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

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.

Gut colonization in preterm infants supplemented with bovine colostrum in the first week of life: An explorative pilot study.

BACKGROUND: In the first weeks after birth, enteral feeding and bacterial colonization interact to influence gut maturation in preterm infants. Bovine colostrum (BC) has been suggested as a relevant supplementary diet when own mother's milk (MM) is insufficient or absent. This pilot trial tests whether the supplement type, BC or donor human milk (DM), affects gut colonization in preterm infants during the first week of life. METHODS: On day 7, fecal samples were collected from preterm infants (n = 24) fed BC or DM as a supplement to MM. The gut microbiome (GM) was analyzed by 16S ribosomal RNA amplicon sequencing. Correlations between the relative abundance of specific bacterial taxa and blood chemistry variables, including amino acids, were explored. RESULTS: BC-supplemented infants showed a lower relative abundance of the families Lactobacillaceae and Enterococcaceae than DM infants. Planococcaceae were more abundant in infants delivered by cesarean birth vs vaginally. The relative abundance of bacterial families, specifically Enterobacteriaceae, correlated negatively with plasma levels of multiple essential and nonessential amino acids (valine, isoleucine, lysine, histidine, and arginine). CONCLUSION: The nature of nutrition supplements (BC or DM) just after birth may affect GM development and nutrient metabolism in the neonatal period of preterm infants. The exploratory nature of our study calls for confirmation of these results and their possible long-term clinical implications for preterm infants.

COpenhagen Neuroplastic TRaining Against Contractures in Toddlers (CONTRACT): protocol of an open-label randomised clinical trial with blinded assessment for prevention of contractures in infants with high risk of cerebral palsy.

INTRODUCTION: Contractures are frequent causes of reduced mobility in children with cerebral palsy (CP) already at the age of 2-3 years. Reduced muscle use and muscle growth have been suggested as key factors in the development of contractures, suggesting that effective early prevention may have to involve stimuli that can facilitate muscle growth before the age of 1 year. The present study protocol was developed to assess the effectiveness of an early multicomponent intervention, CONTRACT, involving family-oriented and supervised home-based training, diet and electrical muscle stimulation directed at facilitating muscle growth and thus reduce the risk of contractures in children at high risk of CP compared with standard care. METHODS AND ANALYSIS: A two-group, parallel, open-label randomised clinical trial with blinded assessment (n=50) will be conducted. Infants diagnosed with CP or designated at high risk of CP based on abnormal neuroimaging or absent fidgety movement determined as part of General Movement Assessment, age 9-17 weeks corrected age (CA) will be recruited. A balanced 1:1 randomisation will be made by a computer. The intervention will last for 6 months aiming to support parents in providing daily individualised, goal-directed activities and primarily in lower legs that may stimulate their child to move more and increase muscle growth. Guidance and education of the parents regarding the nutritional benefits of docosahexaenic acid (DHA) and vitamin D for the developing brain and muscle growth will be provided. Infants will receive DHA drops as nutritional supplements and neuromuscular stimulation to facilitate muscle growth. The control group will receive standard care as offered by their local hospital or community. Outcome measures will be taken at 9, 12, 18, 24, 36 and 48 months CA. Primary and secondary outcome measure will be lower leg muscle volume and stiffness of the triceps surae musculotendinous unit together with infant motor profile, respectively. ETHICS AND DISSEMINATION: Full approval from the local ethics committee, Danish Committee System on Health Research Ethics, Region H (H-19041562). Experimental procedures conform with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT04250454. EXPECTED RECRUITMENT PERIOD: 1 January 2021-1 January 2025.

Bovine Colostrum for Preterm Infants in the First Days of Life: A Randomized Controlled Pilot Trial.

OBJECTIVES: Mother's own milk (MM) is the best nutrition for newborn preterm infants, but is often limited in supply just after birth. Pasteurized human donor milk (DM), and especially preterm infant formula (IF) are less optimal diets than MM. We hypothesized that it is feasible to use bovine colostrum (BC), the first milk from cows, as a supplement to MM, during the first weeks after preterm birth. METHODS: In an open-label, randomized, controlled pilot safety trial, supplementation of MM with BC was compared with DM supplementation (Danish unit) or IF supplementation (Chinese unit). If MM was limited or lacking, BC, DM or IF were given according to local feeding guidelines during the first 14 days of life. RESULTS: Forty infants were included and randomized in Denmark and in China, with gestational ages 29.9 ±â€Š0.4 and 31.1 ±â€Š0.2 weeks, respectively. Infants supplemented with BC received more enteral protein (P < 0.05) and tended to reach full enteral feeding earlier (China only). Eight infants fed BC showed a temporary elevation in plasma tyrosine on day 7, versus 2 infants in the DM/IF groups. There were no differences between diet groups in feeding intolerance or clinical adverse events. CONCLUSIONS: Our results indicate that it is feasible to use BC as a supplement to MM during the first weeks of life to increase enteral protein intake in preterm infants. Plasma tyrosine levels may be a good marker for excessive protein intake. A larger randomized trial is required to test the safety and possible short- and long-term clinical benefits of BC supplementation during the first weeks of life for preterm infants.

The influence of probiotics for preterm neonates on the incidence of atopic dermatitis-results from a historically controlled cohort study.

Probiotic supplementation is a promising preventive strategy for atopic dermatitis (AD). To help clarifying the significance of timing with respect to prevention of AD, we here evaluate the benefit of prophylactic use of probiotic supplementation in neonates younger than 30 weeks of gestation. Preterm children from the Department of Neonatology, Rigshospitalet, Denmark from two different admission periods were included in a historically controlled cohort study. Neonates from January 2007 to February 2010, not treated with and neonates from March 2010 to February 2013 treated with probiotic were enrolled. Main outcome was prevalence of AD, and secondary outcomes were use of topical corticosteroids, and number of skin-related visits to GPs and dermatologists. 527 preterm neonates were included in the study, 249 treated and 278 not treated with probiotics. Response rate for the two cohorts was 76.7 and 77.7% respectively. The prevalence of AD was similar in the two groups (20.9% in the probiotic treated group versus 17.1% in the not treated group, p = 0.33). No significant differences were found between the groups with respect to treatment with topical corticosteroids, or visits at GPs or dermatologist. We found no indication that probiotics may prevent AD when administered to neonates <30 gestation weeks from birth until discharge home. Factors influencing the early maturation of the immune system have been assumed to be of particular importance in atopic dermatitis, and hence, our unique cohorts contribute information on how probiotic supplementation may affect the extremely immature immune systems of preterm infants.

Intravenous iron administration together with parenteral nutrition to very preterm Jehovah's Witness twins.

Preterm twin sisters (monozygotic) were born at gestational age 27 weeks and 5 days with birth weights of 935 and 735 g. They were admitted to our neonatal intensive care unit for a period of 1 month. Their parents were Jehovah's Witnesses and refused blood transfusion for their preterm daughters. Subcutaneous erythropoietin and intravenous iron were given as a prophylactic to avoid anaemia.

Dose-response relationship of phototherapy for hyperbilirubinemia.

BACKGROUND AND OBJECTIVE: Using light-emitting diodes during conventional phototherapy, it is possible to reduce the distance from light source to infant, thus increasing light irradiance. The objective of this study was to search for a "saturation point" (ie, an irradiation level above which there is no further decrease in total serum bilirubin [TsB]). This was a prospective randomized study performed in the NICU of Aalborg Hospital, Denmark. METHODS: One hundred fifty-one infants (gestational age ≥ 33 weeks) with uncomplicated hyperbilirubinemia were randomized to 1 of 4 distances from the phototherapy device to the mattress (20, 29, 38, and 47 cm). TsB was measured before and after 24 hours of phototherapy and irradiance every eighth hour. Main outcome was 24-hour decrease of TsB expressed in percent, ( TsB(0-24), difference between TsB(0) and TsB(24) [%]). RESULTS: A highly significant linear relation was seen between light irradiance and TsB(0-24) (%) (P < .001): when the irradiance increased from 20 to 55 µW/cm(2)/nm, TsB(0-24) (%) increased from approximately 30% to 50%. In addition, smooth regression showed no tendency for TsB(0-24) (%) to level off as irradiance increased. TsB(0-24) (%) was negatively correlated to birth weight and positively to formula volume. Average weight gain during phototherapy was 1%, independent of light irradiance. CONCLUSIONS: By using light-emitting diodes, we found a linear relation between light irradiance in the range of 20 to 55 µW/cm(2)/nm and a decrease in TsB after 24 hours of therapy, with no evidence of a saturation point.