Are placental chorionic capillary nucleated red blood cell counts useful compared to umbilical cord blood tests?

OBJECTIVE: To compare measurement of fetal nucleated red blood cell (NRBC) counts in paired histologic samples of the placenta and umbilical cord bloods. METHOD: Forty-five randomly selected pregnancies had two determinations of the NRBC count. A sample of umbilical venous blood had a NRBC count measured and sections of the placenta were examined for their villous capillary NRBC counts. RESULTS: Umbilical venous blood had NRBC/100 white blood cell counts ranging from 0 to 67. Paired evaluation of placental tissue had NRBC counts of 0-5 with 60% being zero compared to 8% zero counts in cord blood. There was no correlation between the paired counts (R(2) = 0.04). CONCLUSION: Umbilical cord blood provides different information on fetal NRBC count than does histologic study of the placenta.     

Transfusion of fetal cord blood cells: an improved method of hematopoietic stem cell transplantation?

Hematopoietic stem cells circulate in the fetal blood and may be isolated from the placenta through the umbilical cord after birth. These cells have been safely isolated, and transplanted into recipients to treat malignancies and marrow failure. Cord blood stem cells may be used for genetic disorders. Compared to other sources of stem cells, recipients of cord blood stem cells have fewer and less severe episodes of graft versus host disease. This may be because intrauterine graft (fetus) versus host (mother) disease is harmful to the pregnancy. Controversies persist surrounding the harvest and use of these cells.     

Are amniotic fluid C-reactive protein and glucose levels, and white blood cell counts at the time of genetic amniocentesis related with preterm delivery?

OBJECTIVE: To compare women with spontaneous preterm delivery before 37 weeks and women who delivered at term with respect to amniotic fluid C-reactive protein (CRP), glucose levels, and white blood cell counts at the time of genetic amniocentesis. STUDY DESIGN: The study was conducted on 216 pregnant women who underwent genetic amniocentesis between the 15th and 18th weeks of gestation at Baskent University Obstetrics and Gynecology Department. All patients were followed until delivery for the occurrence of pregnancy complication. Indications for amniocentesis included abnormal triple test results showing increased risk for Down's syndrome, advanced maternal age and sonographic findings indicative for chromosomal abnormalities. The samples were carried immediately to the laboratory for cytogenetic and biochemical examination. Women with spontaneous preterm delivery before 37 weeks (n = 20) and those who delivered at term (n = 196) were compared with respect to some maternal and infant characteristics, amniotic fluid C-reactive protein, glucose levels, and amniotic fluid white blood cell counts. RESULTS: During the study period 244 patients underwent amniocentesis. A chromosomal abnormality was present in 11 patients. 1 patient had a spontaneous pregnancy loss within 3 weeks after the procedure and 16 patients were delivered for fetal or maternal indications (preeclampsia, fetal growth restriction, placenta previa). The remaining 216 women were included in the study and investigated for the risk of preterm delivery. The prevalence of spontaneous preterm delivery before 37 weeks was 9.3% (20/216). There were no significant differences between the preterm delivery and the term delivery groups with respect to C-reactive protein levels and white blood cell counts. Mean amniotic glucose levels were significantly lower in the preterm delivery group (P<0.05). Amniotic fluid glucose levels of < or = 46 mg/dL had a sensitivity of 100% and NPV of 100%. CONCLUSION: Amniotic fluid glucose levels at the time of genetic amniocentesis are lower in women with spontaneous preterm delivery before 37 weeks compared to those who delivered at term. Amniotic fluid glucose levels of < or = 46 mg/dL at the time of genetic amniocentesis may be more sensitive, cheaper and have higher negative predictive value than C-reactive protein levels and white blood cell counts for the prediction of patients in spontaneous preterm labor. The greatest benefit of amniotic fluid glucose testing might be when the physician judges the patient to be at low risk for preterm delivery.     

Commentary: is it safe to limit allogeneic red blood cell transfusions to neonates?

Two randomized clinical trials, conducted independently, have reported results of neonates transfused with red blood cells (RBCs) given per either liberal (relatively high pretransfusion blood hematocrit levels) or restrictive (relatively low pretransfusion blood hematocrit levels) transfusion programs. Both found fewer RBC transfusions given per restrictive programs and comparable outcomes for several clinical endpoints. However, the Iowa trial found significantly more problems with apnea, intraparenchymal brain hemorrhage and periventricular leukomalacia in infants transfused per the restrictive program - findings not found by the Canadian trial. A critical analysis of both trials and possible reasons for the discrepant findings are discussed. Until definitive data are reported by additional studies, it seems prudent not to severely restrict/limit allogeneic RBC transfusions to neonates - except in approved investigational settings.     

Is intrapartum vibroacoustic stimulation an effective predictor of fetal acidosis?

OBJECTIVE: The hypothesis of this prospective study is that intrapartum vibroacoustic stimulation (VAS) is an effective predictor of fetal acidosis during labor. Various clinical conditions, such as term versus preterm gestation, first stage versus second stage of labor, and fetal heart rate (FHR) variable decelerations versus late decelerations will be tested. METHODS: During the study period, 113 patients were studied prospectively in either active phase of first stage (n = 53) or during the second stage of labor (n = 60). They were selected from cases exhibiting moderate to severe FHR variable decelerations or late decelerations. The fetuses of study subjects received a VAS for three seconds and FHR changes were recorded. Fetal scalp blood pH or umbilical arterial blood pH was obtained within 15 minutes of VAS. The relationship between FHR responses to VAS and fetal blood pH in term and preterm gestations, the relationship of two tests (VAS and fetal blood pH) to type of FHR decelerations, and the predictability of neonatal morbidity by two tests were analyzed. Where appropriate, Fisher's exact test (p < 0.05 was considered statistically different) and the odd ratio with 95% confidence intervals were used for statistical analyses. RESULTS: Excellent association between acceleration response to VAS and pH > or = 7.20, and between a negative response to VAS (no acceleration or decelerations) and pH < 7.20 were found in the first stage of labor, the second stage of labor, and the combination of both stages together (p = 0.0001, OR = 10.6 [3.3-34.0]). It was observed that negative VAS responses for predicting fetal acidosis (pH < 7.20) were comparable between term (> or = 37 weeks) and preterm (< 37 weeks, > or = 34 weeks) fetuses. Since the preterm fetuses enrolled in the study were limited in number, it is difficult to draw adequate conclusions. The positive predictive value (PPV) of fetal acidosis was 67% in both groups of FHR variable decelerations and late decelerations, but the false negative rate of acceleration VAS response for predicting no acidosis was significantly higher in the group of late decelerations (29% vs 8%, p = 0.034). Finally, both a negative VAS response and fetal acidosis (pH < 7.20) have equal predictability for neonatal morbidity. The PPV of NICU admission by a negative VAS response was two times higher than that of fetal acidosis (PPV = 61% vs 29%, p = 0.038). CONCLUSION: We found that intrapartum VAS was an effective predictor of fetal acidosis in cases of FHR variable decelerations, but its predictability for fetal acidosis in cases of FHR late decelerations was limited. Both VAS and fetal blood pH are good predictors of neonatal morbidity.     

Does augmented growth impose an increased risk of fetal death?

OBJECTIVE: Our purpose was to examine the risk of fetal death associated with augmented fetal growth. STUDY DESIGN: All live births recorded in Virginia between January 1, 1991, and December 31, 1993, were examined. Mortality rates were examined for infants born at or beyond 24 weeks' gestational age with weights between the 75th and 90th percentiles, from the 90th to the 95th percentile, and >95th percentile. RESULTS: Mortality rates were found to rise only slightly with birth weights >90th percentile. A recorded diagnosis of maternal diabetes, however, was associated with a significant risk in the presence of augmented fetal growth. Augmented fetal growth without maternal glucose intolerance showed no increase in mortality. CONCLUSION: Augmented fetal growth in the absence of maternal glucose intolerance appeared not to be associated with a significant increase in the risk of death among these births. Increased risk was found when augmented fetal growth was associated with maternal diabetes.     

Does fetal gender affect cytotrophoblast cell activity in the human term placenta? Correlation with maternal hCG levels

BACKGROUND: Pregnant women with female fetuses have higher maternal serum human chorionic gonadotropin (hCG) levels than pregnant women with male fetuses. Ki-67, a cell proliferation and activity marker, is confined mostly in the nuclei of villous cytotrophoblasts of the human placenta. In this study, we examined the effect of fetal gender on the cytotrophoblast cell activity in human term placenta, with special regard to maternal serum and cord blood hCG levels. METHODS: Thirty-four uncomplicated, singleton, term pregnancies (17 male and 17 female fetuses) were recruited in the study. hCG was measured in maternal peripheral serum and umbilical cord blood. Placental samples were collected in each patient during the cesarean section. Cytotrophoblast cell activity was measured by using immunohistochemistry for Ki-67 antigen. Ki-67 staining index values of the cytotrophoblasts were compared between the female and male placentas. RESULTS: Maternal serum and cord blood hCG levels were higher in pregnant women with female fetuses than in those carrying male fetuses. There was no sex difference in Ki-67 immunostaining rates of the cytotrophoblast cells. There was no correlation between maternal serum and cord blood hCG levels and Ki-67 staining index values of the cytotrophoblast cells. CONCLUSIONS: The difference in maternal serum and cord blood hCG levels in correlation with the fetal gender is not associated with cytotrophoblast cell activity in the human term placenta. The gender of the fetus does not seem to affect the regulation of cytotrophoblast cell proliferation.     

Should fetal scalp blood sampling be performed in the case of meconium-stained amniotic fluid?

Objective: To investigate the effect of using fetal scalp blood sampling on the risk of neonatal respiratory distress syndrome (NRDS) with meconium-stained amniotic fluid (MSAF).

Methods: Prospective data collection with regard to MSAF during labor for low-risk term cephalic singleton live birth from 2012 to 2014. Maternal, obstetric and neonatal data were compared according to the occurrence of respiratory distress syndrome (RDS group) or not (no RDS group).

Results: Of 515 newborns born through MSAF, 46 experienced RDS and from them 10 experienced meconium aspiration syndrome. No difference was observed according to maternal characteristic, abnormal fetal heart rate tracing pattern irrespective of its category and cesarean rate. Apgar at one?minute was lower in the group RDS (7.6 versus 8.5, p?<?0.05). The mean umbilical artery pH values did not differ between the two groups. Significant difference between newborns with and without RDS in terms of fetal scalp lactate sampling during the labor (71.1% versus 55.1%, p?<?0.05), and neonatal care unit (NCU) admissions (22.8% versus 10.8%, p?<?0.05). Secondary rather than primary meconium was associated with RDS when performing fetal scalp blood assessment (p?<?0.05). A significant correlation between RDS, fetal scalp blood assessment and MSAF diagnosed during the first stage of labor (after spontaneous rupture of membranes or at amniotomy) was found.

Conclusion: In case of MSAF, fetal scalp blood sampling did not reduce the risk of RDS.     

Fetal cells and cell free fetal nucleic acids in maternal blood: new tools to study abnormal placentation?

The analysis of fetal cells, and more recently cell free fetal nucleic acids, in maternal blood has to date largely been concerned with the development of risk free methods for prenatal diagnosis. Although elevated feto-maternal cell trafficking has long been associated with preeclampsia, it has only recently been shown that this perturbation is an early event in these pregnancies, occurring well in advance of the onset of symptoms. In a separate development, analogous observations have been made concerning the levels of circulatory fetal nucleic acids in maternal plasma. Subsequent studies have shown that changes in these two parameters may also occur in other pregnancy related disorders including preterm labour, intra-uterine growth retardation, hyperemesis gravidarum or even pregnancies at high altitude. A striking finding of these examinations was that preterm labour was associated with an elevated release of cell free fetal nucleic acids but not with an increment in feto-maternal cell trafficking. This suggested that the analysis of the mechanisms regulating trans-placental cell trafficking or liberation of circulatory fetal nucleic acids may provide key insights into the fundamentally different placental lesions underlying these disorders. As such, circulatory fetal cells and nucleic acids may be viewed as new tools to study alterations in placentation.     

Amniotic fluid Clara cell protein concentration in normal pregnancy, a marker of fetal airway growth or fetal lung maturation?

OBJECTIVE: To evaluate the relationship of Clara cell protein (CCP) in amniotic fluid (AF) with the lecithin/sphingomyelin (L/S) ratio, and the concentrations of saturated phosphatidylcholine (Sat PC) and surfactant protein A (SP-A). STUDY DESIGN: AF samples were obtained by amniocentesis from 98 pregnancies without conditions known to influence fetal lung maturation between 25 and 41 weeks of gestation. These samples were used for determinations of CCP, L/S ratio, Sat PC, and SP-A. Simple and multiple linear regressions were used to analyze the data. RESULTS: CCP in AF increased logarithmically with gestational age (R(2)=0.51, p=0.006). The L/S ratio (R(2)=0.41, p<0.001), and the concentrations of Sat PC (R(2)=0.26, p<0.001) and SP-A (R(2)=0.52, p<0.001) also increased with advancing gestation. Weak correlations of CCP with the L/S ratio (R(2)=0.22, p=0.009) and Sat PC (R(2)=0.12, p=0.004), but not with SP-A (R(2)=0.07, p=0.10), were found. Using multiple linear regressions, gestational age was the only predictor of CCP (F=10.9, R(2)=0.13, p=0.015). Conversely, gestational age, Sat PC, and SP-A accounted for most of the variation of the L/S ratio (F=34.7, R(2)=0.61, p=0.0001). CONCLUSION: CCP correlated very poorly with known and widely accepted indices of fetal lung maturation. The increasing concentration of CCP in AF throughout gestation probably reflects growth and development of the fetal airways.     

Lactoferrin level in maternal serum is related to birth anthropometry – an evidence for an indirect biomarker of intrauterine homeostasis?

Abstract

Objective: To investigate the relation between level of antibodies against lactoferrin (LfAb) in maternal serum (MS) and birth anthropometry of healthy full-term newborns.

Methods: The study included 105 pairs of mother-newborn. MS LfAb level was determined using ELISA kit. Spearman’s correlation and Kruskal–Wallis one-way analysis of variance (ANOVA) were applied to establish the relationship between MS LfAb level and birth weight (BW), birth weight-to-birth length ratio (BW/BL), and head circumference (HC) of newborns.

Results: The U-shaped relation of MS LfAb and BW was demonstrated (p?=?.019). Negative correlation between MS LfAb and BW/BL was observed (p?=?.016). The most optimal birth weight and body proportion were observed in newborns of mothers with MS LfAb level of 49?±?4?U/ml.

Conclusions: Significant relationship between MS LfAb and birth anthropometry suggests serum Lf of pregnant women can be considered as a promising indirect biomarker of intrauterine homeostasis, verifiable noninvasively already during pregnancy and thus allowing predict, or even prevent, potential short- and long-term postnatal health consequences.     

Does the use of fetal fibronectin in an algorithm for preterm labor reduce triage evaluation times?

Abstract

Objective: To determine the effectiveness of a novel algorithm based on fetal fibronectin (FFN) for management of preterm labor (PTL).

Methods: A randomized trial was performed on patients who presented with symptoms of PTL at 24–34 weeks. Patients were randomized to algorithms with cervical exams only versus cervical exams plus FFN. In this algorithm, physicians had to discharge patients with a negative FFN result. The primary outcome was the evaluation time for triage. The secondary outcomes were admission to the hospital for PTL, preterm birth <34 weeks and preterm birth <37 weeks.

Results: A total of 76 patients were enrolled and randomized (control n?=?32, FFN n?=?44). There were no differences in triage time, hospital admissions or preterm deliveries (PTDs) between the two groups.

Conclusion: An algorithm based on FFN for management of PTL does not reduce evaluation times for triage, hospital admissions or PTDs.     

Cholesterol transport by the placenta: placental liver X receptor activity as a modulator of fetal cholesterol metabolism?

Cholesterol is an important sterol in mammals. Defects in cholesterol synthesis or intracellular routing have devastating consequences already in utero: the Smith-Lemli-Opitz syndrome, desmosterolosis and Niemann-Pick C1 disease provide examples of severe human inherited diseases caused by mutations in cholesterol metabolism genes. On the other hand, elevated plasma cholesterol concentrations are associated with the development of atherosclerosis which represents a major health risk in Western societies. Moreover, several studies indicate that development of atherosclerosis may already start during fetal life. Hence, a carefully balanced regulation of cholesterol metabolism appears of critical importance for both the development of the fetus and health of the adult. In the adult, the liver X receptor is a key regulator of cholesterol metabolism. Its target genes regulate cellular cholesterol efflux and thereby modulate whole-body cholesterol fluxes. LXR and several of its target genes have recently been demonstrated to be expressed in the placenta, which would provide a means to control delivery of maternal cholesterol to the fetus. Here we discuss the potential role of the placenta in the regulation of fetal cholesterol homeostasis and strategies to influence maternal-fetal cholesterol transfer.