Pilot study of the capabilities of neural network data analysis in predicting placental disorders: A prospective study

To the Editors:

Regulation of amniotic fluid volume: Intramembranous solute and volume fluxes in late gestation fetal sheep

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Ovine Amniotic Fluid Volume Response to Intra-amniotic Balloon Filling

To determine the changes in amniotic fluid (AF) volume and solute concentrations during the last 3 weeks of gestation in fetal sheep with a ligated urachus. AF volume as well as solute concentrations of AF, fetal urine, fetal blood, and maternal blood were measured serially over the last 24 days of gestation in chronically catheterized fetal sheep. Statistical analyses included regression analysis and analysis of variance (ANOVA). Delivery occurred at 145.5 +/- 1.1 (SE) days (n = 11 animals). AF volume averaged 913 +/- 46 mL (n = 119 determinations total from 11 animals) and was unchanged with time when analyzed against either gestational age (P = .9) or time prior to delivery (P = .81). Amniotic osmolality, sodium, chloride, glucose, and calcium concentrations decreased as gestation progressed, while potassium and lactate concentrations increased. Only amniotic lactate underwent a pre-delivery increase in concentration. From multivariate regression, AF solute concentrations correlated positively with fetal blood and urine concentrations and negatively with gestational age. In fetal sheep with a ligated urachus, AF volume does not decrease prior to labor and delivery. This differs from the sharp pre-delivery decrease in AF volume that occurs in rats, mice, and pigs and is similar to the relatively constant AF volume in humans, baboons, and monkeys. Further, pre-delivery changes in AF lactate concentration may reflect the consequences of a low AF volume. Regression analysis suggests that fetal blood and urine independently contribute to AF solute concentrations and that gestational age-specific changes in intramembranous transport also may contribute.

Human amniotic fluid mathematical model: Determination and effect of intramembranous sodium flux

Direct volume measurement at midtrimester amnioinfusion in relation to ultrasonographic indexes of amniotic fluid volume

To test the hypothesis that a substance present in the amniotic fluid could serve as a regulator of amniotic fluid volume, we drained and discarded amniotic fluid while replacing it with lactated Ringer solution that was isotonic to amniotic fluid. Seven ewes with singleton fetuses at 119 +/- 1 days of gestation (mean +/- SE) were instrumented with multiple indwelling catheters in the pedal artery, pedal vein, and amniotic cavity. During the exchange periods, an average of 3,019 +/- 171 ml/day of lactated Ringer solution was infused into the amniotic cavity while an equal amount of amniotic fluid was pumped out and discarded. During the control period, amniotic fluid composition and volume were not altered. Exchange and control periods started with the same amniotic fluid volume, lasted 3 or 4 days, and were randomized with regard to order. Amniotic fluid volume measured by vacuum drainage was 556 +/- 98 ml at the end of the control period and 986 +/- 209 ml (P = 0.03) at the end of the exchange period. Fetal arterial blood gases, hemodynamic parameters and the osmolality gradient between fetal plasma and amniotic fluid were not altered by the exchange process. A linear relationship between the control amniotic fluid volume and the volume at the end of the exchange period (P = 0.003) suggests that the animals with larger control volumes responded to isovolumic dilution with a larger volume increase. We conclude that amniotic fluid may contain a substance that regulates amniotic volume.

Histomorphology of the Placenta and the Placental Bed of Growth Restricted Foetuses and Correlation with the Doppler Velocimetries of the Uterine and Umbilical Arteries

The current study was undertaken to determine simultaneous changes in amniotic fluid (AF) volume and composition across gestation in the pregnant mouse. Young adult mice (6 to 7 weeks old) of the CB6F1 strain were mated overnight. AF was collected on consecutive days from embryonic days 9.5 through 18.5 for measurements of volume and composition. Statistical analysis included one-factor analysis of variance (ANOVA). AF volume increased from 18 +/- 4 (SE) microL on day 9.5 to a maximum of 147 +/- 4 microL on days 15.5 to 16.5 and decreased sharply to 17 +/- 3 microL on day 18.5. AF osmolality was unchanged except for a rise prior to delivery on day 19.5 to 20.5. AF sodium, calcium, and glucose concentrations increased and subsequently decreased as gestation progressed. AF potassium, chloride, and lactate concentrations initially decreased and then increased across gestation. Prior to day 9.5 and after day 18.5, AF volume was too small for volume or compositional determinations. In the mouse, the rise in AF volume from mid gestation to a maximum late in gestation is similar to that in humans while the sharp fall prior to delivery is not. As observed in the fetal sheep, the changes in fluid volume are associated with AF osmolality and solute concentration changes that are correlated with advancing gestational age. These observations together with the feasibility of quantifying AF volume and composition in the mouse fetus demonstrate the possibility of using genetically altered mice as a model for future studies on the molecular mechanisms underlying the regulation of AF volume and composition.

To better understand the mechanisms that regulate amniotic fluid (AF) volume, we measured AF volume and the rates of fetal swallowing and urination in 33 pregnant sheep at 124-142 days gestation. In four of five ewes over 9-18 days, the spontaneous changes in amniotic fluid volume correlated positively with urine flow rate and negatively with the rate of swallowing (R = 0.686, P less than 0.01), such that 47% of the AF volume changes could be attributed to changes in rates of urination and swallowing. Following infusion of one liter of isotonic amniotic saline (n = 12) or mannitol (n = 5), AF volume increased 110%, and after 24 h returned to the control value in the saline group but it remained elevated 59% above control in the mannitol group. AF sodium was unchanged following saline infusion but remained reduced following mannitol. Following withdrawal of 61% of AF over 20-40 min, AF volume averaged 51 and 71% of control at 24 and 48 h, respectively, whereas AF sodium was unchanged. Variations in rates of fetal swallowing or urine formation could not explain the entire changes in AF volume following either the volume infusion or withdrawal. These data suggest that AF volume is regulated within a relatively narrow range and fetal urine formation and swallowing together and transplacental fluid flux each appear to contribute equally to the regulation of AF volume.

Amniotic fluid volume of third-trimester diamniotic twin pregnancies

We sought to determine amniotic fluid (AF) volume in diamniotic twin gestations and to relate these findings to estimates using standard ultrasonic techniques. In this prospective study, AF volume in 45 diamniotic twin gestations at 27-38 weeks was assessed by sonography using the largest vertical pocket technique, the AF index, and the two-diameter pocket method. After the three different sonographic estimations of AF volume, the true amount of AF was determined using amniocentesis and a dye-dilution technique. The individual sac AF volume was less than 500 mL in 35 amniotic cavities, 500-2000 mL in 48 sacs, and greater than 2000 mL in seven. Individual AF volume between 500 and 2000 mL was correctly predicted by sonographic use of the largest vertical pocket in 47 of 48 patients (98%), the AF index in 47 of 48 (98%), and the two-diameter pocket method in 39 of 48 (81%). Estimation of AF volume less than 500 mL was significantly more accurate using the two-diameter pocket method compared with either the AF index (P = .015) or the largest vertical pocket technique (P < .0001). Currently available ultrasonic techniques to assess mid-range AF volume (500-2000 mL) in twin pregnancy are very accurate (81-98%). Oligohydramnios (less than 500 mL) is poorly identified by any sonographic method.

We have previously described a method to measure the amniotic fluid (AF) volume and fetal swallowing rate in near-term sheep by use of 125I-labeled albumin (RISA) and 51Cr-labeled red blood cells (51Cr-RBC). However, when we measured these volumes on consecutive days, reentry of the radionuclides into the amniotic cavity from fetal urine affected the calculated values of AF volume and swallowing rates. In an attempt to clarify the recirculation problem, we injected RISA and Cr-RBC daily for 9 days into the AF of five chronically catheterized pregnant sheep (124 days gestation on the 1st experimental day). We calculated AF volume and fetal swallowing rate, comparing those values to the values corrected for fetal urine isotopic counts. The mean AF volume and fetal swallowing rate measured by RISA were 808 +/- 48 ml (mean +/- SE) and 559 +/- 29 ml/day, respectively. These values were only slightly different from the corrected volumes, 808 +/- 48 ml and 561 +/- 29 ml/day, respectively, because fetal urine 125I activity reached only 4.8% of AF activity even on the 9th day. In contrast, 51Cr-activity in fetal urine on the 9th day showed 47% of the activity of AF. The mean uncorrected AF volume (785 +/- 44 ml) and swallowing rate (561 +/- 31 ml/day) measured by Cr-RBC were different from the corrected values (790 ml and 570 ml/day, respectively). After the 4th day these differences were particularly conspicuous.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim. To evaluate changes in blood flow in the uterine and umbilical arteries in the second trimester of gestation in women with exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection (CMVI).Materials and methods. Using Doppler analysis, 115 patients were examined at 21-24 weeks of pregnancy, uncomplicated and complicated by exacerbation of mild to moderate asthma of cytomegalovirus etiology. The first group was represented by 30 seronegative women with uncomplicated pregnancy. The second group included 30 patients with mild asthma in the stage of exacerbation associated with CMVI, leading to chronic compensated placental insufficiency. The third group consisted of 30 patients with exacerbation of moderate asthma caused by CMVI reactivation, which initiated the development of chronic compensated placental insufficiency. The fourth group consisted of 25 women with moderate asthma in the acute stage against the background of the acute phase of CMVI, leading to the formation of chronic subcompensated placental insufficiency.Results. In women in the second group, in comparison with the first group, the following changes were determined: in the right uterine artery, the systolic-diastolic ratio (SDR) was, respectively, 2.75±0.07 and 2.04±0.03 rel. units (р&lt;0.001), pulsation index (PI) – 1.15±0.04 and 0.76±0.02 rel. units (p&lt;0.001), resistance index (RI) – 0.63±0.01 and 0.51±0.01 rel. units (p&lt;0.001); in the left uterine artery, SDR was, respectively, 2.84±0.09 and 1.98±0.05 rel. units (p&lt;0.001), PI – 1.20±0.05 and 0.74±0.03 rel. units (p&lt;0.001), RI – 0.64±0.01 and 0.49±0.01 rel. units (p&lt;0.001); in the absence of statistically significant differences in the indicators of SDR in the umbilical artery – 3.62±0.09 and 3.41±0.06 rel. units, respectively (р&gt;0.05), PI – 1.23±0.03 and 1.19±0.03 rel. units (p&gt;0.05) and RI – 0.73±0.01 and 0.70±0.01 rel. units (p&gt;0.05). In the third group, in comparison with the second one, vascular resistance did not differ significantly in the right, left uterine arteries and the umbilical cord artery. In patients of the fourth group, in contrast to the third one, higher values of resistance to blood flow were observed: in the right uterine artery – SDR (3.41±0.07 and 2.87±0.07 rel. units, p&lt;0.001), PI (1.48±0.07 and 1.18±0.03 rel. units, p&lt;0.001), RI (0.70±0.01 and 0.65±0.01 relative units, p&lt;0.001); in the left uterine artery – SDR (3.33±0.11 and 2.88±0.09 rel. units, p&lt;0.01), PI (1.45±0.05 and 1.19±0.05 rel. units, p&lt;0.001), RI (0.70±0.01 and 0.68±0.01 rel. units, p&lt;0.01); and also in the umbilical artery – SDR (4.39±0.13 and 3.65±0.12 rel. units, p&lt;0.001), PI (1.45±0.04 and 1.24±0.03 rel. units, p&lt;0.001), RI (0.79±0.01 and 0.72±0.01 rel. units, p&lt;0.001).Conclusion. In the pathogenesis of reduced blood flow in the basin of the uterine and umbilical arteries in women with exacerbation of moderately severe asthma of cytomegalovirus etiology, leading to the development of chronic subcompensated placental insufficiency, compared with uterine cord hemodynamics in asthma in the acute stage, caused by reactivation of CMVI in the second trimester of gestation, which initiates the formation of a chronic compensated form of placental dysfunction in the third trimester of pregnancy, an important role is played by viral stimulation of vasoconstrictor responses.