Correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.

ABSTRACT: The present study was conducted with an attempt to explore the correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.The levels of umbilical cord blood resistin, adiponectin, insulin, growth hormone, leptin, thyrotropin, thyroid hormone (T3, T4), lgM, lgA, lgG, CD4, and CD8 were measured in 180 full-term newborns delivered in hospital from October 2018 to November 2019. The delivery mode, weight, height, and gender at birth were recorded.The levels of resistin, insulin, and growth hormone in umbilical cord blood of newborns delivered vaginally were significantly higher than those born by cesarean section (P < .05), while the levels of adiponectin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable between the 2 groups (P > .05). The levels of resistin, adiponectin, insulin, growth hormone, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 in cord blood of male and female newborns were comparable (P > .05). The newborns with birth weight ≥ 3501 g reported comparable results in the levels of resistin and growth hormone compared with those with birth weight of 3000 to 3500 g (P > .05), but were significantly higher than those with birth weight ≤ 2999 g (P < 0.05). In addition, the levels of adiponectin, insulin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable among the 3 groups (P > .05). Based on Pearson correlation analysis, neonatal umbilical cord blood resistin was positively correlated with adiponectin, leptin, growth hormone, T3, and T4 (r = 0.281, 0.287, 0.321, 0.276, 0.269, P < .05). However, there was no significant correlation between neonatal umbilical cord blood resistin and insulin, TST, lgM, lgA, lgG, CD4, and CD8.The level of serum resistin in neonatal umbilical cord blood was associated with the delivery mode and birth weight, and positively correlated with adiponectin, leptin, growth hormone, T3, and T4. However, no correlation was observed between serum resistin in neonatal umbilical cord blood and insulin, TST, lgM, lgA, lgG, CD4, and CD8.

Relations between second-trimester aneuploidy screening results and prediction of labour induction success in term pregnancies.

We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group (p < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term.IMPACT STATEMENTWhat is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%.What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.

Umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency.

AIMS: The aim of the present study was to evaluate umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency. MATERIALS AND METHODS: Ninety-two pregnant women between 19 and 35-years-old who delivered at term gestational age were included in the study and divided into deficient (n = 32), insufficient (n = 30), and normal (control) vitamin D levels (n = 30). RESULTS: Maternal demographic characteristics and biochemical parameters were similar among groups. The mean umbilical cord P1NP level was 221.4 (211.7-231.0, 95%CI) pg/mL in the vitamin D deficiency group, 282.5 (271.2-293.8, 95%CI) pg/mL in the vitamin D insufficiency group, and 280.9 (270.9-290.8, 95%CI) pg/mL in the control group and significantly lower in vitamin D deficiency group than others (p < .001). Umbilical cord P1NP level was similar in the vitamin D insufficiency group and control group (p = .971). The mean umbilical cord ßCTX level was 5530, 9 (5511.5-5550.3, 95%CI) pg/mL in the vitamin D deficiency group, 5516.3 (5498.4-5534.2, 95%CI) pg/mL in the vitamin D insufficiency group, and 5510 (5491.4-5528.5, 95%CI) pg/mL in the control group, which was statistically similar among the groups (p = .251). CONCLUSION: Our results indicated that vitamin D deficiency during pregnancy affects fetal bone osteoblast activity.

Polymorphism of the Oxytocin Receptor (OXTR) Gene Affects the Circulating Oxytocin Receptor Levels in Late-Term Pregnancy in a Turkish Population.

INTRODUCTION: Postterm and late-term pregnancies still remain a serious health problem, and underlying exact mechanisms are not fully elucidated. These mechanisms are influenced by many factors. OBJECTIVE: The aim of this study was to investigate the relationship between plasma oxytocin and oxytocin receptor levels and oxytocin receptor polymorphisms in term and late-term pregnant women. METHODS: Sixty-eight singleton pregnant women with late-term pregnancy and 83 singleton pregnant women with term parturition were included in this study. A comparison was performed between pregnancies and neonates born at term (37 0/7 and 41 6/7 weeks' gestation). Plasma oxytocin, oxytocin receptor, estradiol, and progesterone levels were measured by using enzyme-linked immunosorbent assay kits. TaqMan® SNP Genotyping Assays and qPCR ProbesMaster were used to investigate the polymorphisms of rs237911, rs2228485, rs53576, and rs2254298. RESULTS: There was not any difference in gene distributions of 4 common single-nucleotide polymorphisms of oxytocin receptor of rs237911, rs2228485, rs53576, and rs2254298 between subjects in late-term and term pregnancy groups. With rs53576 of the GG genotype, serum oxytocin levels were 21.50 ± 10.69 (ng/L) in the late-term group and 62.71 ± 18.01 (ng/L) in the term group (p = 0.049). Oxytocin receptor levels in the late-term and term pregnancy groups of the GG genotype were 17.92 ± 8.15 (pg/mL) and 45.77 ± 11.66 (pg/mL), respectively (p = 0.046). CONCLUSION: Our findings suggest that the rs53576 oxytocin receptor single-nucleotide polymorphism is associated with late-term pregnancy through acting by direct modulation of oxytocin and oxytocin receptor levels.

Hypoxia-inducible factor-1α, hepcidin and interleukin-6 levels in pregnancies with preterm labour.

The aim of the study was to investigate whether serum hypoxia-inducible factor-1alpha (HIF-1α), hepcidin and interleukin-6 (IL-6) concentrations differed between threatened preterm labour (TPL) and uncomplicated pregnancies. This study was conducted on 54 women with TDL pregnancies and 26 healthy pregnant women. The TPL group was further divided into two subgroups according to the gestational age at delivery. Patients who gave birth within 48-72 h after the hospitalisation were referred to as preterm delivery (PD) and who gave birth at ≥37 weeks were referred to as term delivery (TD). Maternal levels of serum HIF-1α, hepcidin and IL-6 were measured with the use of enzyme-linked immunosorbent assay kits. The mean maternal serum HIF-1α, hepcidin and IL-6 levels of PD were significantly higher than TD (p < .001*) and control group (p < .001*). The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group (p=.058, p = .064). The mean maternal serum IL-6 level of TD was significantly higher than the control group (p < .001*). A negative correlation was found between serum concentration of HIF1α, hepcidin, IL-6 with the gestational week of delivery (r = -0.421, p < .01* for HIF-1α; r = -0.578, p < .01* for hepcidin and r = -0.435, p < .01* for IL-6). High levels of HIF-1α, hepcidin and IL-6 may have potential to be used as biomarkers for the differentiation of PD and TD.Impact statementWhat is already known on this subject? It is known that hypoxia-inducible factor-1alpha (HIF-1α) is a hypoxia marker and hepcidin and interleukin-6 (IL-6) increase in inflammation. Our study is the comparison of maternal serum HIF-1α, hepcidin and IL-6 levels between the TPL group (TD and PD) and healthy control group.What the results of this study add? The present study demonstrates that serum HIF-1α, hepcidin and IL-6 levels were significantly higher in TPD group than uncomplicated group. The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group.What the implications are of these findings for clinical practice and/or further research? High levels of HIF-1α, hepcidin and IL-6 may be biomarkers in the determination of true preterm labour within the TPL group.

Role of maternal interleukin-8 (IL-8) in normal-term birth in the human.

Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor ß (TGF-ß) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-ß were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-ß and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-ß production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.

Characterization of Regulatory T Cells in Preterm and Term Infants.

Our study aimed to study regulatory T cells (Tregs) and their expression of CD45RA, HLA-DR, and CD39 in preterm and full-term infants. In an observational study, we used a three-color flow cytometry for determination of Tregs and their expression of CD45RA, HLA-DR, and CD39 in preterm and full-term infants. The percentages of CD4+CD25+highFoxp3+, CD39+ Tregs, HLA-DR+ Tregs and the expression of Foxp3+ in CD4+CD25+highFoxp3 Tregs cells were significantly lower in neonates when compared to healthy adult controls. The levels of naïve resting Tregs (CD45RA+Tregs) were significantly higher in neonates than controls. The percentages of CD4+CD25+highFoxp3+Tregs, total CD4+CD25+ and CD4+CD25+high were significantly higher in preterm infants when compared to the full-term group. Moreover, CD45RA+Tregs were significantly higher in preterm than in term infants. We found significant inverse correlations between the gestational age and the levels of both Tregs (r = - 0.395, p = 0.017) and CD45RA+Tregs (r = - 0.422, p = 0.010). Relative to full-term, the frequencies, and phenotypes of Tregs were affected by prematurity. A larger longitudinal study with a sufficient number of newborns is needed to investigate the Treg pool of term and preterm infants thoroughly and to explore the association between the Treg pool and clinical variables.

Long-term pediatric hematological morbidity of the early-term newborn.

Children born at early term (37 0/7 to 38 6/7 weeks' gestation) are at an increased risk for long-term respiratory, cardiovascular, neurological, and developmental morbidities as compared with children born at full term (39 0/7 to 40 6/7 weeks' gestation). In this population-based cohort analysis, we sought to evaluate the long-term hematological morbidity of early-term born children. The cohort consisted of 223,242 term singleton deliveries. Hospitalizations of the offspring up to 18 years of age involving hematological morbidity were evaluated, including hereditary and acquired anemias, immunodeficiency disorders, coagulation disorders, white blood cell disorders, cytopenias, polycythemia, and myelodysplastic syndrome. Hematological hospitalizations were significantly more common in children delivered at early term as compared with those born at later gestational ages. A Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of hematological-related hospitalizations in the early-term born group (logrank p < 0.001). Using a Cox regression model, early-term delivery was found to be an independent risk factor for childhood hematological morbidity with an adjusted hazard ratio of 1.15 (95%CI 1.01-1.30, p=0.027).Conclusion: Early-term delivery appears to be independently associated with pediatric long-term hematological morbidity of the offspring. What is Known? • It has been shown that children born at early term are at increased risk for short-term adverse outcomes including perinatal mortality. • Early-term infants are also at increased risk for long-term morbidity, mainly respiratory. What is New? • Early-term delivery is also independently associated with long-term hematological morbidity of the offspring.

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels.

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

Leptin, IL-6 and TNF-α levels in umbilical cord blood of healthy term newborns in relation to mode of delivery.

In the development of the foetal immune system, cytokines play an important role in its function. Therefore, we sought to determine whether the mode of delivery affects the expression of leptin, IL-6 and TNF-α in umbilical cord blood in healthy term newborns. We collected 125 samples of umbilical cord blood to analyse leptin, IL-6 y TNF-α levels with multiplex immunoassay (MIA). The samples were classified according to mode of delivery: vaginal delivery (VD) and caesarean section (CS). Leptin and IL-6 had higher concentrations in umbilical cord blood in VD than in CS: 42.55 ng/ml (11.92-104.28) versus 35.20 ng/ml (3.26-9326.76), p = 0.039; 9.32 pg/ml (1.13-2020.31) versus 3.81 pg/ml (0.52-834.69) p < 0.001, respectively. Also, a weak correlation between TNF-α and IL-6 was found (r = 0.238, p = 0.007). The most important finding in our study was the differential concentrations of leptin and IL-6 according to mode of delivery.

Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

Exosomes are secreted nanovesicles that are able to transfer RNA and proteins to target cells. The emerging role of mesenchymal stem cell (MSC) exosomes as promoters of aerobic ATP synthesis restoration in damaged cells, prompted us to assess whether they contain an extramitochondrial aerobic respiration capacity. Exosomes were isolated from culture medium of human MSCs from umbilical cord of ≥37-wk-old newborns or between 28- to 30-wk-old newborns (i.e.,term or preterm infants). Characterization of samples was conducted by cytofluorometry. Oxidative phosphorylation capacity was assessed by Western blot analysis, oximetry, and luminometric and fluorometric analyses. MSC exosomes express functional respiratory complexes I, IV, and V, consuming oxygen. ATP synthesis was only detectable in exosomes from term newborns, suggestive of a specific mechanism that is not completed at an early gestational age. Activities are outward facing and comparable to those detected in mitochondria isolated from term MSCs. MSC exosomes display an unsuspected aerobic respiratory ability independent of whole mitochondria. This may be relevant for their ability to rescue cell bioenergetics. The differential oxidative metabolism of pretermvs.term exosomes sheds new light on the preterm newborn's clinical vulnerability. A reduced ability to repair damaged tissue and an increased capability to cope with anoxic environment for preterm infants can be envisaged.-Panfoli, I., Ravera, S., Podestà, M., Cossu, C., Santucci, L., Bartolucci, M., Bruschi, M., Calzia, D., Sabatini, F., Bruschettini, M., Ramenghi, L. A., Romantsik, O., Marimpietri, D., Pistoia, V., Ghiggeri, G., Frassoni, F., Candiano, G. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples.

BACKGROUND: Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. METHODS AND RESULTS: Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15-4.8) vs 0.3% (0.032-2.23) p = 0.0001 and in neonates <32 weeks of gestational age (GA) compared to those ≥32 wks GA: 0.95% (range 0.18-4.8) and 0.36% (0.15-3.2) respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP) did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL) resulted higher compared to term (p = 0.004) and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168). CONCLUSIONS: We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144)The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies.

Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial.

OBJECTIVE: Delayed umbilical cord clamping (DCC) at birth may provide a better neonatal health status than early umbilical cord clamping (ECC). However, the safety and feasibility of DCC in infants with congenital heart disease (CHD) have not been tested. This was a pilot, randomized, controlled trial to establish the safety and feasibility of DCC in neonates with CHD. STUDY DESIGN: Pregnant women admitted >37 weeks gestational age with prenatal diagnosis of critical CHD were enrolled and randomized to ECC or DCC. For ECC, the umbilical cord was clamped <10 s after birth; for DCC, the cord was clamped ~120 s after delivery. RESULTS: Thirty infants were randomized at birth. No differences between the DCC and ECC groups were observed in gestational age at birth or time of surgery. No differences were observed across all safety measures, although a trend for higher peak serum bilirubin levels (9.2±2.2 vs 7.3±3.2 mg dl(-1), P=0.08) in the DCC group than in the ECC group was noted. Although similar at later time points, hematocrits were higher in the DCC than in the ECC infants during the first 72 h of life. The proportion of infants not receiving blood transfusions throughout hospitalization was higher in the DCC than in the ECC infants (43 vs 7%, log-rank test P=0.02). CONCLUSION: DCC in infants with critical CHD appears both safe and feasible, with fewer infants exposed to red blood cell transfusions than with ECC. A more comprehensive appraisal of this practice is warranted.

Maternal thyrotropin is independently related to small for gestational age neonates at term.

OBJECTIVE: Small for gestational age (SGA) newborns constitute still a major cause of perinatal morbidity and mortality. Overt thyroid disease is a known cause of preterm birth and low birthweight but in its untreated condition it is rare today. In this study, we investigated the possible relation between maternal thyroid function assessed in euthyroid women at each trimester and the incidence of term born SGA neonates. DESIGN: A prospective cohort study was performed. PATIENTS: Thyroid function was assessed at 12, 24 and 36 weeks gestation in 1051 healthy Caucasian women who delivered at ≥ 37 weeks gestation. MEASUREMENTS: One-way anova was used to compare mean TSH and FT4 levels between women with SGA neonates and controls. Multiple logistic regression analysis was performed to adjust for known risk factors of SGA. RESULTS: Seventy (6·7%) SGA neonates were identified and they were significantly more often born to women with a TSH ≥ 97·5th at first and third trimester. Multiple logistic regression analysis showed that smoking (OR: 4·4, 95% CI: 2·49-7·64), pre-eclampsia (OR: 2·8, 95% CI: 1·19-6·78) and TSH ≥ 97·5th percentile (OR 3·3, 95% CI 1·39-7·53) were significantly related to SGA. Maternal FT4 levels and TPO-Ab status were not associated with SGA offspring. CONCLUSIONS: Our data show that TSH levels in the upper range of the reference interval at different trimesters (3·0-3·29 mIU/l) are independently related to an increased risk of delivering SGA neonates at term.

Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood.

Cord blood has gradually become an important source for hematopoietic stem cell transplantation (HSCT) in the human, particularly in pediatric patients. Adoptive cellular immunotherapy of patients with hematologic malignancies after umbilical cord blood transplant is crucial. Cytokine­induced killer (CIK) cells derived from cord blood are a new type of antitumor immune effector cells in tumor prevention and treatment and have increasingly attracted the attention of researchers. On the other hand, it has been suggested that preterm infant cord blood retains an early differentiation phenotype suitable for immunotherapy. Therefore, we determined the phenotypic and functional characterization of CIK cells derived from preterm infant cord blood (PCB-CIK) compared with CIK cells from term infant cord blood (TCB-CIK). Twenty cord blood samples were collected and classified into two groups based on gestational age. Cord blood mononuclear cells (CBMCs) were isolated, cultured and induced to CIK cells in vitro. We used flow cytometry to detect cell surface markers, FlowJo software to analyze the proliferation profile and intracellular staining to test the secretion of cytokines. Finally, we evaluated the antitumor activity of CIK cells against K562 in vitro. Compared with TCB-CIK, PCB-CIK cells demonstrated faster proliferation and higher expression of activated cell surface markers. The secretion of IL-10 was lower in PCB-CIK cells while the expression of perforin and CD107a had no significant difference between the two cell groups. PCB-CIK cells exhibited a high proliferation rate while the cytotoxic activity had no difference between the PCB-CIK and TCB-CIK cells. Hence preterm infant cord blood may be a potential source for immunotherapy.

Hematopoietic stem cells in neonates: any differences between very preterm and term neonates?

BACKGROUND: In the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood. METHODS: CD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity. RESULTS: Preterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133- and ALDH(high) HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood. CONCLUSION: We demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates.

Cord blood netrin-1 and -4 concentrations in term pregnancies with normal, restricted and increased fetal growth.

OBJECTIVE: To determine levels of the possible angioregulatory molecules netrin-1 and -4, in intrauterine-growth-restricted (IUGR), large for gestational age (LGA) (both groups characterized by altered angiogenic mechanisms) and appropriate-for-gestational-age (AGA) pregnancies. METHODS: Cord blood (UC) netrin-1 and -4 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA infants and their mothers (MS). RESULTS: Netrin-1 and -4 concentrations did not differ in all groups. UC netrin-4 increased with gestational age (b = 0.075, 95% CI 0.029-0.121, p = 0.002). In the IUGR group, MS netrin-4 decreased as birth-weight centiles increased [b = -0.058, 95% CI -0.112 to -0.004, p = 0.036]. In the LGA group, MS netrin-1 decreased with advanced gestational age [b = -0.063, 95% CI -0.105 to -0.022, p = 0.004]. In all cases, MS netrin-1 positively correlated with MS netrin-4 (r = 0.299, p = 0.007), while UC netrin-1 negatively correlated with UC netrin-4 (r = -0.239, p = 0.033). CONCLUSIONS: Increased UC netrin-4 levels with advancing gestational age may reflect its effect on fetal development. Decreased maternal netrin-1 levels in the LGA group possibly represent a negative feedback mechanism against increased angiogenesis. Increased maternal netrin-4 levels in IUGR neonates may reflect in utero hypoxia, while the negative correlations between fetal netrin-1 and -4 levels may exert the dynamic balance between their angio- and anti-angiogenic properties.

Differential regulation of brain-derived neurotrophic factor in term and preterm preeclampsia.

Our earlier studies in preeclampsia (PE) suggest a causal relationship between altered angiogenic factors and birth outcomes. Recent studies suggest that brain-derived neurotrophic factor (BDNF) can stimulate angiogenesis. The present study examines the levels of maternal and cord BDNF in women with PE (n = 106; full term [n = 60] and preterm [n = 46]) and normotensive women (n = 95; control) delivering at term. Maternal BDNF levels were lower (P < .05) in women with PE when compared to normotensive women. Cord BDNF levels were higher (P < .01) in women with PE delivering at term, while it was lower (P < .01) in women delivering preterm. Maternal BDNF levels were negatively associated with systolic and diastolic blood pressure (P < .01 for both). Our data for the first time suggest a possible role for BDNF in the pathophysiology of PE. Differential regulation of cord BDNF levels in preterm PE suggests a need to follow-up children to assess the neurodevelopmental effects in later life.

Role of digoxin-like immunoreactive substance in the pathogenesis of transient tachypnea of newborn.

BACKGROUND: Transient tachypnea of newborn (TTN) is usually observed in term or near-term infants. It constitutes an important part of the respiratory distress cases observed in the neonatal intensive care unit (NICU). AIM: This paper examines the effects of digoxin-like immunoreactive substance (DLIS) on fluid and ion balance, hemodynamic and echocardiographic parameters of neonates with TTN. METHODS: Plasma DLIS, Na(+), K(+), urea, creatinine, serum and urine osmolarity, urine FeNa(+), 24-hour urine output, echocardiographic investigation and mean blood pressure, and clinical parameters of disease severity were recorded in TTN group and compared with control on the 1st and 7th days of their lives. RESULTS: Plasma DLIS levels were statistically higher in TTN group (0.66 ± 0.37 ng/mL) compared to control group (0.24 ± 0.20 ng/mL) both on the 1st day (P < 0.01) and the 7th day (P < 0.05). For TTN group, significant correlation was found between plasma DLIS levels and maximum respiratory rate, duration of tachypnea, and length of hospitalization on the 1st day. Plasma DLIS levels were correlated negatively with serum osmolarity levels. Plasma DLIS levels were positively correlated with urine output, urinary FeNa(+) levels, cardiac output, left ventricles end diastolic diameters, and right ventricles end diastolic diameters. CONCLUSIONS: Increased DLIS levels were correlated with disease severity in cases with TTN. This increase may be a primary or secondary event in the disease progress. It may help reduce the fluid overload due to already disturbed cardiac functions in patients by increasing urine output and natriuresis; however it may also contribute to disease pathogenesis, by inhibiting alveolar Na(+)-K(+)-ATPase which further decreases fetal alveolar fluid resorption.