Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates

Abstract: Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication.For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury.Continuous multimodal monitoring as well as monitoring of sleep, sleep–wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care

Could Near Infrared Spectroscopy (NIRS) be the new weapon in our fight against Necrotising Enterocolitis?

There is no ideal single gut tissue or inflammatory biomarker available to help to try and identify Necrotising Enterocolitis (NEC) before its clinical onset. Neonatologists are all too familiar with the devastating consequences of NEC, and despite many advances in neonatal care the mortality and morbidity associated with NEC remains significant. In this article we review Near Infrared Spectroscopy (NIRS) as a method of measuring regional gut tissue oxygenation. We discuss its current and potential future applications, including considering its effectiveness as a possible new weapon in the early identification of NEC

INTERMITTENT HYPOXEMIA IN PRETERM INFANTS

Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Virtually all preterm infants have IH events. Extremely preterm infants have hundreds of IH events per day. The extent of IH is not apparent clinically as accurately documenting cardiorespiratory events for day-to-day patient care management is challenging. High resolution pulse oximeters with 2 second averaging time are currently the ideal methods to measure IH. We have developed novel methods and processes to accurately and efficiently calculate an IH profile that reflects to spectrum of the problem. The natural progression of IH is dynamic. There is low incidence of IH in the few 2 weeks of life, followed by a progressive increase until peak IH at 4-5 week after which IH plateaus. Multiple factors place preterm infants at high risk for increased IH. These factors include respiratory immaturity, lung disease, and anemia. We also show that preterm infants prenatally exposed to opioids or inflammation (due to maternal chorioamnionitis) have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the exposed groups persists beyond the immediate postnatal period. Brief episodes of oxygen desaturations may seem clinically insignificant; however, these events may have a cumulative effect on neonatal outcomes. There is mounting evidence from both animal models and clinical studies suggesting that IH is associated with injury and poor outcomes such as impaired growth, retinopathy of prematurity and neurodevelopmental impairment. In addition data from neonatal animal models and adults with obstructive sleep apnea suggest that IH is pro inflammatory itself. We demonstrate in this document for the first time in preterm infants that IH is associated with increased serum inflammatory marker, C-reactive protein. Finally, a valuable experience throughout this process is working with a talented and dedicated multidisciplinary team. We are a solid example of the value of team science during this new era of clinical and translational research. Our respiratory control research program is one of handful programs nationwide able to perform such high-fidelity studies related to cardiorespiratory events in preterm infants. We will continue to tackle complex questions involving health of infants

Neuromonitoring during newborn transition

Background: Newborn infant neurological function can be measured by monitoring electrical activity (electroencephalography) or cerebral oxygenation via NIRS (near infrared spectroscopy). In practice the clinical applications of electroencephalography (EEG) are limited to monitoring infants following moderate to severe hypoxic ischemic injury (HIE), and for the detection of seizures in at risk infants. NIRS monitoring has been the focus of a number of research trials but has no clinical applications in the immediate newborn period to date, and is not routinely performed in neonatal units. Aim: To assess the feasibility of infant neuromonitoring in the immediate period in two important clinical scenarios. Firstly, to assess the feasibility of monitoring brain activity during the first minutes of life in healthy term infants. Secondly, to assess the feasibility and utility of monitoring newborn preterm infants’ brain activity and cerebral oxygenation in the context of an interventional randomized controlled trial. Methods: 1. Healthy term newborn infants had EEG monitoring performed for the first ten minutes of life. EEG was assessed both qualitatively and quantitatively. All infants had respiratory function monitoring performed simultaneously. 2. Forty-five infants (< 32 weeks gestation) were randomly assigned to different methods of newborn infant cord clamping. All infants had EEG and NIRS monitoring for the first 72 hours of life. Quantitative features of EEG and median NIRS values were compared between groups at 6 and 12 hours of life as a primary outcome measure. Results: 1. Forty-nine infants had EEG recordings. Median (IQR) age at time of initial EEG recording was 3.0 (2·5 to 3·8) minutes. End tidal CO2 and tidal volumes increased over the first 3 minutes of life and then stabilized. Good quality EEG, with continuous mixed frequency activity with a range of 25-50μV, was observed in all infants. The majority of EEG spectral power was within the delta band. 2. There were 45 infants included. One infant died in the delivery room. Median time (IQR) from birth until EEG application was 3.05 (1.85 to 5.38) hrs. For primary outcome measures, data was available for 42/44 (95%) at 6 hrs and 44/44 (100%) at 12 hours. There was no significant difference between groups for measures for EEG values or cerebral NIRS. Conclusion: Infant neuromonitoring in the immediate newborn period is feasible in the first minutes of life in healthy term infants and within the first hours of life in preterm infants. Normative quantitative data for electrical activity in healthy newborn term infants during the first minutes of life is described for the first time. Neuromonitoring during the first day of life as an outcome measure for preterm interventional trials is possible and the outcomes from this research is promising for further trials

Rh Negative Status and Isoimmunization Update: A Case-Based Approach to Care

Prior to the 1970s and the advent of Rho (D) immune globulin (RIG) for Rh negative women, hemolytic disease of the newborn led to morbidity, long-term disabilities, and mortality. Antepartum RIG administration has been a standard of practice since 1983. Yet, Rh isoimmunization (sensitization) and its sequelae have not been completely eradicated. Rh-related issues remain clinical challenges facing perinatal and neonatal nurses. Evidence for the administration of RIG prenatally and during the postpartum period is presented including controversies and challenges. Current information about fetal and neonatal care of erythroblastosis fetalis and immune hydrops is also presented

Non‐Pulmonary Management of Newborns with Respiratory Distress

Due to the developmental immaturity of the lungs and other organs, the premature newborns are more prone to develop respiratory distress syndrome (RDS) and other problems of prematurity. The prevention of heat and water loses improves survival. Intolerance to excessive fluids and electrolytes in the transitional period may affect urine and sodium excretion together with maladaptation of cardiovascular system, the development of heart failure, and deterioration of RDS due to patent ductus arteriosus (PDA) and further development of bronchopulmonary dysplasia (BPD). Closure of PDA is frequently needed. The “trophic feeding” and intensive nutrition as soon as possible prevent weight loss and further growth restriction. Greater sensitivity to pain, short‐ and long‐term effects of inappropriately treated pain, use of opioids and sedatives are of concern in the short‐ and long‐term outcomes. Cardiovascular stability and adequate perfusion of the brain both affect the neurological outcome. Delayed cord clamping and erythropoietin help maintaining adequate levels of circulating hemoglobin which might affect later cognitive outcomes. In the following sections, detailed descriptions of non‐pulmonary management will be presented. We conducted electronic searches of articles on supportive (non‐pulmonary) management of newborns with RDS. Consensus guidelines on newborns with respiratory distress have been reviewed

Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT

BACKGROUND:Being born very premature (i.e. before 32 weeks’ gestation) has an impact on survival and quality of life. Improving care at birth may improve outcomes and parents’ experiences. OBJECTIVES:To improve the quality of care and outcomes following very preterm birth. DESIGN:We used mixed methods, including a James Lind Alliance prioritisation, a systematic review, a framework synthesis, a comparative review, qualitative studies, development of a questionnaire tool and a medical device (a neonatal resuscitation trolley), a survey of practice, a randomised trial and a protocol for a prospective meta-analysis using individual participant data. SETTING:For the prioritisation, this included people affected by preterm birth and health-care practitioners in the UK relevant to preterm birth. The qualitative work on preterm birth and the development of the questionnaire involved parents of infants born at three maternity hospitals in southern England. The medical device was developed at Liverpool Women’s Hospital. The survey of practice involved UK neonatal units. The randomised trial was conducted at eight UK tertiary maternity hospitals. PARTICIPANTS:For prioritisation, 26 organisations and 386 individuals; for the interviews and questionnaire tool, 32 mothers and seven fathers who had a baby born before 32 weeks’ gestation for interviews evaluating the trolley, 30 people who had experienced it being used at the birth of their baby (19 mothers, 10 partners and 1 grandmother) and 20 clinicians who were present when it was being used; for the trial, 261 women expected to have a live birth before 32 weeks’ gestation, and their 276 babies. INTERVENTIONS:Providing neonatal care at very preterm birth beside the mother, and with the umbilical cord intact; timing of cord clamping at very preterm birth. MAIN OUTCOME MEASURES:Research priorities for preterm birth; feasibility and acceptability of the trolley; feasibility of a randomised trial, death and intraventricular haemorrhage. REVIEW METHODS:Systematic review of Cochrane reviews (umbrella review); framework synthesis of ethics aspects of consent, with conceptual framework to inform selection criteria for empirical and analytical studies. The comparative review included studies using a questionnaire to assess satisfaction with care during childbirth, and provided psychometric information. RESULTS:Our prioritisation identified 104 research topics for preterm birth, with the top 30 ranked. An ethnographic analysis of decision-making during this process suggested ways that it might be improved. Qualitative interviews with parents about their experiences of very preterm birth identified two differences with term births: the importance of the staff appearing calm and of staff taking control. Following a comparative review, this led to the development of a questionnaire to assess parents’ views of care during very preterm birth. A systematic overview summarised evidence for delivery room neonatal care and revealed significant evidence gaps. The framework synthesis explored ethics issues in consent for trials involving sick or preterm infants, concluding that no existing process is ideal and identifying three important gaps. This led to the development of a two-stage consent pathway (oral assent followed by written consent), subsequently evaluated in our randomised trial. Our survey of practice for care at the time of birth showed variation in approaches to cord clamping, and that no hospitals were providing neonatal care with the cord intact. We showed that neonatal care could be provided beside the mother using either the mobile neonatal resuscitation trolley we developed or existing equipment. Qualitative interviews suggested that neonatal care beside the mother is valued by parents and acceptable to clinicians. Our pilot randomised trial compared cord clamping after 2 minutes and initial neonatal care, if needed, with the cord intact, with clamping within 20 seconds and initial neonatal care after clamping. This study demonstrated feasibility of a large UK randomised trial. Of 135 infants allocated to cord clamping ≥ 2 minutes, 7 (5.2%) died and, of 135 allocated to cord clamping ≤ 20 seconds, 15 (11.1%) died (risk difference –5.9%, 95% confidence interval –12.4% to 0.6%). Of live births, 43 out of 134 (32%) allocated to cord clamping ≥ 2 minutes had intraventricular haemorrhage compared with 47 out of 132 (36%) allocated to cord clamping ≤ 20 seconds (risk difference –3.5%, 95% CI –14.9% to 7.8%). LIMITATIONS:Small sample for the qualitative interviews about preterm birth, single-centre evaluation of neonatal care beside the mother, and a pilot trial. CONCLUSIONS:Our programme of research has improved understanding of parent experiences of very preterm birth, and informed clinical guidelines and the research agenda. Our two-stage consent pathway is recommended for intrapartum clinical research trials. Our pilot trial will contribute to the individual participant data meta-analysis, results of which will guide design of future trials. FUTURE WORK:Research in preterm birth should take account of the top priorities. Further evaluation of neonatal care beside the mother is merited, and future trial of alternative policies for management of cord clamping should take account of the meta-analysis. STUDY REGISTRATION:This study is registered as PROSPERO CRD42012003038 and CRD42013004405. In addition, Current Controlled Trials ISRCTN21456601. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 8. See the NIHR Journals Library website for further project information