Neurokinin B levels in maternal and umbilical cord blood in preeclamptic and normal pregnancies

Neurokinin (NK) B has been recently demonstrated to be secreted by the placenta in preeclampsia suggesting it may modulate pathophysiological events of the disease. The aim of this study was to investigate whether NKB is the circulating factor associated with preeclampsia or not. In 22 preeclamptic and normotensive pregnant women, the peripheral and umbilical cord blood NKB levels were measured by radioimmunoassay. The NKB levels in women with preeclampsia were 0.70 (0.53-0.92) nmol/L in peripheral blood and 1.92 (1.42-2.35) nmol/L in umbilical cord blood. In normotensive pregnant women, NKB levels were 0.43 (0.29-0.61) nmol/L and 0.14 (0.07-0.33), respectively. Significantly higher levels of NKB were measured in preeclamptic women compared with normotensive pregnant women in umbilical cord blood. These results suggest that NKB enters both fetal and maternal circulation and may modulate fetoplacental hemodynamics.     

Correlation between umbilical vein blood flow and umbilical blood viscosity in normal and complicated pregnancies

Umbilical vein blood flow (UVBF) was studied during the last 24 h before delivery using a combination of real-time and Doppler ultrasonic equipment in 64 normal and pathological pregnancies and the results were correlated with the values of whole blood viscosity taken from the umbilical vein after delivery. UVBF was reduced in the subgroup with chronic fetal distress (n = 14) (P less than 0.001) and the hypertensive pregnancies (n = 17) (P less than 0.05), whereas umbilical blood viscosity was increased only in the subgroup with chronic fetal distress (P less than 0.01) as compared with the normal pregnancies (n = 24). A significant positive correlation was observed between the umbilical blood viscosity and haematocrit values in all the groups of patients. UVBF and blood viscosity had a significant negative correlation in chronic fetal distress (P less than 0.001) and in hypertensive pregnancies (P less than 0.05), but not in normal or diabetic pregnancies (n = 9). Thus haemoconcentration leading to increased fetal blood viscosity may act as an aetiological factor in the reduction of UVBF in developing fetal distress.     

Stem cells from umbilical cord blood

The study of hematopoiesis, the generation of blood cell lines throughout life, has provided conceptual, experimental, and therapeutic approaches useful to all stem cell biologists. From a clinical perspective, no other area of stem cell biology has been applied as successfully as has transplantation of bone marrow and cord blood for the treatment of blood diseases. In the last few years, research in stem cell biology has expanded rapidly to include the study of stem cells from embryonic, fetal, and various adult tissues, engendering novel perspectives regarding the identity, origin, and full therapeutic potential of tissue-specific stem cells. Rather than focusing on the use of cord blood stem cells for reconstitution of bone marrow, this article reviews the biology of stem cells found in the cord blood in the context of cell plasticity and their therapeutic potential for repair of the nervous system.     

Concentration of cord serum placenta growth factor in normal and diabetic pregnancies

OBJECTIVE: To investigate whether maternal diabetes or diabetes-related complications, such as macrosomia and chronic fetal hypoxia, are associated with altered placenta growth factor (PlGF) levels in cord serum. DESIGN: Case-control study. SETTING: Helsinki University Central Hospital, Helsinki, Finland. POPULATION: Sixty-two normal pregnancies, 67 pregnancies complicated by type 1 diabetes and 28 pregnancies complicated by insulin-treated gestational diabetes. METHODS: Cord serum PlGF concentration was measured by an enzyme-linked immunosorbent assay. Amniotic fluid erythropoietin concentration was measured by a chemiluminescent immunologic method. Umbilical artery gas variables were analysed with standard blood gas and pH electrodes. MAIN OUTCOME MEASURE: PlGF concentration in cord serum at birth. RESULTS: Cord serum PlGF concentration was similar in normal pregnancies [13.4 (1.0) ng/L], in pregnancies complicated by type 1 diabetes [15.1 (1.8) ng/L, P= 0.583 vs controls] and in pregnancies complicated by insulin-treated gestational diabetes [13.6 (0.9) ng/L, P= 0.991 vs controls]. Cord serum PlGF did not correlate with relative birthweight. In diabetic pregnancies, cord serum PlGF correlated negatively with amniotic fluid erythropoietin (r=-0.449, P < 0.0001) and positively with umbilical artery Po(2) (r= 0.333, P= 0.001). There was a trend toward lower cord serum PlGF levels in diabetic pregnancies with pre-eclampsia compared with those without any hypertensive disorders. CONCLUSIONS: Maternal diabetes per se is not associated with altered PlGF levels in cord serum. The correlation between PlGF and indices of fetal hypoxia in diabetic pregnancies may be related to the role of PlGF in potentiating the angiogenic response to vascular endothelial growth factor in ischaemia.     

Cerebral and umbilical arterial blood flow velocity waveforms in normal and growth-retarded pregnancies

A combined sector and pulsed Doppler system was used to study the pulsatility index in the fetal internal carotid artery and umbilical artery in 156 normal pregnancies and 42 cases of intrauterine growth retardation (birth weight below the tenth percentile). All pregnancies were in the third trimester. In normal pregnancies, there was a gestational age-related fall in pulsatility index for both the umbilical artery and the umbilical artery/internal carotid artery ratio. No such fall was established for the pulsatility index in the internal carotid artery. In growth-retarded pregnancies, raised pulsatility index values in the umbilical artery were associated with reduced pulsatility index values in the internal carotid artery, suggesting the presence of a "brain-sparing" effect. When fetal causes of growth retardation were excluded, the sensitivities of the pulsatility index in the internal carotid artery, the umbilical artery, and for the umbilical artery/internal carotid artery ratio were 65, 83, and 88% at the 1 standard deviation (SD) cutoff level; and 48, 60, and 70% at the 2 SD cutoff level. Growth-retarded fetuses with structural or chromosomal defects had normal pulsatility index values in the internal carotid artery.     

Concentration of erythropoietin in blood serum of the umbilical cord and in amniotic fluid in normal and complicated pregnancies]

Erythropoietin is the primary hormone controlling erythropoiesis in both adults and fetuses. In extra-fetal life the main organ producing erythropoietin is the kidney which is responsible for producing about 90% of the total amount of this hormone. In fetal life erythropoietin is produced by the liver of the fetus. The erythropoietin production depends on the content of oxygen in blood. This is probably the only physiological stimulus which regulates the production of erythropoietin. The increase of erythropoietin concentration in the umbilical cord serum and in the amniotic fluid has been observed in the states of fetus anoxia. This mainly concerns such complications during pregnancy as the fetus hypotrophy, diabetes, serological conflict, and gestosis.     

Carcinoembryonic antigen (CEA) in normal and pre-eclamptic pregnancies (values in maternal blood,amniotic fluid and umbilical cord blood)

Values of Carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 100 pregnant women divided into 4 groups. In group 1 (49 normal pregnancies) and 2 (17 pre-eclamptic pregnancies), the estimation of CEA was done in maternal vein blood, umbilical cord blood and in amniotic fluid. In group 3 (20 normal pregnancies) CEA was measured separately in blood of the two umbilical vessels as well as in maternal vein blood. In group 4 (14 pregnancies with small-for-date infants) CEA was estimated in umbilical cord blood. The values in amniotic fluid of normal and pre-eclamptic pregnancies were more than 20 times higher than in the other two compartments. A significant correlation was found between the amniotic fluid and umbilical cord blood values (r = 0.500; P < 0.05), as well as between the values in umbilical artery and vein (r = 0.792; P < 0.001). Thus, it is thought that CEA is transferred from the amniotic cavity to the umbilical cord while a part of CEA perhaps is produced by the placenta. Umbilical cord blood values of small-for-date fetuses do not differ significantly from the normal. On the contrary, significantly lower values were obtained in umbilical cord blood and in amniotic fluid of pre-eclamptic women as compared to the normal, but this finding is not useful clinically because of the large standard deviation.     

The effect of umbilical cord blood cytokines on clonogenicity of hemopoietic stem cells isolated from umbilical cord blood

Human umbilical cord blood contains haematopoietic stem cells, which are a potential source of cells for hematopoietic transplants. Early cord blood hematopoietic cells are influenced by so called proinflammatory cytokines, which are present in cord blood serum. In this study we tried to correlate the concentration of these cytokines with the number, viability and clonogenicity of cord blood mononuclear cells. Accordingly, cord blood samples were harvested by employing an "open" collection method. Subsequently, we measured in those samples the concentration of selected pro inflammatory cytokines (Il-1 alpha, Il-1 beta, Il-6, Il-8 and TNF alpha), number of mononuclear cells and evaluated in vitro clonogenicity of myeloid progenitors (CFU-GM). We found the negative correlation between number of mononuclear cells and concentration of TNF alpha, and between number of detectable CFU-GM and concentration of IL-1 beta. Other cytokines, which were studied in this report did not correlate with evaluated parameters.     

Human placental insulin binding in normal and well-controlled diabetic patients

Previous studies of insulin binding to placentas of both insulin-dependent and untreated gestational diabetic patients have described placentas from diabetics to contain fewer insulin receptors than placentas from nondiabetic gravidas. However, these studies were done using membrane fractions prepared from the placentas and at a time when adequacy of antepartum glycemic control in the diabetic patients was not routinely evaluated by self blood sugar measurement or hemoglobin A1 assay. The current study compares specific 125I-insulin binding in vitro to intact placental villi from 15 normal patients with insulin binding to intact villi obtained from 15 insulin-dependent diabetic mothers whose fasting and postprandial blood sugars and hemoglobin A1 levels were maintained in a range normal for term pregnancy. We demonstrate that insulin binding to intact placental villi is the same in this group of diabetic patients as in the nondiabetic patients.     

Ionized calcium levels in umbilical cord blood of women with preeclampsia and normotensive pregnancies

Calcium is essential for normal fetal growth and development. During intrauterine life, the fetus is entirely dependent on the mother and a normally functioning placenta for calcium accretion. Preeclampsia is associated with abnormal calcium metabolism and placental dysfunction. The objective of our study was to investigate ionized calcium levels in the umbilical cord arterial blood of women with preeclampsia and normotensive pregnancies. There were 24 women in the preeclampsia group and 25 in the normotensive group. There was no difference in the cord pH and fetal growth restriction between the two groups. Ionized calcium levels were significantly lower in the preeclampsia group (p?<?0.001). Our results emphasize the need for further studies on the calcium status of infants born to mothers with preeclampsia.     

Evaluation of cord blood ischemia modified albumin in normal pregnancies and pre-eclampsia

Objective: Pre-eclampsia is associated with ischemia and increased oxidative stress, which may lead to modification of plasma albumin to ischemia modified albumin (IMA). Methods: IMA levels were estimated in cord blood of 30 newborns born to pre-eclamptic mothers and compared with 30 normal newborns. IMA was estimated colorimetrically and the results were compared statistically. Results: The levels of IMA were found to be significantly higher (p?<?0.001) in newborns born to pre-eclamptic mothers (0.835?±?0.02 ABSU) as compared to those born to normal mothers (0.325?±?0.01 ABSU). Conclusion: IMA may act as a marker of ischemia and oxidative stress in newborns delivered to pre-eclamptic mothers.     

Troponins,heat shock proteins and glycogen phosphorylase BB in umbilical cord blood of complicated pregnancies

Purpose of the study: Heat shock proteins (Hsp) are evolutionary conserved molecules with a chaperone role in cell survival. We hypothesized that cord blood concentrations of molecules reflecting fetal cardiac muscle insult, including Hsp, troponins cTnI and cTnT, and glycol-phosphorylase BB (GP-BB) would be elevated in pregnancies complicated by gestational diabetes (GDM) or preeclampsia (PIH) compared to healthy controls.

Materials and methods: Pregnant women admitted for delivery at >28 weeks were divided into four groups: healthy patients delivered vaginally (VAG), healthy patients delivered by c-section (CS), patients with PIH, and patients with GDM. Demographics, clinical characteristics, and cord blood concentrations of Hsp, troponins cTnI and cTnT, and GP-BB were compared between groups. Statistical analyses included t-test, Chi square, and Wilcoxon rank sum as appropriate.

Results: cTnI concentrations were significantly higher in the PIH group compared to the GDM and VAG groups and they were higher in the CS group compared to the VAG group. Concentrations of Hsp70 were higher in the GDM group compared to the VAG and CS groups. Concentration of GP-BB was higher in the PIH group compared to the VAG group.

Conclusions: GP-BB and cTNI are the most sensitive markers for PIH-related fetal myocyte injury as is Hsp70 in pregnancies complicated by GDM.     

Insulin-like growth factor 1 and its binding protein 1 during normal and diabetic pregnancies.

Investigations of circulating insulin-like growth factor 1, hPL, and infant size during pregnancy in normal and insulin-dependent diabetic women have yielded conflicting results and have not been analyzed longitudinally. We studied serial changes in maternal serum insulin-like growth factor 1 levels (measured by radioimmunoassay after acid ethanol extraction) throughout pregnancy in 22 normal women and in 38 with insulin-dependent diabetes. The diabetic women had significantly lower serum insulin-like growth factor 1 concentrations than normal women throughout pregnancy and after delivery, although the rates of change in both groups of women were similar. Within-patient analysis showed a significant decrease in serum insulin-like growth factor 1 between 6-12 weeks' gestation and a significant increase between 24-32 weeks, followed by a significant decrease from 36 weeks' gestation to 12 weeks after delivery. Incremental changes in insulin-like growth factor 1 between 24-32 weeks' gestation correlated significantly with incremental changes in hPL (r = 0.40; P less than .001) and with birth weight (r = 0.37; P less than .01), but not with ultrasound measurements of fetal growth. The correlation of increments in insulin-like growth factor 1 and birth weight became nonsignificant when the association of hPL with both insulin-like growth factor 1 and birth weight was taken into account. Neither insulin-like growth factor binding protein 1 (placental protein 12) nor its ratio to insulin-like growth factor 1 showed any association with infant size. The physiologic changes in maternal serum insulin-like growth factor 1 in pregnant diabetic women do not appear related to the increased birth weight of their infants.     

Volumetric umbilical artery blood flow: comparison of the normal versus the single umbilical artery cord

OBJECTIVE: This was a study of the volumetric blood flow in single umbilical artery (SUA) cords as compared to three-vessel cords. Hypothesis: SUA flow will be twice that of an artery in a normal cord. METHODS: We studied 276 patients (24 SUA, 252 normal cord) at 18-40 weeks' gestation utilizing gray-scale and color Doppler. Flow, flow/kg, velocity, artery diameter, Doppler velocimetry indices, estimated fetal weight (EFW) and amniotic fluid index (AFI) were compared. All fetuses were anatomically and cytogenetically normal. RESULTS: Blood flow increased with advancing gestation and the SUA volume was twice that in the normal cord artery. Flow/kg decreased for both cords, with the SUA values twice those of normal cords. Arterial diameter and velocity increased, but to a greater degree in SUA. Velocimetry, although in the normal range, decreased progressively with the resistance indices always lower in the SUA cord. EFW and AFI were the same for both groups. CONCLUSION: Volumetric blood and its components were measured indirectly with ultrasound. The SUA cord artery carried twice the blood volume of an artery in a three-vessel cord. Other flow parameters changed appropriately to explain the increased flow. For the anatomically normal fetus with SUA there was no increase in intrauterine growth restriction.     

Volumetric umbilical artery blood flow: comparison of the normal versus the single umbilical artery cord

Objective : This was a study of the volumetric blood flow in single umbilical artery (SUA) cords as compared to three-vessel cords. Hypothesis: SUA flow will be twice that of an artery in a normal cord. Methods : We studied 276 patients (24 SUA, 252 normal cord) at 18-40 weeks' gestation utilizing gray-scale and color Doppler. Flow, flow/kg, velocity, artery diameter, Doppler velocimetry indices, estimated fetal weight (EFW) and amniotic fluid index (AFI) were compared. All fetuses were anatomically and cytogenetically normal. Results : Blood flow increased with advancing gestation and the SUA volume was twice that in the normal cord artery. Flow/kg decreased for both cords, with the SUA values twice those of normal cords. Arterial diameter and velocity increased, but to a greater degree in SUA. Velocimetry, although in the normal range, decreased progressively with the resistance indices always lower in the SUA cord. EFW and AFI were the same for both groups. Conclusion : Volumetric blood and its components were measured indirectly with ultrasound. The SUA cord artery carried twice the blood volume of an artery in a three-vessel cord. Other flow parameters changed appropriately to explain the increased flow. For the anatomically normal fetus with SUA there was no increase in intrauterine growth restriction.