Neuronal exosome proteins: novel biomarkers for predicting neonatal response to therapeutic hypothermia

ObjectiveCentral nervous system (CNS) derived exosomes can be purified from peripheral blood and have been used widely in adult neurological disease. Application to neonatal neurological disease deserves investigation in the setting of hypoxic–ischaemic encephalopathy (HIE).DesignObservational cohort.SettingLevel III neonatal intensive care unit.ParticipantsTerm/near-term neonates undergoing therapeutic hypothermia (TH) for HIE.InterventionsBlood samples were collected at 0–6, 12, 24, 48 and 96 hours of life.Main outcomes and measuresCNS exosomes were purified from serum using previously described methods. Biomarker protein levels were quantified using standard ELISA methods and normalised to exosome marker CD-81. The slope of change for biomarker levels was calculated for each time interval. Our primary outcome was MRI basal ganglia/watershed score of ≥3.Results26 subjects were included (umbilical artery pH range 6.6–7.29; 35% seizures). An increasing MRI injury score was significantly associated with decreasing levels of synaptopodin between 0–6 and 12 hours (p=0.03) and increasing levels of lipocalin-2 (NGAL) between 12 and 48 hours (p<0.0001). Neuronal pentraxin was not significant. The negative predictive values for increasing synaptopodin and decreasing NGAL was 70.0% and 90.9%, respectively.Conclusions and relevanceOur results indicate that CNS exosome cargo has the potential to act as biomarkers of the severity of brain injury and response to TH as well as quantify pharmacological response to neuroactive therapeutic/adjuvant agents. Rigorous prospective trials are critical to evaluate potential clinical use of exosome biomarkers.

Effect of Delivery by Emergency or Elective Cesarean Section on Nitric Oxide Metabolites and Cortisol Amniotic Concentrations in at Term Normal Newborn Dogs: Preliminary Results

The neonatal response to stress was reported to be related to the type of delivery, that is elective or emergency cesarean sections (ELCS and EMCS, respectively). Nitric oxide (NO) is also reported to be related to uterine inertia, and high levels of NO metabolites (NOs) are associated with physical and emotional stress. The study aimed to assess the concentrations of cortisol (C) and NOs in the amniotic fluid of puppies delivered by ELCS or EMCS. In total, 32 puppies were delivered by ELCS and 22 by EMCS. ANCOVA showed an effect of the ELCS vs. EMCS on both amniotic NOs (p < 0.001) and C (p < 0.001) concentrations. Lower amniotic C concentrations were found at increasing Apgar score (p < 0.001). Higher amniotic NOs concentrations were associated to increasing mother’s parity (p < 0.001), puppies’ birthweight (p < 0.001), and time of labor within the EMCS group (p < 0.05). A positive correlation between birthweight and amniotic NOs concentrations was also found (p < 0.05) in the EMCS group. Due to the possible concurrence of several compartments (maternal, maybe placental, and fetal) to the final amniotic fluid composition, the definition of the role played by the three compartments in the higher C and NOs concentrations found in amniotic fluids collected from puppies delivered by EMCS than ELCS needs further clarification.

Maternal and neonatal response to COVID-19

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to maternal and newborn health has yet to be determined. Several reports suggest pregnancy does not typically increase the severity of maternal disease; however, cases of preeclampsia and preterm birth have been infrequently reported. Reports of placental infection and vertical transmission are rare. Interestingly, despite lack of SARS-CoV-2 placenta infection, there are several reports of significant abnormalities in placenta morphology. Continued research on pregnant women infected with SARS-CoV-2 and their offspring is vitally important.

Neonatal Leukemoid Reaction: A Diagnostic Dilemna

Leukemoid reaction is defined as an absolute neutrophil count(ANC) of >30,000/cumm. First described by Holland and Maurer in 1963 leukemoid reaction is associated with infection, anemia, bronchopulmonary dysplasia, use of antenatal steroids, prematurity. Neonatal leukemoid reaction is seen as a neonatal response to hypoxia and can mimic leukemia. In our case the baby was premature and the leukemoid reaction was due to early onset sepsis. Clinicians need to keep sepsis in mind while dealing with neonatal leukemoid reaction.J Nepal Paediatr Soc 2016;36(3):298-299

Maternal factors regulating preterm infants' responses to pain and stress while in maternal kangaroo care

The relationship between maternal factors and the response of preterm infants to pain and stress experienced during heel puncture while in maternal kangaroo care was investigated. This descriptive study included 42 mothers and their preterm infants cared for in a neonatal unit. Data were collected in the baseline, procedure, and recovery phases. We measured the neonates' facial actions, sleep and wake states, crying, salivary cortisol levels, and heart rate, in addition to the mothers' behavior, salivary cortisol levels, and mental condition. The influence of the maternal explanatory variables on the neonatal response variables were verified through bivariate analysis, ANOVA, and multiple regression. The mothers' behavior and depression and/or anxiety did not affect the neonates' responses to pain and stress, though the mothers' levels of salivary cortisol before the procedure explained the variance in the neonates' levels of salivary cortisol after the procedure (p=0.036). Additionally, the mothers' baseline levels of salivary cortisol along with the neonates' age explained the variance in the neonates' heart rate (p=0.001). The ability of mothers to regulate their own stress contributed to the infants' responses to pain and stress.

Critical Role for CXC Ligand 10/CXC Receptor 3 Signaling in the Murine Neonatal Response to Sepsis

ABSTRACTPrevious studies have suggested that neonates rely heavily on innate immunity for their antimicrobial response to bacterial infections. However, the innate immune response by neonates to bacterial infection remains poorly characterized. Here, we show that in a murine model of neonatal polymicrobial sepsis, CXC ligand 10 (CXCL10) concentrations increase in the blood and peritoneum concordant with the peritoneal recruitment of granulocytes and macrophages. Additionally, CXC receptor 3 (CXCR3) expression on elicited peritoneal macrophages and granulocytes increases following sepsis. Blockade of CXCL10 worsens not only recruitment and phagocytic function of peritoneal granulocytes and macrophages but also survival. Deletion of CXCR3 also significantly increases mortality to a septic challenge. Finally, we demonstrate that the protective adjuvant effect of pretreatment with a Toll-like receptor 4 agonist to neonatal sepsis is dependent on an endogenous CXCL10 response and that pretreatment of neonates with CXCL10 can also significantly improve macrophage and granulocyte function and modestly improve outcome to polymicrobial sepsis. Together, these data suggest a critical role for CXCL10 signaling during neonatal sepsis.