The correlation of ultrasonic placental grading and fetal pulmonary maturation in five hundred sixty-three pregnancies

In a previous study, it was suggested that the presence of a grade III placenta correlates 100% with a mature lecithin/sphingomyelin (L/S) ratio and may replace amniocentesis in confirming fetal lung maturity. In this study that hypothesis was tested in 563 pregnancies. All patients underwent amniocentesis and simultaneously had placental grading. The correlations of placental grade with an L/S ration ≥2 were: grade 0, 17%; grade I, 68%; grade II, 91%; grade III, 93%. The correlations of placental grade with the presence of phosphatidylglycerol (PG) were: grade 0, 17; grade I, 41%; grade II, 79%; grade II, 75%. The false positive rates associated with grade III placenta were, therefore, 7% for mature L/S ratio and 25% for PG present; when combined with a biparietal diameter ≥9.0 cm, a grade III placenta incorrectly predicted lung maturity in 8.5%. We conclude that placental grading is not accurate enough to replace amniocentesis as the standard test of fetal pulmonary maturity.     

Correlation of real-time ultrasonic placental grading with amniotic fluid lecithin/sphingomyelin ratio

Placental grading with real-time ultrasound was performed on 235 patients who underwent amniocentesis for determination of the lecithin/sphingomyelin (L/S) ratio between 31 and 44 weeks' gestation. Grades I, II, and III placentas were encountered in 88, 72, and 75 patients, respectively. Forty-eight percent of Grade I, 69% of Grade II, and 92% of Grade III placentas had mature L/S ratios (L/S greater than or equal to 2.0). All of the 52 patients with a Grade III placenta who underwent repeat cesarean section at term gestation had mature L/S ratios. However, 37% of the pregnancies complicated by maternal or fetal disease, with Grade III placentas, had immature L/S ratios. The gestational age of these six patients ranged from 34 to 37 weeks. These results suggest that a Grade III placenta in normal term gestation has a good correlation with fetal pulmonary maturity as predicted by the amniotic fluid L/S ratio.     

The relationship of placental grade, fetal lung maturity, and neonatal outcome in normal and complicated pregnancies

Ultrasonically diagnosed maturity changes in the placenta, Grades 0 to III, have been previously shown to correlate with fetal lung maturity. In a prospective study of 230 term and preterm complicated pregnancies, we compared the relationship between sonographic placental grading, amniotic fluid phospholipids, and neonatal outcome. The frequencies of gestational age less than 38 weeks, lecithin/sphingomyelin (L/S) ratio less than 2.0, negative phosphatidylglycerol, and neonatal hyaline membrane disease were found to decrease as placental grade advanced from 0 to III. Patients were divided into subgroups on the basis of maternal complications. In patients with Grade III placentas, the frequencies of gestational age less than 38 weeks and L/S ratio less than 2.0 were significantly increased when the subgroup of patients with chronic hypertension was compared individually to both of the subgroups, repeat cesarean section deliveries, and Classes A, B, and C diabetes mellitus (both with p less than 0.05) All three infants who developed hyaline membrane disease in association with Grade III placentas were from pregnancies of less than 38 weeks complicated by chronic hypertension. These findings suggest that the presence of a Grade III placenta is affected by both gestational age and pregnancy complications. Hence, when an elective cesarean section delivery is being planned near term gestation, a Grade III placenta is a reliable predictor of lung maturity. In preterm complicated pregnancies, an ultrasound-diagnosed Grade III placenta may still be associated with hyaline membrane disease.     

Reproducibility of placental maturity grade classification using a dynamic ultrasonography

Objective: To evaluate the agreement between ultrasonographers in classifying placental maturity grade using examination videos.

Methods: A prospective, cross-sectional study was conducted using 25 videos of ultrasonographic examinations of single, healthy pregnancies ≥?34?+?0 weeks. The Grannum (grades 0, I, II and III) and Julio (grades 0, 1, 2A, 2B and 3) classifications were used for placental maturity grade. The videos were evaluated on two occasions by 10 experienced ultrasonographers. Intra- and inter-observer agreements were evaluated using the Kappa (k) coefficient of agreement.

Results: According to the Grannum classification, the inter-observer agreement coefficients were good for grades III and 0 (k?=?0.69 and 0.738, respectively) and moderate for grades I and II (k?=?0.401 and 0.593, respectively) placentas. According to the Julio classification, the inter-observer agreement coefficients were good for grades 0 and 3 (k?=?0.738 and 0.651, respectively), moderate for grades 1 and 2A (0.401 and 0.413, respectively) and poor for grade 2B (k?=?0.161). Intra-observer coefficients for the Grannum and Julio classifications ranged from 0.567 to 0.890 and from 0.446 to 0.790, respectively.

Conclusion: Placental maturity grading using the Grannum and Julio classifications demonstrated moderate/good intra- and inter-observer agreements on examination videos evaluation.     

Detection of intrauterine growth retardation: a new use for sonographic placental grading

Intrauterine growth retardation (IUGR) is a major source of perinatal death and long-term neurobehavioral morbidity, but its diagnosis antenatally remains difficult. Advanced placental maturity (Grade III), as determined on ultrasound examination, has previously been reported to be a marker of term gestation. In this study of 109 pregnancies which resulted in the birth of infants weighing less than or equal to 2,700 gm, the hypothesis that a Grade III placenta, according to Grannum's classification, can differentiate small-for-gestational age (SGA) infants from small non-SGA infants was tested. Of the study patients, 44 had Grade III placentas and 65 had non-Grade III (0, I, II) placentas within 1 week of delivery. The presence of a Grade III placenta was followed by the delivery of a SGA infant 59% of the time, and 62% of the SGA infants could be correctly identified (p less than 0.001). The association of a Grade III placenta and SGA birth was maintained in patients at less than or equal to 34 weeks of gestation--Grade III placenta was significantly related to the delivery of SGA infants with a true positive rate of 62% and a sensitivity of 66% (p less than 0.008). These results were consistent with the concept that for small fetuses documentation of "maturity" can be used to discriminate those with IUGR from those without this problem. Furthermore, placental "maturation," as detected sonographically, appears to be accelerated in association with IUGR, consistent with the anatomic concept of premature placental senescence. Thus, in situations in which the fetus is known to be small, sonographic grading of the placenta may be helpful in detecting IUGR.     

Advanced ultrasonic placental maturation in twin pregnancies

The mean length of twin pregnancies is shorter than that of singleton pregnancies. The possibility that the shorter gestation of twins is associated with advanced fetal maturational changes was studied in relation to placental maturation. For this purpose, the sonographically determined placental gradings of 158 twin pregnancies and 474 singleton pregnancies were compared at different gestational ages. The percent distributions of placental grades, from I to III, were significantly different throughout the third trimester, with a preponderance of Grade III placentas in the twin group (p less than 0.001). Considering the reported association of Grade III placentas with advanced gestation as well as fetal lung maturity, the present study suggests earlier maturational changes in twin fetuses compared with singleton fetuses.     

Value of placental enzymes, endocrinologic parameters of pregnancy and placental perfusion in cases of intrauterine growth retardation

The serum HCS concentration and urine estriol (E3) content was determined just before delivery in mature but intrauterine retarded and mature eutrophic cases. The hormonal parameters and the placental perfusion index (PPI) were determined in each case parallel. The mitochondrial glutamate dehydrogenase (GLDH) and the glycolytic lactate dehydrogenase (LDH) activity in the placentas were determined immediately after the placentas were born. Among the cases in which intrauterine retarded newborns were born the half of the women had gestosis during their pregnancy and the half had not any problem. It has been found that serum HCS concentration and urine E3 content were significantly lower in the pathologic groups compared to the control. The placental LDH activity significantly increased in both of the dysmature groups. The GLDH activity was normal in the toxemic cases but decreased significantly in the cases where the newborns were dysmature and the mother had no toxemia. There was a correlation between the serum HCS concentration and placental GLDH activity in non-toxemic cases. The perfusion was significantly lower in the toxemic cases only. At the same time there was no correlation between the placental perfusion and endocrine parameters or enzyme activities in both of the pathologic groups.     

Relationship of placental grade to fetal pulmonary maturity and respiratory distress syndrome

Real-time sonographic placental grading was performed on 215 patients who had amniocentesis for determination of fetal pulmonary maturity between 26 and 42 weeks of gestation. The results of this placental grading were correlated with clinical gestational age and fetal pulmonary maturity, assessed by lecithin-sphingomyelin ratio, phosphatidylglycerol, and the subsequent presence or absence of respiratory distress syndrome. This study showed a statistically significant correlation of placental grade with gestational age, pulmonary maturity, and respiratory distress. Grade 3 placentas were seen in 20% of the cases studied, and in every instance was associated with an absence of subsequent neonatal respiratory distress. Placental grade appeared to be an accurate predictor of fetal pulmonary maturity in the population studied.     

The fetal biophysical profile in pregnancies with grade III placentas

The components of the fetal biophysical profile of pregnancies with grade III placentas and good outcome were retrospectively analyzed and compared to the fetal biophysical components of pregnancies with grade 0 to II placentas. The results of the present study suggest that the dynamic components of the fetal biophysical profile (nonstress test, fetal breathing movements, fetal movements, fetal tone) are not altered in the presence of a grade III placenta and good pregnancy outcome; however, a greater incidence of reduced amniotic fluid volume was found in the presence of grade III placenta. The clinical significance of grade III placenta is discussed.     

Studies on surface tension of amniotic fluid with special emphasis on evaluating fetal lung maturity

In order to establish a simple and rapid test for the determination of fetal lung maturity, surface tension (ST) of lipid extracts prepared from amniotic fluid samples obtained from 54 women was measured by Wilhelmy's method. The patterns of ST were classified into three types. Type I: ST of 45 dyne/cm or more at 200 microliters of extract and 36 dyne/cm or more at 350 microliters. Type II: ST of 45 dyne/cm or more at 200 microliters and less than 36 dyne/cm at 350 microliters. Type III: ST less than 45 dyne/cm at 200 microliters. L/S ratio was 2 or more (greater than or equal to 2) in 7 of 23 cases (30.4%) with Type I patterns, 2 of 6 cases (33.3%) with Type II patterns, and 24 of 25 cases (96.0%) with Type III patterns. ST of mature amniotic fluid centrifuged for 10 min. at 5,000 X g and 10,000 X g was higher than ST of mature amniotic fluid centrifuged at 450 X g and 1,000 X g, but ST of immature amniotic fluid showed no significant difference in ST at different centrifugal forces. Contamination with meconium and blood was found to lower ST of immature amniotic fluid remarkably. ST of amniotic fluid lipid extract appeared to be a simple, rapid and reliable method for the assessment of fetal lung maturity.     

Morphologic findings in the placenta in intrauterine fetal growth retardation

The placentas of 105 small-for-dates infants and 190 newborns of normal birth weight were investigated morphologically. Each of these two groups consists of premature newborns and mature newborns. Macroscopic and microscopic data were evaluated by means of a so called data bank. --The weight and the area of attachment were determined. The histologic findings were classified in two groups: 1. Disturbances of placental maturation, 2. Morphologic changes in consequence of reduced uteroplacental blood flow. A marked increase of hypoplastic placentas was found among immature and mature small-for-dates infants. Retarded placental maturity was found more frequently among mature small-for-dates infants then among prematures. Among these, placentas with signs of a reduced uteroplacental perfusion were found more frequently. --It is assumed that the pathogenetic course is different in placentas of premature and mature small-for-dates infants.     

Glucocorticoids inhibit placental cytokines from cultured normal and preeclamptic placental explants

Glucocorticoids are used in pregnancy to enhance fetal lung maturity as well as to ameliorate antepartum and postpartum HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, but it is not clear if glucocorticoids can modulate placental cytokine production. The aim of this study is to examine the effect of glucocorticoids at equivalent doses used for fetal lung maturity on placental tissue production of cytokines (IL-10, IL-6 and TNF-alpha). Placental biopsies were taken from the decidual surface of term placentas of normal pregnancy (n = 5) and preeclampsia (n = 5). Villous explants were cultured with increasing concentrations of glucocorticoids (betamethasone and methyl-prednisolone, 0.0025 microM, 0.25 microM and 25 microM). The dose effect of glucocorticoids on cytokines (TNF-alpha, IL-6 and IL-10) production was examined using ELISA. There was a stepwise reduction of TNF-alpha (23.6-97.5% reduction) and IL-6 (13.7-71% reduction) with increasing doses of betamethasone and methyl-prednisolone from placentas of women with preeclampsia and normal pregnancy. However, IL-10 was not altered in conditioned medium by increasing doses of glucocorticoids. Our data suggest that the ratio of pro-inflammatory to anti-inflammatory cytokine (Th1/Th2) is potentially altered by exogenous glucocorticoids. These changes have a favourable effect on the ratio in preeclampsia with a reduction in the potentially vascular active pro-inflammatory cytokines but without altering or decreasing the necessary anti-inflammatory cytokine IL-10 production in placental tissue.     

Ultrasonic evidence of placental calcification at 36 weeks' gestation: maternal and fetal outcomes

BACKGROUND: To determine the significance of an inappropriately mature placenta on ultrasound examination (Grannum classification), in a low-risk obstetric population. Scans were performed at 36 weeks' gestation. The study group comprised patients demonstrating a grade III placenta, and the control group comprised patients not demonstrating a grade III placenta. METHODS: A total of 1802 low-risk patients were scanned using serial directed real-time ultrasound at 36 weeks' gestation to determine placental maturity. RESULTS: The incidence of a grade III placenta at 36 weeks' gestation was 3.8% (68/1802). A grade III placenta was associated with young maternal age and cigarette smoking, p < 0.01. The incidence of proteinuric pregnancy-induced hypertension in the study and control groups was 7.4% (5/68) and 1.56% (27/1734), respectively, p < 0.01. The proportion of infants with a weight less than the 10th centile at birth in the study and control groups was 17.6% (12/68) and 5.6% (97/1734), respectively, p < 0.01. CONCLUSIONS: Ultrasound detection of a grade III placenta at 36 weeks' gestation in a low-risk population helps to identify the "at-risk" pregnancy. It helps to predict subsequent development of proteinuric pregnancy-induced hypertension and may help in identifying the growth-restricted baby.     

The ultrasonic changes in the maturing placenta and their relation to fetal pulmonic maturity.

A practical classification of placental maturity changes has been developed based on a review of multiple ultrasound evaluations of placental texture over a 4 year period. This classification grades placentas from 0 to 3 according to specific ultrasonic findings at the basal and chorionic plates as well as within the substance of the organ itself. The placentas of 129 patients were graded according to this system at the time of ultrasound evaluation. Eighty-six patients had placentas classified as Grade 1 or greater and all of these had lecithin-sphingomyelin (L/S) ratio determinations performed. Mature L/S ratios (2.0) were found in 68% of Grade I (21/31), 88% of Grade II (28/32), and 100% of Grade III placentas (23/23). These results suggest a correlation between maturational changes of the placenta as seen by ultrasound and fetal pulmonic maturity as indicated by L/S ratio.     

No Correlation Between Ultrasound Placental Grading at 31–34 Weeks of Gestation and a Surrogate Estimate of Organ Function at Term Obtained by Stereological Analysis

We test the experimental hypothesis that early changes in the ultrasound appearance of the placenta reflect poor or reduced placental function. The sonographic (Grannum) grade of placental maturity was compared to placental function as expressed by the morphometric oxygen diffusive conductance of the villous membrane. Ultrasonography was used to assess the Grannum grade of 32 placentas at 31–34 weeks of gestation. Indications for the scans included a history of previous fetal abnormalities, previous fetal growth problems or suspicion of IUGR. Placentas were classified from grade 0 (most immature) to grade III (most mature). We did not exclude smokers or complicated pregnancies as we aimed to correlate the early appearance of mature placentas with placental function. After delivery, microscopical fields on formalin-fixed, trichrome-stained histological sections of each placenta were obtained by multistage systematic uniform random sampling. Using design-based stereological methods, the exchange surface areas of peripheral (terminal and intermediate) villi and their fetal capillaries and the arithmetic and harmonic mean thicknesses of the villous membrane (maternal surface of villous trophoblast to adluminal surface of vascular endothelium) were estimated. An index of the variability in thickness of this membrane, and an estimate of its oxygen diffusive conductance, were derived secondarily as were estimates of the mean diameters and total lengths of villi and fetal capillaries. Group comparisons were drawn using analysis of variance. We found no significant differences in placental volume or composition or in the dimensions or diffusive conductances of the villous membrane. Subsequent exclusion of smokers did not alter these main findings. Grannum grades at 31–34 weeks of gestation appear not to provide reliable predictors of the functional capacity of the term placenta as expressed by the surrogate measure, morphometric diffusive conductance.     

Fetoplacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human placental cotyledon

OBJECTIVE: The purpose of this study was to evaluate fetoplacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. STUDY DESIGN: Two cotyledons from each placenta were selected from preeclamptic (n=8) and normotensive (n=7) pregnancies. In one cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10(-10)mol and 10(-11.5) mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. RESULTS: Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P=.02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P<.01), but not in normotensive placentas. Fetoplacental vascular response to angiotensin II was not affected by preeclampsia or magnesium sulfate. CONCLUSION: In placentas from preeclamptic pregnancies there is increased fetoplacental perfusion pressure, which decreases with exposure to sulfate.     

Contractility of placental vascular smooth muscle cells in response to stimuli produced by the placenta: roles of ACE vs. non-ACE and AT1 vs. AT2 in placental vessel cells

Our previously published work has shown that non-ACE angiotensin II (Ang II) generating system is dominate in the placenta and may play a critical role in regulation of placental vascular contractile function. In the present study, using a collagen gel contraction assay we further studied contractility of placental vascular smooth muscle cells (VSMCs) in response to factors produced by preeclamptic (PE) placentas. Placental VSMCs/type-1 collagen gels were incubated with PE placental conditioned medium in the presence or absence of inhibitors or receptor blockers. Captopril (an ACE inhibitor), chymostatin (a non-ACE chymase inhibitor), losartan (an AT1 receptor blocker) and PD123,319 (an AT2 receptor blocker) were used to study the specific ACE vs. non-ACE and AT1 vs. AT2 effects on placental VSMC contractility, respectively. Our results showed that chymostatin, but not captopril, and PD123,319, but not losartan, significantly attenuated placental VSMC/collagen gel contraction, p<0.01, respectively. The inhibitory effects of chymostatin and PD123,319 were dose-dependent. Our results suggest that chymase, a non-ACE Ang II generating enzyme, may contribute significantly to Ang II generated in the placenta vascular tissue and that the AT2 receptor may play an important role in the regulation of Ang II induced contractility of placental VSMCs. These results provide new insights into Ang II generation and Ang II receptor regulation of vessel contractile function in the placental vasculature. These results also suggest the potential role of increased chymase activity and altered AT2 receptor function in placental related pregnancy disorders such as preeclampsia and IUGR.     

Macroscopically determined placentary conditions in the case of underweight neonates (author's transl)

The placentary conditions (weight of placenta, placenta/infant weight index, kind of attachment of the umbilical cord and allantochorial vasculature) of underweight neonates (eutrophic premature infants and hypotrophic babies born at term), which were macroscopically determined under routine clinical conditions, are compared with those of eutrophic babies born at term after clinically and anamnestically normal pregnancies. Significantly lower weights of placenta and significantly higher placenta/infant weight indices of underweight neonates must be differently assessed for prematurely born babies and hypotrophic infants born at term. The significant increase in the case of underweight neonates of the disperse type of allantochorial vasculature does not suggest any significant relations to either lower weights of placenta or lower weights of newborn infants within the individual classification groups. There is no increase in the number of marginal-velamentous attachments of umbilical cords in the case of underweight neonates. Also, reference is made to the limited importance of macroscopically determined placentary conditions to individual cases.     

Use of femur length measured by ultrasonography to predict fetal maturity

The ultrasonographic criteria of biparietal diameter greater than or equal to 9.2 cm and a grade III placenta have been shown to correlate with fetal maturity in the fetus of a nondiabetic mother in our population. These two criteria have helped reduce the incidence of third-trimester amniocenteses by 66.6% at our institution. Occasionally, however, because of fetal position, we are unable to obtain an accurate biparietal diameter. We therefore carried out a prospective study of 120 patients to evaluate the relationship between femur length of greater than or equal to 7.3 cm and fetal maturity. In this study, the addition of the femur length criterion increased the specificity of the ultrasonographic criteria for fetal maturity from 66.6% to 85%. The data suggest that femur length could be used along with the biparietal diameter and placental grade as an alternative to amniocentesis in term nondiabetic pregnancies.     

Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia

OBJECTIVE: To investigate the alterations of syncytin, a fusogenic membrane protein involved in syncytiotrophoblastic layer formation, and its receptor ASCT2 expression in placental development and pre-eclampsia. DESIGN: Analyses of syncytin and ASCT2 expression in placentas from different stages of pregnancy and women with pre-eclampsia and in cytotrophoblasts cultured in normoxic and hypoxic conditions. SETTING: Placental samples were collected from a tertiary medical centre. POPULATION: Sixteen women with pre-eclampsia and 58 pregnant women presented as pregnancy (5-19 weeks of gestation) for elective termination, preterm birth, or normal term delivery. METHODS: The quantitative real-time polymerase chain reaction was used to study the syncytin and ASCT2 expression during placental development in 35 placentas from women without pre-eclampsia (ranged from 5 to 40 weeks of gestation) and the alterations of pre-eclamptic placentas (n=16) compared with gestational-age-matched controls (n=16). Western blot analysis was performed to study the protein level of syncytin in pre-eclamptic placentas and gestational-age-matched controls. The hypoxic effect on trophoblastic syncytin and ASCT2 expression was further studied in cytotrophoblasts cultured in 2% oxygen (n= 7). MAIN OUTCOME MEASURES: Syncytin and ASCT2 messenger RNA (mRNA) in placental tissue and cytotrophoblasts. RESULTS: The level of syncytin mRNA expression increased significantly since the first trimester of pregnancy until 37 weeks of gestation, when the level of syncytin expression was reduced. The ASCT2 mRNA expression was decreased significantly since the second trimester and was relatively stable since then to 40 weeks of gestation. Furthermore, a significant reduction in syncytin mRNA expression was observed in pre-eclamptic placentas and cytotrophoblasts cultured in hypoxia, but not a reduction in ASCT2 mRNA expression. Correlatively, the protein level of syncytin was decreased in pre-eclamptic placentas. CONCLUSIONS: A reduced placental expression of syncytin but not ASCT2 may contribute to altered cytotrophoblastic cell fusion processes and disturbed placental function in pre-eclampsia. Correspondingly, hypoxia decreases syncytin but not ASCT2 gene expression in cultured cytotrophoblasts.