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Prostate-specific antigen in amniotic fluid of normal and abnormal pregnancies.

OBJECTIVE: To examine if prostate-specific antigen (PSA) is present in amniotic fluid or maternal serum during pregnancy and if its presence is associated with fetal abnormalities. METHODS: Samples tested included amniotic fluids from 853 pregnant women for whom amniocentesis was performed; 312 nonpregnant women who donated blood; 259 pregnant women who donated blood at various gestational ages. Amniotic fluid or serum PSA was measured with an ultrasensitive time-resolved immunofluorometric procedure. 372 pregnancies were studied for the presence of genotypic or phenotypic fetal abnormalities. RESULTS: PSA was present in most amniotic fluids; the median PSA concentration increased from gestational week 11 to 22 and stabilized thereafter until delivery. The most prominent PSA concentration change occurred during gestational weeks 13-14. Pregnant women had significantly higher serum PSA concentrations than nonpregnant women; the pattern of serum PSA concentration change during pregnancy was similar to that of amniotic fluid; however, serum PSA concentrations were lower by a factor of 20-40. No association existed between amniotic fluid PSA and maternal age, gender of fetus, or length of abstinence of mother from sexual intercourse. After gestational week 15, fetuses with trisomy 21 or 18, anencephaly, or renal disorders were associated with low amniotic fluid PSA levels. CONCLUSION: Our data suggest that PSA may play a role in fetal development, especially at gestational ages between 13-20 weeks. The diagnostic usefulness of PSA in identifying fetal abnormalities remains to be determined.

Amniocentesis↗

Adrenomedullin concentrations in early 2nd-trimester amniotic fluid: relation to preterm delivery and fetal growth at birth.

OBJECTIVE: The purpose of this study was to evaluate whether adrenomedullin concentrations in the early 2nd-trimester amniotic fluid predict preterm delivery or fetal growth at birth. METHODS: The adrenomedullin concentrations in early 2nd-trimester amniotic fluid were measured in 70 pregnancies with term delivery and in 3 pregnancies with preterm delivery. Total and free adrenomedullin concentrations were measured from early 2nd-trimester amniotic fluid samples using an immunoradiometric assay. RESULTS: The amniotic fluid total adrenomedullin concentrations in women with preterm delivery were significantly higher (129.7 +/- 19.6 fmol/ml) than those in women with term delivery (92.5 +/- 28.2 fmol/ml; p < 0.05). There were no significant differences for amniotic fluid free adrenomedullin concentrations and free/total adrenomedullin ratios between the two groups. Total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid showed an inverse correlation both with birth weight (r = 0.27, p < 0.05, and r = 0.21, p < 0.05) and height (r = 0.30, p < 0.05, and r = 0.28, p < 0.05). There were no correlations between placental weight and total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid. CONCLUSIONS: These results suggest that adrenomedullin concentrations in the early 2nd-trimester amniotic fluid might be related to further in utero fetal growth and that high levels of adrenomedullin in the early 2nd-trimester amniotic fluid may be involved in the occurrence of preterm delivery.

Adrenomedullin↗

Low levels of amniotic fluid placental alkaline phosphatase in Down's syndrome.

OBJECTIVE: To investigate amniotic fluid placental alkaline phosphatase (PLAP) levels in normal and trisomy 21 pregnancies. DESIGN: Cross sectional study. SETTING: A tertiary referral prenatal diagnostic service. SUBJECTS: Three hundred and eleven women with singleton pregnancies of normal karyotype between 10 and 23 weeks gestation and 31 women with pregnancies associated with trisomy 21 Down's syndrome. OUTCOME MEASURES: PLAP levels were measured by immunoradiometric assay in amniotic fluid obtained by amniocentesis. RESULTS: Amniotic fluid PLAP was detectable from 12 weeks gestation and the median value rose to a peak of 4.57 iu/l at 18 weeks. Pregnancies associated with Down's syndrome had significantly lower levels with a median multiple of median (MoM) of 0.638, (U = 3374, P = 0.0016, 95% CI = 0.50, 0.89). For the 20 women with trisomy 21 pregnancies detected at 16 to 18 weeks, the median MoM was 0.482, (U = 3694, P = 0.0011, 95% CI = 0.37, 0.85). CONCLUSION: These data demonstrates that PLAP levels are reduced in the amniotic fluid of women carrying a fetus with trisomy 21.

Alkaline Phosphatase↗

Isoelectric focusing pattern of human amniotic fluid alpha-fetoprotein.

Isoelectric focusing (IEF) of amniotic fluid alpha-fetoprotein (AFP) in thin-layer polyacrylamide gels containing 8 M urea followed by immunoblotting reveals at least nine bands, band I lying next to the cathode. Compared with 298 amniotic fluid samples from normal pregnancies, we found that the density of band V was increased in seven cases of fetal death. In 16 amniotic fluid samples from pregnancies with open neural tube defects (ONTD), band V disappeared or was markedly decreased. In seven cases with elevated AFP and positive acetylcholinesterase (AChE) due to contamination with fetal blood, no difference in pattern was observed compared with samples from normal pregnancies. It is suggested that IEF of AFP and subsequent immunoblotting are an apparently diagnostic test for ONTD and intrauterine fetal death (IUFD).

Acetylcholinesterase↗

Amniotic fluid composition responds to changes in maternal dietary carbohydrate and is related to metabolic status in term fetal rats.

The objective of this study was twofold: 1) to determine whether amniotic fluid composition responded to differences in the level or source (glucose vs. fructose) of maternal dietary carbohydrate, and 2) to establish whether any dietary-induced changes in amniotic fluid composition correlated with maternal or fetal metabolic status at term. Pregnant rat dams were fed graded levels (0, 4, 12 and 60%) of glucose or fructose in a triglyceride-based diet (Experiment 1) or isoenergetic low carbohydrate diets having 4% glucose equivalents as glucose, fructose, or lipid-glycerol (Experiment 2) throughout pregnancy. Amniotic fluid and maternal and fetal samples were collected at term (d21). Results demonstrated a significant increase in amniotic fluid glucose and a significant decrease in amniotic fluid uric acid as the level of carbohydrate increased in the maternal diet. Pearson correlation coefficients showed amniotic fluid glucose to be positively associated with maternal and fetal liver glycogen and fetal weight; amniotic fluid uric acid and urea nitrogen were negatively correlated with these same measures. Regression analysis indicated that amniotic fluid glucose was predictive of fetal body weight and fetal liver glycogen at term. The findings show that amniotic fluid can be modified by maternal diet and suggest that composition of amniotic fluid might be used as an accessible nutritional indicator of carbohydrate status in the developing fetus.

Amniotic Fluid↗

Fetal heart rate patterns associated with amniotic fluid embolism.

Two cases with recorded fetal heart rate response during maternal amniotic fluid embolus are reported. Fetal heart rate abnormalities can be associated with the development of amniotic fluid embolus or occur during the acute events of amniotic fluid embolus. Attention to the management of amniotic fluid embolus in the mother must not neglect the fetus. Improvement of maternal oxygenation and perfusion can effect intrauterine resuscitation; however, when this is not successful early delivery of the fetus may be necessary for its survival.

Adult↗

[Clinical significance of echogenic amniotic fluid at term pregnancy].

PURPOSE: This study is aimed to determine the clinical significance of echogenic amniotic fluid. MATERIAL AND METHODS: I surveyed 9 at term pregnancies in which the amniotic fluid was echogenic. Morphologic characteristics of amniotic fluid were assessed from samples taken at amniocentesis or upon delivery within one day after last sonographic examination. RESULTS: In pregnancies with echogenic amniotic fluid, assessment revealed clear fluid in 4 cases (44.5%), vernix caseosa in 4 (44.5%), and meconium in 1 (11.0%). CONCLUSIONS: Echogenic amniotic fluid on prenatal sonography is not predictive of fetal distress.

Adult↗

Elevated amniotic fluid amino acid levels in fetuses with gastroschisis.

Our objective was to measure maternal plasma and amniotic fluid amino acid concentrations in pregnant women diagnosed as having fetuses with gastroschisis in the second trimester of pregnancy. Twenty-one pregnant women who had fetuses with gastroschisis detected by ultrasonography (gastroschisis group) in the second trimester and 32 women who had abnormal triple screenings indicating an increased risk for Down syndrome but had healthy fetuses (control group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal plasma samples were taken simultaneously. The chromosomal analysis of the study and control groups was normal. Levels of free amino acids and non-essential amino acids were measured in plasma and amniotic fluid samples using EZ:fast kits (EZ:fast GC/FID free (physiological) amino acid kit) by gas chromatography (Focus GC AI 3000 Thermo Finnigan analyzer). The mean levels of essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) and non-essential amino acids (alanine, glycine, proline, and tyrosine) in amniotic fluid were found to be significantly higher in fetuses with gastroschisis than in the control group (P < 0.05). A significant positive correlation between maternal plasma and amniotic fluid concentrations of essential and nonessential amino acids was found only in the gastroschisis group (P < 0.05). The detection of significantly higher amino acid concentrations in the amniotic fluid of fetuses with a gastroschisis defect than in healthy fetuses suggests the occurrence of amino acid malabsorption or of amino acid leakage from the fetus into amniotic fluid.

Adult↗

High amniotic fluid erythropoietin levels are associated with an increased frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies.

AIMS/HYPOTHESIS: In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies. METHODS: A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section. RESULTS: The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004). CONCLUSIONS/INTERPRETATION: Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.

Adult↗

Evidence for the presence of N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor ligands in human amniotic fluid and fMLP receptor modulation by physiological labour.

OBJECTIVES: The presence of amniotic binding sites for N-formyl-methionyl-leucyl-phenylalanine (fMLP), an inflammatory peptide, and its ability to induce prostaglandin E2 synthesis in the human amnion prompted us to investigate for: (1) the presence of fMLP receptor ligands (fMLPRL) in the amniotic fluid; (2) expression of the fMLP receptor in amniotic tissue; (3) the effect of amniotic fMLPRL on neutrophil cyclic AMP (cAMP) level and calcium concentration ([Ca2+]i) during physiological pregnancy and labour. METHODS: Binding assays were performed on neutrophils to determine the presence of fMLRL in the amniotic fluid at the 17th week of pregnancy, as well as at term, before and after the onset of labour. The expression of fMLP receptor mRNA was evaluated by RT-PCR, the cAMP level by a radiochemical assay, and the calcium concentration by Fura-2 AM fluorescence measurement. RESULTS: fMLPRLs were detectable in amniotic fluid throughout pregnancy, and their levels did not vary during gestation. Labour significantly increased both the amniotic fMLPRL level and the expression of fMLP receptor in amnion tissue. The increased amniotic fMLPRL concentration noted during labour significantly increased neutrophil cAMP level and [Ca2+]i. CONCLUSIONS: These findings demonstrate for the first time the presence of fMLP receptor ligands in amniotic fluid, and indicate a modulation of the fMLP system by the events of physiological labour.

Amniotic Fluid↗

[Respiratory distress in newborns born to hypertensive mothers and acid-base equilibrium and the ion composition of the amniotic fluid].

Twenty-five samples of amniotic fluid obtained by amniocentesis from 25 pregnant women with hypertension in the 35 to 40 weeks of pregnancy were studied. The following biochemical determinations were done in the samples: acid-base equilibrium (pH, pO2, pCO2, base deficit, standard HCO3- and total CO2), concentrations of potassium and sodium ions, total and ionised calcium and inorganic phosphorus. The results were analysed depending on the presence of the respiratory distress syndrome in the newborn, and were subjected to statistical analysis. It was found that determination of acid-base equilibrium and concentrations of K+, Na+, total and ionised Ca++ and inorganic phosphorus in the amniotic fluid of hypertensive women are probably without prognostic significance with respect to the development of the respiratory distress syndrome in newborns.

Acid-Base Equilibrium↗

Amniotic fluid cultures: post-cesarean section endomyometritis and neonatal infections.

Amniotic fluid cultures in 54 consecutive patients undergoing cesarean section were compared in regard to intrapartum and postpartum events. Neonatal outcome and cultures were also compared with amniotic fluid findings. Positive amniotic cultures were obtained in 57% and showed a multiplicity of organisms. Development of endomyometritis was correlated with a heavy growth of bacteria in culture. Positive cultures were significantly associated with duration of labor greater than eight hours and presence of ruptured membranes at the time of cesarean section. Thirty-three percent of the patients with positive cultures had intact membranes at the time of operation. Eighty-eight percent of cultures from infants and amniotic fluid grew organisms in common. Implications of the study for the pathogenesis of postcesarean endomyometritis and neonatal morbidity are discussed.

Amniotic Fluid↗

Amino acids in amniotic fluid in the second trimester of gestation.

The concentrations of amino acids in amniotic fluid have been used in the prenatal diagnosis of several inherited metabolic disorders. However, previous studies have usually examined only a small number of control amniotic fluid samples. We have, therefore, measured the amino acids in amniotic fluid samples from 183 normal pregnancies between the 13th and the 23rd wk gestation of women ranging in age from 17 to 43 yr. The concentrations of Ala, Lys, Val, Glu, Pro, Thr, and Gly, in descending order, accounted for about 70% of the amino acids in amniotic fluids. A negative correlation with gestational age (-0.34 to -0.24) was found for Leu, Val, Ile, Phe, Lys, Ala, Asp, Tyr, Glu, and Pro, with Leu showing the greatest rate of change. The concentration of Gln increased slightly (r = 0.18), whereas the other amino acids did not change significantly during this period. Statistically significant positive correlations, at all gestational ages, were observed among Val, Leu, and Ile. These branched-chain amino acids also correlated positively with Phe, Lys, Asp, Thr, Ser, Glu, Pro, Gly, Ala, and Tyr, and the amino acids within this group correlated with each other. Additionally, strong positive correlations were observed between Phe and Tyr and between Gly and Ser. No significant correlations were found between any of the amino acids and maternal age or fetal sex. Significant positive correlations between amino acids may be indicative of common transport or degradative pathways and suggest that maintenance of specific relative concentrations in amniotic fluid may be essential for normal fetal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Spectrophotometric characteristics of the amniotic fluid in Rh isoimmunization following intrauterine fetal blood transfusions].

The amniotic fluids of 7 pregnant women with Rh-isoimmunization were examined. On the basis of the data of this investigation as well as of the clinical and ultrasound data intrauterine blood transfusions were made in fetuses--from 4 to 8 in number. Forty two spectrophotometric analyses were made in all, but the amniotic fluids were examined before intrauterine blood transfusions as well as before the performance of each subsequent blood transfusion. The authors found changes in the characteristic of the amniotic fluid after intrauterine blood transfusion, which were manifested by the fact that the pigment peak of delta 450 nm was reduced, but the peak of delta 410 nm was increased. In connection with these findings after intrauterine blood transfusions delta 450 nm lost its diagnostic and prognostic value. delta 410 nm before intrauterine blood transfusions manifested gravity of fetal hemolytic disease. After intrauterine blood transfusions its increase was due to blood transfusions and accumulation of methemoglobin in the amniotic fluid.

Amniotic Fluid↗

Amniotic fluid concentrations of adrenomedullin in preterm labor.

OBJECTIVE: To determine whether adrenomedullin levels in amniotic fluid were associated with preterm labor. METHODS: We measured immunoreactive adrenomedullin in amniotic fluid collected by amniocentesis from 36 women with clinical diagnosis of preterm labor or preterm premature rupture of membranes (PROM) and from 18 normal pregnant women. RESULTS: Amniotic fluid from cases of PROM and failure to respond to tocolysis were associated significantly with higher amniotic fluid adrenomedullin concentrations (177.0 +/- 22.5 pg/mL and 182.7 +/- 22.0 pg/mL, respectively, P < .01) than that from uncomplicated pregnancies (101.2 +/- 28.1 pg/mL) or preterm labor responsive to tocolysis (102.3 +/- 26.8 pg/mL). CONCLUSION: Amniotic fluid adrenomedullin is higher than normal in cases of PROM and preterm labor unresponsive to tocolysis, perhaps indicating enhanced synthesis from placenta or fetal membranes being stimulated by bacterial products.

Adrenomedullin↗

[The effect of amniotic fluid on Neisseria gonorrhoeae].

This study shows the antibacterial effect of amniotic fluid collected on 10 women from 32 to 38 weeks. Two techniques were used. The first is a quantitative analysis of a bacterial culture with amniotic fluid as compared to controls, with inhibition by the amniotic fluid demonstrated. The second is a morphologic analysis of gonorrheal cultures by electron microscopy, showing alteration of the bacteria when amniotic fluid is present. These facts are of interest when one tries to understand the discrepancy between high rates of discovery of bacteria during pregnancy and low rates of intra-amniotic infection by Neisseria gonorrhoeae.

Amniotic Fluid↗

On the prenatal diagnosis of congenital adrenal hyperplasia (CAH) by measurement of amniotic fluid 17-alpha-hydroxyprogesterone, aldosterone and cortisol.

Forty amniotic fluid samples of both sexes were collected in the 16th gestational week and analysed for 17 alpha-hydroxyprogesterone (17-OHP), cortisol, and aldosterone. Hormone concentrations were also analyzed in amniotic fluid of a male fetus postnatally diagnosed as having the salt-losing form of congenital adrenal hyperplasia (CAH). The mother also had CAH of the non-salt-losing type. Hormone concentrations were also determined prenatally in two pregnancies at risk. Amniotic fluid from the pregnancy with the CAH fetus had an approx. six-fold elevated 17 alpha-hydroxyprogester one level, whereas cortisol and aldosterone levels were within the normal range when compared with controls. Hormone concentrations in the two pregnancies at risk were within normal limits and subsequently a healthy boy and a healthy girl were born. Institution of cortisone in the mother during early pregnancy was made in one of the pregnancies. The treatment was withdrawn when normal amniotic hormonal levels were obtained. No sex difference in concentrations of 17-OHP or cortisol was found in the controls, whereas there was a marked sex difference in aldosterone levels (p less than 0.005) with male fetuses having higher concentrations. Diagnosis of CAH in the 16th gestational week can be made by analysing amniotic fluid concentrations of 17 OHP. As cortisol and aldosterone levels were within normal range of the CAH-fetus, they are probably of little use for the prenatal diagnosis of CAH-fetuses/or to differentiate the simple virilizing and the salt-losing forms of CAH. Restriction fragment length polymorphism (RFLP)- analyses of the 21-hydroxylase gene in the fetus gave little further information.

Adrenal Hyperplasia, Congenital↗

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Routine measurement of amniotic fluid alpha-fetoprotein during amniocentesis may not be warranted in centers with expertise in targeted ultrasonographic imaging.

Adolescent↗