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Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates.

ABSTRACT: Introduction: Fetal inflammatory response syndrome (FIRS), defined as elevated umbilical cord blood interleukin-6 (IL-6) values > 11 pg/ml, is associated with an increased risk of neonatal morbidity and mortality. The primary aim of the present study was to evaluate a potential influence of FIRS on cerebral oxygen saturation (crSO2) and fractional tissue oxygen extraction (cFTOE) during immediate postnatal transition in preterm neonates. The secondary aim was to analyze the potential influence of FIRS on cerebral injury and mortality. Methods: Secondary outcome parameters of prospective observational studies were analyzed. Preterm neonates with measured IL-6 values from umbilical cord blood and cerebral near-infrared spectroscopy (NIRS) measurements during immediate transition after birth were included. Preterm neonates with FIRS (FIRS group) were matched 1:1 for gestational age (± 1 week) to preterm neonates without FIRS (non-FIRS group). crSO2, cFTOE, arterial oxygen saturation (SpO2), heart rate (HR), and fraction of inspired oxygen (FiO2) were compared between both groups. In addition, cerebral injury and mortality were compared between both groups. Results: A total of 46 preterm neonates were included. Twenty-three neonates in the FIRS group [median gestational age 32.1 (IQR 30.3-33.0) weeks; median IL-6 19.7 (IQR 12.2-37.0) pg/ml] were compared to 23 neonates in the non-FIRS group [gestational age: 32.0 (30.4-33.1) weeks; IL-6: 5.4 (3.0-6.7) pg/ml]. cFTOE showed significantly lower values within the first 4 min and a trend toward lower values in minute 5 after birth in the FIRS group. There were no significant differences in crSO2 within the first 15 min after birth between the two groups. SpO2 was significantly lower in minutes 5 and 6 and HR was significantly lower in minutes 2 and 4 after birth in the FIRS group compared to the non-FIRS group. Survival without cerebral injury was similar in both groups. Conclusion: In preterm neonates with FIRS the crSO2 was similar despite significantly lower cFTOE values during the first minutes after birth. This observation may be a result of compromised oxygen consumption and delivery in the first minutes after birth in neonates with FIRS.

SUBMITTER: Wolfsberger CH

PROVIDER: S-EPMC7387571 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates.

Wolfsberger Christina Helene CH Bruckner Marlies M Baik-Schneditz Nariae N Schwaberger Bernhard B Mileder Lukas Peter LP Avian Alexander A Urlesberger Berndt B Pichler Gerhard G

Frontiers in pediatrics 20200722

<b>Introduction:</b> Fetal inflammatory response syndrome (FIRS), defined as elevated umbilical cord blood interleukin-6 (IL-6) values > 11 pg/ml, is associated with an increased risk of neonatal morbidity and mortality. The primary aim of the present study was to evaluate a potential influence of FIRS on cerebral oxygen saturation (crSO2) and fractional tissue oxygen extraction (cFTOE) during immediate postnatal transition in preterm neonates. The secondary aim was to analyze the potential infl ...[more]

PMID: 32793528

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Project description:Background Prematurity is associated with increased risk for morbidity and mortality. Aim of this study was to evaluate whether cerebral oxygenation during fetal-to-neonatal transition period was associated with long-term outcome in very preterm neonates. Methods Preterm neonates ≤ 32 weeks of gestation and/or ≤ 1500 g with measurements of cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth were analysed retrospectively. Arterial oxygen saturation (SpO2) and heart rate (HR) were measured with pulse oximetry. Long-term outcome was assessed at two years using “Bayley Scales of Infant Development” (BSID-II/III). Included preterm neonates were stratified into two groups: adverse outcome group (BSID-III ≤ 70 or testing not possible due to severe cognitive impairment or mortality) or favorable outcome group (BSID-III > 70). As the association between gestational age and long-term outcome is well known, correction for gestational age might disguise the potential association between crSO2 and neurodevelopmental impairment. Therefore, due to an explorative approach the two groups were compared without correction for gestational age. Results Forty-two preterm neonates were included: adverse outcome group n = 13; favorable outcome group n = 29. Median(IQR) gestational age and birth weight were 24.8 weeks (24.2–29.8) and 760 g (670–1054) in adverse outcome group and 30.6 weeks (28.1–32.0) (p = 0.009*) and 1250 g (972–1390) (p = 0.001*) in the favorable outcome group, respectively. crSO2 was lower (significant in 10 out of 14 min) and cFTOE higher in adverse outcome group. There were no difference in SpO2, HR and fraction of inspired oxygen (FiO2), except for FiO2 in minute 11, with higher FiO2 in the adverse outcome group. Conclusion Preterm neonates with adverse outcome had beside lower gestational age also a lower crSO2 during immediate fetal-to-neonatal transition when compared to preterm neonates with age appropriate outcome. Lower gestational age in the adverse outcome group would suggest beside lower crSO2 also lower SpO2 and HR in this group, which were however similar in both groups. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-023-03960-z.

Project description:ObjectiveTo investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone.DesignMulticentre, multinational, randomised controlled phase 3 trial.Setting11 tertiary neonatal intensive care units in six countries in Europe and in Canada.Participants1121 pregnant women (<32 weeks' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group.InterventionPreterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation.Main outcome measureThe primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge.ResultsCerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) v control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70).ConclusionMonitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates (<32 weeks' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant.Trial registrationClinicalTrials.gov NCT03166722.

Project description:A robust inflammatory response occurs in the hours and days following cerebral ischemia. However, little is known about the immediate innate immune response in the first minutes after an ischemic insult in humans. We utilized the use of circulatory arrest during cardiac surgery to assess this.Twelve neonates diagnosed with an aortic arch obstruction underwent cardiac surgery with cardiopulmonary bypass and approximately 30 minutes of deep hypothermic circulatory arrest (DHCA, representing cerebral ischemia). Blood samples were drawn from the vena cava superior immediately after DHCA and at various other time points from preoperatively to 24 hours after surgery. The innate immune response was assessed by neutrophil and monocyte count and phenotype using FACS, and concentrations of cytokines IL-1?, IL-6, IL-8, IL-10, TNF?, sVCAM-1 and MCP-1 were assessed using multiplex immunoassay. Results were compared to a simultaneously drawn sample from the arterial cannula. Twelve other neonates were randomly allocated to undergo the same procedure but with continuous antegrade cerebral perfusion (ACP).Immediately after cerebral ischemia (DHCA), neutrophil and monocyte counts were higher in venous blood than arterial (P = 0.03 and P = 0.02 respectively). The phenotypes of these cells showed an activated state (both P <0.01). Most striking was the increase in the 'non-classical' monocyte subpopulations (CD16(intermediate); arterial 6.6% vs. venous 14%; CD16+ 13% vs. 22%, both P <0.01). Also, higher IL-6 and lower sVCAM-1 concentrations were found in venous blood (both P = 0.03). In contrast, in the ACP group, all inflammatory parameters remained stable.In neonates, approximately 30 minutes of cerebral ischemia during deep hypothermia elicits an immediate innate immune response, especially of the monocyte compartment. This phenomenon may hold important clues for the understanding of the inflammatory response to stroke and its potentially detrimental consequences.ClinicalTrial.gov: NCT01032876.

Project description:IntroductionRespiratory morbidities in neonates are often progressive and life-threatening, and its early prediction is crucial. Intrauterine inflammation is one of the key control variables of respiratory morbidities in both very preterm and term neonates; however, little is known about its effects in the remaining group of moderate-to-late preterm neonates born between 32+0 and 36+6 weeks of gestation. This study aimed to confirm whether intrauterine inflammation is associated with respiratory morbidities in moderate-to-late preterm neonates.MethodsA single-center retrospective observational study was conducted in neonates born between 32+0 and 34+6 weeks of gestation between April 2013 and March 2018. The correlation between respiratory morbidities (defined as a requirement for invasive mechanical ventilation longer than the median duration of 3 days) and intrauterine inflammation was assessed using multivariable logistic regression analysis.ResultsThe study population comprised 242 neonates born at 33.7 ± 0.8 weeks of gestation and weighing 1,936 ± 381 g. The multivariable model to predict the outcome comprised respiratory distress syndrome (odds ratio [OR]: 9.1; 95% confidence interval [CI]: 3.7-22.5; p < 0.001), lower gestational age (per week; OR: 0.5; 95% CI: 0.3-0.8; p < 0.005), higher birth-weight z-score (OR: 1.6; 95% CI: 1.2-2.2; p < 0.005), lower cord blood pH (per 0.10; OR: 0.5; 95% CI: 0.3-0.7; p < 0.005), and chorioamnionitis (OR: 2.8; 95% CI: 1.1-7.2; p < 0.05).ConclusionTogether with the incidence of respiratory distress syndrome and gestational age, chorioamnionitis and high birth-weight z-scores were associated with an increased incidence of respiratory morbidities in moderate-to-late preterm neonates. The deleterious impact of intrauterine inflammation on the lungs may be common in neonates of virtually all gestational ages. Traditional admission policy of neonatal intensive care units based on a threshold birth-weight, may leave a group of neonates without close observation despite their increased risks for respiratory morbidities.

Project description:BackgroundTransition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia-ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO2) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO2) and heart rate (HR).Methods/designCOSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO2, SpO2, and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO2 and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities.DiscussioncrSO2 monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO2 with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury.Trial registrationClinicalTrials.gov Identifier: NCT03166722 . Registered March 5, 2017.

Project description:IntroductionUp to 50% of preterm infants admitted to intensive care units require cardiocirculatory support. The aim of the present study was to assess whether simultaneous monitoring of cerebral tissue oxygenation index (cTOI) and peripheral tissue oxygenation index (pTOI) using near-infrared spectroscopy (NIRS) in combination with dedicated intervention guidelines may help avoiding arterial hypotension and catecholamine administration in preterm neonates.Study designPreterm neonates <37 weeks of gestation were included in a single center randomized controlled study. Blood pressure was measured non-invasively or invasively. In the NIRS group, simultaneous cTOI and pTOI monitoring was used starting within 6 h after birth for 24 h to calculate changes in cTOI/pTOI ratio over time. Depending on these changes, interventions including echocardiography, administration of volume or patent ductus arteriosus treatment were performed. In the control group, only routine monitoring and treatment were performed and NIRS signals were not visible. The primary outcome was burden of hypotension within 48 h after initiation of NIRS monitoring.Results49 preterm neonates were included in each group: NIRS group 33.1 (32.0-34.0) (median: 25-75 centile) weeks of gestation and control group 33.4 (32.3-34.3) weeks of gestation. In the NIRS group, echocardiography was performed in 17 preterm neonates due to NIRS measurements, whereby six neonates received further treatment. Percentage of neonates with any hypotensive episode during the 48-h observational period was 32.6% in the NIRS group and 44.9% in the control group (p = 0.214). Burden of hypotension (i.e., %mmHg of mean arterial pressure < gestational age) was 0.0 (0.0-2.1) mmHg h in the NIRS group and 0.4 (0.0-3.3) mmHg h in the control group (p = 0.313), with observed burden of hypotension being low in both groups. No severe adverse reactions were observed.ConclusionIn preterm neonates using simultaneous peripheral and cerebral NIRS measurements for early detection of centralization followed by predefined interventions led to a non-significant reduction in burden of arterial hypotension.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT01910467.

Project description:Background and aim: Neonatal brain monitoring is increasingly used due to reports of brain injury perioperatively. Little is known about the effect of sedatives (midazolam) and anesthetics (sevoflurane) on cerebral oxygenation (rScO2) and cerebral activity. This study aims to determine these effects in the perioperative period. Methods: This is an observational, prospective study in two tertiary pediatric surgical centers. All neonates with a congenital diaphragmatic hernia received perioperative cerebral oxygenation and activity measurements. Patients were stratified based on intraoperatively administrated medication: the sevoflurane group (continuous sevoflurane, bolus fentanyl, bolus rocuronium) and the midazolam group (continuous midazolam, continuous fentanyl, and continuous vecuronium). Results: Intraoperatively, rScO2 was higher in the sevoflurane compared to the midazolam group (84%, IQR 77-95 vs. 65%, IQR 59-76, p = < 0.001), fractional tissue oxygen extraction was lower (14%, IQR 5-21 vs. 31%, IQR 29-40, p = < 0.001), the duration of hypoxia was shorter (2%, IQR 0.4-9.6 vs. 38.6%, IQR 4.9-70, p = 0.023), and cerebral activity decreased more: slow delta: 2.16 vs. 4.35 μV 2 (p = 0.0049), fast delta: 0.73 vs. 1.37 μV 2 (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48-31.22 μV 2) and a 5-fold increase in gamma (1.42-7.58 μV 2) were observed in the midazolam group. Conclusion: Sevoflurane-based anesthesia resulted in increased cerebral oxygenation and decreased cerebral activity, suggesting adequate anesthesia. Midazolam-based anesthesia in neonates with a more severe CDH led to alarmingly low rScO2 values, below hypoxia threshold, and increased values of EEG power during the first 30 min of surgery. This might indicate conscious experience of pain. Integrating population-pharmacokinetic models and multimodal neuromonitoring are needed for personalized pharmacotherapy in these vulnerable patients. Trial Registration: https://www.trialregister.nl/trial/6972, identifier: NL6972.

Dataset Information

Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates.

Publications

Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates.

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