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Elevated monocyte chemotactic protein-1 in amniotic fluid is a risk factor for pregnancy loss.

OBJECTIVE: Pregnancy loss after mid-trimester amniocentesis occurs in 0.5-1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinically silent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide variety of cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/or fetal death. METHOD: A retrospective case-control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancy loss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay (sensitivity, 18.3 pg/ml). The Kolmogorov-Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis was performed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1. RESULTS: MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those with a normal pregnancy outcome (pregnancy loss, mean 2.95 +/- 0.19 pg/ml vs. normal outcome, mean 2.78 +/- 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis (area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7-31.1), a sensitivity of 70%, and a specificity of 76%. CONCLUSION: A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 than those who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinical implications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of the procedure.

Abortion, Spontaneous↗

Fetal hyperechogenic kidney with normal amniotic fluid volume: a diagnostic dilemma.

OBJECTIVE: To determine the prognostic value of sonographically detected fetal hyperechogenic kidneys with normal amniotic fluid volume. METHODS: Seven cases of hyperechogenic fetal kidneys were identified by sonography over a 7-year period (1996--2002). Increased renal echogenicity was diagnosed when the renal parenchyma was of greater echogenicity than adjacent liver tissue. Amniotic fluid volume was measured by the semiquantitative sonographic technique known as the amniotic fluid index (AFI). RESULTS: Three of the live-born infants had autosomal dominant polycystic kidney disease and one had autosomal recessive polycystic kidney. In the remainder, autopsy study revealed multifocal renal dysplasia in two cases and normal kidneys in one. CONCLUSIONS: Increased renal echogenicity with normal amniotic fluid volume in a fetus without other anomalies is a difficult diagnostic dilemma. Although it is usually indicative of renal parenchymal disease with possible renal failure after birth or in early childhood, in some cases, it represents a normal variant. .

Amniotic Fluid↗

Direct prediction of amniotic fluid volume in the third trimester by 3-dimensional measurements of intrauterine pockets: a tool for routine clinical use.

OBJECTIVE: To develop an ultrasonographic technique for direct prediction of amniotic fluid volume. STUDY DESIGN: While women with near-term pregnancies were in the supine position, the intrauterine space was divided into 2 hemispheres and each hemisphere was further subdivided into 3 segments. The maximum distances along the 3 axes of amniotic fluid pocket in each segment were measured, and the volume was calculated as a half-ellipsoid or a crescent-cylinder. A sum of these calculations (prediction of amniotic fluid volume [pAFV]) was made and correlated with amniotic fluid volume measured at delivery (mAFV). RESULTS: In 714 deliveries, a high correlation coefficient of 0.896 between mAFV (mean +/- SD, 296.5 +/- 199.2 mL; range, 20 to 1480 mL) and pAFV (mean +/- SD, 300.2 +/- 180.8 mL; range, 27 to 1262 mL) was obtained. The regression equation was mAFV = 0.968pAFV + 8.68. CONCLUSION: The regression equation suggested that pAFV could be a direct predictor of intrauterine amniotic fluid volume in the third trimester.

Amniotic Fluid↗

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.

Abortion, Spontaneous↗

Induction of labor and perinatal outcome: the impact of the amniotic fluid index.

OBJECTIVE: The purpose was to determine the impact of the amniotic fluid index on the perinatal outcome of patients admitted for induction of labor at term. STUDY DESIGN: Patients (n=180) included in the study were those admitted for induction of labor at 37-42 weeks' gestation, with unfavorable cervix and intact membranes. The amniotic fluid index (AFI) was determined in all patients using the four-quadrant technique within 24 h of the induction of labor. Patients were divided into two groups based on their AFI: the oligohydramnios group with AFI < or = 5 cm (n = 66) and a normal group with AFI > 5 cm (n = 114). The perinatal outcomes of the two groups were compared. RESULTS: The two groups were similar with regard to maternal age, gestational age, and birth weight. Meconium staining of the amniotic fluid was significantly higher in the group with AFI < or = 5 cm (p = 0.040). The number of cesarean deliveries due to fetal distress was significantly higher even after adjusting for other confounding factors in the group with AFI < or = 5 cm (adjusted OR 6.52 [95% CI 1.82, 23.2]; p < or = 0.0001). There was no significant difference between the two groups with regard to Apgar scores or neonatal admission. CONCLUSION: Induction of labor at term in patients with oligohydramnios is associated with an increased risk of cesarean delivery due to fetal distress.

Adult↗

Fetal oxygen saturation measured by pulse oximetry during labour with clear or meconium-stained amniotic fluid.

OBJECTIVE: To compare fetal oxygen saturation, scalp pH and arterial cord blood gases in cases of clear or meconium-stained amniotic fluid with and without meconium aspiration (MAS). STUDY DESIGN: Thirty-eight women in labour at term with abnormal fetal heart rate were included. Fetal oxygen saturation was continuously monitored using a Nellcor N-400 fetal pulse oximeter and FS-14 sensor. Fetal scalp blood samples were taken systematically at full dilatation or immediately before cesarean section. Arterial cord blood gases were analysed at birth. Fetal oxygen saturation, scalp pH and neonatal blood gases were compared between fetuses with clear amniotic fluid, meconium-stained amniotic fluid without MAS and meconium stained amniotic fluid with MAS. RESULTS: Moderate or thick meconium was observed in 13 cases during labour. Three newborns had a meconium aspiration defined as meconium below the vocal cords. No differences were observed in scalp pH, scalp base excess, umbilical arterial blood pH or base excess between groups. On the other hand, fetal oxygen saturation (fSpO2) obtained before birth was significantly lower in cases of MAS when compared to the other groups. This difference appears to be large compared to that which might be attributed to meconium and its direct effect on fetal pulse oximetry readings. Fetal oxygen saturation dropped dramatically in cases with meconium aspiration between the first stage of labour (44.7 +/- 8.0%) and the last measurement before birth (27.0 +/- 8.5%). CONCLUSION: Meconium aspiration is more likely to be associated with fetal hypoxemia than with fetal acidosis.

Adult↗

Amniotic fluid alpha1fetoprotein in the diagnosis of neural tract malformations.

Amniotic fluid alpha1fetoprotein levels were determined in 400 pregnancies. The normal range for alpha1fetoprotein in amniotic fluid was defined by 350 samples from normal pregnancies. Elevated levels of alpha1fetoprotein were detected in 17 out of 18 pregnancies which gave rise to infants with neural tract abnormalities. The significance of this test in the antenatal diagnosis of neural tract abnormalities is discussed together with the possible reasons for "false negative" and "false positive" results. There were no complications in an individual series of 105 consecutive amniocenteses.

Alpha-Globulins↗

Oxytocin and vasopressin in the rat do not readily pass from the mother to the amniotic fluid in late pregnancy.

In order to see whether the mother contributes to the vasopressin or oxytocin levels of amniotic fluid, these peptides were measured under conditions (1) in which the fetus lacks vasopressin (Brattleboro strain) and (2) where high maternal oxytocin and vasopressin plasma levels were induced by means of a controlled-delivery Accurel-collodion device. No vasopressin could be demonstrated in amniotic fluid of vasopressin-deficient fetuses present in a heterozygous (i.e., vasopressin-synthetizing mother). High peptide levels on the maternal side of Wistar rats generally failed to affect the amniotic fluid levels. The increase that was occasionally seen in amniotic vasopressin was probably due to fetal release concomitant with growth retardation. Amniotic vasopressin is derived from the fetus. Since amniotic fluid oxytocin is neither derived from the mother nor from the fetal brain, other fetal sources should be considered.

Amniotic Fluid↗

The use of amniotic fluid viscosity measurements to establish fetal lung maturity.

A Haake viscosimeter was used to determine the viscosity of amniotic fluid and this value correlated with fetal lung maturity. The results were evaluated along the weeks of pregnancy and compared to those obtained using Gluck's method (lecithin/sphingomyelin ratio (L/S). Using 91 separate amniotic fluid samples, free of meconium and blood contamination, we found that the new method was quick and easy to perform. Thirty-one neonates were delivered within 48 h of the amniotic fluid sampling and the percentage of correct prediction of respiratory distress syndrome (RDS) was 71% with a mature L/S ratio and 83% with viscosity less than 1.17 cP. In cases with an immature L/S ratio (value below 2) the correct prediction of RDS was 64%; with the fluorescence polarization (FP) technique it was 91%. We conclude that the amniotic fluid FP value is a reliable index of fetal lung maturity and risk for developing RDS and has also specific technical and diagnostic advantages over the L/S ratio.

Amniotic Fluid↗

[Dopamine, noradrenaline and serotonin levels in amniotic fluid during the second trimester in normal and pathologic pregnancy].

Authors measured the dopamine (DA), noradrenaline (NA) and serotonin (5-HT) contents of amniotic fluid between 19 and 21 weeks with fluorimetric method. The amniotic fluid samples were obtained by transabdominal amniocenteses performed due to elevated maternal serum-alphafetoprotein levels and suspect ultrasound findings. They considered as normal values the average of 30 amniotic fluid samples obtained from pregnant women who gave birth to healthy babies at term. The mean values (mean+SE) of normal cases were 136.6 + 20.2 nmol/l for DA, 29.5 + 9.4 nmol/l for NA and 72.6 + 4.9 nmol/l for 5-HT. Against these values, in cases of open spina bifida the level of NA showed no significant difference, the DA level was higher (p < 0.05) and the 5-HT level was also higher (p < 0.001). The DA level was found higher (p < 0.05) in cases of intrauterine retardation as well, however there was no difference in the NA and 5-HT levels in these cases. In cases of preterm deliveries, none of the above parameters showed differences. Authors suggest that in cases of spina bifida the measurement of 5-HT in the amniotic fluid can be a complementary diagnostic method. They also state that no prognosis about the outcome of pregnancies can be expected from such examinations.

Amniotic Fluid↗

Enzyme analysis of amniotic fluid for prenatal diagnosis of cystic fibrosis in high-risk pregnancies.

We determined the activity concentrations of alkaline phosphatase (ALP), ALP isoenzymes, gamma-glutamyltransferase (GGT), and alpha-glucosidase (AGL) in 1200 unselected amniotic fluids and in amniotic fluids from 40 pregnancies at high risk for cystic fibrosis (CF). From the results we established the normal range and CF-predictive cutoff values for these enzymes in the second trimester of pregnancy. In all predicted normal pregnancies that went to term, normal children were born. Among the predicted affected pregnancies, 14 were terminated and two went to term, one resulting in a CF-affected child and the other in a healthy child. Evidence for CF was found in all 13 aborted fetuses examined (the parents of one refused to allow autopsy). We noted no differences in the amniotic fluid enzyme activities for the Arab and various Jewish ethnic groups living in Israel. We conclude that prenatal diagnosis of CF among the Israeli population at risk for CF is feasible by means of a reliable, fast, and economic test in the second trimester of pregnancy.

Alkaline Phosphatase↗

Amniotic fluid index in the uncomplicated term pregnancy. Prediction of outcome.

OBJECTIVE: To establish whether an association between oligohydramnios and pregnancy outcome is present in the uncomplicated term pregnancy. STUDY DESIGN: Pregnancies with a singleton fetus in cephalic presentation at term (> or = 37 weeks), a reactive non-stress test and an antepartum amniotic fluid index performed within four days of delivery between January 1994 and September 1998 were identified. Excluded were those with any maternal or fetal complication or unavailable outcome information. The primary outcome measure was rate of operative vaginal or abdominal delivery for a nonreassuring fetal heart rate tracing. Statistical analysis included Fisher's exact test and one-way analysis of variance, with a two-tailed P < .05 considered significant. RESULTS: Two hundred thirty-two women met the inclusion criteria; of them, 44 (19%) had an amniotic fluid index < or = 5 cm. There was no difference in the operative delivery rate for a nonreassuring fetal heart tracing between those with a normal amniotic fluid index > 5 cm vs. < or = 5 cm (39 [21%] vs. 5 [11%], P > .05). In addition, there were no differences between the two groups in rates of neonatal intensive care unit admissions or five-minute Apgar scores < 7. Patients with a normal amniotic fluid index had a significantly lower labor induction rate (96 [51%] vs. 42 [98%], P < .001) and higher rate of meconium-stained amniotic fluid (65 [35%] vs. 7 [16%], P = .01) than those with a low amniotic fluid index. CONCLUSION: In the uncomplicated pregnancy at term, an amniotic fluid index < or = 5 cm increases the incidence of labor induction but does not appear to affect the rate of operative delivery for abnormal fetal heart rate tracings.

Adolescent↗

Down syndrome with pure partial trisomy 21q22 due to a paternal insertion (4;21) uncovered by uncultured amniotic fluid interphase FISH.

OBJECTIVE: To emphasize the usefulness and reliability of fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells in the prenatal diagnosis of common chromosomal aneuploidies. METHODS: FISH analyses utilizing centromeric, locus-specific or whole chromosome paint DNA probes specific for chromosomes X, Y, 13, 18, 21, and 4 were performed on uncultured amniotic fluid cells or the peripheral blood specimen from the father. Routine chromosome analysis was carried out as well. RESULTS: A prenatal case with partial trisomy 21 due to a paternal cryptic insertion (4;21) was ascertained by a rapid overnight FISH on uncultured amniotic fluid cells. The fetus was delivered at term and had classical features of Down syndrome. CONCLUSION: Our results stress the importance of FISH on uncultured amniotic fluid cells to supplement routine cytogenetics, especially in cases with abnormal ultrasound findings.

Adult↗

Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells.

The presence and biochemical characteristics of human brain natriuretic peptide (hBNP) in the amniotic fluid at various gestational ages were investigated. The hBNP-like immunoreactivity (hBNP-LI) levels in amniotic fluid, determined by RIA, were 118.7 +/- 57.6 pmol/L (mean +/- SEM; n = 5) and 107.7 +/- 8.7 pmol/L (n = 9) in the first and second trimesters of pregnancy, respectively; it was significantly decreased to 28.4 +/- 5.1 pmol/L (n = 9) in the third trimester. However, human atrial natriuretic peptide-like immunoreactivity (hANP-LI) was not detected (< 0.3 pmol/L) in any of these samples. Northern blot analysis demonstrated hBNP mRNA in human amnion tissue. Moreover, cultured amnion cells secreted a significant amount of hBNP-LI (100-200 fmol/10(6) cells/day), but not hANP-LI, into the culture medium. The synthesis of hBNP in cultured amnion cells was further confirmed using the polymerase chain reaction. High performance gel permeation chromatography of hBNP-LI extracted from human amniotic fluid and the culture medium of amnion cells revealed that the predominant molecular form of hBNP-LI in both samples was the hBNP precursor, with an approximate mol wt of 12 kilodaltons. These findings indicate that hBNP is present in the human amniotic fluid, and that amnion cells synthesize hBNP and secrete it into the amniotic cavity.

Amniotic Fluid↗

Amniotic fluid testosterone and fetal sex determination in the first half of pregnancy.

The concentration of freely extractable testosterone in amniotic fluid was measured in 54 patients whose gestational ages ranged from 10 to 20 weeks; 31 of the fetuses were male and 23 were female. The mean amniotic fluid testosterone concentration was significantly higher with a male fetus than with a female fetus. On only 7 out of 31 occasions was the presence of a male fetus associated with amniotic fluid testosterone values below 100 pg/ml, whereas the values associated with a female fetus were never higher than 90 pg/ml. After 14 weeks gestation no amniotic fluid testosterone level was lower than 120 pg/ml in the presence of a male fetus.

Amniotic Fluid↗

Maternal, fetal, and amniotic fluid transport of thyroxine, triiodothyronine, and iodide in sheep: a kinetic model.

A mathematical model of iodine kinetics in maternal and fetal sheep has been developed by combining separate iodide, T3, and T4 subsystems. The individual subsystem models were developed from literature studies of maternal-fetal exchange under thyroid-blocked and unblocked conditions. Rates of exchange, concentrations, and spaces of distribution were calculated by the SAAM computer program. The models for each of the subsystems required exchange compartments within the mother and fetus, exchanges between maternal and fetal circulations, and between the fetus and amniotic fluid. The fetal-amniotic fluid exchange was observed directly for iodide and indirectly for T3 and T4. No exchange between mother and amniotic fluid was required. It is possible that the amniotic fluid acts as a reservoir for these and other substances. Maternal-fetal kinetics suggest that low fetal T3 levels are maintained by an active transport of T3 from fetus to mother, a decreased transport from mother to fetus, and a low fetal T3 production. The model also requires that all fetal T3 loss occur via transport to the maternal system rather than via fetal utilization. In contrast, the fetal T4 system is largely autonomous, the small maternal exchange not significantly contributing to the fetal T4 economy. Fetal iodide seems to be supplied by a facilitated bidirectional exchange with the mother.

Amniotic Fluid↗

[Sexually transmitted microorganisms and immunoglobulins in the amniotic fluid in mothers who carry sexually transmitted diseases].

Fetal behaviour as an intrauterine patient is unknown. In the diagnosis of sexually transmitted diseases (STD) and in the criteria for treatment only the mother is considered leaving the fetus out. The presence of immunoglobulin M in the amniotic fluid is an indicator of fetal infection and could allow an accurate diagnosis of fetal disease or treatment, if the measurement is related to the presence or absence of organism in the amniotic fluid. In this way, the study of fetal behaviour under these conditions could be done. The objective of this research was to determine the presence of STD organism in the amniotic fluid of the STD infected pregnant women and to evaluate the prevalence and evolution of these pathologies in the fetus. No STD organism, nor immunoglobulin M were found in the 13 samples of amniotic fluid (8 pre and 5 post-treatment) of infected pregnant women. The presence of microorganisms and its relation to immunoglobulin M was not observed. More cases are needed to arrive to a conclusion regarding fetal immunology and to a better understanding of antibacterial properties of the amniotic fluid. We concluded that no contamination in the amniotic fluid or fetal infection was found in pregnant women with STD.

Amniotic Fluid↗

Uterine artery blood flow response to correction of amniotic fluid volume.

OBJECTIVE: Our purpose was to investigate whether acute alterations of amniotic fluid volume affect uteroplacental perfusion. STUDY DESIGN: Three groups of patients of comparable gestational age were studied in a fetal medicine referral unit: (1) eight pregnancies with severe polyhydramnios because of twin-twin transfusion syndrome undergoing therapeutic amnioreduction, (2) seven with severe oligohydramnios undergoing diagnostic amnioinfusion, and (3) six control women having invasive procedures of similar duration without manipulation of amniotic fluid volume. Color Doppler imaging was used to measure uterine artery impedance index values and quantitative blood flow before and within 15 minutes of the end of the procedure. RESULTS: Quantitative flow measurements increased after amnioreduction (74% median increase of volume flow, range 22% to 329%, p < 0.01) and decreased after amnioinfusion (33% median decrease of volume flow, range 17% to 51%, p < 0.05). Impedance index values increased after amnioinfusion (25% median increase in pulsatility index, range 4% to 71%, p < 0.05) and did not alter with amnioreduction. There were no significant changes in the control group. CONCLUSION: Acute changes in amniotic fluid volume alter uteroplacental perfusion. In twin-twin transfusion syndrome amelioration in uterine flow may improve fetal condition and explain in part the success of serial amnioreduction therapy.

Amniotic Fluid↗