Cord Blood Of Preterm Infants Research Articles

Association of cord blood Ang-1 and sCD105 levels with bronchopulmonary dysplasia in preterm infants

BackgroundTo investigate the relationship between cord blood levels of Angiopoietin-1 (Ang-1) and S-endoglin (sCD105) and bronchopulmonary dysplasia (BPD) in preterm infants.MethodsSixty-one preterm infants admitted to the neonatal intensive care unit of the study hospital between July 2021 and September 2022 were included. Cord blood was collected after the birth of premature infants. Ang-1 and sCD105 levels were quantified using the vascular endothelial growth factor enzyme-linked immunosorbent assay. Preterm infants were divided into BPD and non-BPD groups, and differences in Ang-1 and sCD105 levels between the two groups were compared. A binary logistic model was used to assess the association between low and high levels Ang-1 and BPD in preterm infants.ResultsIn the study, there were 20 preterm infants with BPD (32.8%) and 41 preterm infants with non-BPD (67.2%). Ang-1 concentration levels were lower in the BPD group than in the non-BPD group (7105.43 (5617.01–8523.00) pg/ml vs. 10488.03 (7946.19–15962.77) pg/ml, P = 0.027). However, the sCD105 concentration levels were not significantly different between the BPD and non-BPD groups (P = 0.246). A median Ang-1 concentration of 8800.40 pg/ml was calculated. Logistic regression analysis showed that after adjusting for gestational age, birth weight, and maternal prenatal steroid hormone application, the odds ratio (OR) was 8.577 for the risk of BPD in preterm infants with Ang-1 concentrations of ≤ 8800.40 pg/ml compared to those with Ang-1 concentrations of > 8800.40 pg/ml (OR: 8.577, 95% confidence interval: 1.265–58.155, P = 0.028).ConclusionOur study indicated that Ang-1 levels in the cord blood of preterm infants may be associated the risk of BPD. In the future, we will continue to conduct study with large samples.

Decreased level of TREM like Transcript 1 (TLT-1) is associated with prematurity and promotes the in-utero inflammatory response to maternal lipopolysaccharide (LPS) exposure.

The occurrence of preterm birth is associated with multiple factors including bleeding, infection and inflammation. Platelets are mediators of hemostasis and can modulate inflammation through interactions with leukocytes. TREM like Transcript 1 (TLT-1) is a type 1 single Ig domain receptor on activated platelets. In adults, it plays a protective role by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. TLT-1 is expressed in human placenta and found in cord blood. We thus hypothesized that TLT-1 deficiency is associated with prematurity and fetal inflammation. To test this hypothesis, we examined cord blood levels of soluble TLT-1 (sTLT) in premature and term infants and compared the inflammatory response in C57BL/6 (WT) and TLT-1-/- (treml1-/- , KO) mice given intraperitoneal LPS mid-gestation RESULTS: The preterm infant cord blood level of sTLT was significantly lower than that found at term. On exposure to LPS, histology of KO (as compared to WT) placenta and decidua showed increased hemorrhage, and KO decidual RNA expression of IL-10 was significantly lower. KO fetal interface tissues (placenta, membranes, amniotic fluid) over time showed increased expression of inflammatory cytokines such as IL-6, IFN-γ,and TNF, but not MCP-1. However, fetal organs showed similar levels. There is a potential association between insufficient TLT-1 expression and increased fetal inflammatory responses in the setting of prematurity. The data support further study of TLT-1 in the mechanistic link between bleeding, inflammation and preterm birth, and perhaps as a biomarker in human pregnancy.

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.

The association of serum vitamin D level and neonatal respiratory distress syndrome

BackgroundNeonatal respiratory distress syndrome (NRDS) is a critical disease in premature infants. Vitamin D plays an important role in promoting the development of fetal lung structure and the formation of pulmonary surfactants. This study aimed to investigate the correlation between the serum 25(OH)D3 level in the cord blood of premature infants and the prognosis of NRDS.MethodsThis retrospective study recruited 82 preterm infants (gestational age 28-36 weeks) diagnosed with NRDS as the NRDS group, and 82 non-NRDS preterm infants as the control group, respectively. The diagnostic efficiency of 25(OH)D3 on NRDS was revealed by receiver operating characteristics curve (ROC) analysis. Enzyme linked immunosorbent assay (ELISA) was performed to evaluate the 25(OH)D3 level in the serum of the cord blood in preterm neonates. The NRDS risk indicators were identified by the multivariate logistic regression analysis.ResultsCord blood 25(OH)D3 levels were significantly lower in NRDS preterm infants than control group infants. 25(OH)D3 levels in cord blood can be used to predict NRDS in preterm infants. In addition, 25(OH)D3 levels in cord blood were positively correlated with Apgar score (1 min/5 min) and negatively correlated with oxygen support/CPAP duration in preterm infants with NRDS. 25(OH)D3 in cord blood <57.69 nmol/L (24 ng/ml), gestational age <31 weeks, birth weight <1.86 kg, Apgar score (1 min) <7 and Apgar score (5 min) < 8 were independent risk factors for NRDS.Conclusion25(OH)D3 level is an independent risk factor for NRDS in preterm infants.

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants.

The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23–36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.

Cord blood antimicrobial peptide LL37 levels in preterm neonates and association with preterm complications

BackgroundCathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications.MethodsSingleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48–72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed.ResultsCord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37.ConclusionCord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

Cholesterol Uptake Capacity in Cord Blood of Preterm Infants.

There is insufficient research on cholesterol uptake capacity (CUC) in preterm infants; therefore, the relationship between CUC and cholesterol transport in preterm infants is unclear. This study aimed to clarify the relationship between CUC and anthropometric measurements, high-density lipoprotein cholesterol (HDL-C) levels, and HDL-C subclasses in preterm infants. Fifty-eight preterm infants were divided into small-for-gestational age (n = 20) (SGA) and appropriate-for-gestational age (AGA) (n = 38). CUC was measured using a fully automated immunoassay system, HI-1000. HDL-C subclasses were measured using high-performance liquid chromatography. SGA showed significantly lower HDL-C and CUC levels than AGA. We found a positive correlation between CUC and birth weight, birth height, and birth head circumference in preterm infants. Moreover, CUC had a strong relationship with HDL-C and very large, large, and medium HDL-C in preterm infants. In preterm infants, CUC is associated with normal growth and may indicate the ability to transport cholesterol forward by large-or medium-size HDL.

Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis.

IntroductionPreterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.PopulationFor objective one 59 term infants [mean gestational age (GA) 39+4 (37+3 to 42+0)] and 55 preterm infants [mean GA29+0(23+3 to 32+0)] with umbilical cord samples available were included; for objective two we studied 96 preterm infants [mean GA29+1(23+2 to 32+0)] for whom placental histology and postnatal blood samples were available.MethodsPlacental histopathology was used to identify reaction patterns indicative of HCA, and a customized immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.ResultsThe umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 8 immune proteins on postnatal day 5 (BDNF, C3, C5a, C9, IL-8, MCP-1, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.ConclusionPreterm birth is associated with a distinct immune profile in umbilical cord blood and preterm infants exposed to HCA with evidence of a fetal inflammatory response have specific alterations in immune function that are apparent on day 5 of postnatal life.

Cord Blood Levels of Angiopoietin-Like 7 (ANGPTL7) in Preterm Infants.

Objective ANGPTL7 is a member of the angiogenin-like protein family. Compared to other members, ANGPTL7 is the least known. Recent studies have explored the relationship between ANGPTL7 and multiple pathological processes and diseases. However, there is no research about ANGPTL7 in neonates. This study was designed to investigate the concentration of ANGPTL7 in cord blood of preterm infants. Method Singleton infants born in November 2017 to June 2019 in the study hospital were enrolled in the study. Maternal and neonatal clinical data were collected. ANGPTL7 levels in cord blood and serum on the third day after birth were measured by an enzyme-linked immunosorbent assay. Result A total of 182 infants were enrolled in this study. Patients were categorized into two groups by gestational age (102 preterm, 80 full-term). ANGPTL7 levels in preterm infants were significantly higher than that in full-term babies (t = 15.4, P < 0.001). In multiple line regression analysis, ANGPTL7 levels independently correlated with gestational age (β = −0.556, P < 0.001). There is also no correlation between preterm outcomes and ANGPTL7 levels. Cord blood levels of ANGPTL7 were significantly higher than those in serum on the third day after birth (t = 13.88, P < 0.001). Conclusion Cord blood ANGPTL7 levels are higher in preterm infants than full-term babies. The levels are independently influenced by gestational ages and attenuated significantly after birth. The underlying mechanism needs to be further studied.

Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants

Preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) have accelerated lung aging and poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis and fibrosis. Here we test the hypothesis that decreased cord Klotho levels in preterm infants predict increased BPD–PH risk and early Klotho supplementation prevents BPD-like phenotype and PH in rodents exposed to neonatal hyperoxia. In experiment 1, Klotho levels were measured in cord blood of preterm infants who were enrolled in a longitudinal cohort study. In experiment 2, using an experimental BPD–PH model, rat pups exposed to room air or hyperoxia (85% O2) were randomly assigned to receive every other day injections of recombinant Klotho or placebo. The effect of Klotho on lung structure, PH and cardiac function was assessed. As compared to controls, preterm infants with BPD or BPD–PH had decreased cord Klotho levels. Early Klotho supplementation in neonatal hyperoxia-exposed rodents preserved lung alveolar and vascular structure, attenuated PH, reduced pulmonary vascular remodeling and improved cardiac function. Together, these findings have important implications as they suggest that perinatal Klotho deficiency contributes to BPD–PH risk and strategies that preserve Klotho levels, may improve long-term cardiopulmonary outcomes in preterm infants.

Optimizing Measurement of Vascular Endothelial Growth Factor in Small Blood Samples of Premature Infants

To establish a method that allows for the reliable assessment of vascular endothelial growth factor (VEGF-A) concentrations in very small blood samples of preterm infants. Systemic VEGF measurements are important in view of the most appropriate Anti-VEGF drug to be used for the treatment of acute retinopathy of prematurity (ROP). Cord blood samples from preterm (n = 6) infants, blood samples from preterm infants with treatment requiring ROP (n = 12), and blood samples from healthy adults (n = 10) were collected. Serum, citrate plasma, and serum from recalcified citrate blood were obtained. Levels of VEGF-A and platelet factor-4 (PF-4) were quantified by ELISA or AlphaLISA immunoassay. VEGF-A levels could be detected by both assays, with the AlphaLISA generating slightly lower levels in healthy adults, but not in cord blood of preterm infants. In plasma samples, VEGF levels ranged from non detectable to 181 pg/ml. PF-4 concentrations were between 0.16–3.88 µg/ml. Values of VEGF-A and PF-4 in serum and recalcified serum were significantly higher compared to plasma through the release of these cytokines after platelet activation. In plasma samples of infants with ROP, VEGF-A could always be detected and its values ranged from 19.50 to 245.91 pg/ml and PF-4 concentrations were between 0.1 and 3.3 µg/ml. Using the AlphaLISA kit, we were able to detect VEGF in small sample volumes (5 µl plasma or serum/well) in premature infants with treatment requiring ROP and to monitor platelet activation by PF-4 detection. Minimal blood probe volumes reduce phlebotomy losses avoiding the risk of iatrogenic anemia, thus allowing close monitoring of the cytokine levels in these very fragile infants.

The effects of umblical cord clamping time on lymphocyte subgroups in term and late preterm infants.

To evaluate the effect of umblical cord clamping time on lymphocyte subgroups in term and late preterm infants. Seventy-four infants between 34 and 41 weeks of gestation were included in the study. Of these, 37 were umbilical cord clamped immediately after birth and the remaining 37 were clamped after waiting one minute. Babies were divided into two groups as term and preterm. The prenatal, natal, postnatal characteristics of the infants were recorded. Hematologic and lymphocyte subgroups were investigated in cord blood and venous blood at day 7. Lymphocyte subgroups were evaluated using flow cytometry. With the delay of cord clamping, the leucocytes count and the percentage of CD3+T lymphocytes in cord blood of preterm infants decreased and this decrease continued at day 7. On the contrary, CD19+B lymphocyte levels in the cord blood of preterm infants increased, and this increase continued at day 7. Also, the percentage of CD4+T lymphocytes of preterm infants decreased with the delay of cord clamping at day 7. There was no difference between groups for the rate of sepsis development. With the delay of cord clamping, the leucocytes count, the percentage of CD3+T, and CD4+T lymphocytes decreased, and the percentage of CD19+B lymphocytes increased in preterm infants. The delay in cord clamping time in term and preterm infants seems to have no impact on the rate of sepsis development. Larger series of studies are needed to assess the effect of these findings on the development of infection in late preterm infants who have delayed cord clamping.

FEATURES OF THE CONTENT OF ENDOTHELIAL PROGENITOR CELLS IN UMBILICAL CORD BLOOD OF PRE-TERM AND FULL-TERM NEWBORNS

The purpose of the study : determination of content of circulating endothelial cellsin umbilical cord blood in orderto assessthe regenerative potential of the endothelium in newborns. 29 newborn babies were examined: 18 pre-term infants (gestational age 30–35 weeks) and 11 full-term infants (gestational age 38–41 weeks). Determination of the number of circulating endothelial cells was determined in mixed umbilical cord blood of all children their phenotyping was carried out by cytofluorometry method using fluorochromes-labeled monoclonal antibodies. Circulating endothelial cells were defined as CD45–, CD133+, VEGFR2, CD34–, endothelial progenitor cells were defined as CD45–, CD133+, VEGFR2+, CD34+. It was revealed that in umbilical cord blood of pre-term infants was decreased both the total number of circulating endothelial cells and endothelial progenitor cells compared to full-term infants. Moreover, in preterm infants was observed higher percentage of endothelial progenitor cells, rather than mature endothelial cells. In blood of full-term infants was observed higher percentage of mature endothelial cells compared to endothelial progenitor cells and their number increases with increasing birth weight of the newborn. The decrease in the number of endothelial progenitor cells in pre-term infants is associated with impaired endothelial function. CD45–CD133+VEGFR2+CD34+ cells are involved in reparation of damaged endothelium and reduction in their number in the blood reflects the reduction of its regenerative potential.

Presepsin as a predictor of early onset neonatal sepsis in the umbilical cord blood of premature infants with premature rupture of membranes

The aim of this study was to investigate whether presepsin level in umbilical cord blood can be used as a predictor of early onset neonatal sepsis (EONS) in preterm labor with premature rupture of membranes (PROM), allowing rational use of antibiotics. All preterm infants between 24+0 and 36+6weeks of gestation born to pregnant women with PROM were enrolled in the study. Blood samples were obtained from clamped umbilical cords after delivery of the neonate and prior to the delivery of the placenta for C-reactive protein and presepsin measurement. A diagnosis or suspicion of EONS was based on clinical symptoms or laboratory results in the absence of positive blood culture. A total of 288 women were included in the study and delivered at 31+4weeks (range, 25-36+5weeks). Microbial invasion of the amniotic cavity was identified in 62 women (81.6%) with EONS and in 31 (14.6%) without (P=0.004). The prevalence of EONS was 26.4% (76/288). Median umbilical cord presepsin was significantly higher in neonates with EONS than in those without: 2,231pg/mL (range, 1,442-3,988pg/mL) versus 275pg/mL (range, 116-326pg/mL; P<0.000). On logistic regression analysis the only independent predictor of EONS was umbilical cord blood presepsin (OR, 12.6; 95% CI: 2.5-28.1, P=0.000). Umbilical cord blood presepsin is a predictor for EONS in preterm infants with PROM and may help to reduce the unnecessary use of antibiotics.

Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period.

Preterm delivery is the leading cause of perinatal morbidity and mortality. Among the most important complications in preterm infants are peri- or postnatal infections. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells. Emerging evidence suggests that granulocytic MDSC (GR-MDSC) play a pivotal role in mediating maternal-fetal tolerance. The role of MDSC for postnatal immune-regulation in neonates is incompletely understood. Until the present time, nothing was known about expression of MDSC in preterm infants. In the present pilot study, we quantified GR-MDSC counts in cord blood and peripheral blood of preterm infants born between 23 + 0 and 36 + 6 weeks of gestation (WOG) during the first 3 months of life and analysed the effect of perinatal infections. We show that GR-MDSC are increased in cord blood independent of gestational age and remain elevated in peripheral blood of preterm infants during the neonatal period. After day 28 they drop to nearly adult levels. In case of perinatal or postnatal infection, GR-MDSC accumulate further and correlate with inflammatory markers C-reactive protein (CRP) and white blood cell counts (WBC). Our results point towards a role of GR-MDSC for immune-regulation in preterm infants and render them as a potential target for cell-based therapy of infections in these patients.

Oxidative stress and DNA damage in the cord blood of preterm infants

Preterm birth infants are more susceptible to oxidative stress and aftermaths unwanted outcomes such as DNA damage due to hyperoxic stress.In this study, we compared the DNA strand breaks as one of the results of DNA oxidation in white blood cells, malondialdehyde (oxidative stress marker), catalase and superoxide dismutase activity, and total antioxidant capacity (markers of antioxidant defense) in a cord blood plasma of a group of preterm (n=25) and full term births (n=25).The primary DNA damage and plasma oxidative stress markers were significantly higher in a preterm group (p<0.05). Cord plasma activity of superoxide dismutase was significantly lower in preterm infants (p≤0.001). However, there were no significant differences in the cord blood total antioxidant capacity, catalase activity and malondialdehyde in preterm and term infants. Among the oxidative stress markers, the malondialdehyde concentration showed the strongest effect size (1.54; 95%CI: 0.9–2.17). For comet parameters, the most powerful effect size was observed for tail length (5.24; 95% CI: 4.05–6.42). However, tail DNA percent and tail moment were also significantly higher in cases compared to controls. Significant negative correlation was observed between comet assay parameters and birth weight and gestational age when all cases and controls entered into the analysis. There was no significant association between the levels of oxidative stress markers and early DNA damage in cord blood plasma with future nutritional tolerance in preterm infants.In the present study, the primary DNA damage and plasma oxidative stress markers significantly were increased in a preterm group. Preterm babies are more prone to the outcomes related to the early DNA damage. Tail DNA percent does not depend on experimental conditions as other parameters (tail length and thus also tail moment) and can be used for comparison with other studies.

Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

BackgroundEarly onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.MethodsIn this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results.ResultscEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.ConclusionThis study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

Deep Sequencing of 16S rRNA Gene Amplicons to Screen Umbilical Cord Blood of Preterm Infants

Deep Sequencing of 16S rRNA Gene Amplicons to Screen Umbilical Cord Blood of Preterm Infants

Placental histological examination and the relationship with oxidative stress in preterm infants

BackgroundPrenatal conditions of enhanced oxidative stress (OS) linked to inflammation or hypoxia have been associated with impaired fetal growth and preterm delivery. Little is known regarding biomarkers of OS in the cord blood of preterm infants and placental histological patterns. ObjectivesTo test the hypothesis that placental lesions indicating chorioamnionitis (CA) or vascular underperfusion (VU) are associated with increased OS in the offspring. Methods120 neonates born below 29+6 weeks of gestational age (GA) were enrolled. Histological characteristics of placentas from their mothers were classified as normal (CTRL group), histological CA (HCA) and vascular underperfusion (VU). Serum concentrations of isoprostanes (IsoPs), non-protein bound iron (NPBI) and advanced oxidative protein products (AOPP), were determined in cord blood. ResultsIsoPs, NPBI and AOPP were significantly increased in HCA group compared to CTRL group. The multivariable regression model, adjusted for GA, maternal age, parity, maternal diabetes, maternal obesity and presence/absence of fetal growth restriction (FGR), showed a significant association between the presence of HCA and increased OS biomarkers levels in cord blood (IsoPs: p = 0.006; NPBI: p = 0.014; AOPP: p = 0.007). Placental VU lesions were significantly associated with higher umbilical IsoPs, NPBI and AOPP levels (IsoPs: p = 0.008; NPBI: p = 0.002; AOPP: p = 0.040). In the cases of placental VU lesions associations were also found between high AOPP levels and low GA (p = 0.002) and the presence of fetal growth restriction (p = 0.014). ConclusionsPlacental lesions indicating inflammation or impaired perfusion are associated with higher cord blood levels of OS biomarkers explaining the fetal susceptibility to oxidative injury and the need of antioxidant protection.

DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants.

The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus, we investigated the associations of DNA methylations of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) with metabolic profiles in cord blood of term and preterm infants.We measured metabolic profiles in cord blood samples of 85 term and 85 preterm infants. DNA methylation and mRNA expression levels of MC4R and HNF4α in cord blood cells were quantified using pyrosequencing and real-time PCR. Triglyceride (TG) levels were grouped by percentile as low (<10th percentile), mid (11th-89th percentiles), and high (>90th percentile). A multiple linear regression model was used to assess the differential effects of DNA methylation on metabolic indices in cord blood between term and preterm infants.The beta-coefficients for associations between TG levels and methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter differed significantly between term and preterm infants (P = 0.04 and P = 0.003, respectively). DNA methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter were significantly lower in preterm infants in the high-TG group compared with those in the mid- and low-TG groups (P = 0.01). Notably, preterm infants in the high-TG group had higher TG levels in cord blood than term infants in the high-TG group (60.49 vs 54.57 mg/dL). In addition, MC4R and HNF4α expression levels were higher in preterm infants than in term infants (P < 0.05).Epigenetic alterations of the newly identified genes MC4R and HNF4α in early life might contribute to metabolic profile changes, especially increased TG levels, in the cord blood of preterm infants.