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Prediction of fetal anemia in pregnancies with red-cell alloimmunization: comparison of middle cerebral artery peak systolic velocity and amniotic fluid OD450.

OBJECTIVE: To compare the accuracy of Doppler velocimetry (middle cerebral artery peak systolic velocity, MCA-PSV) and amniocentesis (amniotic fluid delta optical density 450 (OD450)) for the detection of fetal anemia against the gold standard of fetal blood sampling (FBS). METHODS: Thirty-eight pregnancies were identified to be at risk of fetal anemia from immune causes between January 2000 and May 2002. In a cross-sectional diagnostic accuracy study, MCA-PSV and amniotic fluid delta OD450 values were plotted on reference charts and compared to an FBS obtained within the subsequent 7 days. Receiver-operating characteristics (ROC) curves were used and the area under the curve (AUC) calculated to compare the overall accuracy of the two tests. Sensitivity, specificity and likelihood ratios for positive (LR+) and negative (LR-) test results were generated for specific thresholds of MCA-PSV and delta OD450. RESULTS: For MCA-PSV (n = 38), the AUC was 0.71 (95% CI 0.57-0.85) and for amniotic fluid delta OD450 (n = 22) it was 0.68 (95% CI 0.49-0.87) compared with FBS within 7 days. Sensitivity, specificity and LR+, LR- for MCA-PSV were 64%, 81%, 3.4 and 0.5, respectively, and 53%, 71%, 1.9 and 0.7 for amniotic fluid OD450, respectively. CONCLUSION: MCA-PSV and OD450 have similar test accuracy in detecting fetal anemia. MCA-PSV is non-invasive and therefore presents no risk of miscarriage or preterm labor and thus is a preferable method of screening for fetal anemia.

Amniocentesis↗

High levels of fetal membrane activin beta A and activin receptor IIB mRNAs and augmented concentration of amniotic fluid activin A in women in term or preterm labor.

The aim of the present study was to evaluate whether spontaneous labor at term and pathological preterm labor are associated with changes in the expression of activin A and activin receptor mRNAs in fetal membranes. In addition, amniotic fluid activin A concentration in women delivering at term or undergoing preterm labor was also measured. The expression of activin beta A subunit and activin receptor type II and type IIB mRNAs was assessed by reverse transcriptase-PCR on specimens of amnion and chorion collected from patients delivering at term or undergoing preterm labor. Control specimens were collected from women delivered by elective cesarean section who had not experienced labor. A specific two-site ELISA was used to measure activin A concentrations in the amniotic fluid. A cross-sectional study of amniotic fluid retrieved by amniocentesis from 109 pregnant women was carried out. Patients were classified into the following groups: (1) healthy controls at term but not in labor (n = 25); (2) healthy controls at term in spontaneous labor (n = 40); (3) healthy controls between 23 and 36 weeks of gestation (n = 12); (4) patients in preterm labor responding to tocolytic treatment (n = 19); (5) patients in preterm labor with subsequent delivery (n = 13). Activin beta A subunit and activin receptor type IIB mRNA levels in both the chorion and amnion in women delivering at term or after preterm labor were significantly higher than in women delivering without undergoing labor (P < 0.01). Expression of activin receptor type II mRNA in membranes did not differ among the three groups of women. Amniotic fluid activin A concentration in patients in labor was significantly higher than in those at term but not in labor (P < 0.01). Patients in preterm labor had significantly higher amniotic fluid activin A concentrations than women at the same stage of gestation (P < 0.01). The highest values were found in women undergoing preterm labor and subsequent delivery. In conclusion, spontaneous labor and preterm labor are characterized by increased synthesis and release of activin A from amniotic and chorionic cells and by an augmented expression of activin type IIB receptor.

Activin Receptors↗

The effect of regular maternal exercise on erythropoietin in cord blood and amniotic fluid.

OBJECTIVE: Our purpose was to test the hypothesis that continuing regular, high-intensity exercise until the onset of labor produces significant fetal hypoxemia, as evidenced by elevated erythropoietin levels in the fetal compartment. STUDY DESIGN: Erythropoietin levels were measured in samples of amniotic fluid and cord blood obtained from fetuses born to 31 exercising women and 29 matched controls. RESULTS: Erythropoietin levels (mean +/- SEM) in amniotic fluid obtained at the time of membrane rupture (9 +/- 2 vs 11 +/- 2 mU/ml) and in cord blood (38 +/- 6 vs 53 +/- 16 mU/ml) and amniotic fluid at delivery (9 +/- 1 vs 24 +/- 12 mU/ml) were no different in women who exercised regularly until the onset of labor. In both groups the majority of elevated cord blood levels (> 50 mU/ml) could be explained by labor events. Amniotic fluid erythropoietin levels correlated directly (r = 0.52) with cord blood hematocrit and increased slowly during labor. CONCLUSION: We conclude that the initial hypothesis is incorrect and speculate that cord blood erythropoietin reflects fetal oxygenation during labor, whereas amniotic fluid erythropoietin primarily reflects the adequacy of oxygenation before the onset of labor.

Adult↗

Nonfatal amniotic fluid embolism. Three possible cases and a new clinical definition.

Three obstetrical patients who experienced cardiovascular collapse followed by disseminated intravascular coagulation were cared for by the author during residency training and 5 years of private practice. All patients survived. Their clinical courses were strongly reminiscent of those of patients described in the medical literature who ultimately died with the diagnosis of "amniotic fluid embolism." Paradoxically, the mere fact of survival is generally regarded as proof that a given individual did not have an amniotic fluid embolism. Proposed herein is a new clinical definition of amniotic fluid embolism syndrome that could apply to patients who survive as well as to those who die. With this definition in mind, the prevalence and prognosis of amniotic fluid embolism syndrome is reexamined. Finally, the traditional assumption that this syndrome is a result of amniotic fluid leakage into the maternal circulation is challenged. A new source is suggested and some new thoughts regarding treatment are provided.

Adult↗

Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy.

OBJECTIVE: The feto-placental unit is the major source of circulating concentrations of inhibin A and activin A in human pregnancy. The aim of this study was to measure the amniotic fluid concentrations of inhibin A, inhibin B, activin A and follistatin in pregnancies bearing male and female fetuses. DESIGN AND METHOD: Amniotic fluid samples collected by amniocentesis were stored at -20 degrees C. Dimeric inhibins, 'total' activin A and 'total' follistatin were measured using specific two-site enzyme immunoassays. Samples were assayed blindly and the information on fetal sex was obtained from the cytogenetics laboratory. RESULTS: Data show that amniotic fluid concentrations of inhibin A, inhibin B and activin A gradually increase with gestation whilst concentrations of follistatin are similar between weeks 15 and 20 of pregnancy. Mean amniotic fluid levels of inhibin A and inhibin B at 16 and 17 weeks gestation and mean activin A levels at 15 and 16 weeks gestation are considerably lower in pregnancies with male (n=24) compared with female (n=28) fetuses. Levels of follistatin are not different in the male and female fetal pregnancies at any studied gestation. CONCLUSIONS: The results indicate that amniotic fluid contains high concentrations of inhibins (A and B), activin A and follistatin in early pregnancy suggesting that these hormones are produced by the fetal membranes and may be involved in the development of the fetus.

Activins↗

A rapid electrochemical assay of lecithin in amniotic fluid using a fluoride ion-sensitive electrode.

An electrochemical method is described for the determination of lecithin in rat and human amniotic fluid. Choline is released from lecithin enzymatically by phospholipase D and the hydrogen peroxide released by the action of choline oxidase is quantitatively determined by peroxidase-catalyzed rupture of the covalent C-F bond of 4-fluorophenol. The concentration of F- ions in solutions is determined by a fluoride sensitive electrode from the resulting cell potential difference recorded before and 10 min after addition of a solution containing phospholipase D, choline oxidase and horseradish peroxidase. Lecithin levels in rat amniotic fluid increased from about 10 mumol/l on the 20th day of gestation to 80 mumol/l on day 21, which corresponds to the time of spontaneous delivery. In human amniotic fluid the lecithin concentrations determined with this new method parallel those already reported. They were approximately 10 to 50 mumol/l between the 15th and 18th weeks of gestation and increased from 5- to 7-fold between the 37th and 41st weeks of pregnancy. This method was only slightly influenced by the presence of blood or meconium contamination in the amniotic fluid.

Amniotic Fluid↗

Differentiation in human amniotic fluid cell cultures: chorionic gonadotropin production.

Two of the distinguishable cell classes subcultured from human amniotic fluid were examined for their capability to produce human chorionic gonadotropin (hCG) as determined by radioimmunoassay. The class that predominates in most cultures used for prenatal genetic diagnosis, previously termed AF (for amniotic fluid), secretes hCG into the culture medium. Dermal fibroblasts do not, nor does another type of cultured cell from amniotic fluid, previously termed F because of a resemblance to fibroblasts. Primary AF cultures produce more hCG than do subcultures. Evidence that this hormone is intact hCG is provided by its immunoreactivity with antisera raised against the beta-subunit and against the intact molecule of hCG. Furthermore, a dose-response curve for hormone in culture medium is parallel to that of highly purified intact hCG. It is postulated that AF cultures are derived from fetal membranes and retain properties of trophoblast.

Amniotic Fluid↗

[Concentration of the cellular fibronectin in amniotic fluid and plasma in the peripartum period].

OBJECTIVES: Numerous publications recommending the determination of fibronectin (FN) and fetal fibronectin (fFN) during pregnancy and delivery have appeared. The aim of this study was to analyse the level of cellular fibronectin concentration in amniotic fluid and blood plasma of patients between 38 to 42 pregnancy weeks. MATERIAL AND METHODS: The research comprised 79 women in 38-42 weeks of pregnancy. The FN concentration was determined in amniotic fluid and plasma by the solid phase immunoenzymatic method (ELISA) with the use of mice monoclonal antibody (TaKaRa FN 30-8). RESULTS: The FN concentration in amniotic fluid ranged from 0.001 to 0.18 mg/ml whereas in plasma from 0.15 to 3.0 mg/ml. In the cases of determination of FN in amniotic fluid the most of the samples (64 of 83; 77%) were enclosed between 0.025 and 0.08 mg/ml. In plasma 70% of the results (57 of 81) ranged from 0.25 to 0.8 mg/ml. CONCLUSIONS: In 38-40 weeks of pregnancy cellular FN concentration increases whereas in 41-42 weeks it decreases gradually. No differences were observed in the fibronectin concentration level in the blood plasma and amniotic fluid of pregnant women as compared to parturients.

Adult↗

Human beta-endorphin and beta-lipotropin levels in maternal and fetal plasma and amniotic fluid.

We measured beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels in human maternal and fetal plasma and amniotic fluid, simultaneously. It appeared evident that maternal circulating levels of beta-EP (n = 11, 163.9 +/- 12.9 pg/ml, mean +/- S.E.) and beta-LPH (n = 11, 413.0 +/- 25.9 pg/ml) at delivery were significantly (p less than 0.01) higher than those of maternal plasma at term (beta-EP; n = 4, 18.3 +/- 2.1 pg/ml, beta-LPH; 213.4 +/- 24.3 pg/ml) and those of amniotic fluid (beta-EP; n = 5, 8.5 +/- 1.2 pg/ml, beta-LPH; 215.1 +/- 44.9 pg/ml). Fetal beta-EP levels (n = 11, 79.1 +/- 5.8 pg/ml) were significantly (p less than 0.01) higher than those of amniotic fluid. These data suggest that the origin of amniotic fluid beta-EP may be an increased synthesis in the maternal and fetal pituitary gland but not in the placenta.

Amniotic Fluid↗

Concanavalin A reactivity pattern of human amniotic fluid AFP examined by crossed affino-immunoelectrophoresis. A definite test for neural tube defect?

The percentage of alpha-fetoprotein (AFP) not reacting with concanavalin A (con A) was determined by crossed line affino-immunoelectrophoresis in amniotic fluid from 25 pregnancies with neural tube defects (NTD) and other fetal abnormalities giving rise to elevated AFP levels, and from 128 pregnancies with normal outcome. The percentage of con A non-reactive AFP is significantly lower in the presence of fetal abnormalities (mean 3.4%, range: 0.0-6.3, n = 25), compared to the percentage found in normal pregnancies (mean 17.2%, range: 6.6-35.8%, n = 128). In amniotic fluid samples from normal pregnancies, the percentage of con A non-reactive AFP in 84 cases with total AFP levels lying within the 95% reference interval was not significantly different from the percentage found in 44 cases with levels above the 95% reference interval. The percentage of non-reactive AFP in fetal serum and cerebrospinal fluid was of the same magnitude as found in amniotic fluids of pregnancies with fetal abnormalities. It is concluded that analysis of the percentage of con A non-reactive AFP by crossed line affino-immunoelectrophoresis is a simple, reliable and apparently diagnostic test for NTD and other abnormalities with leakage of fetal serum or cerebrospinal fluid into the amniotic fluid. The test should therefore be used in all cases with only marginally elevated AFP levels, so false positives may be avoided.

Amniotic Fluid↗

High levels of human chromogranin A in umbilical cord plasma and amniotic fluid at parturition.

OBJECTIVE: The human placenta is a neuroendocrine organ that produces several hypothalamic and pituitary hormones that are secreted during pregnancy and parturition into maternal and fetal circulation and amniotic fluid. Human chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla and released in response to several stressful events. During pregnancy, intrauterine tissues express and synthesize CgA mRNA and peptide and secret it into the biologic fluids of pregnancy, so we investigated whether maternal, umbilical, and amniotic human CgA levels are affected by the stress of parturition. METHODS: We measured pregnancy CgA levels in maternal and umbilical cord plasma and in amniotic fluid at term (39-40 weeks), by enzyme-linked immunosorbent assay at elective cesarean (n = 16), after spontaneous vaginal delivery (n = 12), and longitudinally throughout labor and 2 hours postpartum. RESULTS: CgA levels were highest in umbilical cord blood (P <.001). Umbilical cord plasma and amniotic fluid CgA levels were significantly higher at spontaneous vaginal delivery than at cesarean (P <.001), and the levels were not changed in maternal plasma according to cervical dilatation and postpartum. CONCLUSIONS: The present findings showed that the stress of parturition increased CgA levels in umbilical cord plasma and amniotic fluid and was probably of fetal origin. Whatever the mode of delivery, CgA levels in infants were much more elevated than in mothers, providing evidence for an unusual and sustained high level of sympathoadrenal stimulation in full-term neonates.

Adult↗

Continuous-wave Doppler ultrasound and decreased amniotic fluid volume in pregnant women with intact or ruptured membranes.

The cause(s) of decreased amniotic fluid in the absence of fetal anomalies and intrauterine growth retardation is not clear. A prospective study was performed to evaluate umbilical and uterine artery Doppler velocimetric results in pregnancies complicated by decreased amniotic fluid. Three medically high-risk groups were studied: women with (1) normal fluid and intact membranes, (2) decreased fluid and intact membranes, and (3) decreased fluid and ruptured membranes. The decreased fluid/intact membranes group had a significantly increased incidence of abnormal uterine artery waveforms (diastolic notching or absence of end-diastolic velocity); however, uterine systolic/diastolic ratios were not significantly different. The umbilical systolic/diastolic ratios were marginally higher in the intact membranes/decreased fluid group when compared with the ruptured membranes group. This study suggests that problems with maternal blood supply to the placenta may be related to decreased amniotic fluid when membranes are intact.

Adult↗

Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers.

This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chrysotile and crocidolite asbestos, and ceramic fibers. The response of human (amniotic fluid cells) and rodent (Syrian hamster embryo fibroblasts, SHE) cells to fiber treatment was compared using the micronucleus assay. The data of the rodent studies were taken from a previous investigation (Dopp, E. et al. (1995) Environ. Health Perspect., 103, 268-271). All types of mineral fibers caused a significant increase of micronucleated cells. The kinetochore analysis revealed that all three types of asbestos and ceramic fibers yielded similar effects. Approximately 50% of the induced micronuclei were kinetochore-negative indicating formation through clastogenic events. Human amniotic cells were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. This again demonstrates that SHE cells are more susceptible to chromosomal changes than human amniotic fluid cells. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed information about specific structural chromosome aberrations in the 1 (cen-q12) and 9 (cen-q12) regions and about abnormal numbers of chromosomes in interphase human amniotic fluid cells. Using this FISH approach we found a statistically significant increase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in interphase human amniotic cells after exposure to asbestos and ceramic fibers compared to control cells. The number of hyperdiploid cells was also significantly increased. Our results show that asbestos fibers as well as ceramic fibers are inducers of structural and numerical chromosomal aberrations in human amniotic fluid cells.

Amniotic Fluid↗

Amniotic fluid volume increase after amnioinfusion of a fixed volume.

Amnioinfusion of 250 ml of normal saline solution was performed in 30 laboring women at greater than or equal to 37 weeks' gestation with oligohydramnios as defined by an amniotic fluid index of less than or equal to 5 cm. A total of 50 amnioinfusions were performed. Amniotic fluid volumes, as assessed by the amniotic fluid index, increased by a mean of 4.3 +/- 1.5 cm after infusion. We conclude that in women with oligohydramnios, 250 ml of amnioinfusate will increase the amniotic fluid index by approximately 4 cm.

Amnion↗

Tolerance of simulated amniotic fluid in premature neonates.

OBJECTIVE: To assess the tolerance of simulated amniotic fluid enterally administered in premature neonates. DESIGN: A multicentered, Phase I, dose-escalation trial was accomplished among 30 preterm neonates. Groups of 10 patients received 5, 10, or 20 mL/kg/d enterally of the amniotic fluid solution, divided into every-3-hour dosing, for 3 days. MAIN OUTCOME MEASURES: Amount and character of emesis, stools, and gastric residuals; changes in abdominal girth; presence of a skin rash; blood pressure instability; the diagnosis of necrotizing enterocolitis (NEC) or intestinal perforation. RESULTS: Thirty patients were studied: 10 received 5 mL/kg/d, 10 received 10 mL/kg/d, and 10 received 20 mL/kg/d of amniotic solution. Gestational ages ranged from 25 to 31 weeks. The Data Safety and Monitoring Board met after each group of 10 patients completed the study, reviewed the outcome measurements, and recommended continuance of the study. Dosing was discontinued for 3 patients prior to receiving all 24 doses because of gastric residuals (n = 1; 5 mL/kg), stage I NEC (n = 1; 10 mL/kg), or symptomatic patent ductus arteriosus (n = 1; 20 mL/kg). The remaining patients completed the doses with no evidence of intolerance: specifically, no increased gastric residuals, increased abdominal girth, diarrhea, blood pressure change, rash, NEC, or intestinal perforation. CONCLUSIONS: Enteral administration of an amniotic fluid-like solution to preterm neonates is well tolerated in doses <or=20 mL/kg/d.

Amniotic Fluid↗

[Correlation between reduced amniotic fluid volume and Doppler spectra of fetal blood vessels at term].

The aim of this study was to determine, whether foetuses with reduced amniotic fluid in other-wise uncomplicated pregnancies at term show signs of redistribution of blood flow analogous to foetuses with intrauterine growth retardation. In 33 pregnancies > or = 37 gestational weeks with the largest pocket of amniotic fluid < 2 cm, flow velocity waveforms were recorded for the umbilical artery, middle cerebral artery and renal artery and compared with those of foetuses of the same gestational age and normal amniotic fluid volume. No difference was found in the resistance index (umbilical artery and middle cerebral artery), the pulsatility index (renal artery), or for the cerebral-placental ratio between these two collectives. We conclude, that Doppler examination of foetal vessels does not help to clarify the phenomenon of decreasing amniotic fluid volume during the final period of gestation. We suggest, that the decrease is not caused by renovascular changes, but has intra- or extrarenal causes.

Amniotic Fluid↗

Amniotic fluid cardiac troponin T in pathological pregnancies with evidence of chronic fetal hypoxia.

AIM: To determine if prenatally measured cardiac troponin T in the amniotic fluid (Am-TnT) could be used as a marker of fetal myocardial hypoxia and necrosis in pathological pregnancy characterized by increased concentration of amniotic fluid erythropoietin (Am-EPO) as a sign of chronic fetal hypoxia. METHOD: We measured Am-TnT and Am-EPO in 29 pathological and 5 uncomplicated pregnancies. Samples of amniotic fluid were collected prospectively during elective amniocentesis (n=15), cesarean sections (n=17), and before elective induction of labor in two pregnancies with stillbirth. Am-TnT and Am-EPO were determined by chemiluminescent immunological method. RESULTS: Am-TnT was undetectable in normal pregnancies, but it was detectable in 9 of 29 amniotic fluid samples from pathological pregnancies, with a median value of 0.030 microg/L (range, 0.010-111.6 microg/L). Am-EPO values were above normal values (>11 U/L) in all pathological pregnancies. Am-EPO concentration showed positive correlation with the Am-TnT concentration (r=0.526, P=0.003). Median concentration of Am-EPO in 9 pregnancies with detectable Am-TnT was 198 U/L (range, 16-3,378 U/L). In 20 pathologic pregnancies with undetectable Am-TnT, the median concentration of Am-EPO was 39 U/L (range, 12-293 U/L). There was no statistically significant difference between the groups (P=0.051). CONCLUSION: Am-TnT is measurable in some pathological pregnancies with signs of fetal chronic hypoxia and myocardial involvement and could be potentially used as a biochemical marker of fetal myocardial injury.

Amniocentesis↗

Sexual dimorphism in the levels of amniotic fluid leptin in pregnancies at 16 weeks of gestation: relation to fetal growth.

OBJECTIVE: To investigate whether in the first half of pregnancy levels of leptin in amniotic fluid are sexually dimorphic, and are related to fetal growth. STUDY DESIGN: Samples of amniotic fluid were collected during amniocentesis from 211 pregnancies with a single fetus with a normal karyotype (107 from male fetuses). Fetal growth was evaluated at 16 and 32 weeks of gestation, by sonography, and in a subset of 137 women at delivery. RESULTS: Amniotic fluid leptin was significantly lower in male than female fetuses (7.91+/-0.36 ng/ml versus 10.45+/-0.38 ng/ml; p = 0.0001). In females, levels of leptin were inversely related to BPD measured at 16 weeks (r = -0.241; p = 0.013) to biparietal diameter (BPD) (r = -0.281; p = 0.0076) and abdominal circumference (r = 0.268; p = 0.0107) measured at 32 weeks of gestation and to neonatal weight (r = -0.236; p = 0.051), neonatal weight/height (r = -0.271; p = 0.026) or neonatal Kaup index (r = 0.255; p = 0.045). Leptin was not related to any fetal parameter in males. CONCLUSIONS: Levels of leptin in amniotic fluid at 16 weeks of gestation are sexually dimorphic and are inversely related to fetal growth, particularly of females.

Adult↗