Autophagy markers in umbilical cord blood-derived PBMCs and their association with preterm morbidities: a prospective multicenter cohort study.

Seroprevalance of pertussis antibodies in maternal and cord blood of preterm and term infants

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

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. Cytokine‑induced 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 invitro. 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 invitro. 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.

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.

Preterm infants are very susceptible to infections. Immune response mechanisms in this group of patients and factors that influence cord blood mononuclear cell populations remain poorly understood and are considered insufficient. However, competent immune functions of the cord blood mononuclear cells are also described. The aim of this work was to evaluate the T-cell population (CD3+) with its subpopulations bearing T-cell receptor (TCR) αβ or TCR γδ in the cord blood of preterm infants born before 32 weeks of gestation by mothers with or without an intrauterine infection. Being a pilot study, it also aimed at feasibility check and assessment of an expected effect size. The cord blood samples of 46 infants age were subjected to direct immunofluorescent staining with monoclonal antibodies and then analyzed by flow cytometry. The percentage of CD3+ cells in neonates born by mothers with diagnosis of intrauterine infection was significantly lower than in neonates born by mothers without infection (p = 0.005; Mann–Whitney U test). The number of cells did not differ between groups. Infection present in the mother did not have an influence on the TCR αβ or TCR γδ subpopulations. Our study contributes to a better understanding of preterm infants’ immune mechanisms, and sets the stage for further investigations.

Interferon γ-inducible protein-10 (IP-10) is one of the potent inflammatory mediators. This research aims to compare cord blood IP-10 levels in preterm infants with or without antenatal preterm prelabor rupture of the membranes (PPROM), fetal inflammatory response syndrome (FIRS) and prematurity related morbidities. We enrolled 85 newborns with gestational age below 37 weeks. Umbilical cord blood samples were obtained at delivery and stored. Cord blood IP-10 and interleukin (IL)-6 levels measured with ELISA test. All enrolled preterm infants have been followed-up for prematurity related conditions including respiratory distress syndrome, early and late onset sepsis, necrotising enterocolitis, intraventricular haemorrhage, premature retinopathy, bronchopulmonary dysplasia and mortality. FIRS defined as IL-6 levels of umbilical cord above 11 pg/ml. Cord blood median IP-10 levels were significantly higher in PPROM group (n=27, 31.8%) than in the group without PPROM (IP-10=345.6 pg/ml vs. 28.3 pg/ml, p<0.001). Cord blood median IP-10 levels were significantly higher in preterm infants with FIRS (n=36, 42.4%) compared to infants without FIRS (p<0.001). Cord blood median IP-10 levels were also higher in preterm infants with early onset sepsis than those without early onset sepsis (p=0.019). We did not observe relationship between cord blood IP-10 levels and other prematurity-related complications. Increased cord blood IP-10 levels have been observed in preterm infants with fetal inflammation and who developed early onset sepsis. Cord blood IP-10 could be considered an early marker for intrauterine inflammation and its effect on fetal outcomes, such as the development of neonatal sepsis in 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.

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 Effect of Platelets on Thrombin Generation in Cord Blood and Peripheral Neonatal Blood in the Premature Infant; The Event Study

Background and Objective:Umbilical cord blood which can be obtained by a non-invasive method can be informative about the clinical status of the newborn. It was aimed to establish reference intervals for umbilical cord blood parameters, and to compare complete blood count results between umbilical cord and venous blood samples in this study.Methods:This study was conducted at Medipol University Sefaköy Hospital, Department of Pediatrics, Istanbul, Turkey. A total of 1898 newborns who were born in a two-year period between January 2018 and December 2019 were included in the study. Venous blood samples were taken from 184 of them, and umbilical cord blood samples were taken from 1714 newborns.Results:The percentiles were determined according to gender and delivery method for the hematological parameters of umbilical cord blood. While mean platelet, eosinophil and mean corpuscular volume values were similar between the groups (p>0.05 for each), and significant differences were found between the groups in terms of all other mean hematological parameters (p<0.05 for each).Conclusion:The results of the complete blood count of umbilical cord blood samples can provide reliable information about the newborn. There are significant differences between umbilical cord and venous blood samples in terms of hematological parameters. For these reasons, it is necessary to determine reliable value ranges for umbilical cord blood hematological parameters in newborns. Data of our study can be a guide for further studies and clinicians.

Origins of the discipline ‘neonatal haematology’, 1925-75

Timing of cord clamping in very preterm infants: more evidence is needed

To determine levels of antimicrobial polypeptides (AMP) in cord blood of term and preterm neonates and to investigate influencing factors. In a single-centre study, n = 139 preterm infants and n = 36 term infants were included. AMP levels were analysed in supernatants of whole cord blood cultures with a standardised concentration of 5 × 10(6) white blood cells/mL via enzyme-linked immunosorbent assay (ELISA). Lactoferrin, human neutrophil peptides (HNP) 1-3 and bacterial permeability-increasing protein (BPI) expression in cord blood of preterm infants were influenced by the cause of preterm delivery, that is increased levels in infants with clinical amniotic infection. AMP levels also weakly correlated with white blood cell and neutrophil count at birth. In the whole cohort, no association between gestational age or birthweight with AMP levels was found. In the subgroup of infants without clinical amniotic infection (n = 77 preterm infants, n = 36 healthy term infants), we noted a weak correlation between gestational age and lactoferrin, calprotectin and HNP1-3 levels. In addition to that, we observed higher levels of lactoferrin and HNP1-3 in large-for-gestational-age infants. Our study confirms that several factors influence cord blood AMP levels which underlines the difficulties of using AMP levels as biomarkers of immunological response.

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.

Coronavirus disease (COVID-19) during pregnancy may have an impact on preterm morbidities due to the inflammatory nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Exposure to intrauterine inflammation could result in adverse consequences in preterm infants. We aimed to determine the effect of maternal coronavirus disease on preterm morbidities at a tertiary neonatal intensive care unit. This observational cohort study compared the clinical outcomes of preterm infants < 37 gestational weeks with and without maternal COVID-19. The study was conducted in a tertiary-level neonatal intensive care unit between March 2020 and December 2021. Demographics and clinical data of the study groups were collected from the medical files. A total of 254 infants (127 in the maternal COVID-19 group and 127 in the control group) were included in the study. Respiratory distress syndrome, early and late neonatal sepsis, intraventricular hemorrhage, patent ductus arteriosus (PDA), necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity rates were similar between groups. In the subgroup analysis, the rate of PDA was significantly higher in preterm infants ≤1,500 g with maternal SARS-CoV-2 infection (38 vs. 15% p = 0.023). Presence of maternal COVID-19 was found to be an independent predictor for PDA in very low birthweight infants, as revealed by multivariate analyses (odds ratio: 3.4; 95% confidence interval: 1.12-10.4; p = 0.031). Mortality rates and duration of hospitalization were similar in both groups. Our results suggest that COVID-19 infection during pregnancy seems to have no adverse effect on preterm morbidities and mortality. However, maternal COVID-19 was found to be a risk factor for PDA in preterm infants ≤1,500 g. · The effect of maternal COVID-19 on preterm morbidities still has not well defined.. · Maternal COVID-19 seems to have no adverse effect on preterm morbidities and mortality.. · The exact impact of the COVID-19 on fetal/neonatal health is yet to be clarified..