The presence of fine AChE neurofibrils in the ganglionated segment has contributed to the debate surrounding intestinal neuronal dysplasia. Quantitative assay of cholinesterase activity confirms the pattern of histochemical staining. AChE is particularly increased in relation to butrylcholinesterase, with one molecular form, the G4 tetrameric form, predominating. It is likely that the raised levels of AChE in aganglionic tissue are the transcriptional consequence of the abnormalities in signalling molecules that characterize HSCR. Evidence suggests that this AChE is functioning in a nonenzymatic capacity to promote cell adhesion and differentiation and that the hypertrophied nerves and neurofibrils may be the result of this increased AChE expression.

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A prospective study of amniotic fluid cholinesterases: Comparison of quantitative and qualitative methods for the detection of open neural tube defects

Wyvill¹,

Hullin²,

Elder³

et al. 1984

Prenatal Diagnosis

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The value of quantitative and qualitative methods of cholinesterase (ChE) analysis in the detection of open neural tube defect (NTD) has been assessed in a prospective survey of 1495 mid-trimester amniotic fluids. Using a quantitative method the mean ChE values were much lower in fluids from pregnancies of normal outcome but it was not possible to discriminate these fluids completely from those associated with NTD pregnancies, particularly when the specimens were contaminated with blood. Similarly, measurement of acetylcholinesterase (AChE) activity alone by three different methods also failed to eliminate the overlap between the two groups. In contrast, polyacrylamide gel electrophoresis revealed only a single band of ChE activity in 1408 out of 1410 fluids from pregnancies with a normal outcome whilst amniotic fluids from all 60 cases of open NTD, 6 out of 7 cases of exomphalos and 3 out of 4 cases of intra-uterine death gave the characteristic second faster-running AChE band. A qualitative gel method which requires the same amount of ChE activity to be loaded from each amniotic fluid is an effective method for pre-natal diagnosis of NTDs.

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Amniotic-Fluid Acetylcholinesterase and Neural-Tube Defects

Cited by 22 publications

References 6 publications

Diagnosis of Neural Tube Defects by Estimation of Amniotic Fluid Acetylcholinesterase

Diagnosis of Neural Tube Defects by Estimation of Amniotic Fluid Acetylcholinesterase

Acetylcholinesterase in Hirschsprung?s disease

A prospective study of amniotic fluid cholinesterases: Comparison of quantitative and qualitative methods for the detection of open neural tube defects

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