IMPORTANCEBecause children in a preverbal stage of development are unable to voice their feelings, they completely depend on their caregiving team for the interpretation and management of their pain and discomfort. Thus, accurately validated scales to assess pain and sedation levels are crucial.OBJECTIVE To provide clinicians a complete overview on the validity and reliability of the existing pain and sedation scales for different target populations (preterm infants, term infants, and toddlers) and in different clinical contexts.EVIDENCE REVIEW BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycCRITIQUES, PsycINFO, PSYNDEXplus Literature and Audiovisual Media, and PSYNDEXplus Tests were the databases screened from their inception to August 2018. All studies examining the validity or reliability of a given pain or sedation scale for patients in a preverbal stage of development were included in this systematic review. Those scales that were tested for at least construct validity, internal consistency, and interrater reliability were subsequently scored using the consensus-based standards for the selection of health measurement instruments (COSMIN) checklist.FINDINGS In total, 89 validation articles comprising 65 scales were included. Fifty-seven scales (88%) were useful for assessing pain, 13 scales (20%) for assessing sedation, and 4 scales (6%) for assessing both conditions. Forty-two (65%) were behavioral scales, and 23 (35%) were multidimensional scales. Eleven scales (17%) were validated for infants on mechanical ventilation. Thirty-seven scales (57%) were validated for preterm infants, 24 scales (37%) for term and preterm infants, 7 scales (11%) for term-born children, 7 scales (11%) for preterm infants, term infants, and toddlers, and 17 scales (26%) for term infants and toddlers. Twenty-eight scales (43%) considered construct validity, internal consistency, and interrater reliability.CONCLUSIONS AND RELEVANCE Clinicians should consider using scales that are validated for at least construct validity, internal consistency, and interrater reliability, combining this information with the population of interest and the construct the scale is intended to measure.

Summary Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.

This method enables the visualisation of sleep state in preterm infants which can assist clinical management in the neonatal intensive care unit.

Auditory sensory memory is an important ability for successful language acquisition and processing. The mismatch negativity (MMN) in response to auditory stimuli has been proposed as an objective tool to measure the existence of auditory sensory memory traces. By increasing interstimulus intervals, attenuation of MMN peak amplitude and increased MMN peak latency have been suggested to reflect duration and decay of sensory memory traces. The aim of the present study is to conduct a systematic review of studies investigating sensory memory duration with MMN. Searches of electronic databases yielded 743 articles. Of these, 37 studies met final eligibility criteria. Results point to maturational changes in the time span of auditory sensory memory from birth on with a peak in young adulthood, as well as to a decrease of sensory memory duration in healthy aging. Furthermore, this review suggests that sensory memory decline is related to diverse neurological, psychiatric, and pediatric diseases, including Alzheimer's disease, alcohol abuse, schizophrenia, and language disorders. This review underlines that the MMN provides a unique window to the cognitive processes of auditory sensory memory. However, further studies combining electrophysiological and behavioral data, and further studies in clinical populations are needed, also on individual levels, to validate the MMN as a clinical tool for the assessment of sensory memory duration.

OBJECTIVE: To evaluate the implementation of a neonatal pain and sedation protocol at 2 ICUs. METHODS:The intervention started with the evaluation of local practice, problems, and staff satisfaction. We then developed and implemented the Vienna Protocol for Neonatal Pain and Sedation. The protocol included well-defined strategies for both nonpharmacologic and pharmacologic interventions based on regular assessment of a translated version of the Neonatal Pain Agitation and Sedation Scale and titration of analgesic and sedative therapy according to aim scores. Health care staff was trained in the assessment by using a video-based tutorial and bedside teaching. In addition, we performed reevaluation, retraining, and random quality checks. Frequency and quality of assessments, pharmacologic therapy, duration of mechanical ventilation, and outcome were compared between baseline (12 months before implementation) and 12 months after implementation. RESULTS:Cumulative median (interquartile range) opiate dose (baseline dose of 1.4 [0.5-5.9] mg/kg versus intervention group dose of 2.7 [0.4-57] mg/kg morphine equivalents; P = .002), pharmacologic interventions per episode of continuous sedation/analgesia (4 [2-10] vs 6 [2-13]; P = .005), and overall staff satisfaction (physicians: 31% vs 89%; P , .001; nurses: 17% vs 55%; P , .001) increased after implementation. Time on mechanical ventilation, length of stay at the ICU, and adverse outcomes were similar before and after implementation.CONCLUSIONS: Implementation of a neonatal pain and sedation protocol at 2 ICUs resulted in an increase in opiate prescription, pharmacologic interventions, and staff satisfaction without affecting time on mechanical ventilation, length of intensive care stay, and adverse outcomes. Pediatrics 2013;132:e211-e218 AUTHORS:

Background: Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE). Objective: Our aimwas to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II. Methods: aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO₂), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values. Results: At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO₂ (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). Conclusions: In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling.

The N-PASS sedation subscale reliably detected oversedation, but failed to differentiate between adequate and undersedation. We therefore recommend using additional methods to ensure adequate assessment of sedation in neonates.

Background: The Bayley Scales of Infant and Toddler Development, third edition (Bayley-III) are widely used to assess the development of children born preterm. However, it is still unclear whether US norms are adequate for use in other populations. In 2014, the German version of the Bayley-III with German norms was published. Objectives: We aimed to compare the performance of very-preterm infants at one, two, and three years of age using the German versus US norms of the Bayley-III. Methods: All children born prior to 32 weeks of gestational age during 2012 and 2015 and taking part in the follow-up program of the Medical University of Vienna were assessed and scored according to both German and US norms by two expert clinical psychologists at the age of one, two, and three years of age. Results: In total, 843 tests were obtained from 450 children. When looking at scaled scores for cognitive, language, and motor outcomes, preterm children achieved significantly lower scores in nearly all subtests with the German as compared to the US norms. In addition, the proportion of impaired children scoring < 1 standard deviation (SD) and < 2 SD below the norm was significantly higher in nearly all subtests when using the German compared to the US norms (p < 0.05). Conclusions: Applying German and US norms of the Bayley-III leads to different outcomes in very-preterm children, and these differences are statistically significant and clinically relevant. Thus, comparisons of outcomes of very-preterm children using culturally specific norms are problematic, and these findings have to be considered.