Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study.

BACKGROUND/AIM: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens. METHODS: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay. RESULTS: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 µg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations. CONCLUSIONS: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency.

Molecular mechanisms of oxidative stress-related neonatal jaundice.

Oxidative stress is a pathological condition characterized by an overload of oxidant products, named free radicals, which are not well counteracted by antioxidant systems. Free radicals induce oxidative damage to many body organs and systems. In neonatal red blood cells, free-radical mediated-oxidative stress leads to eryptosis, a suicidal death process of erythrocytes consequent to alteration of cell integrity. Neonatal red blood cells are targets and at the same time generators of free radicals through the Fenton and Haber-Weiss reactions. Enhanced eryptosis in case of oxidative stress damage may cause anemia if the increased loss of erythrocytes is not enough compensated by enhanced new erythrocytes synthesis. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates. High levels of bilirubin are recognized to be dangerous for the central nervous system in newborns, however, many studies have highlighted the antioxidant function of bilirubin. Recently, it has been suggested that physiologic concentration of bilirubin correlates with higher antioxidant status while high pathological bilirubin levels are associated with pro-oxidants effects. The aim of this educational review is to provide an updated understanding of the molecular mechanisms underlying erythrocyte oxidant injury and its reversal in neonatal idiopathic hyperbilirubinemia.

Vascular Endothelial Growth Factor as Molecular Target for Bronchopulmonary Dysplasia Prevention in Very Low Birth Weight Infants.

Bronchopulmonary dysplasia (BPD) still represents an important burden of neonatal care. The definition of the disease is currently undergoing several revisions, and, to date, BPD is actually defined by its treatment rather than diagnostic or clinic criteria. BPD is associated with many prenatal and postnatal risk factors, such as maternal smoking, chorioamnionitis, intrauterine growth restriction (IUGR), patent ductus arteriosus (PDA), parenteral nutrition, sepsis, and mechanical ventilation. Various experimental models have shown how these factors cause distorted alveolar and vascular growth, as well as alterations in the composition and differentiation of the mesenchymal cells of a newborn's lungs, demonstrating a multifactorial pathogenesis of the disease. In addition, inflammation and oxidative stress are the common denominators of the mechanisms that contribute to BPD development. Vascular endothelial growth factor-A (VEGFA) constitutes the most prominent and best studied candidate for vascular development. Animal models have confirmed the important regulatory roles of epithelial-expressed VEGF in lung development and function. This educational review aims to discuss the inflammatory pathways in BPD onset for preterm newborns, focusing on the role of VEGFA and providing a summary of current and emerging evidence.

Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.

Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic-ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long-term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin-sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)-Akt, and p-ERK proteins in rat brain cortexes. PKCα increased in HI-injured rats and further increased with melatonin. p-Akt and p-ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.

Short-term morbidity and types of intrapartum hypoxia in the newborn with metabolic acidaemia: a retrospective cohort study.

OBJECTIVES: To assess labour characteristics in relation to the occurrence of Composite Adverse neonatal Outcome (CAO) within a cohort of fetuses with metabolic acidaemia. DESIGN: Retrospective cohort study. SETTING: Three Italian tertiary maternity units. POPULATION: 431 neonates born with acidaemia ≥36 weeks. METHODS: Intrapartum CTG traces were assigned to one of these four types of labour hypoxia: acute, subacute, gradually evolving and chronic hypoxia. The presence of CAO was defined by the occurrence of at least one of the following: Sarnat Score grade ≥2, seizures, hypothermia and death <7 days from birth. MAIN OUTCOME MEASURES: To compare the type of hypoxia on the intrapartum CTG traces among the acidaemic neonates with and without CAO. RESULTS: The occurrence of a CAO was recorded in 15.1% of neonates. At logistic regression analysis, the duration of the hypoxia was the only parameter associated with CAO in the case of an acute or subacute pattern (odds ratio [OR] 1.3; 95% CI 1.02-1.6 and OR 1.04; 95% CI 1.0-1.1, respectively), whereas both the duration of the hypoxic insult and the time from PROM to delivery were associated with CAO in those with a gradually evolving pattern (OR 1.13; 95% CI 1.01-1.3 and OR 1.04; 95% CI 1.0-1.7, respectively). The incidence of CAO was higher in fetuses with chronic antepartum hypoxia than in those showing CTG features of intrapartum hypoxia (64.7 vs. 13.0%; P < 0.001). CONCLUSIONS: The frequency of CAO seems related to the duration and the type of the hypoxic injury, being higher in fetuses showing CTG features of antepartum chronic hypoxia. TWEETABLE ABSTRACT: This study demonstrates that in a large population of neonates with metabolic acidaemia at birth, the overall incidence of short-term adverse outcome is around 15%. Such risk seems closely correlated to the duration and the type of hypoxic injury, being higher in fetuses admitted in labour with antepartum chronic hypoxia than those experiencing intrapartum hypoxia.

Improving Care in Neonatal Intensive Units During the COVID-19 Pandemic: A Survey on Electronic Health Communication.

Background: A novel virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started spreading through Italy and the world from February 2020, and the pandemic threatened the family-centred care (FCC) model used in the neonatal intensive care unit (NICU). Teleconferences and video calls were employed to keep parents in contact with their babies. This study aimed to evaluate satisfaction and stress levels between parents in the telematic family-centred care group (T-FCC) versus the FCC group and the no Family-Centred Care (N-FCC) group. Methods A prospective cohort pilot study was carried out from April to May 2020. A parental stressor scale and the NICU satisfaction questionnaire were administered to parents at the time of discharge of their newborns. Parents in T-FCC group could see their newborns via video calls, while those in the FCC and N-FCC groups were extracted from our previously published database. Results Parents in the T-FCC group were more satisfied and less stressed than those in the N-FCC group. Experiences of the mothers and fathers in the T-FCC group were similar. However, the FCC group showed the best results. Conclusion The T-FCC group showed satisfaction with the quality of information received about their babies and felt that their privacy was considered and respected by the medical staff. Parents were also less stressed because they could monitor what happens to the baby through a video, however, they could not intervene if there was a problem. Data support the use of video calls to improve insight into clinical conditions and communication between doctors, nurses, and parents during the pandemic.

Peripheral Saturation and Perfusion Index on the First Day of Life Play a Role in Early Discharge of Healthy Term Newborns.

Introduction: Pulse oximetry screening is a safe, feasible test, effective in identifying congenital heart diseases in otherwise well-appearing newborns. Uncertainties still persist on the most effective algorithm to be used and the timing of screening. The aim of this study was to evaluate the role of the pulse oximetry screening associated with the peripheral perfusion index performed in the first 24 hours of life for the early detection of congenital heart diseases and noncongenital heart diseases in the newborns. Materials and Methods: A prospective observational cohort study was conducted. The enrollment criteria were as follows: term newborns with an APGAR score >8 at 5 minutes. The exclusion criteria were as follows: clinical signs of prenatal/perinatal asphyxia or known congenital malformations. Four parameters of pulse oximetry screening were utilized: saturation less than 90% (screening 1), saturation of less than 95% in one or both limbs (screening 2), difference of more than 3% between the limbs (screening 3), and preductal peripheral perfusion index or postductal peripheral perfusion index below 0.70 (screening 4). The likelihood ratio, sensibility, specificity, and positive and negative predictive values for identification of congenital heart diseases or noncongenital heart diseases (suspicion of perinatal infection and any respiratory diseases) were evaluated. Results: The best predictive results for minor congenital heart disease were obtained combining screening 3 and screening 4 (χ 2 (1) = 15,279; p < 0.05; OR = 57,900 (9,465-354,180)). Screening 2, screening 3, and screening 4 were predictive for noncongenital heart diseases (χ 2 (1) = 11,550; p < 0.05; OR = 65,744 (10,413-415,097)). Combined screenings 2-4 were predictive for both congenital heart disease and noncongenital heart disease (χ 2 (1) = 22,155; p < 0.05; OR = 117,685 (12,972-1067,648)). Conclusions: Combining peripheral saturation with the peripheral perfusion index in the first 24 hours of life shows a predictive role in the detection of minor congenital heart diseases and neonatal clinical conditions whose care needs attention.

Pediatric Multisystem Syndrome Associated with SARS-CoV-2 (MIS-C): The Interplay of Oxidative Stress and Inflammation.

Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (MIS-C) is characterized by persistent fever and evidence of single or multiorgan dysfunction, and laboratory evidence of inflammation, elevated neutrophils, reduced lymphocytes, and low albumin. The pathophysiological mechanisms of MIS-C are still unknown. Proinflammatory mediators, including reactive oxygen species and decreased antioxidant enzymes, seems to play a central role. Virus entry activates NOXs and inhibits Nrf-2 antioxidant response inducing free radicals. The biological functions of nonphagocytic NOXs are still under study and appear to include: defense of epithelia, intracellular signaling mechanisms for growth regulation and cell differentiation, and post-translational modifications of proteins. This educational review has the aim of analyzing the newest evidence on the role of oxidative stress (OS) in MIS-C. Only by relating inflammatory mediators to OS evaluation in children following SARS-CoV-2 infection will it be possible to achieve a better understanding of these mechanisms and to reduce long-term morbidity. The link between inflammation and OS is key to developing effective prevention strategies with antioxidants to protect children.

Potential benefits of melatonin to control pain in ventilated preterm newborns: An updated review.

Infants admitted to neonatal intensive care units are repeatedly stimulated by painful events, especially if intubated. Preterm infants are known to have greater pain perception than full term infants due to immaturity of descending inhibitory circuits and poor noxious inhibitory modulation. Newborns exposed to repetitive painful stimuli are at high risk of impairments in brain development and cognition. Chronic pain is induced and supported by proinflammatory cytokines, free radicals, and reactive oxygen species creating a self- sustaining vicious circle. Melatonin is a neurohormone secreted by the pineal gland with antioxidant and anti-inflammatory functions. This review describes the in-depth beneficial effects of melatonin for pain control in ventilated preterm newborns. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The rationale behind the use of melatonin for pain control has also been taken into account in this review. Besides, this review addresses safety concerns and dosages. The potential benefits of melatonin have been assessed against neurological disorders, respiratory distress, microbial infections, and as analgesic adjuvant during ventilation. Additionally, a possible approach for the use of melatonin in ventilated newborns will be discussed.

The challenge to define the optimal prophylactic regimen for vitamin K deficiency bleeding in infants.

Infants are at risk of vitamin K deficiency that may lead to vitamin K deficiency bleeding (VKDB). Although many vitamin K prophylactic regimens have been developed throughout the years, still cases of late form VKBD may occur. The introduction of combined prophylactic strategy with prolonged oral prophylaxes after the intramuscular dose at birth has showed a decrease of the late severe VKDB incidence. Nevertheless, there is still lack of consensus about the administration scheme after the first dose at birth. CONCLUSION: Late form VKBD is not eradicated, and the best prophylactic regimen in term and preterm infants is still an open debate.

Management of Congenital Diaphragmatic Hernia (CDH): Role of Molecular Genetics.

Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily on lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. Despite its clinical relevance, CDH multifactorial etiology is still not completely understood. We reviewed current knowledge on normal diaphragm development and summarized genetic mutations and related pathways as well as cellular mechanisms involved in CDH. Our literature analysis showed that the discovery of harmful de novo variants in the fetus could constitute an important tool for the medical team during pregnancy, counselling, and childbirth. A better insight into the mechanisms regulating diaphragm development and genetic causes leading to CDH appeared essential to the development of new therapeutic strategies and evidence-based genetic counselling to parents. Integrated sequencing, development, and bioinformatics strategies could direct future functional studies on CDH; could be applied to cohorts and consortia for CDH and other birth defects; and could pave the way for potential therapies by providing molecular targets for drug discovery.

Oxidative Stress and Respiratory Diseases in Preterm Newborns.

Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.

Melatonin pharmacokinetics and dose extrapolation after enteral infusion in neonates subjected to hypothermia.

INTRODUCTION: Neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia may benefit from adjunctive therapy with melatonin. However, melatonin safety, pharmacokinetics (PK), and dosage in this sensitive population are still unknown. METHODS AND RESULTS: This study assessed the PK and safety of melatonin enteral administration to neonates with HIE undergoing hypothermia. Melatonin was infused at 0.5 mg/kg in five neonates with HIE undergoing hypothermia. Infusion started 1 hour after the neonates reached the target temperature of 33.5°C. Blood samples were collected before and at selective times after melatonin infusion. Abdominal complications or clinically significant changes in patients' vital signs were not found during or after melatonin. The peak plasma concentration reached 0.25 µg/mL. The area under the curve in 24 hours was 4.35 µg/mL*h. DISCUSSION: Melatonin half-life and clearance were prolonged, and the distribution volume decreased compared to adults. In silico simulation estimated that the steady state can be reached after four infusions. Hypothermia does not affect melatonin PK. In humans high blood concentrations with lower doses can be achieved compared to animal experimentation, although intravenous administration is advised in the neonate population. Our study is a preparatory step for future clinical studies aimed at assessing melatonin efficacy in HIE.

Identification of a panel of cytokines in neonates with hypoxic ischemic encephalopathy treated with hypothermia.

PURPOSE: Inflammation is a crucial but understudied mechanism of neuronal injury after hypoxia-ischemia. The aim was to identify a panel of cytokines involved in brain injury in neonates with hypoxic ischemic encephalopathy (HIE). METHODS: Ten newborns with HIE undergoing to therapeutic hypothermia (TH, HIE Group) and 8 healthy newborns (CTRL Group) were enrolled. For the HIE group, 5 samples were collected: between 0 and 6 h of life (time 1), 12 h (time 2), 24 h (time 3), 48 h (time 4) and 96 h of life (time 5). For the CTRL group, one sample was collected. A panel of 48 inflammatory cytokines was determined in all samples. Data were analyzed using multivariate statistical analysis (Principal component analysis, PCA) RESULTS: 17 cytokines, among 48 analyzed, were found to be significantly different, initially, between the CTRL and HIE groups: 12 with reported pro-inflammatory effects and 5 with reported anti-inflammatory effects. In the HIE group cytokines showed a decreasing trend during the TH and at the end of treatment comparable to the CTRL group. IL-18 did demonstrate a slight increase at time 3 during HT but decreased steadily at sampling times, 4 and 5. CONCLUSIONS: Our data demonstrates that many pathways of the inflammatory cascade are activated following hypoxic-ischemic injury. This information will increase our understanding of changes in cytokines over time in neonates with HIE undergoing TH.

Rooming-in Reduces Salivary Cortisol Level of Newborn.

BACKGROUND: Rooming-in practice improves breastfeeding and reduces newborn stress reactivity. When this modality is not available, partial rooming-in after birth can be considered. Salivary cortisol levels (SCLs) are considered reliable biomarkers to indicate stress. OBJECTIVE: To test the hypothesis that rooming-in duration impacts neonatal stress response in hospitalized newborns. DESIGN/METHODS: Forty term newborns, enrolled in the Neonatology and Obstetrics Nursing, C.G. Ruesch, Naples, Italy, were divided, according to the mother's choice, into the study (SG; n = 20) and control (CG; n = 20) groups if they received full (24 hs) or partial (14 hs) rooming-in care, respectively. Saliva samples were collected from all babies between 7:00 a.m. and 8:00 a.m. of the 3rd day of life by using oral swab. Salivary cortisol levels were measured using an enzyme immunoassay kit (Salimetrics LLC, PA, USA). RESULTS: A statistically significant difference in the SCLs between SG and CG was found (median: 258 ng/dl versus 488.5 ng/dl; p = 0.048). CONCLUSIONS: Data support the practice of full rooming-in care compared with partial rooming-in. The rooming-in duration clearly reduces SCLs and likely neonatal stress. These lower SCLs may have long-term positive effects reducing the risk of metabolic syndrome, high blood pressure, and cognitive and behavioural changes.

Oxidative Stress Biomarkers: Establishment of Reference Values for Isoprostanes, AOPP, and NPBI in Cord Blood.

Oxidative stress (OS) is a common pathogenic factor involved in the onset of several diseases in humans, from immunologic disorders to malignancy, being a serious public health problem. In perinatal period, OS has been associated with adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are mediated by increased production of free radicals (FRs) following various mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation, mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism. FRs have short half-life, and their measurement in vivo is faced with many challenges. However, oxyradical derivatives are stable and thus may be measured and monitored repeatedly. The quantification of OS is based on the measurement of specific biomarkers in biologic fluids and tissues, which reflect induced oxidative damage to lipids, proteins, and DNA. Prostanoids, non-protein-bound iron (NPBI), and advanced oxidation protein products (AOPP) are actually considered truly specific and reliable for neonatal injury. Defining reference values for these biomarkers is necessary to investigate their role in neonatal diseases or also to evaluate the success of treatments. In this work, we wanted to define laboratory reference values for biomarkers of OS in a healthy population of term newborns.

An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis: Current Strategies and Future Prospects.

Neonatal sepsis is a clinical syndrome mainly associated with a bacterial infection leading to severe clinical manifestations that could be associated with fatal sequalae. According to the time of onset, neonatal sepsis is categorized as early- (EOS) or late-onset sepsis (LOS). Despite blood culture being the gold standard for diagnosis, it has several limitations, and early diagnosis is not immediate. Consequently, most infants who start empirical antimicrobial therapy do not have an underlying infection. Despite stewardship programs partially reduced this negative trend, in neonatology, antibiotic overuse still persists, and it is associated with several relevant problems, the first of which is the increase in antimicrobial resistance (AMR). Starting with these considerations, we performed a narrative review to summarize the main findings and the future prospects regarding antibiotics use to treat neonatal sepsis. Because of the impact on morbidity and mortality that EOS and LOS entail, it is essential to start an effective and prompt treatment as soon as possible. The use of targeted antibiotics is peremptory as soon as the pathogen in the culture is detected. Although prompt therapy is essential, it should be better assessed whether, when and how to treat neonates with antibiotics, even those at higher risk. Considering that we are certainly in the worrying era defined as the "post-antibiotic era", it is still essential and urgent to define novel strategies for the development of antibacterial compounds with new targets or mechanisms of action. A future strategy could also be to perform well-designed studies to develop innovative algorithms for improving the etiological diagnosis of infection, allowing for more personalized use of the antibiotics to treat EOS and LOS.

Hypoxic ischemic brain injury: animal models reveal new mechanisms of melatonin-mediated neuroprotection.

Oxidative stress (OS) and inflammation play a key role in the development of hypoxic-ischemic (H-I) induced brain damage. Following H-I, rapid neuronal death occurs during the acute phase of inflammation, and activation of the oxidant-antioxidant system contributes to the brain damage by activated microglia. So far, in an animal model of perinatal H-I, it was showed that neuroprostanes are present in all brain damaged areas, including the cerebral cortex, hippocampus and striatum. Based on the interplay between inflammation and OS, it was demonstrated in the same model that inflammation reduced brain sirtuin-1 expression and affected the expression of specific miRNAs. Moreover, through proteomic approach, an increased expression of genes and proteins in cerebral cortex synaptosomes has been revealed after induction of neonatal H-I. Administration of melatonin in the experimental treatment of brain damage and neurodegenerative diseases has produced promising therapeutic results. Melatonin protects against OS, contributes to reduce the generation of pro-inflammatory factors and promotes tissue regeneration and repair. Starting from the above cited aspects, this educational review aims to discuss the inflammatory and OS main pathways in H-I brain injury, focusing on the role of melatonin as neuroprotectant and providing current and emerging evidence.

Correlation between intrapartum CTG findings and interleukin-6 levels in the umbilical cord arterial blood: A prospective cohort study.

OBJECTIVE: to investigate the correlation between the intrapartum CardioTocoGraphic (CTG) findings "suggestive of fetal inflammation" ("SOFI") and the interleukin (IL)-6 level in the umbilical arterial blood. STUDY DESIGN: prospective cohort study conducted at a tertiary maternity unit and including 447 neonates born at term. METHODS: IL-6 levels were systematically measured at birth from a sample of blood taken from the umbilical artery. The intrapartum CTG traces were retrospectively reviewed by two experts who were blinded to the postnatal umbilical arterial IL-6 values as well as to the neonatal outcomes. The CTG traces were classified into "suggestive of fetal inflammation (SOFI)" and "no evidence of fetal inflammation (NEFI) according to the principles of physiologic interpretation the CTG traces. The CTG was classified as "SOFI" if there was a persistent fetal heart rate (FHR) increase > 10 % compared with the observed baseline FHR observed at the admission or at the onset of labor without any preceding repetitive decelerations. The occurrence of Composite Adverse Outcome (CAO) was defined as Neonatal Intensive Care Unit (NICU) or Special Care Baby Unit (SCBU) admission due to one or more of the following: metabolic acidaemia, Apgar score at 5 min ≤ 7, need of neonatal resuscitation, respiratory distress, tachypnoea/polypnea, jaundice requiring phototherapy, hypotension, body temperature instability, poor perinatal adaptation, suspected or confirmed early neonatal sepsis. MAIN OUTCOME MEASURES: To compare the umbilical IL-6 values between the cases with intrapartum CTG traces classified as "SOFI" and those classified as "NEFI"; to assess the correlation of umbilical IL-6 values with the neonatal outcome. RESULTS: 43 (9.6 %) CTG traces were categorized as "SOFI"; IL-6 levels were significantly higher in this group compared with the "NEFI" group (82.0[43.4-325.0] pg/ml vs. 14.5[6.8-32.6] pg/mL; p <.001). The mean FHR baseline assessed 1 h before delivery and the total labor length showed an independent and direct association with the IL-6 levels in the umbilical arterial blood (p <.001 and p = 0.005, respectively). CAO occurred in 33(7.4 %) cases; IL-6 yielded a good prediction of the occurrence of the CAO with an AUC of 0.72 (95 % CI 0.61-0.81). CONCLUSION: Intrapartum CTG findings classified as "SOFI" are associated with higher levels of IL-6 in the umbilical arterial blood.