Amniotic Fluid Alpha-fetoprotein Concentration Research Articles

High-Risk Pregnancy Is Associated With Increased Alpha-Fetoprotein Concentrations in the Amniotic Fluid and Foal Plasma

This study aimed to determine alpha-fetoprotein (AFP) concentrations in amniotic fluid, plasma of mares and respective foals: carrying normal pregnancies and delivering healthy foals (n = 20; Group 1); carrying apparently normal pregnancies and delivering sick foals (n = 15; Group 2); carrying high-risk pregnancies and delivering sick foals (n = 14; Group 3). High-risk pregnancy was defined by a history of premature udder development/lactation or increased of the combined thickness of the uterus and placenta, or vulvar discharge and/or mares' systemic illness. Sick foals were affected by neonatal encephalopathy, sepsis, prematurity/dysmaturity, or hypoxic-ischemic encephalopathy. Based on histological examination of the chorioallantois, AFP trend was analyzed in pregnancies with pathologic (PFM) and normal fetal membranes (NFM). Concentrations of AFP were measured using a commercially available immunoassay previously validated for horses. Mares' plasma AFP did not change during the last 15–20 days of pregnancy in the three groups, and there was no difference among them. Amniotic fluid AFP was higher in Group 3 (P = .014). Foals’ plasma AFP concentration was higher from birth to 72hours in foals of Group 2 and 3 than in healthy ones, and foals of Group 3 had the highest value. The strong association (r = 0.84; P < .0001) between AFP in amniotic fluid and foals' plasma at birth is likely due to the presence of AFP in fetal urine. AFP was higher in pregnancy with PFM than with NFM in mare's plasma at admission (P = .031), amniotic fluid (P = .004), foal's plasma at birth (P = .002), at 24 (P = .005) and at 72 hours of life (P = .004). AFP is higher in pregnancy with histopathological lesions of the chorioallantois providing the evidence of the differences between pregnancy with a normal placental barrier and the more compromised ones. The increased AFP concentration in the amniotic fluid and plasma of high-risk foals suggests upregulation.

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death.

Routine assessment of amniotic fluid alpha‐Fetoprotein in early second‐trimester amniocentesis is no longer justified

Open fetal neural tube defects are often followed by an increase in alpha-Fetoprotein concentration in amniotic fluid. For over 25 years there has been a routine to measure amniotic fluid alpha-Fetoprotein in conjunction with early genetic amniocentesis. The efficacy of such a screening test in a low-risk population has been questioned but never evaluated in a Swedish population. Data were reviewed retrospectively from all consecutive early second-trimester genetic amniocenteses from two hospitals during the years 1993-2003. Indications for the genetic amniocenteses were maternal age > or = 35 years, maternal anxiety or a history of fetal aneuploidy. A questionnaire was sent to all obstetric clinics in Sweden regarding current common policy and experience of routine amniotic fluid alpha-Fetoprotein measurements, in the detection of open fetal neural tube defects. A total of 1,813 samples were included. In eight cases (0.4%) the amniotic fluid alpha-Fetoprotein concentrations were > or = 3 multiples of median, but five of them were false positive (63%). Out of the three true positive cases, one had clinical relevance. In the other two cases the detection of open fetal neural tube defects was of subordinate importance. In Sweden, during 2004, 91% of the obstetric clinics performed routine assessment of amniotic fluid alpha-Fetoprotein at second-trimester genetic amniocentesis, but only 9% regarded the analysis useful in clinical practice. According to our results, routine measurement of amniotic fluid alpha-Fetoprotein in early second-trimester genetic amniocentesis, to rule out a risk of open fetal neural tube defects, does not seem justified. The clinical usefulness seems to be limited.

PRENATAL SCREENING FOR CONGENITAL NEPHROSIS IN EAST FINLAND: RESULTS AND IMPACT ON THE BIRTH PREVALENCE OF THE DISEASE

Congenital nephrosis of the Finnish type (CNF) is inherited as an autosomal recessive trait which maps to the long arm of chromosome 19. The disease causes massive proteinuria, and renal transplantation in early neonatal life is the only effective treatment. Prenatal diagnosis, usually in high-risk families, depends on the analysis of alpha-fetoprotein (AFP) levels in maternal serum (MS) or amniotic fluid (AF). We studied the effectiveness of MSAFP measurement as a method of screening all pregnant women for congenital nephrosis. Between 1 January 1979 and 31 December 1992, all pregnant women (N = 110,858) attending maternity care units in East Finland were offered serum AFP measurement as part of a screening programme. All patients whose MSAFP value was > or = 2.5 multiples of the median (MOM) at 15-18 weeks' gestation were given an ultrasound examination and if no morphological abnormality was found, they were then offered amniocentesis. Altogether, 105,880 pregnant women (96 per cent) in East Finland participated in the screening for CNF. A total of 47 cases of CNF were diagnosed during the study period. Elevated AFP concentrations in maternal serum and amniotic fluid (> or = 2.5 MOM) were found in all screened (44/105,880) affected pregnancies except one. The most typical feature of a CNF pregnancy was a very high AFP concentration in the amniotic fluid. As a result of the screening, the prevalence at birth of CNF decreased from 1:2600 to 1:11,086. The possibility of CNF has to be taken into account in pregnancies with a ¿false-positive' elevated AFP result (normal ultrasound and no detectable acetyl cholinesterase).

Maternal serum alpha‐fetoprotein and fetal trisomy‐21 in women 35 years and older: Implications for alpha‐fetoprotein screening programs

A retrospective study of 3,411 women who underwent midtrimester amniocentesis for fetal chromosome analysis between June 1979 and August 1984 was performed to evaluate an association between low maternal serum alpha-fetoprotein (AFP) concentrations and Down syndrome (DS) pregnancies. A total of 71 pregnancies was found with abnormal fetal chromosomes; of these, 26 cases were trisomy-21 and 10 cases were trisomy-18. The maternal serum AFP in women with DS fetuses was relatively lower than levels in women with fetuses that had normal chromosomes. In addition, the AFP concentrations in amniotic fluid were decreased in cases involving DS fetuses. We have estimated the risks for DS pregnancy at all maternal ages and most serum AFP concentrations. Using these calculations, genetic counselors will be able to provide more accurate risk estimates for trisomy-21 following maternal serum AFP testing.

Amniale AFP-Konzentration in Schwangerschaften mit numerischen Chromosomenaberrationen

Amniotic fluid alpha-fetoprotein concentration were measured in 360 normal pregnancies between 15 and 23 weeks gestation. Taking into account the effect of gestational age the mean and SD were calculated, confirming the physiological decrease in AFP levels at the beginning of the second trimester. By comparison 25 pregnancies with trisomic states (23 trisomy 21, 2 trisomy 18) showed AFP levels below the control mean in 19 cases. In 5 cases we found AFP concentrations above the control mean, partly even not included in the range of 1 SD and in one case the AFP concentration was at the control mean. These results lend further support to the observation of lower amniotic fluid AFP levels in pregnancies with numerical chromosomal aberrations. In all but 6 cases AFP levels ranged not more than 1 SD below the control mean. No clinical consequences can therefore be based on these data.

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.

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.

Outcome of pregnancies associated with raised serum and normal amniotic fluid alpha fetoprotein concentrations.

Outcome of pregnancies associated with raised serum and normal amniotic fluid alpha fetoprotein concentrations.

Hydrocephalus and abnormal digits after failed first-trimester prostaglandin abortion attempt

The possible teratogenic effects of prostaglandins (PGs) in humans have not been investigated in detail, yet these drugs appear to be deleterious in laboratory animals. A case report is presented of congenital anomalies in a newborn infant whose mother received intravaginal PG 7 weeks after conception but failed to abort. The infant was delivered after 34 weeks' gestation with a birth weight of 2.34 kg. The mother had been placed in an experimental protocol using intravaginal PG 15-methyl F2alpha. She received 1 mg, then another 3 mg after 1 hour and was sent home with instructions to call in 24 hours if no tissue was passed. She experienced nausea, vomiting, and intense abdominal cramping but no vaginal blood or tissue loss occurred. She then decided to continue the pregnancy and did not mention these events when she went to a different clinic for prenatal care. Routine ultrasound examination at 24 weeks disclosed dilated lateral cerebral ventricles, which progressively enlarged over the next 3 weeks. No other anomalies were seen. Amniotic fluid alpha-fetoprotein concentration was normal, and karotype was 46,XY. Referral was made to Yale-New Haven Hospital, where at 27 weeks a silastic catheter was placed by Dr. Richard Berkowitz through the fetal skull into the left lateral ventricle under ultrasound guidance, creating a ventriculoamniotic shunt. There was an initial decrease in the size of the left lateral ventricle and improvement in thickness of the corticle mantle. The right ventricle remained enlarged, and the left dilated again after 4-6 weeks, indicating probable blockage of the shunt. The infant was delivered at 34 weeks by cesarean section after pulmonary maturity was demonstrated by amniotic fluid L/S ratio. At birth the Apgar score was 9 at 5 minutes and maturity ratings were consistent with 34-35 weeks. The head was large, the circumference being 34 1/2 cm. The face was not dysmorphic but the ears appeared slightly small. The most striking abnormality concerned the digits of all 4 limbs; all were tapered and shortened with hypoplastic or absent nails. There was a left simian crease. The infant had a shrill cry and was hypertonic but a good suck was present. Radiographs of the hands revealed missing or hypoplastic distal phalanges of all fingers; the middle phalanges of the 3rd and 4th digits of the right hand also were absent. More proximal osseous structures were normal. A search of the literature failed to reveal a report of the association of hydrocephalus and these digital anomalies.

Reactivity of amniotic fluid alpha-fetoprotein with concanavalin A-sepharose in pre-natal diagnosis of fetal malformations

The proportion of concanavalin A-non-reactive alpha-fetoprotein was determined in 215 amniotic fluid samples from second trimester pregnancies. the median percentage for concanavalin A-non-binding alpha-fetoprotein was 35.5% at the 15th week and 32.2% at the 18th gestational week. Nineteen of the 23 pregnancies with various fetal malformations showed highly elevated total alpha-fetoprotein levels. In this group, the value for non-reactive alpha-fetoprotein was below the normal range in 12 out of 13 samples collected at 15-17 weeks of pregnancy and in four out of six samples at 18-19 weeks. Four pathological pregnancies had only moderately elevated total alpha-fetoprotein levels (5.3-7.9 SD above the mean) and two of these samples had a low percentage of the concanavalin A-non-binding fraction. The amniotic fluid alpha-fetoprotein concentration was between 3 and 5 SD and over 5 SD above the mean in four and seven normal pregnancies, respectively. The concanavalin A-fractionation classified correctly 10 out of these 11 cases. The results indicate that the determination of the proportion of concanavalin A-non-binding alpha-fetoprotein is a useful supplementary test to the total alpha-fetoprotein assay.

Neural-tube defect risk assessment for individual pregnancies using alphafetoprotein and acetylcholinesterase test results.

Pregnancies at risk of being associated with (open) neural tube defects can be identified by maternal serum and amniotic-fluid alphafetoprotein (AFP) concentrations in excess of established screening cut-off valves in conjunction with the results of an amniotic fluid electrophoretic acetylcholinesterase screening test. The risk associated with the AFP cut-off values are formulated in terms of a population screening programme. These "population risks" are of little value in the assessment of test results from individual "at-risk" pregnancies, especially when the observed AFP concentrations are in proximity to the "cut-off" values. A complete risk assessment procedure for individual pregnancies is described and presented in graphical form to permit immediate access by clinical staff.

Reactivity of amniotic fluid alpha-fetoprotein with concanavalin A in relation to gestational age: clinical implications.

We used concanavalin A crossed-line affinity immunoelectrophoresis to determine the percentage of concanavalin A nonreactive alpha-fetoprotein in amniotic fluid samples from pregnancies with normal and abnormal fetuses. In 167 samples from pregnancies with a normal outcome and normal values for total alpha-fetoprotein concentration in amniotic fluid the percentage decreased from a median value of 27.4% in the 13th week to 8.5% in the 21st week of gestation, and a statistically significant (p < 0.001) average decrease of 1.7% per week was found from the 14th to the 19th week. A similar average decrease (2.2%) was found in 22 pregnancies from which two or more samples were obtained. The clinical significance of this decrease is discussed. Of 108 samples from patients with above-normal values for total alpha-fetoprotein and a normal outcome, seven had a total alpha-fetoprotein above recommended cut-off values, and only one of these had a low percentage of concanavalin A nonreactive alpha-fetoprotein. In contrast, for all 27 samples from pregnancies with a severe fetal malformation this percentage was low, even in one case where the total alpha-fetoprotein concentration was below the recommended cut-off value.

Prenatal Diagnosis of Congenital Nephrosis in 23 High-Risk Families

AULA, PERTTI; RAPOLA, JUHANI; KARJALAINEN, OLAVI; LINDGREN, JAN; HARTIKAINEN, ANNA L. and; SEPPÄLÄ, MARKKU Author Information

Amniotic Fluid Cell Morphology in Early Antenatal Prediction of Abortion and Low Birth Weight

The morphology of rapidly adherent (RA) amniotic fluid cells was examined in 201 pregnant women referred for amniocentesis because of two sequential high serum alpha-fetoprotein (AFP) concentrations. Out of 43 amniotic fluid samples containing increased amounts of AFP, 42 had neural or peritoneal cells predominating among the RA cells, the outcome being an infant with a neural-tube defect or exomphalos. In the other case with a raised amniotic fluid AFP concentration but only anterior placental cells the infant was normal. In 25 amniotic fluid samples containing normal amounts of AFP distinctive new patterns of RA cells were observed, termed fetal distress cells. These pregnancies resulted in five spontaneous abortions and 20 infants with birth weights under 2500 g. Fetal distress cells were not detected in any of the remaining 133 samples. One pregnancy was terminated because of a chromosomal abnormality, and there were seven twin pairs not recognised on ultrasonography before amniocentesis. The remaining 125 pregnancies went to term, resulting in infants with birth weights exceeding 2500 g. The results suggest that RA-cell morphology will prove to be of value in the early antenatal prediction of spontaneous abortion and low birth weight.

Amniotic fluid cell morphology in early antenatal prediction of abortion and low birth weight.

The morphology of rapidly adherent (RA) amniotic fluid cells was examined in 201 pregnant women referred for amniocentesis because of two sequential high serum alpha-fetoprotein (AFP) concentrations. Out of 43 amniotic fluid samples containing increased amounts of AFP, 42 had neural or peritoneal cells predominating among the RA cells, the outcome being an infant with a neural-tube defect or exomphalos. In the other case with a raised amniotic fluid AFP concentration but only anterior placental cells the infant was normal. In 25 amniotic fluid samples containing normal amounts of AFP distinctive new patterns of RA cells were observed, termed fetal distress cells. These pregnancies resulted in five spontaneous abortions and 20 infants with birth weights under 2500 g. Fetal distress cells were not detected in any of the remaining 133 samples. One pregnancy was terminated because of a chromosomal abnormality, and there were seven twin pairs not recognised on ultrasonography before amniocentesis. The remaining 125 pregnancies went to term, resulting in infants with birth weights exceeding 2500 g. The results suggest that RA-cell morphology will prove to be of value in the early antenatal prediction of spontaneous abortion and low birth weight.

Prenatal diagnosis of congenital nephrosis in 23 high-risk families.

The efficacy of maternal serum and amniotic fluid alpha-fetoprotein (AFP) estimation for the prenatal detection of congenital nephrosis was assessed in 23 pregnancies of couples with a previously affected child. At 15 to 18 weeks' gestation, amniotic fluid AFP concentration was elevated in seven of 23 cases, and maternal serum AFP level in five of these. Legal abortion was carried out at 18 to 19 weeks in all those cases where he amniotic fluid AFP concentration was abnormally high, and in all cases the fetus was found to be affected. The diagnosis of intrauterine congenital nephrosis was obvious by electron microscopic examination of the fetal kidney, but not by light microscopy. The child was born without congenital nephrosis in all 16 cases where amniotic fluid AFP level was normal, and in 16 of 18 cases (89%) where maternal serum AFP concentration was normal. Thus, the amniotic fluid AFP assay is more reliable and is recommended whenever congenital nephrosis is suspected on the basis of family history.

Fetal-maternal distribution of ovine alpha-fetoprotein.

The concentration of ovine alpha-fetoprotein (AFP) was determined in sheep fetal, maternal, and neonatal sera and amniotic fluid by radioimmunoassay. The fetal serum AFP concentration was highest during the first third of pregnancy and continued to decline with fetal and neonatal development. Total fetal synthesis of AFP was highest during the late middle and early latter third of pregnancy. Amniotic fluid AFP concentration was highest during the early middle third of pregnancy. Maternal serum AFP was not elevated above nonpregnant control levels during the first two-thirds of pregnancy, but instead showed a tendency to be elevated only during the last third of pregnancy. The fetal physiological distributions of ovine and human AFP in fetal serum and amniotic fluid appear to be similar, whereas in maternal serum the pattern of AFP levels differs in the two species as a function of gestational age.

Amniotic fluid alpha-fetoprotein levels and the prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands.

Amniotic fluid alpha-fetoprotein (AFP) concentrations were measured in 2180 patients at risk of fetal abnormality because of previous history, family history, advanced maternal age, suspected fetal growth retardation and hydramnios. In 12 patients investigated before 20 weeks gestation, pregnancy was terminated because of a raised amniotic fluid AFP-level: 11 fetuses had neural tube defects (NTDs) and one had a congenital nephrosis. There were no false negative results in the 1927 patients tested before 20 weeks and with a pregnancy of known outcome. In patients tested after 20 weeks, the amniotic fluid AFP concentration was raised in 20 cases of anencephaly, in 9 fetuses with severe congenital malformations without NTD and in one apparently normal fetus. Of 428 patients with a previous offspring who had a NTD, only 8(1.9 per cent) again had a fetus with a NTD.

Alpha-Fetoprotein values in monkey (Macaca mulatta) pregnancy.

The pregnant rhesus monkey's (Macaca mulatta) potential as a model for understanding the dynamics of alpha-fetoprotein (AFP) metabolism in human pregnancy was evaluated. AFP levels in maternal and fetal serum and amniotic fluid were determined by radioimmunoassay. Significant correlations were found between decreasing maternal serum, fetal serum and amniotic fluid AFP concentrations and increasing gestational age. However, these data are not consistent with the AFP changes reported in human pregnancy. It appears that this animal has limited applicability as a model in this aspect of human pregnancy.