The developmental phenotype of motor delay in extremely preterm infants following early-life respiratory adversity is influenced by brain dysmaturation in the parietal lobe.

BACKGROUND: Research indicates that preterm infants requiring prolonged mechanical ventilation often exhibit suboptimal neurodevelopment at follow-up, coupled with altered brain development as detected by magnetic resonance imaging (MRI) at term-equivalent age (TEA). However, specific regions of brain dysmaturation and the subsequent neurodevelopmental phenotype following early-life adverse respiratory exposures remain unclear. Additionally, it is uncertain whether brain dysmaturation mediates neurodevelopmental outcomes after respiratory adversity. This study aims to investigate the relationship between early-life adverse respiratory exposures, brain dysmaturation at TEA, and the developmental phenotype observed during follow-up in extremely preterm infants. METHODS: 89 infants born < 29 weeks' gestation from 2019 to 2021 received MRI examinations at TEA for structural and lobe brain volumes, which were adjusted with sex-and-postmenstrual-age expected volumes for volume residuals. Assisted ventilation patterns in the first 8 postnatal weeks were analyzed using kmlShape analyses. Patterns for motor, cognition, and language development were evaluated from corrected age 6 to 12 months using Bayley Scales of Infant Development, third edition. Mediation effects of brain volumes between early-life respiratory exposures and neurodevelopmental phenotypes were adjusted for sex, gestational age, maternal education, and severe brain injury. RESULTS: Two distinct respiratory trajectories with varying severity were identified: improving (n = 35, 39%) and delayed improvement (n = 54, 61%). Compared with the improving group, the delayed improvement group exhibited selectively reduced brain volume residuals in the parietal lobe (mean - 4.9 cm3, 95% confidence interval - 9.4 to - 0.3) at TEA and lower motor composite scores (- 8.7, - 14.2 to - 3.1) at corrected age 12 months. The association between delayed respiratory improvement and inferior motor performance (total effect - 8.7, - 14.8 to - 3.3) was partially mediated through reduced parietal lobe volume (natural indirect effect - 1.8, - 4.9 to - 0.01), suggesting a mediating effect of 20%. CONCLUSIONS: Early-life adverse respiratory exposure is specifically linked to the parietal lobe dysmaturation and neurodevelopmental phenotype of motor delay at follow-up. Dysmaturation of the parietal lobe serves as a mediator in the connection between respiratory adversity and compromised motor development. Optimizing respiratory critical care may emerge as a potential avenue to mitigate the consequences of altered brain growth and motor developmental delay in this extremely preterm population.

Sensitivity and specificity of the Neonatal Visual Assessment to predict motor and cognitive outcomes in infants born very preterm.

BACKGROUND: Very preterm infants are at increased risk of neurodevelopmental impairments. The Neonatal Visual Assessment (NVA) assesses visual function and outcomes and has been used to assess early neurodevelopmental outcomes. This study aimed to compare NVA results of very preterm and term-born infants and to calculate the sensitivity and specificity of the NVA at term equivalent age (TEA) and three months corrected age (CA) to predict motor and cognitive outcomes at 12 months CA in very preterm infants. METHODS: This prospective observational cohort study recruited infants born before 31 weeks gestation and a healthy term-born control group. The NVA was assessed at TEA and three months CA, and neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, Third Edition; Neurosensory Motor Developmental Assessment; Alberta Infant Motor Scale) were performed at 12 months CA. The sensitivity and specificity of the NVA to predict outcomes were calculated based on a previously published optimality score. RESULTS: 248 preterm (54 % male) and 46 term-born infants (48 % male) were analysed. The mean NVA scores of preterm and term-born infants were significantly different at TEA (preterm 3.1±2.1; term-born 1.2±1.7, p < 0.001). The NVA had moderate sensitivity (59-78 %) and low specificity (25-27 %) at TEA, and low sensitivity (21-28 %) and high specificity (86-87 %) at three months CA for the prediction of preterm infants' outcomes at 12 months CA. CONCLUSION: The NVA at TEA and three months CA was not a strong predictor of motor and cognitive impairments in this contemporary cohort of very preterm infants.

School Readiness Predictors of Early Academic Achievement in Children Born Very Preterm.

OBJECTIVE: This study examined associations of school readiness measures obtained before school entry with academic achievement at early school age in children born very preterm (VPT, gestational age ≤ 30 weeks) and children born full term (FT, GA ≥ 37 weeks). METHOD: The sample included 38 children born VPT and 30 born FT recruited at age 4 years and followed to early school age. Measures of readiness included tests of global cognition, executive function, motor abilities, and preacademic skills, as well as caregiver behavior ratings. Tests of math, reading, and spelling were administered to assess school-age achievement. Analyses that controlled for socioeconomic status and accounted for inclusion of siblings compared the groups on the achievement tests and identified measures of readiness related to school-age achievement. RESULTS: Achievement difficulties were more pronounced in the VPT group and associated with problems in multiple readiness domains. Effect sizes for these associations were largest for measures of spatial ability, executive function, and preacademic skills. Some associations remained significant when controlling for global cognitive ability at age 4 years, and others were significant only for the VPT group. CONCLUSION: Findings suggest that deficits on tests in multiple readiness domains assessed before school entry in children born VPT or FT are associated with early school-age achievement. The most pronounced readiness deficits in the VPT group at age 4 years were also among those most closely associated with later difficulties in achievement. Further research is needed to refine assessment of school readiness in children born VPT.

Longitudinal effects of early exposure to intermittent hypoxia on autonomic cardiovascular control in very preterm infants.

INTRODUCTION: Cardiorespiratory control is immature in infants born preterm compared to those born at term. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if the amount of time spent with apnoea and periodic breathing in the neonatal unit was associated with longitudinal changes in autonomic control assessed using heart rate variability. METHODS: Twenty-nine very preterm infants (10 M 19F) were studied during supine daytime sleep on 4 occasions. Study 1: 32-36 weeks post menstrual age (PMA) (n = 29), Study 2: 36-40 weeks PMA (n = 27), Study 3: 3-months corrected age (CA) (n = 20) and Study 4: 6-months CA (n = 26). The percentage total sleep time (%TST) spent having apnoeas in active (AS) and quiet sleep (QS) at each study was calculated. Total power, low frequency (LF, sympathetic + parasympathetic activity) high frequency (HF, parasympathetic activity), and LF/HF (sympathovagal balance) were calculated. Infants were divided into two groups based on the %TST spent with apnoeas above and below the median in AS and QS at Study 1. Data were normalised and compared with two-way ANOVA with Bonferroni post-hoc tests. RESULTS: When apnoeas were included in the analysis, in QS Total power and HF power were higher, and when apnoeas were excluded HF power was higher in QS but lower in AS in the above median group at Study 4. CONCLUSION: This study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control.

Impact of a mindfulness-based intervention on neurobehavioral functioning and its association with large-scale brain networks in preterm young adolescents.

AIM: Adolescents born very preterm (VPT; <32 weeks of gestation) face an elevated risk of executive, behavioral, and socioemotional difficulties. Evidence suggests beneficial effects of mindfulness-based intervention (MBI) on these abilities. This study seeks to investigate the association between the effects of MBI on executive, behavioral, and socioemotional functioning and reliable changes in large-scale brain networks dynamics during rest in VPT young adolescents who completed an 8-week MBI program. METHODS: Neurobehavioral assessments and resting-state functional magnetic resonance imaging were performed before and after MBI in 32 VPT young adolescents. Neurobehavioral abilities in VPT participants were compared with full-term controls. In the VPT group, dynamic functional connectivity was extracted by using the innovation-driven coactivation patterns framework. The reliable change index was used to quantify change after MBI. A multivariate data-driven approach was used to explore associations between MBI-related changes on neurobehavioral measures and temporal brain dynamics. RESULTS: Compared with term-born controls, VPT adolescents showed reduced executive and socioemotional functioning before MBI. After MBI, a significant improvement was observed for all measures that were previously reduced in the VPT group. The increase in executive functioning, only, was associated with reliable changes in the duration of activation of large-scale brain networks, including frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks. CONCLUSION: The improvement in executive functioning after an MBI was associated with reliable changes in large-scale brain network dynamics during rest. These changes encompassed frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks that are related to different executive processes including self-regulation, attentional control, and attentional awareness of relevant sensory stimuli.

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants.

Objective.Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from>700extremely preterm infants to identify physiologic features that predict respiratory outcomes.Approach. We calculated a subset of 33 HCTSA features on>7 M 10 min windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on>3500HCTSA algorithms. We hypothesized that the best HCTSA algorithms would compare favorably to optimal PreVent physiologic predictor IH90_DPE (duration per event of intermittent hypoxemia events below 90%).Main Results.The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850).Significance. These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90_DPE as an optimal predictor of respiratory outcomes.

Neonatal neurobehavior associated with developmental changes from age 2 to 3 in very preterm infants.

OBJECTIVE: Understand how high-risk infants' development changes over time. Examine whether NICU Network Neurobehavioral Scale (NNNS) profiles are associated with decrements in developmental outcomes between ages 2 and 3 years in infants born very preterm. STUDY DESIGN: The Neonatal Outcomes for Very preterm Infants (NOVI) cohort is a multisite prospective study of 704 preterm infants born <30 weeks' gestation across nine university and VON affiliated NICUs. Data included infant neurobehavior measured by NNNS profiles at NICU discharge and the Bayley Scales of Infant and Toddler Development (BSID-III) at ages 2 and 3 years. Generalized estimating equations tested associations between NNNS profiles and BSID-III composite score changes between ages 2 and 3 years. RESULTS: The final study sample included 433 infants with mean gestational age of 27 weeks at birth. Infants with dysregulated NNNS profiles were more likely to have decreases in BSID-III Cognitive (OR = 2.66) and Language scores (OR = 2.53) from age 2 to 3 years compared to infants with more well-regulated neurobehavioral NNNS profiles. Further, infants with more well-regulated NNNS profiles were more likely to have increases in BSID-III Cognitive scores (OR = 2.03), rather than no change, compared to infants with dysregulated NNNS profiles. CONCLUSIONS AND RELEVANCE: Prior to NICU discharge, NNNS neurobehavioral profiles identified infants at increased risk for developing later language and cognitive challenges. Findings suggests that neonatal neurobehavior provides a unique, clinically significant contribution to the evaluation of very preterm infants to inform treatment planning for the most vulnerable.

Negative central activity in extremely preterm newborns: EEG characterization and relationship with brain injuries and neurodevelopmental outcome.

OBJECTIVE: To characterize Negative Central Activity (NCA), an overlooked electroencephalographic activity of preterm newborns and investigate its relationship with brain injuries, dysfunction, and neurodevelopmental outcome. METHODS: 109 preterm infants (23-28 weeks) were retrospectively included. NCA were selected at the negative peak on EEG. Individual averaged NCA were automatically characterized. Brain structural data were collected from cranial ultrasounds (cUS). The neurodevelopmental outcome at two years of age was assessed by the Denver Developmental Screening Test-II. RESULTS: Thirty-six (33%) children showed NCA: 6,721 NCA were selected, a median of 75 (interquartile range, 25/157.3) per EEG. NCA showed a triphasic morphology, with a mean amplitude and duration of the negative component of 24.6-40.0 µV and 222.7-257.3 ms. The presence of NCA on EEG was associated with higher intraventricular haemorrhage (IVH) grade on the first (P = 0.016) and worst neonatal cUS (P < 0.001) and poorer neurodevelopmental outcome (P < 0.001). CONCLUSIONS: NCA is an abnormal EEG feature of extremely preterm newborns that may correspond to the functional neural impact of a vascular pathology. SIGNIFICANCE: The NCA relationships with an adverse outcome and the presence/severity of IVH argue for considering NCA in the assessment of pathological processes in the developing brain network and for early outcome prediction.

Respiratory and chest wall mechanics in very preterm infants.

Data on static compliance of the chest wall (Ccw) in preterm infants are scarce. We characterized the static compliance of the lung (CL) and Ccw to determine their relative contribution to static compliance of the respiratory system (Crs) in very preterm infants at 36 wk postmenstrual age (PMA). We also aimed to investigate how these compliances were influenced by the presence of bronchopulmonary dysplasia (BPD) and impacted breathing variables. Airway opening pressure, esophageal pressure, and tidal volume (VT) were measured simultaneously during a short apnea evoked by the Hering-Breuer reflex. We computed tidal breathing variables, airway resistance (R), and dynamic lung compliance (CL,dyn), inspiratory capacity (IC), and Crs, CL, and Ccw. Functional residual capacity was assessed by the multiple breath washout technique (FRCmbw). Breathing variables, compliances, and lung volumes were adjusted for body weight. Twenty-three preterm infants born at 27.2 ± 2.0 wk gestational age (GA) were studied at 36.6 ± 0.6 wk PMA. Median and interquartile range (IQR) Crs/kg is 0.69 (0.6), CL/kg 0.95 (1.0), and Ccw/kg 3.0 (2.4). Infants with BPD (n = 11) had lower Crs/kg (P = 0.013), CL/kg (P = 0.019), and Ccw/kg (P = 0.027) compared with infants without BPD. Ccw/CL ratio was equal between groups. FRCmbw/kg (P = 0.044) and IC/kg (P = 0.005) were decreased in infants with BPD. Infants with BPD have reduced static compliance of the respiratory system, the lungs, and chest wall. Decreased Crs, CL, and Ccw in infants with BPD explain the lower FRC and IC seen in these infants.NEW & NOTEWORTHY Data on chest wall compliance in very preterm infants in the postsurfactant era are scarce. To our knowledge, we are the first group to report data on static respiratory system compliance (Crs), lung compliance (CL), and chest wall compliance (Ccw) in preterm infants with and without bronchopulmonary dysplasia (BPD) in the postsurfactant era.

Optimizing trajectories of social adaptive competencies after extreme prematurity during the first 1000 days.

Over 75% of surviving extremely preterm infants do not have major neurodevelopmental disabilities; however, more than half face difficulties with communication, coordination, attention, learning, social, and executive function abilities. These "minor" challenges can have a negative impact on educational and social outcomes, resulting in physical, behavioral, and social health problems in adulthood. We will review assessment tools for social-emotional and adaptive functional skills in early childhood as these determine family and early childhood supports. We highlight bronchopulmonary dysplasia as an example of the critical intersections of parental wellbeing, medical and developmental adaptive trajectories in infancy and early childhood, and partnerships between child neurologists and community medical and developmental professionals. We examine studies of engaging parents to promote developmental trajectories, with a focus on supporting parent-child interactions that underlie communication, social-adaptive behaviors, and learning in the first 1000 days of life. Recommendations for neurodevelopmental surveillance and screening of extremely preterm infants can also be applied to infants with other risk factors for altered neurodevelopment.

Mri findings, looking behaviour and affect recognition in very preterm children: A pilot study.

Children born very preterm often exhibit atypical gaze behaviors, affect recognition difficulties and are at risk for cerebral white matter damage. This study explored links between these sequalae. In 24 12-year-old children born very preterm, ventricle size using Evans and posterior ventricle indices, and corpus callosum area were used to measure white matter thickness. The findings revealed a correlation between less attention towards the eyes and larger ventricle size. Ventricle and posterior corpus callosum sizes were correlated to affect-recognition proficiency. Findings suggest a link between white matter damage, gaze behavior, and affect recognition accuracy, emphasizing a relation with social perception.

Physical activity and cognitive function in adults born very preterm or with very low birth weight-an individual participant data meta-analysis.

OBJECTIVE: Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association. STUDY DESIGN: Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase. RESULTS: Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments. CONCLUSION: Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Disrupted resting-sate brain network dynamics in children born extremely preterm.

The developing brain has to adapt to environmental and intrinsic insults after extremely preterm (EPT) birth. Ongoing maturational processes maximize their fit to the environment and this can provide a substrate for neurodevelopmental failures. Resting-state functional magnetic resonance imaging was used to scan 33 children born EPT, at < 27 weeks of gestational age, and 26 full-term controls at 10 years of age. We studied the capability of a brain area to propagate neural information (intrinsic ignition) and its variability across time (node-metastability). This framework was computed for the dorsal attention network (DAN), frontoparietal, default-mode network (DMN), and the salience, limbic, visual, and somatosensory networks. The EPT group showed reduced intrinsic ignition in the DMN and DAN, compared with the controls, and reduced node-metastability in the DMN, DAN, and salience networks. Intrinsic ignition and node-metastability values correlated with cognitive performance at 12 years of age in both groups, but only survived in the term group after adjustment. Preterm birth disturbed the signatures of functional brain organization at rest in 3 core high-order networks: DMN, salience, and DAN. Identifying vulnerable resting-state networks after EPT birth may lead to interventions that aim to rebalance brain function.

Associations of Parental Distress and Behavior with School Readiness in Children Born Very Preterm.

OBJECTIVE: Children born very preterm (VPT; gestational age [GA] <31 weeks) have robust school readiness difficulties relative to children born full-term (FT; GA ≥37 weeks). This study examined whether four aspects of parental well-being and behavior-distress, harshness, responsiveness and positive control, and cognitive stimulation-were linked to school readiness in a sample of children born VPT <31 weeks GA and whether these characteristics similarly impact VPT and FT children. METHODS: Parents of 4-year-olds born VPT (n = 55) and FT (n = 38) reported on parental distress, behavior, and cognitive stimulation. Children's cognition, executive function, motor skills, preacademic abilities, and behavior were assessed via neuropsychological tests and parent-report questionnaires. RESULTS: For both groups of children, higher psychological distress and harshness were associated with more behavior problems, and more cognitive stimulation was associated with higher scores on tests of cognitive, motor, and preacademic abilities. More parental distress was associated with lower cognitive ability only for children born VPT and more harshness was associated with lower preacademic skills only for children born FT. CONCLUSIONS: Identifying modifiable family factors associated with school readiness in children born VPT is essential for informing family-based interventions to improve school readiness in this population. Findings suggest that distress, harshness, and cognitive stimulation may be reasonable targets for interventions to improve school readiness in children born VPT.

Socioeconomic disadvantage and parental mood/affective problems links negative parenting and executive dysfunction in children born very preterm.

Poverty increases the risk of poorer executive function (EF) in children born full-term (FT). Stressors associated with poverty, including variability in parenting behavior, may explain links between poverty and poorer EF, but this remains unclear for children born very preterm (VPT). We examine socioeconomic and parental psychosocial adversity on parenting behavior, and whether these factors independently or jointly influence EF in children born VPT. At age five years, 154 children (VPT = 88, FT = 66) completed parent-child interaction and EF tasks. Parental sensitivity, intrusiveness, cognitive stimulation, and positive and negative regard were coded with the Parent-Child Interaction Rating Scale. Socioeconomic adversity spanned maternal demographic stressors, Income-to-Needs ratio, and Area Deprivation Index. Parents completed measures of depression, anxiety, inattention/hyperactivity, parenting stress, and social-communication interaction (SCI) problems. Parental SCI problems were associated with parenting behavior in parents of children born VPT, whereas socioeconomic adversity was significant in parents of FT children. Negative parenting behaviors, but not positive parenting behaviors, were related to child EF. This association was explained by parental depression/anxiety symptoms and socioeconomic adversity. Results persisted after adjustment for parent and child IQ. Findings may inform research on dyadic interventions that embed treatment for parental mood/affective symptoms and SCI problems to improve childhood EF.

Cardiac cycle: an observational/interventional study protocol to characterise cardiopulmonary function and evaluate a home-based cycling program in children and adolescents born extremely preterm.

INTRODUCTION: Extremely preterm (EP)/extremely low birthweight (ELBW) individuals may have an increased risk for adverse cardiovascular outcomes. Compared with term-born controls, these individuals have poorer lung function and reduced exercise capacity. Exercise interventions play an important role in reducing cardiopulmonary risk, however their use in EP/ELBW cohorts is unknown. This study, cardiac cycle, aims to characterise the cardiopulmonary system of children and adolescents who were born EP compared with those born at term, following acute and chronic exercise bouts. METHODS AND ANALYSIS: The single-centre study comprises a home-based exercise intervention, with physiological characterisation at baseline and after completion of the intervention. Fifty-eight children and adolescents aged 10-18 years who were born EP and/or with ELBW will be recruited. Cardiopulmonary function assessed via measures of blood pressure, arterial stiffness, capillary density, peak oxygen consumption, lung clearance indexes and ventricular structure/function, will be compared with 58 age-matched and sex-matched term-born controls at baseline and post intervention. The intervention will consist of a 10-week stationary cycling programme, utilising Zwift technology. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of the Royal Children's Hospital Melbourne under HREC2019.053. Results will be disseminated via peer-reviewed journal regardless of outcome. TRIAL REGISTRATION NUMBER: 12619000539134, ANZCTR.

Creating an optimal observational sleep stage classification system for very and extremely preterm infants.

BACKGROUND: Sleep plays a major role in neuronal survival and guiding the fetal brain's development. Preterm infants in the neonatal intensive care unit are exposed to numerous external stimuli that can severely disrupt their sleep/wake patterns. Currently, almost no behavioral classification scales are validated for preterm infants. This study aims to develop a new, easy-to-use, validated visual sleep stage classification system for preterm infants with a gestational age between 25 and 37 weeks. METHODS: The Behavioral Sleep stage classification for Preterm Infants (BeSSPI) consists of four sleep-wake stages; active sleep (AS), quiet sleep (QS), intermediate sleep (IS) and wake (W), which are classified using seven items. Items include eye movements, body movements, facial movements, vocalizations, heart rate, respiratory pattern and activity level. RESULTS: 69 preterm infants were observed (24 + 6-36 + 0 weeks GA at birth; 25 + 2-36 + 6 weeks PMA at observation; 57.3% male). Across all 69 infants, the BeSSPI was based on 10,922 min of observed behavior, with 4264 min AS (38.83%), 2873 min QS (26.16%), 2887 min IS (26.29%), and 957 min W (8.72%). For the final BeSSPI, an interrater agreement of κ = 0.80 was reached. Additionally, construct, content, face validity, and expert validity were carefully assessed and deemed satisfactory. CONCLUSIONS: We developed a method to evaluate sleep-wake stages that is simple for all neonatal healthcare providers to learn and use. The BeSSPI is of high reliability and validity. Furthermore, it can be used in all preterm age-groups. Therefore, this novel instrument may improve rigor and reproducibility for future preterm sleep research.

Parental perspective on important health outcomes of extremely preterm infants.

BACKGROUND AND OBJECTIVE: Neonatal outcome research and clinical follow-up principally focus on neurodevelopmental impairment (NDI) after extremely preterm birth, as defined by the scientific community, without parental input. This survey aimed to investigate parental perspectives about the health and development of their preterm children. METHODS: Parents of children aged 18 months to 7 years born <29 weeks' gestational age presenting at a neonatal follow-up clinic over a 1-year period were asked to evaluate their children's health and development. They were also asked the following question: 'if you could improve two things about your child, what would they be?' Responses were analysed using mixed methods. Logistic regressions were done to compare parental responses. RESULTS: 248 parents of 213 children (mean gestational age 26.6±1.6 weeks, 20% with severe NDI) were recruited. Parents evaluated their children's health at a median of 9/10. Parental priorities for health improvements were (1) development, mainly behaviour, emotional health and language/communication (55%); (2) respiratory heath and overall medical fragility (25%); and (3) feeding/growth issues (14%). Nineteen per cent explicitly mentioned 'no improvements'. Parents were more likely to state 'no improvements' if child had no versus severe NDI OR 4.33 (95% CI 1.47 to 12.75)) or if parents had no versus at least a high school diploma (OR 4.01 (95% 1.99 to 8.10)). CONCLUSIONS: Parents evaluate the health of their preterm children as being very good, with positive perspectives. Parental concerns outside the developmental sphere should also be addressed both in clinical follow-up and research.

Systemic Inflammation in the First 2 Weeks after Birth as a Determinant of Physical Growth Outcomes in Hospitalized Infants with Extremely Low Gestational Age.

OBJECTIVE: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. STUDY DESIGN: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. RESULTS: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, -2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (-0.17 z-score; 95% CI, -0.27 to -0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (-0.21 length z-scores; 95% CI, -0.38 to -0.04), and had smaller head circumferences (-0.18 z-scores; 95% CI, -0.33 to -0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (-0.12; 95% CI, -0.22 to -0.02); IL-6 elevation on day 7 was associated with shorter length (-0.27; 95% CI, -0.43 to -0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. CONCLUSIONS: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.

[Formula: see text]Are multidisciplinary neurodevelopmental profiles of children born very preterm at age 2 relevant to their long-term development? A preliminary study.

To identify distinctive multidisciplinary neurodevelopmental profiles of relatively healthy children born very preterm (VPT) and describe the longitudinal course of these profiles up to age 10. At 2 years of corrected age, 84 children born VPT underwent standardized testing for cognitive, language, speech, motor, behavioral, and auditory nerve function. These data were submitted to factor and cluster analysis. Sixty-one of these children underwent cognitive, language, and behavioral assessment again at age 10. Descriptive statistics were used to analyze longitudinal trajectories for each profile. Four neurodevelopmental profiles were identified at age 2. Profile 1 children (n = 22/26%) had excellent cognitive-language-motor function, normal behavioral and auditory nerve function, but showed an unexpected severe decline up to age 10. Profile 2 children (n = 16/19%) had very low behavioral function, low cognitive-language-motor function, and accelerated auditory nerve function. Their scores remained low up until age 10. Profile 3 children (n = 17/20%) had delayed auditory nerve function, low behavioral function, and slightly lower cognitive-language-motor function. They showed the most increasing trajectory. Profile 4 children (n = 29/35%) had very low cognitive-language-motor function, normal behavioral and auditory nerve function, but showed wide variation in their trajectory. Our preliminary study showed that a multidisciplinary profile-oriented approach may be important in children born VPT to improve counseling and provide targeted treatment for at risk children. High performers at age 2 may not be expected to maintain their favorable development. Behavioral problems might negatively impact language development. Delayed auditory nerve function might represent a slow start and catch-up development.