Cord Blood Of Term Infants Research Articles

TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells.

Preterm infants are more susceptible to severe bacterial and viral infectious diseases than their full-term counterparts. A major contributor to this increased susceptibility may be due to differences in their ability to respond to pathogens. While studies have demonstrated altered bacterial Toll-like receptor (TLR) responses, there is limited data on viral TLR responses in preterm infants. In this study, cord blood mononuclear cells (CBMCs) from 10 moderately preterm (30.4-34.1 wGA), 10 term (37-39.5 wGA) infants, and 5 adults were stimulated with TLR2 (lipoteichoic acid), TLR3 (poly I:C), TLR4 (lipopolysaccharide), TLR7/8 (R848), and TLR9 (CpG-ODN 2216) agonists. Following stimulation, the cellular response was measured by intracellular flow cytometry to detect cell-specific NF-κB (as a marker of the inflammatory response), and multiplex assays were used to measure the cytokine response. This study found that preterm and term infants exhibit very similar baseline TLR expression. In response to both bacterial and viral TLR agonists comparing cell-specific NF-κB activation, preterm infants exhibited increased monocyte activation following LTA stimulation; however, no other differences were observed. Similarly, no difference in cytokine response was observed following stimulation with TLRs. However, a stronger correlation between NF-κB activation and cytokine responses was observed in term infants following poly I:C and R848 stimulation compared to preterm infants. In contrast, despite similar TLR expression, adults produced higher levels of IFN-α following R848 stimulation compared to preterm and term infants. These findings suggest preterm and term infants have a similar capacity to respond to both bacterial and viral TLR agonists. As preterm infants are more likely to develop severe infections, further research is required to determine the immunological factors that may be driving this and develop better interventions for this highly vulnerable group.

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns

BackgroundTo date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS.MethodsIn this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants.ResultsDuring the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 – 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 – 1307) rather than in infants without (467 pg/ml, IQR 369 – 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden’s Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis.ConclusionsMaximum Youden’s index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics.

IFNγ-Producing γ/δ T Cells Accumulate in the Fetal Brain Following Intrauterine Inflammation.

Intrauterine inflammation impacts prenatal neurodevelopment and is linked to adverse neurobehavioral outcomes ranging from cerebral palsy to autism spectrum disorder. However, the mechanism by which a prenatal exposure to intrauterine inflammation contributes to life-long neurobehavioral consequences is unknown. To address this gap in knowledge, this study investigates how inflammation transverses across multiple anatomic compartments from the maternal reproductive tract to the fetal brain and what specific cell types in the fetal brain may cause long-term neuronal injury. Utilizing a well-established mouse model, we found that mid-gestation intrauterine inflammation resulted in a lasting neutrophil influx to the decidua in the absence of maternal systemic inflammation. Fetal immunologic changes were observed at 72-hours post-intrauterine inflammation, including elevated neutrophils and macrophages in the fetal liver, and increased granulocytes and activated microglia in the fetal brain. Through unbiased clustering, a population of Gr-1+ γ/δ T cells was identified as the earliest immune cell shift in the fetal brain of fetuses exposed to intrauterine inflammation and determined to be producing high levels of IFNγ when compared to γ/δ T cells in other compartments. In a case-control study of term infants, IFNγ was found to be elevated in the cord blood of term infants exposed to intrauterine inflammation compared to those without this exposure. Collectively, these data identify a novel cellular immune mechanism for fetal brain injury in the setting of intrauterine inflammation.

Regulatory T Cells in Human Cord Blood of Preterm and Term Infants

Regulatory T (Treg) cells are a subset of CD4+ T cells that play key roles in the maintenance of immunologic self-tolerance and negative control of immune responses. Treg cells are defined based on expression of CD4, CD25, and transcription factor forkhead box P3 (FoxP3). FoxP3 controls the development and function of Treg cells and can be used as a reliable marker of Treg cells, however, its intracellular localization prohibits its use for the isolation of viable Treg cells. Most FoxP3+ Treg cells express low levels of CD127 in adult peripheral blood, however, the expression of CD127 in cord blood (CB) Treg cells of preterm and term infants at each gestational age remains unknown. Being that CD127 is a cell surface marker, it enables the isolation of viable Treg cells by flow cytometric sorting for further analysis. We analyzed CD4+CD25+FoxP3+ and CD4+CD25+CD127− T cells in preterm and term CB at various gestational ages.CB samples were obtained at Iwate Medical University hospital from preterm and term neonates who had no hereditary disorders, hematologic abnormalities, or immunodeficiency diseases. Of 103 total samples, 36 were obtained from preterm (24–36 gestational weeks) neonates and 67 were obtained from term (37–41 gestational weeks) neonates. Out of 36 preterm infants, 9 were diagnosed with chorioamnionitis histologically. None of the mothers involved in the study had any specific underlying diseases. CB mononuclear cells were isolated and analyzed by FACSCalibur flow cytometer and CellQuestPro software (BD Biosciences).No differences were observed in the proportions of CD25+FoxP3+ (median 4.5%) and CD25+CD127− (median 5.0%) cells in the CD4+ T-cell population. A strong correlation was found between the proportions of CD25+FoxP3+ and CD25+CD127− cells in the CD4+ T-cell population (r=0.96). The proportion of CD25+FoxP3+ cells in the CD4+ T-cell population in the CB of neonates at 24-26, 27-29, and 30-32 gestational weeks was significantly higher than in the CB of neonates at 37-38 and 39-41 gestational weeks. The proportion of CD25+CD127− cells in the CD4+ T-cell population in the CB of neonates at 24-26, 27-29, and 30-32 gestational weeks was also higher than in the CB of neonates at 37-38 and 39-41 gestational weeks. The absolute number of both CD4+CD25+FoxP3+ and CD4+CD25+CD127− T cells did not differ between the CB of preterm and term neonates. Absolute lymphocyte counts in preterm CB were significantly lower than term infants (P<0.05). The proportions of CD25+FoxP3+ and CD25+CD127− cells in the CD4+ T-cell population did not differ between preterm infants with histological chorioamnionitis (n=9) and no histological chorioamnionitis (n=27).We showed that CD127 is preferable to FoxP3 as a marker for identifying Treg cells in CB of various gestational ages and would be useful for separating Treg cells by flow cytometry for therapeutic applications. The proportions of Treg cells in the CB of preterm infants were significantly higher than in the CB of term infants. The high Treg proportion during early gestation suggests that fetal naive T cells have a high propensity to differentiate into Treg cells in response to antigenic stimulation, such as by maternal alloantigens. The functional implications of the high proportion of Treg cells in preterm CB are unknown but may be important for the suppression of undesirable alloimmune reactions to maternal derivatives in utero and the maintenance of tolerance during pregnancy. DisclosuresNo relevant conflicts of interest to declare.

Lipopolysaccharide and soluble CD14 in cord blood plasma are associated with prematurity and chorioamnionitis

Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, causes preterm birth in animals and has been implicated as a factor triggering preterm labor and systemic complications in humans. Little is known regarding LPS in the cord blood (CB) of term and preterm infants and its association with maternal and fetal characteristics. CB was obtained from term (n = 15) and preterm infants (n = 76) after delivery. Plasma levels of LPS, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured using commercially available kits (limulus amebocyte lysate and enzyme-linked immunosorbent assay). Four linear regression models were created in order to identify independent variables that predict plasma LPS levels. The analyte levels were significantly higher in preterm vs. term infant CB: LPS (24.48 vs. 1 pg/ml; P = 0.0009), CRP (87.9 vs. 47 ng/ml; P = 0.01), and sCD14 (0.32 vs.0.35 µg/ml; P = 0.013). There was a (significant) positive correlation between CB LPS levels and gestational age, birth weight, CRP levels, sCD14 levels, and association with both clinical and histological chorioamnionitis. Our data suggest that LPS is associated with preterm labor and inflammation (CRP elevation and chorioamnionitis). These findings may be relevant to the understanding of the role of LPS in prematurity and its role in preterm morbidities.

Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns

BackgroundThe frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity.MethodsThe study groups consisted of 90 preterm (23–36 weeks of gestational age) and 52 full-term (37–41 weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+), enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent (Oct-4, Nanog), early neural (β-III-tubulin), and oligodendrocyte lineage (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables.ResultsWe found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p < 0.0001) and extensively decreases in preterm babies during next six weeks after birth. Finally, the growth of burst-forming unit of erythrocytes (BFU-E) and colony-forming units of granulocyte-macrophage (CFU-GM) obtained from CB of premature neonates is higher than those obtained from CB of full-term infants and strongly correlates with the number of CB-derived CSPCs.ConclusionWe conclude that CB HSCs are markedly associated with the development of premature birth complications. Thus, HSCs ought to be considered as the potential target for further research as they may be relevant for predicting and controlling the morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs circulating in CB are inversely associated with the birth weight of preterm infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal organism.

Reduced birth weight in relation to pesticide mixtures detected in cord blood of full-term infants

Previous research has shown that prenatal exposure to pesticides may be associated with decreased fetal growth. The specific pesticides investigated and results reported across studies have been inconsistent, and there is a mounting need for the consideration of mixtures rather than individual agents in studies of health outcomes in relation to environmental exposures. There are also many individual pesticides that have not been investigated in human health studies to date. We conducted a pilot study in rural Zhejiang province, China, measuring 20 non-persistent pesticides (10 insecticides, 6 herbicides, 3 fungicides, and 1 repellant) in umbilical cord blood of 112 full term (>37weeks) infants. The pesticides detected with the greatest frequency were diethyltoluamide (DEET) (73%), a repellant, and vinclozolin (49%), a fungicide. The samples had detectable concentrations for a mean of 4.6 pesticides (SD=1.9) with a maximum of 10. Adjusting for potential confounders, newborn birth weight was inversely associated with the number of pesticides detected in cord blood (p=0.04); birth weight decreased by a mean of 37.1g (95% CI, −72.5 to −1.8) for each detected pesticide. When assessing relationships by pesticide type, detection of fungicides was also associated with decreased birth weight (adjusted β=−116g [95% CI, −212 to −19.2]). For individual pesticides analyzed as dichotomous (detect vs. non-detect) variables, only vinclozolin (adjusted β=−174g [95% CI, −312 to −36.3]) and acetochlor (adjusted β=−165g [95% CI, −325 to −5.7]) were significantly associated with reduced birth weight. No significant associations were seen between birth weight and individual pesticides assessed as continuous or 3-level ordinal variables. Our findings from this pilot investigation suggest that exposure to fungicides may adversely impact fetal growth. Exposure to mixtures of multiple pesticides is also of concern and should be explored in addition to individual pesticides. Additional research is needed to establish causality and to understand the function and impact of fungicides and pesticide mixtures on fetal development.

The impact of hyaluronan on monocyte Toll-like receptor expression in term infant cord blood

To explore the possible effects of hyaluronan, an endogenous mediator of inflammation, on monocyte surface expression of Toll-like receptors 2 and 4 in human umbilical cord blood ex vivo, and in a model mimicking Gram-negative neonatal sepsis. Term infant cord blood was obtained after elective caesarean sections, n = 15. Both unstimulated and lipopolysaccharide-stimulated (10 ng/mL) blood was incubated with 500 μg/mL high- or low-molecular-weight hyaluronan for 6 h. Expression of Toll-like receptors 2 and 4 on monocytes was measured using flow cytometry, and plasma concentrations of proinflammatory cytokines and matrix metalloproteinase 9 were analysed. RESULTS (MEAN ± SEM): We found a significant decrease in Toll-like receptor 4 expression in the presence of high-molecular-weight hyaluronan (HMW HA) in unstimulated blood (median fluorescence intensity 141 ± 7.3 vs. 163 ± 9.8, p = 0.019). There were no significant changes in Toll-like receptor 2 expression. Levels of cytokines and matrix metalloproteinase 9 increased in the presence of both forms of hyaluronan. Our results confirm that hyaluronan affects the neonatal immune response. The biological significance of these findings requires further clarification. More studies are needed to validate the possible down-modulation of Toll-like receptor 4 exerted by HMW HA.

Neonatal T-cell maturation and homing receptor responses to Toll-like receptor ligands differ from those of adult naive T cells: relationship to prematurity

Inflammation and infection are associated with premature birth and with activation of the fetal immune system. We hypothesized that exposure to microbial Toll-like receptor (TLR) ligands plays an important role in neonatal T-cell maturation and that early exposure to microbial products may result in early T-cell maturation and a tendency for these matured effector cells to change their homing receptor patterns. Expression of the CD45RO marker was induced in term neonatal T cells after in vitro exposure to TLR ligands for 7 days. Interestingly, naive T cells from adult blood were unaffected by TLR ligand exposure. In addition, neonatal T cells had more cells with decreased expression of the α4β7 integrins and increased expression of CCR4 after in vitro exposure of TLR ligands-similar to the expression of these molecules in adult naive T cells. These findings are relevant for the understanding of neonatal T-cell maturation and may contribute to our understanding of multiorgan inflammatory complications of prematurity. Cord blood was obtained from term and preterm infants. Using flow cytometry, we identified a mature (CD45RO(+)) phenotype in preterm infant cord blood (CB) T cells that had decreased expression of the α4β7 integrins and increased expression of the C-C chemokine receptor 4 (CCR4) as compared with term infant CB.

Human Umbilical Cord Blood-Derived Stromal Cells Are Superior to Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Inducing Myeloid Lineage Differentiation In Vitro

Stromal cells and mesenchymal stem cells (MSCs), 2 important cell populations within the hematopoietic microenvironment, may play an important role in the development of hematopoietic stem/progenitor cells. We have successfully cultured human umbilical cord blood-derived stromal cells (hUCBDSCs). It has been demonstrated that MSCs also exist in hUCB. However, we have not found any reports on the distinct characteristics of hUCBDSCs and human umbilical cord blood-derived mesenchymal stem cells (hUCBDMSCs). In this study, hUCBDSCs and hUCBDMSCs were isolated from the cord blood of full-term infants using the same density gradient centrifugation and cultured in the appropriate medium. Some biological characteristics and hematopoietic supportive functions were compared in vitro. hUCBDSCs were distinct from hUCBDMSCs in morphology, proliferation, cell cycle, passage, immunophenotype, and the capacity for classical tri-lineage differentiation. Finally, quantitative real-time polymerase chain reaction analysis revealed that granulocyte colony-stimulating factor (G-CSF) gene expression was higher in hUCBDSCs than that in hUCBDMSCs. Enzyme-linked immunosorbent assay revealed that the secretion of G-CSF, thrombopoietin (TPO), and granulocyte macrophage colony-stimulating factor (GM-CSF) by hUCBDSCs was higher than that by hUCBDMSCs. After coculture, the granulocyte/macrophage colony-forming units (CFU-GM) of hematopoietic cells from the hUCBDSC feeder layer was more than that from the hUCBDMSC feeder layer. Flow cytometry was used to detect CD34(+) hematopoietic stem/progenitor cell committed differentiation during 14 days of coculture; the results demonstrated that CD14 and CD33 expression in hUCBDSCs was significantly higher than their expression in hUCBDMSCs. This observation was also true for the granulocyte lineage marker, CD15. This marker was expressed beginning at day 7 in hUCBDSCs. It was expressed earlier and at a higher level in hUCBDSCs compared with hUCBDMSCs. In conclusion, hUCBDSCs are different from hUCBDMSCs. hUCBDSCs are superior to hUCBDMSCs in supporting hematopoiesis stem/progenitor cells differentiation into myeloid lineage cells at an early stage in vitro.

Glucocorticoid receptor expression and cortisol level in cord blood of term infants

Objective. To examine the expression levels of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMCs) and serum cortisol levels in cord blood from term infants.Methods. The study population consisted of 172 term infants who were delivered from healthy pregnant women. GRalpha and GRbeta expression levels, and serum cortisol level in cord blood were determined by real-time PCR and ELISA, respectively.Results. Detection rates of GRalpha, GRbeta, and GAPDH were 100%, 63.4%, and 100%, respectively. The expression level of GRalpha was about 200 times that of GRbeta. There were no associations between GR expression level and clinical variables. There were significant associations of low UmApH, maternal gravidity or parity, and vaginal delivery with a high cortisol level; however, there were no correlations between GR expression levels and cortisol level.Conclusions. It is considered that glucocorticoid effects could be expected from the fetal period to the neonatal period, because GRalpha expression level was not related to perinatal factors, GRbeta expression level, and cortisol level in term infants. Further studies of larger populations including very preterm and small for gestational age infants are necessary to determine the balance of expression between GRalpha and GRbeta, and cortisol level.

The effect of hyperglycemia on neonatal immune responses in-vitro

Introduction. Acute hyperglycemia is considered as a pro-inflammatory state and is related to an adverse outcome in critically ill adults. Neonates are susceptible to infections and systemic inflammatory response syndrome induced by pro-inflammatory cytokines. This study focuses on the interaction between neonatal glucose homeostasis and the pro-inflammatory cytokine production in term and preterm infants in-vitro.Methods. We analyzed the pro-inflammatory cytokine production in whole cord blood of term infants (n = 10), preterm infants > 32 weeks (n=16) and preterm infants ≤32 weeks of gestational age (n = 13) and in adult controls (n=14) using an in-vitro sepsis-model. Whole blood was pre-incubated with different concentrations of glucose (0–1000 mg/dl) and insulin (0–62.5 IE/l) and stimulated with lipopolysaccharide. The intracytoplasmatic TNF-α, IL-6, and IL-8 response was measured by flow cytometry.Results. In-vitro hyperglycemia induced a dose-dependent increase of IL-8 in all age groups while TNF-α was demonstrated to be stimulated by glucose in cord blood samples of preterm infants ≤32 weeks of gestational age and term infants. In contrast, insulin showed no significant effects on pro-inflammatory cytokine production in-vitro.Conclusion. Acute hyperglycemia may induce pro-inflammatory cytokine responses in neonatal whole blood in-vitro. These data provide a basis for further in-vitro signal transduction studies and in-vivo investigations about the significance of neonatal glucose homeostasis and its impact on long-term outcome of this susceptible patient cohort.

Evidence for age-related differences in human fibrinogen

Fibrinogen has previously been demonstrated to exist in a 'fetal' form, in cord blood of term infants, with increased sialic acid content compared to adult fibrinogen. The functional implications of these differences are reflected in prolonged thrombin clotting times in newborns as well as differences in polymerization of fibrin from 'fetal' fibrinogen. Despite numerous studies of fibrinogen structure and function, the age at which 'fetal' fibrinogen reverts to the adult form, as well as the physiological significance of this phenomenon remains unknown. This study was designed to determine whether the difference between the 'fetal' and the 'adult' fibrinogen molecule persists in a 'childhood' form throughout progression from infancy to adulthood. The results demonstrate that although the concentration of fibrinogen from day 1 neonates is decreased compared to adult fibrinogen, functional activity of this protein is comparable in both age groups. In addition, despite there being quantitatively less fibrinogen in day 3 and 11-16-year age groups, this protein is functionally more active compared to adult fibrinogen. In addition, the molecular weight of the Aα fibrinogen chain was consistently higher by up to 1500 Da in neonates and children compared to adults, suggesting age-specific differences in posttranslational modification of this chain of the protein.These age-related differences in fibrinogen could provide a protective mechanism against excessive polymerization and proteolysis of this protein, providing a possible explanation of the thromboprotective mechanism that is functioning in neonates and children.

Progressive increase of CD7- T cells in human blood lymphocytes with ageing.

CD7 is one of the major surface antigens expressed very early during T cell ontogeny. Lack of CD7 expression on mature T cells is regarded as a classical feature of malignant T cells in certain forms of cutaneous T cell lymphoma. Previously, we identified a CD7- subset of peripheral blood T lymphocytes in normal human individuals. In this study we determined the portion of CD7- T cells in the peripheral blood of healthy volunteers ranging in age from 8 months to 90 years (n = 85) and in cord blood of full-term infants (n = 14). Furthermore, this CD7- subset was characterized in detail by the use of MoAbs and three-colour flow cytometry. In cord blood no CD7- T cells could be detected. After birth, percentage and absolute number of CD7- T cells increased with age. Independently of age, most CD7-CD3+ cells belonged to the CD4+ subpopulation. Focusing on the latter we could demonstrate the predominance of the CD45RO+CD45RA- phenotype in the CD7- subset. Furthermore, CD7- T cells contained a higher number of cells expressing activation markers and the CD57 antigen, but a reduced number of CD62L+ cells in comparison with CD7+ T cells.

Cytokine Expression in Response to Bacterial Antigens in Preterm and Term Infant Cord Blood Monocytes

Background: Neonatal susceptibility to bacterial infection is associated with an immature immune system, but the role of different bacterial antigens in specific responses is largely unknown. Objective: To evaluate differences in intracellular cytokine response to physiologically relevant bacterial antigens in term and preterm infants as compared with adults. Methods: Cord blood samples from preterm and term neonates and adult peripheral blood samples were cultured ex vivo with and without whole heat-killed bacteria. Intracellular leukocyte production of interleukin (IL)-6, IL-10, IL-12, and IL-8 responses was assessed by flow cytometry. Results: Monocytes were the primary producers of all mediators. Escherichia coli was the most potent stimulant. Lactobacillus plantarum299v activated fewer monocytes as compared with E. coli for all responses (p < 0.05), except for IL-12 in term neonates. IL-6 response to Staphylococcus epidermidis was lower in both groups of neonates as compared with adults (p = 0.023 and p = 0.001). IL-8 response to S. epidermidis was lower in term as compared with preterm neonates and adults (p = 0.003). IL-10 response to group B streptococci was lower in term neonates as compared with adults and higher in preterm as compared with term neonates (p = 0.015). Conclusions: Monocytes from term neonates compared to preterm neonates show a downregulated anti-inflammatory response to specific bacteria. High neonatal response to pathogenic E. coli in the preterm infant could cause uncontrolled inflammatory response, while lower IL-6 response to S. epidermidis in neonates may indicate a basis for vulnerability to S. epidermidis infection.

115 Adiponectin in Cord Plasma Correlates with Gestational Age

Background: Adiponectin is an adipocte-derived hormone that improves insulin sensitivity. Adiponectin is present in cord blood of term infants, but it has not been studied in preterm infants. The effects of gestational age and fetal growth pattern on adiponectin concentration at birth are unknown. Methods: 197 newborn infants were studied. Of them 122 were born at 22–32 wk gestation (bw 455 – 2010g), and 75 at 36 – 42 wk gestation (bw 2140 – 4630g). At birth a blood sample was drawn from umbilical vein. Plasma was separated and the concentration of adiponectin was determined with ELISA (R&D Systems). Results: In the preterm infants the concentration of adiponectin ranged from 0.08 to 31.4 ìmol/L and in term infants it was 4.4 – 54.8 ìmol/L. Significant correlations existed between adiponectin and gestational age in both preterm (p< 0.0001) and term (p< 0.0001) infants. In preterm infants birthweight standard deviation score correlated with adiponectin (p= 0.0001), whereas in term infants no such relationship was found (p= 0.2). No association was found between adiponectin and ponderal index in preterm or term infants. Conclusion: At birth a strong correlation exists between the concentration adiponectin and gestational age. Adiponectin may play physiological roles in fetal development and in postnatal adaptation.

Plasma xanthine oxidase activity and lipid hydroperoxide levels in preterm infants.

Ischemia-reperfusion injury may affect morbidity and mortality in preterm and asphyxiated term infants. Reoxygenation of hypoxic tissues leads to the formation of free oxygen radicals by xanthine oxidase that may induce lipid peroxidation, enzyme inhibition, and DNA strand breakage. We measured arterial cord blood samples from 36 healthy term infants for baseline values and arterial blood sampled at 1 and 4 h after birth from 45 preterm infants admitted for intensive care for serial estimates of plasma xanthine oxidase activity and lipid hydroperoxide levels. Mean +/- SEM plasma xanthine oxidase activity in cord blood of term infants was 2.3 +/- 0.4 mU/mL and lipid hydroperoxide levels were 2.6 +/- 0.3 nmol/mL. Eighteen of the 45 preterm infants met the criteria defining poor outcome (poor outcome group) and had lower umbilical arterial pH and base excess than the 27 preterm infants in the control group. Mean plasma xanthine oxidase activity increased from 2.7 +/- 0.4 at 1 h to 4.7 +/- 0.6 mU/mL at 4 h of age (p < 0.001) in the poor outcome group and decreased from 2.1 +/- 0.3 to 1.1 +/- 0.2 mU/mL (p = 0.004) in the control group. Lipid hydroperoxide levels in the poor outcome group increased from 2.8 +/- 0.6 nmol/mL at 1 h to 4.3 +/- 0.6 nmol/mL at 4 h of age (p < 0.001) and decreased from 2.1 +/- 0.6 to 1.6 +/- 0.2 nmol/mL (p = 0.008) in the control group. At 4 h of age, xanthine oxidase activity and lipid hydroperoxide levels were significantly higher in the poor outcome group than in the controls (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Phagocytic activities in neonatal monocytes.

Monocytes play an essential role in cellular host defense as circulating phagocytes, as well as precursors of macrophages. We investigated the principal phagocytic activities in monocytes from cord blood of term infants by analysing adherence, random migration, chemotaxis, bactericidal activity, phagocytosis-associated chemiluminescence, production of superoxide anion (O-2) and generation of hydrogen peroxide (H2O2). All phagocytic functions of monocytes from neonates were shown quantitatively to be comparable to those of cells from healthy adult volunteers. The increased susceptibility of the human neonate to serious systemic infections cannot be related to an abnormality in monocyte function.

Cell-Mediated Immunity in the Newborn: Clinical Aspects

The clinical observation that the human newborn infant is uniquely susceptible to certain viral, fungal, protozoan, and bacterial infections has suggested that neonates may have impaired cell-mediated immune function. In order to diagnose primary cellular immunodeficiency during the neonatal period, it is necessary to define carefully normal cell-mediated immunity in term infants, premature infants, and infants with intrauterine growth retardation. CELLULAR IMMUNITY: TERM INFANTS The total lymphocyte count of a newborn infant is greater than 3,000/cu mm. Ferguson1 evaluated 25 healthy term infants (mean birth weight 3,130 gm) as control subjects for a study of children with intrauterine growth retardation. The healthy infants' total lymphocyte counts were 5,101 ± 1,821/cu mm. The subpopulation of lymphocytes that form total E rosettes and thus are defined as thymic derived lymphocytes has been reported as normal or decreased in term infant cord blood. In Ferguson's study, newborn E rosettes were 58% ± 7% in comparison to adult E rosettes of 57% ± 10%. Using comparable methods, four additional studies documented a decreased percent of E-rosette-forming cells in the cord blood of the newborn. The percent of total rosette formation in 13 cord blood samples averaged 33.3% ± 7.6% with a control adult mean in 15 samples of 5l.0% ± 6.5%.2 E rosettes were present in lower proportion in cord blood (53%) than in adult blood (65%) in a study by Campbell et al.3 Smith et al4 reported 53% rosette-forming cells in cord blood samples in contrast to 60% in adult samples. Ben-Zwi et a15 found 50% E-rosette-forming cells in cord blood in contrast to 59% in adult blood.