Amniotic Fluid Alpha-fetoprotein Levels Research Articles

Alphafetoprotein levels in amniotic fluid from 8 to 18 weeks of pregnancy.

The aim of this study was to ascertain the normal range of amniotic fluid alphafetoprotein (AFP) levels from 8 to 18 weeks of pregnancy. Amniotic fluid samples obtained by amniocentesis were analysed by radioimmunoassay for AFP. From 8 to 12 weeks, fluid was obtained by transvaginal amniocentesis prior to termination of pregnancy. Samples from 13 to 18 weeks were obtained from amniotic fluid specimens submitted for cytogenetic analysis. A tertiary referral prenatal diagnostic service. Two hundred thirty-seven women between 8 and 18 weeks gestation. High levels of AFP were present in amniotic fluid at 8 weeks (median 83.0 kU/ml), falling rapidly to 11 weeks (median 19.9 kU/ml) (P < 0.01). Levels then rose to a peak at 13 weeks (median 30.7 kU/ml), thereafter falling to 18 weeks. A single coherent view of the levels of AFP from 8 to 18 weeks of pregnancy is presented for the first time. The rapid changes and complex pattern of AFP levels in early pregnancy suggest that interpretation of amniotic fluid AFP levels in the diagnosis of neural tube defects may be more difficult between 8 and 13 weeks of pregnancy than in the second trimester.

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 platelet factor 4 and beta-thromboglobulin as markers of structural abnormalities.

Platelet factor 4 (PF4) and beta-thromboglobulin (BTG) are unique markers of irreversible platelet activation. We measured PF4 and BTG in amniotic fluid from 102 genetic amniocenteses, in which 78 had normal amniotic fluid alpha-fetoprotein (AFP) levels with normal pregnancies, and 24 had high amniotic fluid AFP levels with abnormal pregnancies. PF4 and BTG were significantly higher in the abnormal pregnancy/elevated amniotic fluid AFP group (p < 0.002 in each case) and correlated with AFP expressed as multiples of the median (p < 0.05 and p < 0.0001, respectively). Our results are compatible with passage of PF4 and BTG across fetal membranes and/or enhanced fetal platelet activation in fetuses with structural anomalies and elevated AFP.

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.

Early amniocentesis: alphafetoprotein levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum between 8 and 13 weeks

The aim was to establish a normal range of alphafetoprotein (AFP) concentrations in amniotic fluid from 8 to 12 weeks gestation, and to determine any difference between AFP levels in amniotic fluid and extraembryonic coelomic fluid. 150 women had a transvaginal ultrasound guided amniocentesis before termination of an apparently normal first trimester pregnancy. Separately identified samples of amniotic fluid and extraembryonic coelomic fluid were obtained and assayed by radioimmunoassay for AFP. In amniotic fluid, very high levels of AFP were present at 8 weeks, levels falling rapidly up to 10 weeks after which there was a slight rise. Thus over the period 8 to 10 weeks, there was a significant inverse correlation between amniotic fluid AFP and gestational age (r = 0.67; P less than 0.001). In extraembryonic coelomic fluid, by contrast there was no trend in AFP relative to gestational age. The rapidly changing levels of AFP from 8 to 10 weeks as well as the small volume of the amniotic cavity makes the use of amniocentesis impracticable before 11 weeks gestation. The lack of any relation between AFP levels in amniotic fluid and extraembryonic coelomic fluid emphasises the importance of identifying the site of amniocentesis in the first trimester.

The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.

Early antenatal sonographic diagnosis of conjoined syncephalus-craniothoraco-omphalopagus twins. Case report

The paper describes the prenatal ultrasonographic diagnosis of conjoined syncephalus-craniothoraco-omphalopagus twins at 13 weeks' gestation. The mother, after genetic counseling, decided to interrupt the pregnancy. The fetal karyotype, the maternal serum and amniotic fluid alpha-fetoprotein levels were normal. The diagnosis was confirmed by pathologic examination of the fetus after termination of pregnancy.

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.

Detection and enumeration of colonic mucosal cells in amniotic fluid using a colon epithelial‐specific monoclonal antibody

Since its introduction, prenatal diagnosis of chromosomal and metabolic disorder by midtrimester amniocentesis has relied upon the use of a mixture of fetal cells obtained from amniotic fluid. Little knowledge has been gained in the sorting of these cells for diagnosis of tissue-specific disorders. In an attempt to determine the contribution of fetal colonic mucosal cells to the overall amniocyte population, we used the colonic epithelial-specific monoclonal antibody (MC-Ab) 7E12H12, IgM isotype. Specimens of the small intestine, colon, buccal mucosa, kidney, urinary bladder, and umbilical cord were obtained from electively aborted normal fetuses of 12-28 weeks' gestation. All of these specimens were examined with 7E12H12 by the immunoperoxidase technique. The MC-Ab reacted with the colonic epithelial cells but not with any of the other tissues. In addition, 40 amniotic fluid samples obtained from women between 16 and 18 weeks of gestation, who underwent amniocentesis because of advanced maternal age, were tested using a fluorescent activated cell sorter. Among the amniotic fluid specimens examined, 18.4 +/- 10.3 per cent cells reacted with 7E12H12. Double immunofluorescence studies revealed that all Mc-Ab-stained cells contained secretory component, confirming that they were epithelial in origin. All fetuses whose amniotic fluid was analysed had normal karyotypes and amniotic fluid alpha-fetoprotein levels that were also normal. This study demonstrates that cell-specific Mc-Ab can be used to detect colon cells in the amniotic fluid and that colon cells contribute significant numbers in the mixture of amniotic fluid cells.(ABSTRACT TRUNCATED AT 250 WORDS)

SPONTANEOUS RESOLUTION OF CYSTIC HYGROMA IN A 46,XX NORMAL FEMALE

We report a case of nuchal cystic hygroma with spontaneous resolution detected by ultrasound examination at 13 weeks' gestation. Fetal karyotype and amniotic fluid alpha-fetoprotein levels were normal. Extreme caution in evaluating this situation is stressed.

Amniotic fluid alpha‐fetoprotein, gamma‐glutamyltranspeptidase, and autosomal trisomies

Alpha-fetoprotein (AFP) concentration and gamma-glutamyltranspeptidase (GGT) activity have been analysed in amniotic fluid from a series of 65 pregnancies with autosomal trisomies. AFP values were reduced on average to 60 per cent of normal in cases of trisomy 21, but were not significantly different from normal in cases of trisomies 18 and 13. GGT activities were uniformly lower (44 per cent of normal) for all types of autosomal trisomy. A review of the literature indicates that over 85 per cent of Down's pregnancies but only 39 per cent of trisomy 18 and 13 pregnancies have amniotic fluid AFP levels below the normal median value, while the corresponding figures for GGT are 91 per cent for Down's syndrome and 96 per cent for trisomies 18 and 13.

Intracranial Malignant Teratoma Diagnosed in a Fetus

The authors describe a case of intracranial malignant teratoma in a 28-week fetus, discovered on assessment of the mother's excessive abdominal enlargement. Alpha-fetoprotein levels in amniotic fluid and serum were high. Ultrasonography revealed a large, solid intracranial mass. The fetus was viable until completion of a cesarean delivery, at which time the heart stopped. At autopsy, the fetal brain was found to have been extensively replaced by a solid, cystic tumor, which proved to be a malignant teratoma comprising elements of all three germ cell layers. The authors' experience and review of the reported cases indicate that prenatal malignant intracranial teratoma can be safely and accurately diagnosed, and that immediate delivery or cranial decompression may be advisable when the diagnosis is established. The usefulness and limitations of ultrasonography are particularly emphasized.

Amniotic fluid acetylcholinesterase: Implications of an inconclusive result

The implications of an "inconclusive" acetylcholinesterase test (a faint but true band) in amniotic fluid were studied over a 2 1/2-year period in our laboratory. One thousand one hundred fifty-four amniotic fluid samples were tested for acetylcholinesterase and alpha-fetoprotein; the rate of an inconclusive acetylcholinesterase result was 3.3% (38 of 1154). Fourteen such results were found in patients with a high amniotic fluid alpha-fetoprotein level (23.3%), and 24 results were associated with normal amniotic fluid alpha-fetoprotein levels (2.19%). The rates of congenital fetal malformation associated with an inconclusive acetylcholinesterase result in the two groups were 57.14% and 37.5%, respectively. In amniotic fluid samples obtained before 15 weeks' gestation, there was a higher rate of inconclusive acetylcholinesterase tests (9.29%), but a lower percentage of malformed fetuses were found compared with later in pregnancy (2.46% and 56%, respectively). Thus we suggest the terminology "equivocal" for early specimens and "suspicious" for later specimens. If obtained in early second trimester and the ultrasound scan is normal, such findings implicate the need for a careful search for fetal malformations. A positive pregnancy outcome may be expected in most cases.

Amniotic fluid alpha‐fetoprotein levels and prenatal diagnosis of autosomal trisomies

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha-fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0.72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0.8 MoM and 20 per cent were over 1.0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut-off level of 0.70 MoM for completion of chromosome analysis. Using a higher cut-off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.

Neurone Specific Enolase in Amniotic Fluid: A Potential Marker of Anencephaly

Normal values for neurone specific enolase in amniotic fluid have been found to follow a non gaussian distribution with a 1-99 centile range of 1.10-4.32 micrograms/L. Neurone specific enolase levels have been shown to be raised in the amniotic fluid of pregnancies complicated by anencephaly, although not those complicated by open spina bifida. Neurone specific enolase measured by radioimmunoassay is capable of totally discriminating between normal pregnancies and those complicated by anencephaly. The study demonstrates the possible value of investigating other neuronal proteins which may find value as adjuncts to amniotic fluid Alpha fetoprotein levels in the prenatal diagnosis of Neural Tube Defects.

Differential staining techniques in amniotic fluid cytology diagnosis of neural tube defects: A prospective study of 129 pregnancies

In order to assess the utility of amniotic fluid cytology in the diagnosis of neural tube defects (NTDs), we performed a prospective study of 129 pregnancies selected for maternal age or history of prior congenital defects or multiple stillbirths. Amniotic fluid obtained between the 16th and 22nd weeks of gestation was cytocentrifuged and stained with hematoxylineosin (H&E), Papanicolaou, and Diff-Quik. Chromosomal analysis, amniotic fluid alpha fetoprotein (AFP) level, and eventual pregnancy outcome were recorded for each case. The AFP levels were normal in 128 cases, including two closed NTDs (meningomyelocele and encephalocele). Three patients had abnormal chromosomal studies: two with 47,XXX and one with trisomy 21. Of these 128 cases, 16 had inadequate cytologic preparations; the remainder, including the five aforementioned patients, showed predominantly squamous cells, amnion cells, and minicells. Other cell types, including genito-urinary cells, umbilical cord cells, respiratory cells, and macrophages, were also present in smaller numbers. One case exhibited a large population of small, darkly staining neural cells and large macrophages. The AFP in this case was markedly elevated, and the fetus was noted to be anencephalic. We found the H&E to be the preferred stain for both cytologic detail and minicell preservation; however papanicolaou was better for bloody specimens. Amniotic fluid cytology may provide a rapid and inexpensive method of confirming the diagnosis of open NTDs.

Trisomy 18 and maternal serum and amniotic fluid alpha‐fetoprotein

Maternal serum and amniotic fluid alpha-fetoprotein levels were studied retrospectively in a total of 58 pregnancies with trisomy 18. In those pregnancies uncomplicated by either fetal exomphalos or neural tube defect the midtrimester maternal serum alpha-fetoprotein (MSAFP) levels were markedly reduced, the median value for 38 such pregnancies being 0.6 multiples of the median (MoM). Trisomy 18 with exomphalos was associated with a higher median MSAFP, but still within the normal range: 1.1 MoM, (nine pregnancies); trisomy 18 with exomphalos and neural tube defect (NTD) was associated with grossly raised levels: median MSAFP was 4.5 MoM (three pregnancies). Amniotic fluid alpha-fetoprotein (AFAFP) levels were normal in uncomplicated trisomy 18 pregnancies: median AFAFP, for 19 pregnancies, was 1.1 MoM. Exomphalos alone, or together with neural tube defect, was associated with greatly elevated levels of AFAFP; for exomphalos alone median AFAFP was 9.59 MoM (four pregnancies), and for exomphalos with neural tube defect the median AFAFP was 23.95 Mom (three pregnancies). Screening with low and high MSAFP, routine ultrasound, and amniocentesis on all women aged 35 years or over, together might identify over 50 per cent of pregnancies with trisomy 18.

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.

AFP transport across the fetal membranes in the human

In this investigation the original observation of a correlation between the concentration of amniotic fluid albumin and maternal serum alpha fetoprotein (AFP), as a proof for amniotic fluid-derived AFP in the maternal compartment is confirmed at 15 and 16 weeks of gestation. In contrast to the earlier reported highly significant relation in this study the correlation is only weak, especially at 15 weeks. This might be in agreement with a more frequent absence of raised maternal serum AFP levels in cases of raised amniotic fluid AFP levels prior to 16 weeks of gestation. Transamniotic AFP transport contributes a minor part of the AFP present in the maternal compartment, as also indicated by the lack of correlation between AFP concentrations in amniotic fluid and maternal serum.

Antenatal screening for congenital nephrosis in Finland by maternal serum alpha-fetoprotein.

In the Kuopio and North-Karelia districts of Finland 10724 pregnancies were screened for congenital nephrosis by maternal serum alpha-fetoprotein (AFP) measurement. Outcome was known for 10504 (98%) pregnancies, of which 509 (4 X 8%) had a serum AFP level greater than or equal to 2 X 5 multiples of the normal median (MoM) at 15-18 weeks gestation. After exclusion of those women who had a normal serum AFP level (less than 2 X 5 MoM) in a second sample, 'wrong dates' or multiple pregnancy, 267 (2 X 5%) remained with a high serum AFP level. Amniocentesis was carried out in 225 (2 X 1%) and 16 women had an amniotic fluid AFP level greater than 10 SD above the normal mean. In this group there were six fetuses with congenital nephrosis (four confirmed and two suspected), six other serious malformations (including an intrauterine death) and four without obvious abnormality. In the 98% pregnancies followed up there were no infants with congenital nephrosis that had been missed. Babies with congenital nephrosis require permanent hospitalization and have a mean survival of 8 months. In Finland, within certain areas, the birth prevalence is as high as 1 in 2600 per year. In such areas maternal serum AFP measurement appears to be a useful method of screening for congenital nephrosis. The service was also well accepted since 94% of the women with raised serum AFP levels wished to be screened again in a future pregnancy.