Elevated Amniotic Fluid Alpha-fetoprotein Research Articles

Routine measurement of amniotic fluid alpha-fetoprotein and acetylcholinesterase: the need for a reevaluation

The objective of the study was to evaluate whether the current screening regimen of measuring amniotic fluid alpha-fetoprotein (AF-AFP) at the time of amniocentesis and reflex acetylcholinesterase testing vs ultrasound alone to detect neural tube and ventral wall defects offers improved diagnostic accuracy and cost benefit. A retrospective chart review on all patients who had amniocentesis performed at 1 center over the past 11 years was performed. Those with an elevated AF-AFP were compared with those whose AF-AFP was within normal limits. Ultrasound findings and outcomes were reviewed in all cases to assess whether neural tube defects (NTDs) or ventral wall defects (VWDs) were missed by AF-AFP or ultrasound screening. A cost-benefit analysis was then performed. Of 6232 women who underwent amniocentesis between January 2002 and December 2012, 81 had an elevated AF-AFP with or without a positive acetylcholinesterase (AChE). Of these 81 women, 13 had NTDs and 5 had VWDs. The sensitivity of the detailed ultrasound was 100% in detecting NTDs and VWDs, whereas that of the AF-AFP ranged from 22% to 77%, with the inclusion of AChE. The total expenditure for AF-AFP in our sample set (n = 6232 amniocentesis at $76.00 per AF-AFP) was $473,632, and all NTDs and VWDs were detected by ultrasound. Translated to a national laboratory (>42,447 samples/year), the cost savings in 2011 alone would be $3,225,972. Given the accuracy of high-resolution ultrasound in the detection of both NTDs and VWDs, measuring AF-AFP and AChE as a reflex-screening test is not a cost-effective approach.

The importance of investigating for uniparental disomy in prenatally identified balanced acrocentric rearrangements

We report the finding of paternal isodisomy for chromosome 14 in a fetus found to have a der(14;14)(q10;q10) by amniocentesis. The pregnancy was complicated by severe polyhydramnios and elevated amniotic fluid alpha-fetoprotein (AFP). The infant showed features consistent with paternal uniparental disomy (UPD) including postnatal growth retardation, poor respiratory function, feeding difficulties, and evidence of hypertrophic cardiomyopathy. The present case, in addition to other reported cases of UPD involving balanced acrocentric rearrangements, supports testing for UPD in prenatally detected Robertsonian translocations and isochromosomes.

A reappraisal of amniotic fluid alpha-fetoprotein measurement at the time of genetic amniocentesis and midtrimester ultrasonography.

To evaluate the contemporary utility of amniotic fluid alpha-fetoprotein measurement as a complementary test for fetal abnormalities at the time of invasive genetic testing. A review of amniotic fluid alpha-fetoprotein test results was conducted to determine the frequency with which elevated alpha-fetoprotein values added independent diagnostic information and altered clinical management. Amniotic fluid specimens processed for alpha-fetoprotein between 1995 and 1998 were included. Elevated alpha-fetoprotein cases were classified as either incidental to the fetal abnormality diagnosed or central to the identification of a fetal anomaly on the basis of whether an ultrasonographic examination had already identified the anomaly before amniocentesis. The costs associated with alpha-fetoprotein testing were used to estimate the expenditure per pregnancy in which elevated alpha-fetoprotein values would add discriminatory diagnostic value. A hypothetical national cost model was constructed to explore the utility of selective rather than routine amniotic fluid alpha-fetoprotein measurement. Eighty-two (3%) of 2769 amniotic fluid alpha-fetoprotein values were elevated. In only 1 instance was the elevated result found to be partially discriminatory (e.g., an established diagnosis of microcephaly with an associated small encephalocele identified after the elevated amniotic fluid alpha-fetoprotein value prompted repeated ultrasonographic assessment). Sixty-one other neural tube defects were detected by ultrasonography alone (myelomeningocele, n = 28; anencephaly, n = 24; and encephalocele, n = 9). Thus, an elevated alpha-fetoprotein result added diagnostic precision in only 1 (0.036%) of 2769 cases. Cost estimates suggested that routine amniotic fluid alpha-fetoprotein assessment resulted in a $219,000 expenditure per informative case. Routine measurement of amniotic fluid alpha-fetoprotein during amniocentesis may not be warranted in centers with expertise in targeted ultrasonographic imaging.

Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein

To compare the prognostic values of unexplained elevated amniotic fluid alpha-fetoprotein (AF AFP > or = 2.0 multiples of the median [MoM]) and unexplained elevated maternal serum alpha-fetoprotein (MSAFP > or = 2.5 MoM). We accessed a data base containing the results of MSAFP screening tests, genetic amniocenteses, and pregnancy outcome data on all women undergoing second-trimester genetic amniocentesis from October 1988 through August 1994. After excluding all patients whose elevated AFP levels had any identifiable cause (positive AF acetylcholinesterase, AF blood contamination, fetal malformation or aneuploidy, multiple gestation, etc), 5743 cases were analyzed. Relative risks (RR) for selected pregnancy complications were determined. Elevated MSAFP, with any AF AFP, was associated with fetal growth restriction (RR 2.5, 95% confidence interval [CI] 1.4-4.4), stillbirth (RR 3.5, 95% CI 1.4-8.3), preeclampsia (RR 2.8, 95% CI 1.1-7.0), and preterm delivery (RR 2.8, 95% CI 2.3-3.4). Elevated AF AFP, with any MSAFP, was associated with preeclampsia (RR 4.4, 95% CI 2.0-10.0) and preterm delivery (RR 1.7, 95% CI 1.3-2.4). Elevation of both AF AFP and MSAFP was associated with preterm delivery (RR 4.0, 95% CI 2.8-5.7). When elevated AF AFP was found in association with a normal MSAFP, the RR to develop preeclampsia was 4.6 (95% CI 1.9-11.2). Maternal serum alpha-fetoprotein is a better predictor of late pregnancy complications than AF AFP. However, unexplained elevated AF AFP appears to be especially predictive of preeclampsia.

A multidirectional sonographic approach to elevated amniotic alpha-fetoprotein or positive acetylcholinesterase

To evaluate the combined transvaginal and transumbilical ultrasonographic approach in cases of elevated amniotic fluid (AF) alpha-fetoprotein (AFP) and/or acetylcholinesterase in the second trimester. Nine pregnant women with normal sonographic results were referred because of elevated AF AFP and/or acetylcholinesterase and screened using a transvaginal and transumbilical 6.5-MHz ultrasound transducer. All women were at 17–21 weeks' gestation. The fetal skull and the vertebral column were scanned in both perpendicular and tangential planes for maximal exploitation of the axial resolution of the transducer, in both directions and in two to three planes. Despite increased AF AFP and/or present acetylcholinesterase, no fetal malformation was detected in any of the nine cases. Open neural tube defects were not detected by the diagnostic technique. All nine women were delivered of term healthy neonates without malformations. Our preliminary data suggest that targeted sonographic screening combining transvaginal and transumbilical approaches may reliably rule out an open neural tube defect larger than 0.3 mm. This may influence the decision-making process when termination of pregnancy is considered in cases of high AF AFP and/or positive acetylcholinesterase.

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.

Elevated levels of amniotic fluid alpha-fetoprotein: sonographic evaluation.

From 1978 to 1990, 263 fetuses with an elevated level of amniotic fluid alpha-fetoprotein (AF-AFP) (> 2.0 multiples of the median) were examined with targeted fetal sonography. All cases of AF-AFP elevation among 22,355 genetic amniocenteses were represented. Sonography correctly showed 32 open neural-tube defects, including 20 myelomeningoceles, and depicted 94% (63 of 67) of the anomalous fetuses. Two of five anomalous fetuses with normal sonograms, however, had extremely high AF-AFP levels leading to prospectively correct diagnoses of congenital nephrosis. Therefore, programmatically, 97% (65 of 67) of the anomalous fetuses were recognized. The three programmatic misdiagnoses were all detected in the neonatal period and surgically corrected; subsequent development was normal. The combination of an elevated AF-AFP level and a detailed sonogram allowed distinction between a normal and an anomalous fetus in 99% of cases. When elevated levels are noted, AF-AFP analysis followed by detailed sonography is highly successful for the detection and characterization of anomalous fetuses and the recognition of normal fetuses with physiologic increases of this protein in the amniotic fluid.

A Co-Twin Fetus Papyraceus as a Cause of Elevated AFP and Acetylcholinesterase in the Amniotic Fluid of the Normal Co-Twin

An elevated amniotic fluid alpha-fetoprotein (AF-AFP) level together with a positive acetylcholinesterase (AChE) band is strongly predictive of neural tube defect (NTD) in the fetus. We report such results in a pregnancy in which the fetus was found to be normal after termination. Among the placental fragments was found a sac containing a prenatally undetected co-twin fetus papyraceus. We suggest that pregnant women with such laboratory results but lacking sonographic evidence of NTD should have a high-level untrasonographic investigation, as well as a thorough pathologic examination of both placenta and fetus in cases of termination.

Prenatal ascertainment of triploidy by maternal serum alpha‐fetoprotein screening

We report our experience in ascertaining fetal triploidy during routine maternal serum alpha-fetoprotein (MSAFP) screening. Three cases were identified after elevated MSAFP tests. Two of the three had normal amniotic fluid alpha-fetoprotein (AFAFP). The third had amniocentesis too late for AFAFP interpretation. Three additional cases were detected by amniocentesis without prior MSAFP screening and none had an elevated AFAFP. A literature review revealed eight triploid fetuses detected as a result of an elevated MSAFP. Of the five with AFAFP quantitation, only one had an abnormal value and the elevation was minimal. In these 14 cases from our own and other reports, ultrasound findings of placental and fetal abnormalities were often noted, but a pattern diagnostic of triploidy was not present. We conclude that, for optimal prenatal detection of triploidy, fetal karyotyping should be included when an amniocentesis is performed for elevated MSAFP.

Elevated alpha-fetoprotein and a normal fetal sonogram: association with placental abnormalities

This report documents the outcome of 25 pregnancies with elevated serum alpha-fetoprotein levels on two separate samplings despite normal anatomic appearance of the fetus on a detailed "consultative" sonographic examination. Six of these also had elevated amniotic fluid alpha-fetoprotein. All fetuses in this series were anatomically normal at time of delivery; one aborted fetus was triploid. Of the 25 pregnancies, 16 had sonographically demonstrable placental hemorrhage, eight retroplacental and eight subchorionic. One had hydropic changes in the placenta associated with triploidy. Of the subgroup of six pregnancies in which both serum and amniotic fluid values were elevated, one had a retroplacental hemorrhage, one had a subchorionic hemorrhage, and one had diffuse hydropic changes in the placenta. A control group of 112 patients with normal alpha-fetoprotein levels yielded four with small (less than 2 cm3) subchorionic hemorrhage. The occurrence rate of placental hemorrhage in women with elevated alpha-fetoprotein and normal fetus was 64%, whereas the control group of patients with normal alpha-fetoprotein had a 3.6% occurrence rate of placental hemorrhage. Sonographically detectable placental abnormalities may be associated with elevated alpha-fetoprotein in serum and/or amniotic fluid samples. Such abnormalities may occur because of fetomaternal admixture associated with placental hemorrhage and/or intraamniotic bleeding resulting from subchorionic hemorrhage.

Biamnial elevated alpha‐fetoprotein and positive acetylcholinesterase in twins, one with anencephaly

Anencephaly in twin B was accompanied by elevated amniotic fluid alpha-fetoprotein (AFP) and a positive acetylcholinesterase (AChE) band on gel electrophoresis in both twin sacs, although twin A was normal. AChE results did not help distinguish the false positive AFP in this set of twins, implying that AChE may diffuse transamniotically as has been previously postulated for AFP. In light of the low concordance rate for neural tube defects in twins, patient counselling in this situation must include the information that AFP and AChE may be falsely elevated in normal twin when the other twin has a neural tube defect.

Placental chorioangioma: a rare cause of elevated amniotic fluid alpha-fetoprotein.

Journal of Ultrasound in MedicineVolume 5, Issue 4 p. 221-222 Case Reports Placental chorioangioma: a rare cause of elevated amniotic fluid alpha-fetoprotein. D A Willard, D A Willard Department of Radiology, West Virginia Universty Hospitals, Inc., Morgantown, West VirginiaSearch for more papers by this authorJ B Moeschler, J B Moeschler Department of Maternal and Child Care, Dartmouth Hitch cock Medical Center. Hanover, New Hampshire Formerly of the Department of Genetics, West Virginia University Hospitals, Inc., Morgantown , West VirginiaSearch for more papers by this author D A Willard, D A Willard Department of Radiology, West Virginia Universty Hospitals, Inc., Morgantown, West VirginiaSearch for more papers by this authorJ B Moeschler, J B Moeschler Department of Maternal and Child Care, Dartmouth Hitch cock Medical Center. Hanover, New Hampshire Formerly of the Department of Genetics, West Virginia University Hospitals, Inc., Morgantown , West VirginiaSearch for more papers by this author First published: 01 April 1986 https://doi.org/10.7863/jum.1986.5.4.221Citations: 7AboutPDF 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.Citing Literature Volume5, Issue4Apr 1986Pages 221-222 RelatedInformation

Pathological pregnancies. Results of amniotic fluid studies and fetal outcome.

Late amniocenteses (greater than 20 weeks' gestation) were performed in 114 pregnancies with no a priori genetic risk, but referred because of abnormal clinical and/or ultrasound findings suggesting fetal malformations. Reasons for referral included polyhydramnios (51 cases), oligohydramnios (15 cases), fetal growth retardation (FGR) (16 cases) and abnormal fetal ultrasound findings excluding anencephaly (32 cases). In 42 of these cases, referral was motivated by a combination of the above abnormal findings. When polyhydramnios was the sole anomaly (25 cases), 5 fetuses were malformed (20%), abnormal fetal karyotype and/or elevated amniotic fluid alphafetoprotein (AFP) were demonstrated in 2 cases. Oligohydramnios was the sole anomaly in one case; the infant died of prematurity. Fetal growth retardation was the sole anomaly in 14 cases, 11 otherwise normal newborns were small for date, 2 died at birth and 1 was malformed (1/14, 7%). In this group all fetal karyotypes were normal and in 2 cases amniotic fluid AFP were increased. In the 32 pregnancies without abnormal amniotic fluid volume and/or FGR and with fetal malformation(s) suggested by ultrasound, all malformations except one (ovarian cyst possibly ruptured during birth) were confirmed at birth, amniotic fluid AFP was elevated, and/or karyotype was abnormal in 6 cases. In 42 pregnancies where more than one alarm sign was present, abnormal karyotype and/or elevated amniotic fluid AFP level were recorded in 21 of the 39 cases where amniocentesis was performed, 33 fetuses were malformed (79%) and 13 died in the perinatal period (31%). The high incidence of abnormal results of amniocentesis found in this survey of pathological pregnancies, particularly in those with multiple alarm signs, emphasizes the need for amniocentesis in these situations.

Sonography, a complementary examination to alpha-fetoprotein testing for fetal neural tube defects.

Neural tube defects (NTDs) are among the most common congenital anomalies in the United States, with an estimated prevalence of 16 per 10,000 births. The measurement of amniotic fluid alpha-fetoprotein (AF-AFP) concentration has been used to detect NTDs since the early 1970s. When the AF-AFP concentration is elevated, ultrasonography is commonly used to confirm the presence of a NTD. In this study, patient charts, amniocentesis records, and ultrasound reports from a three-year period were reviewed. The 97 fetuses identified as being at high risk for NTDs were divided into four groups: those with high AF-AFP concentrations (Groups 1 and 2, with from 3 to 5 standard deviations (SD) above the mean and with more than 5 SD above the mean, respectively): those referred from other institutions because of suspicious sonographic results (Group 3); and those at risk because of a previous sibling with a NTD (Group 4). Ultrasonography was 100 per cent sensitive and 100 per cent specific in diagnosing NTDs. Thus, in pregnancies with an elevated AF-AFP concentration, ultrasonography can reliably identify normal fetuses as well as differentiate between those with NTDs and those with other congenital anomalies. Also, since AF-AFP concentrations decline after 20 weeks' gestation, ultrasonography may be a better test than a repeat amniocentesis in equivocal cases of AF-AFP elevation.

Alphafetoprotein (AFP), concanavalin A non-reactive AFP and specific acetylcholinesterase in amniotic fluid from pathological pregnancies. Predictive values for open spina bifida

Alphafetoprotein (AFP) and concanavalin A non-reactive alphafetoprotein determination and the acetylcholinesterase (AchE) qualitative test have been performed on amniotic fluid samples from 33 normal pregnancies, 44 pregnancies with fetal malformations and 8 normal pregnancies with elevated amniotic fluid alphafetoprotein (3 false positive AFP results, 5 contaminations with fetal blood). The validities of these three tests in detecting abnormal pregnancies are compared. The usefulness of the existing complementary tests in the detection of neural tube defects in a low neural tube defect incidence area is discussed. Risk figures for open spina bifida according to the prior risk situation and the results of maternal serum AFP, amniotic fluid AFP, AchE qualitative test and ultrasound examination have been calculated.

Sonography as a procedure complementary to alpha-fetoprotein testing for neural tube defects.

Forty-four fetuses were studied sonographically because of an elevated amniotic fluid alpha-fetoprotein level noted during routine amniocentesis, questionable findings during an ultrasound examination at another institution, or a history of a neural tube defect in prior pregnancy. Eleven neural tube defects, 16 non-neural tube defect anomalies, and 17 normal fetuses were all correctly identified by sonography. Ultrasound answers the need for a second diagnostic tool to complement the alpha-fetoprotein measurement.

Prenatal diagnosis of neural tube defects: predictive value of AF-AFP in a low-risk population.

Amniotic fluid alpha-fetoprotein (AF-AFP) determinations were performed on 1,215 women who were at low risk for fetal neural tube defects and who were undergoing mid-trimester amniocentesis for cytogenetic indications, primarily age-related aneuploidy. Maternal sera obtained before amniocentesis and amniotic fluids were assayed in duplicate for alpha-fetoprotein by radioimmunoassay. Of the 1,215 low-risk women, eight (0.7%) had significant elevations of AF-AFP (greater than or equal to +5 SD). In none of the cases was the elevation associated with a fetal neural tube defect. Two cases with elevated AF-AFP were associated with chromosome aberrations; one with impending fetal demise; one with fetal blood contamination; and one case was due to a laboratory error. In one case, no source for the elevated AFP was found, and a normal infant was delivered at term. In the final two cases, the cause of the elevated AF-AFP was a fetal abdominal wall defect (one gastroschisis and one omphalocele). The predictive value of an elevated AFP varies with the population screened, and is reduced by routine ultrasonography before amniocentesis, which at least identifies anencephaly. In a low-risk population, an elevated AF-AFP is most often not associated with a fetal neural tube defect. Because of the low predictive value and the nonspecificity of AF-AFP, genetic counselors should reconsider the recommendation of routine AF-AFP in low-risk maternal populations.

Alpha-fetoprotein and albumin in experimentally-induced exencephaly in the rat.

Alpha-fetoprotein and albumin were quantified in the sera and amniotic fluids from control, Vitamin A-treated non-exencephalic and Vitamin A-treated exencephalic rat fetuses. Exencephaly was associated with amniotic fluid alpha-fetoprotein concentrations which were significantly elevated over those of Vitamin A-treated non-exencephalic and of untreated fetuses. Amniotic fluid albumin concentrations also were higher in the exencephalic fetuses than in the non-exencephalic fetuses. Serum alpha-fetoprotein and albumin concentrations were lower in the exencephalic than in the non-exencephalic fetuses. The results are cosistent with simple diffusion across a defective barrier as the cause of elevated amniotic fluid alpha-fetoprotein concentrations in the presence of open neural tube defects. This experimental model of neural tube defects result in changes in amniotic fluid alpha-fetoprotein similar to those changes found in human amniotic fluid alpha-fetoprotein concentrations in the presence of neural tube defects.

Sounding board: Antenatal diagnosis, alpha fetoprotein and the FDA.

Elevated amniotic fluid alpha fetoprotein (AFP) levels have been associated with neural tube defects and may be associated with fetal death, omphalocele, and congenital nephrosis. AFP levels determined in 2694 cases where amniotic fluid samples were obtained for routine antenatal genetic studies resulted in the detection of 9 cases (1 in 300) of open neural tube defects. Thus AFP determination is important in every second trimester amniotic fluid sample obtained. However, the U.S. Food and Drug Administration (FDA) banned the commercial distribution of serologic reagents for AFP testing in 1973, thereby limiting availability of AFP assays to a few large centers. The FDA should establish criteria to license AFP reagents immediately so that they may be available for routine use.

The molecular nature of alpha-fetoprotein in anencephaly and spina bifida

The origin of elevated amniotic fluid alpha-fetoprotein (AFP) concentrations in central nervous system malformations has been investigated. From immunodiffusional, immunoelectrophoretic and heat stability studies there is no evidence for an altered molecular form of the protein, nor is there evidence for increased fetal synthesis of a normal protein. It is suggested that the most plausible explanation is leakage of AFP from fetal serum and cerebrospinal fluid through the lesion in open central nervous system malformations.