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Subjective versus objective evaluation of amniotic fluid volume of pregnancies of less than 24 weeks' gestation: how can we be accurate?

This study was undertaken to compare subjective versus objective ultrasonic evaluation of amniotic fluid volume in pregnancies of less than 24 weeks' gestation. Amniotic fluid volume was subjectively (visualization without ultrasonic measurements) and objectively (visual interpretation with ultrasonic measurements) evaluated in 42 singleton pregnancies undergoing termination. The actual amniotic fluid volume was then determined using a dye-dilution technique. The women evaluated were in their mid-20s, primarily African American, and between 15 and 23 weeks' gestation. There was no significant difference in the total number of correct estimates of amniotic fluid volume when the data were stratified by level of operator experience (P = .34), ultrasonic technique (P = .33), or the combined correct subjective versus combined correct objective estimates (P = .68). We have concluded that the accuracy of amniotic fluid volume assessment in pregnancies of less than 24 weeks is not influenced by the level of operator experience or the type of ultrasonic measurement.

Amniotic Fluid↗

Ritodrine concentrations in maternal and fetal serum and amniotic fluid.

Ritodrine hydrochloride concentrations were measured by radioimmunoassay in maternal and fetal sera and amniotic fluid from eight, pregnant, volunteers. Each patient agreed to have 420 micrograms . kg-1 of ritodrine infused intra-venously over two hours prior to elective cesarian section. During infusion a blood sample was taken every 30 minutes from a maternal peripheral vein. Once anesthesia was established the infusion was discontinued. During surgery, samples were drawn from maternal peripheral vein, uterine vein, umbilical artery and vein, and amniotic fluid. All the children delivered were healthy and had a normal course during the neonatal period. Ritodrine concentrations in maternal and fetal compartments at the time of cesarian section were 54.2 +/- 11.8 ng/ml (mean +/- S.D.) in maternal peripheral vein, 37.5 +/- 10.3 ng/ml in uterine vein, 15.8 +/- 4.8 ng/ml in umbilical artery, 16.6 +/- 8.9 ng/ml in umbilical vein, and 15.2 +/- 8.7 ng/ml in amniotic fluid. There was a statistically significant difference (p less than 0.02, paired-t test) between the mean ritodrine concentrations in sera from the maternal peripheral vein and uterine vein. This difference probably reflects transplacental passage. The mean ratio of fetal vein and peripheral maternal vein serum ritodrine concentrations was 0.30 +/- 0.13 (mean +/- SD). The similarity between mean ritodrine concentrations in amniotic fluid, and sera from umbilical arterial and venous blood was striking. These results suggest that the fetus does not conjugate the drug.

Amniotic Fluid↗

Effect of amniotic fluid upon prostaglandin E2 and I2 production by cultured human myometrial cells.

OBJECTIVE: Our goal was to study the effect of amniotic fluid obtained at 16 and 39 weeks of gestation in normal human pregnancies upon prostaglandin production by human myometrial cells in culture. STUDY DESIGN: Amniotic fluid, sampled either at 16 weeks, during amniocentesis, or at 39 weeks, during caesarean section before labor, was fractionated by molecular-weight and then incubated with human myometrial cells in culture. We then used radioimmunoassay to measure PGE(2) and PGI(2) production. RESULTS: The "3-30 kDa" fraction of amniotic fluid sampled at 16 weeks significantly inhibited PGE(2) and PGI(2) production by human myometrial cells. When amniotic fluid was sampled at 39 weeks, it stimulated both PGE(2) and PGI(2) production, and the ">30 kDa" fraction increased levels of PGE(2) considerably more than of PGI(2) (420.0+/-88.0 ng/10(6)cells versus 188.2+/-21.4 ng/10(6)cells, P<0.001). CONCLUSION: Amniotic fluid contains substances whose effects in cultured myometrial cells vary according to gestational age and type of prostaglandin. These data suggest that the fetus plays a role in the regulation of myometrial activity during pregnancy.

Amniocentesis↗

Increased midtrimester amniotic fluid activin A: a risk factor for subsequent fetal death.

OBJECTIVE: The objective of this study was to determine whether concentrations of activin A and corticotropin-releasing factor in amniotic fluid can identify patients at risk of fetal death. STUDY DESIGN: A retrospective case-control study of women who have had a midtrimester amniocentesis was designed. Case subjects consisted of patients who had a spontaneous fetal death after the procedure, whereas the control group consisted of patients who had a normal pregnancy outcome after midtrimester amniocentesis. Dimeric activin A was measured by a specific 2-site enzyme immunoassay, and corticotropin-releasing factor was measured by a specific and sensitive radioimmunoassay after acidic extraction. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and chi2 tests and regression analysis. RESULTS: First, activin A was detectable in all amniotic fluid samples. Second, the concentration of activin A in amniotic fluid increased with advancing gestational age. Third, patients who subsequently had a fetal death had a higher median concentration of activin A than those with a normal pregnancy outcome (P <.01). Fourth, an amniotic fluid concentration of activin A greater than the 95th confidence interval for gestational age was found in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P <.005). Finally, the median concentration of corticotropin-releasing factor in amniotic fluid was not different in case subjects and control subjects. CONCLUSIONS: An elevated concentration of activin A in amniotic fluid identifies women at risk of fetal death.

Activins↗

Amniotic fluid catecholamines and metabolites in intrauterine growth retardation.

Simultaneous determinations of amniotic fluid levels of the catecholamines dopamine (DA), norepinephrine (NE), and epinephrine (E), and the intraneuronal metabolites of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and NE, 3,4-dihydroxyphenylglycol (DOPEG), were made, by radioenzymatic assay, in pregnancies resulting in growth-retarded (n = 14) and normal (n = 63) infants. Significant elevations in the mean concentration of NE (p less than 0.000005), E (p less than 0.005), and DOPEG (p less than 0.000001) as well as a significant decrease in the mean concentration of DOPAC (p less than 0.000001) were found in pregnancies resulting in growth-retarded infants as compared to pregnancies resulting in normal infants. Amniotic fluid DOPEG levels were found to be the most discriminative. As amniotic fluid catecholamines are predominantly of fetal origin, these findings suggest that an increase in adrenergic activity and a decrease in dopaminergic activity occur in intrauterine growth retardation as a response to chronic stress.

3,4-Dihydroxyphenylacetic Acid↗

Rapid prediction of pulmonary maturity by amniotic fluid lipid globule formation.

Utilizing the surface tension (ST) lowering properties of an amniotic fluid lipid extract, it was noted that the amniotic fluid lipid layer formed a subsurface globule when the ST reached 36.9 dynes/cm +/- 0.1877 (SEM). The amount of required extract to achieve globule formation varied with the degree of fetal pulmonary maturity and the volume required could be used to differentiate pulmonary maturity (less than or equal to 320 microliter), transitional status (340 to 440 microliter), and pulmonary immaturity (greater than 460 microliter), as related to fetal outcome (amniotic fluid obtained within 48 hours of delivery). Of the 70 patients studied, the 7 (100%) who developed respiratory distress syndrome (RDS) were predicted correctly. Nine of 70 (12.1%) gave false negative results (predicted pulmonary immaturity, no RDS developed); there were no false positives. Globule measurements of a separate series of 74 samples were compared with their L/S ratios. Twenty-two of 24 (91.7%) samples termed mature had an L/S greater than 2.0, while 32 of 42 with a value termed immature had an L/S less than or equal to 1.9. The physical events in the establishment of the monolayer and subsequent globule formation are discussed. This method now provides a rapid and reliable screening indicator of fetal pulmonary maturity.

Amniotic Fluid↗

Amniotic fluid volume and its relationship to fetal fluid balance: review of experimental data.

The studies described above collectively suggest that, whenever there is a decrease in fluid balance in the fetus, both fetal urine flow and tracheal secretion into the amniotic space are decreased. Conversely, when fetal hydration is increased, both urine and tracheal flows into the amniotic fluid may be increased. These observations suggest the hypothesis that, except under pathological conditions, aberrations in amniotic fluid volume may be the consequence of the existing state of hydration of the fetus. In addition, it appears that under many circumstances, these deviations from normal in fetal fluid balance may be due to maternal influences. Of course, the concept that fetal fluid balance is the primary factor determining amniotic fluid volume needs to be modified to incorporate transmembrane fluxes. However, these fluxes have yet to be documented as they relate to amniotic fluid volume and its regulation.

Amniotic Fluid↗

Detection of intra-amniotic infection in a rabbit model by proteomics-based amniotic fluid analysis.

OBJECTIVE: This study was undertaken to identify intra-amniotic infection caused by several different organisms in a rabbit model by using proteomics. STUDY DESIGN: Twenty infected and 18 uninfected amniotic fluid samples were subjected to proteomic analysis by surface-enhanced laser desorption ionization (SELDI-TOF, Ciphergen Biosystems, Fremont, Calif), 1- and 2-dimensional gel electrophoresis, and tandem mass spectrometry (MS/MS). RESULTS: Detailed SELDI-TOF spectra revealed a constitutive 4.0 kd peak in all animals. Infected samples also displayed a signature double peak at 3.6 kd. A SELDI-TOF signature profile for intra-amniotic infection predicted positive amniotic fluid and/or fetal cultures with a sensitivity of 90% and specificity of 83%. Similar proteomic profiles were obtained regardless of the infecting organism. The 3.6 kd peak appeared to contain rabbit calgranulin C and rabbit calcyclin, members of the S100 family of calcium binding proteins. CONCLUSION: Amniotic fluid proteomic analysis was able to detect intra-amniotic infection in this experimental rabbit model. S100 proteins may be involved in the host inflammatory response to intra-amniotic infection.

Amniotic Fluid↗

alpha-Fetoprotein levels of paired samples between the amniotic fluid and maternal serum from 16 to 18 weeks' gestation in Chinese women.

To assess the relationship between alpha-fetoprotein (AFP) concentrations of amniotic fluid and maternal serum from 16 to 18 weeks' gestation, 890 paired samples of maternal serum and amniotic fluid were collected from women with normal singleton pregnancies. The gestational age was determined by ultrasonographic dating before amniocentesis, and the AFP measurements were performed by a single reference laboratory. There was a significant rise in the maternal serum AFP (MSAFP) concentration from 16 to 18 weeks' gestation. Amniotic fluid AFP concentrations significantly declined from 16 to 18 weeks' gestation. This study failed to demonstrate any statistical relationship between the AFP concentration of maternal serum and amniotic fluid (r = 0.031). This finding indicates that amniotic fluid AFP levels cannot be predicted by MSAFP levels between 16 and 18 weeks' gestation. Simple diffusion may not be the only mechanism for the transfer of AFP through the fetal membrane to maternal circulation.

Amniotic Fluid↗

Flecainide distribution, transplacental passage, and accumulation in the amniotic fluid during the third trimester of pregnancy.

OBJECTIVE: To study the disposition of flecainide acetate and its transplacental passage (both into the fetus and in the amniotic fluid) during the third trimester of pregnancy. DATA SOURCES: Reference articles and books are identified in the text. A literature review is presented. CASE SUMMARY: Flecainide distribution, transplacental passage, and accumulation into the amniotic fluid were studied in a patient at term presenting with a fetal supraventricular tachycardia diagnosed at 33 4/7 weeks of gestation. The fetal tachycardia was accompanied by cardiac failure with placental anasarca and hydramnios. Flecainide 100 mg po bid was prescribed initially; by the time of delivery, the dosage had been decreased to 50 mg bid. At delivery day (39 5/7 weeks), the pharmacokinetics of total flecainide were studied at plateau. DATA SYNTHESIS: The concentrations of flecainide at birth in fetal and maternal blood and in amniotic fluid were 235.4, 241.2, and 6426.5 micrograms/L, respectively. Calculation of a fetomaternal blood accumulation ratio of 0.97 showed that, at this gestational age, flecainide penetrates the placental membrane easily without accumulation in fetal blood. In contrast, the concentration of flecainide in amniotic fluid was approximately 27-fold that measured in maternal peripheral blood. Our results suggest the following: (1) close to term, the metabolic clearance (fetal hepatic clearance) of flecainide offers a high yield and its excretion by the fetal kidney is efficient; (2) given that amniotic fluid is constantly swallowed, it seems that, in contrast to what is seen in adults (relative oral bioavailability > or = 95 percent), the oral bioavailability of flecainide is possibly low in the fetus at term or close to term; under such circumstances, the drug would accumulate passively within the gestational sac; and (3) an alternative explanation is that the concentration in the fetus is, in part, the result of both transplacental crossing of the drug and reabsorption orally from the amniotic fluid. CONCLUSIONS: The regular therapeutic monitoring of flecainide is necessary and sufficient in the mother as the concentrations found appear to accurately reflect the degree of fetal accumulation. Because previous studies in infants and children have indicated few toxic adverse effects attributed to flecainide, it appears that the risk to a sucking infant of ingesting toxic amounts of flecainide in human breast milk is very low. Finally, the child of the patient described here has normal initial growth and development at the present time. The transplacental penetration of a drug can be considered, according to gestational age and the disorder being treated, as being of no consequence, dangerous, or desirable. Flecainide appears to fall into this last category.

Adult↗

Cesarean delivery. Microbial colonization in amniotic fluid.

OBJECTIVE: To determine the frequency, clinical significance and causative factors behind intraamniotic microbial colonization in uninfected parturients at the time of cesarean delivery. STUDY DESIGN: Amniotic fluid specimens for bacterial and mycoplasmal cultures were obtained by direct aspiration at cesarean section from 251 pregnant women (24-43 completed weeks) who had no clinical infection at the time of the operation. The symptoms of maternal infection were followed postoperatively for the first week of the puerperium. RESULTS: The prevalence of amniotic fluid microbial invasion was 29% (72/251). In patients not in labor and with intact membranes, it was 13% (20/158); in patients in labor and with intact membranes, 23% (5/22); and in those with ruptured membranes, 66% (47/71). The most common species isolated were Ureaplasma urealyticum, Lactobacillus species and coagulase-negative staphylococci. In the total 251 patients, clinically evident postoperative endometritis was observed in 6 (2%) and wound infection in 10 (4%). In patients operated on and with intact membranes, no risk factors were found as regards amniotic fluid microbial colonization. In patients operated on after rupture of the membranes, the only significant risk factor as regards amniotic fluid microbial invasion was use of an internal monitor before the operation (P < .0003) (relative risk 10.7, 95% confidence limit 2.9-39.4). The relative risk of postoperative endometritis was 2.3 (95% confidence limit 1.3-4.3) in patients with microbial invasion of the amniotic cavity as compared to patients without invasion. The corresponding risk value for post-operative wound infection was 1.4 (95% confidence limit 0.6-3.1). CONCLUSION: Though the incidence of microbial invasion of the amniotic fluid before surgery was unexpectedly high, its clinical significance as regards maternal puerperal morbidity appeared to be low. The use of internal monitoring during labor was the only significant risk factor as regards amniotic fluid microbial colonization in patients operated on after membrane rupture.

Amniotic Fluid↗

A randomised comparison between amniotic fluid index and maximum pool depth in the monitoring of post-term pregnancy.

OBJECTIVE: To compare the impact of two different ultrasound methods for assessing amniotic fluid volume on the incidence of obstetric interventions in post-term pregnancies. DESIGN: A prospective randomised controlled trial. SETTING: Liverpool Women's Hospital. PARTICIPANTS: Five hundred women with singleton, uncomplicated pregnancies with gestational age > or = 290 days. INTERVENTIONS: Random allocation to fetal monitoring by either: 1. amniotic fluid index and computerised cardiotocography, or 2. maximum pool depth and computerised cardiotocography. MAIN OUTCOME MEASURES: Primary: caesarean section. Secondary: the number of abnormal monitoring tests, induction of labour, intrapartum management and neonatal outcome. RESULTS: The number of abnormal amniotic fluid indices was significantly higher than the number of abnormal maximum pool depths (10% vs 2.4%; OR 4.51, 95% CI 1.82-11.21; P = 0.0008) which resulted in more inductions for abnormal post-term monitoring in the amniotic fluid index group (14.8% vs 8.4%; OR 1.89; 95% CI 1.07-3.33; P = 0.0362) and more intrapartum electronic fetal monitoring (94.4% vs 88.4%; OR 2.21; 95% CI 1.13-4.29; P = 0.0255). There were no other statistically significant differences in outcomes related to labour and delivery, but there was a trend towards more caesarean sections in the amniotic fluid index group (18.8% vs 13.2%), in particular caesarean sections for fetal distress (8% vs 4%). There were no perinatal deaths and no statistically significant differences in perinatal outcome between the two groups. CONCLUSIONS: Published reference ranges for amniotic fluid index overestimate the number of abnormal results in post-term pregnancies. Their use, when compared with maximum pool depth, is likely to increase the number of obstetric interventions with, as yet, an uncertain impact on perinatal mortality and morbidity. It is possible that antepartum fetal assessment in pregnancies where the risk of adverse perinatal outcome is very low may cause, rather than prevent morbidity.

Adult↗

Delayed amniotic fluid embolism following caesarean section under spinal anaesthesia.

A case of amniotic fluid embolus is described with an acute onset occurring 90 min after surgical delivery in a mildly pre-eclamptic primigravida undergoing Caesarean section for a breech presentation. Severe disseminated intravascular coagulation and massive postpartum haemorrhage were corrected and she went on to make a full recovery. The pathophysiology of amniotic fluid embolism is discussed and new diagnostic tests are reviewed. It is suggested that in this patient an amniotic fluid collection in dilated uterine veins was mobilised as venous tone returned following the offset of spinal anaesthesia and sympathetic blockade.

Adult↗

[Aspiration of meconium stained amniotic fluid (author's transl)].

Respiratory distress following aspiration of meconium stained amniotic fluid can be found in about 3% of newborn infants. The lethality rate of this disease is high. Pathophysiology and variability of the clinical course as well as radiological findings and further diagnostic procedures are being described. The therapeutic concept requires recognition of meconium stained amniotic fluid as early as possible, early suctioning of the nasopharynx, intubation and endotracheal suction. Further therapy consists in physical procedures, i. e. lavage, suctioning, positioning, vibration and percussing of the chest, and inhalation. Antibiotics can only be recommended if infection of the amniotic fluid has been proven.

Amniotic Fluid↗

Disappearance of para-amino-hippurate from amniotic fluid.

Eight pregnant women and three pregnant sheep received 400 mg of para-amino-hippurate (PAH) intraaminotically. Serial samples of amniotic fluid and maternal blood were obtained. In sheep samples of fetal blood were also withdrawn. PAH appeared in maternal plasma in all the cases. In all pregnant women PAH disappeared slowly from amniotic fluid (50% in 4 hours). In one ewe the study was performed as in humans and showed the same pattern of disappearance. In the other two, fetal urine was drained outside the amniotic fluid and PAH disappeared from it at a much faster rate (90% in 4 hours). PAH concentration in fetal urine was 100 times higher than in fetal plasma. Our findings in pregnant women seem to suggest that PAH disappears from the amniotic sac by a diffusion mechanism. On the other hand the results found in sheep also suggest that the fetus may have an active role in PAH concentration in amniotic fluid, eliminating part of the substance into maternal blood across the placenta but returning a major portion to the amniotic fluid with fetal urine.

Aminohippuric Acids↗

Thrombin-antithrombin III complexes and antithrombin III in amniotic fluid.

We measured thrombin-antithrombin III (TAT) complexes and antithrombin III (AT III) in amniotic fluid and blood plasma of 39 parturient women. TAT was measured by ELISA. Partigen plates were used for measuring the antigen of AT III, and activity was determined using chromogenic substrate. While AT III activity and AT III antigen were below 20% of plasma values, TAT concentration was 2-4 times higher in amniotic fluid than in blood plasma (over twice at the onset of labour, i.e. 54.2 +/- 26.4 and 20.7 +/- 10.7 ng/ml, and approximately 4 times after childbirth, i.e. 108.9 +/- 49.2 ng/ml in amniotic fluid and 27.8 +/- 13.2 ng/ml in blood plasma, respectively). We have concluded that thrombin generation and TAT formation in amniotic fluid are are of significantly higher intensity than in plasma, and they increase during labour.

Adult↗

Filtration and recirculation of early amniotic fluid. Evaluation of cell cultures from 100 diagnostic cases.

Due to the low cell concentration, cultures from early amniotic fluid specimens usually require 2-3 weeks in culture prior to karyotyping. The purpose of this study was to evaluate the culture quality of amniotic fluid cells from early pregnancy, obtained by a new filter technique. The hypothetical advantage of the technique was that the increased cell yield might reduce the culture time before karyotyping. Culture quality was assessed by the number of colonies, the percentage of colonies containing mitoses in filter and control cultures, and the culture time. The setting was a consecutive clinical trial. One hundred samples were obtained from ongoing pregnancies at 11-14 weeks of gestation (mean 12.8 weeks). By circulating a mean of 26 ml of amniotic fluid through a cell filter system leading the cell-free fluid back to the amniotic cavity, the cell yield was increased in the sample of 7 ml corresponding to the dead space of the filter system. The culture results were compared with control cultures from 5 ml samples drawn from the same pregnancies prior to recirculation. The cultures from the first flushing of the filter system yielded 2.6 times more colonies and in total 4.2 times more colonies were found in the three cultures grown from each filter sample when compared with the control cultures. Moreover, the filter cultures showed significantly more colonies with mitoses. The mean culture time was 8.0 days for the filter cultures, from which the karyotypes were analysed. The controls would have needed more time in culture to fulfil the diagnostic criteria for karyotyping. One case of 47,XY,+21 was found; the rest had normal karyotypes. We conclude that the filter technique improves the culture quality of early amniotic fluid samples and allows early arrest of the cultures.

Amniocentesis↗

Total cortisol in amniotic fluid and fetal lung maturation.

Total cortisol was determined by radioimmunoassay in 48 samples of amniotic fluid obtained at various stages of normal pregnancy. Before the 34th week, all cortisol levels were less than 40 ng per milliliter. At 35 to 40 weeks the mean value was 2.4 times higher than that at 20 to 34 weeks. In pregnancies greater than 40 weeks, a further increase in total amniotic-fluid cortisol was observed, and values greater than 120 ng per milliliter were found only in patients of this group. A good rank correlation between cortisol and lecithin/sphingomyelin ratio was found in 43 samples (r = 0.83, p less than 0.001). No respiratory-distress syndrome of the newborn occurred when total amniotic-fluid cortisol was greater than 60 ng per milliliter (16 patients). Total amniotic-fluid cortisol may reflect initiation of fetal lung maturation, and may help identify pregnancies with a gestation period of over 40 weeks.

Amniotic Fluid↗