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Visual field biases have been identified as markers of atypical lateralization in children with developmental conditions, but this is the first investigation to consider early lateralized gaze behaviors for social stimuli in preterm infants. Eye‐tracking methods with 51 preterm (33 male, 92.1% White) and 61 term‐born (31 male, 90.1% White) infants aged 8–10 months from Edinburgh, UK, captured the development of visual field biases, comparing gaze behavior to social and non‐social stimuli on the left versus right of the screen. Preterm infants showed a significantly reduced interest to social stimuli on the left versus right compared to term children (d =.58). Preterm children exhibit early differential orienting preferences that may be an early indicator of atypical lateralized function. [ABSTRACT FROM AUTHOR]

Background: Hospital-based kangaroo mother care can help reduce preventable newborn deaths and has been recommended by the World Health Organization in the care of low birthweight babies weighing 2000 g or less. However, implementation has been limited. The objective of this review is to understand the barriers and facilitators of kangaroo mother care implementation in health facilities in sub-Saharan Africa, where there are the highest rates of neonatal mortality in the world.Methods: A systematic search was performed on MEDLINE, Web of Science, Cumulative Index to Nursing and Allied Health, African Journals Online, African Index Medicus as well as the references of relevant articles. Inclusion criteria included primary research, facility-based kangaroo mother care in sub-Saharan Africa. Studies were assessed by the Critical Appraisal Skills Programme Qualitative Checklist and the National Institutes of Health quality assessment tools and underwent narrative synthesis.Results: Thirty studies were included in the review. This review examined barriers and facilitators to kangaroo mother care practice at health systems level, health worker experiences and perspectives of mothers and their families. Strong local leadership was essential to overcome barriers of inadequate space, limited budget for supplies, inadequate staffing, lack of guidelines and policies and insufficient supportive supervision. Workload burdens, knowledge gaps and staff attitudes were highlighted as challenges at health workers' level, which could be supported by sharing of best practices and success stories. Support for mothers and their families was also identified as a gap.Conclusion: Building momentum for kangaroo mother care in health facilities in sub-Saharan Africa continues to be a challenge. Strengthening health systems and communication, prioritizing preterm infant care in public health strategies and supporting health workers and mothers and their families as partners in care are important to scale up. This will support sustainable kangaroo mother care implementation as well as strengthen quality of newborn care overall. PROSPERO registration: CRD42020166742. [ABSTRACT FROM AUTHOR]

Background: The Australian Early Development Census (AEDC) provides a measure of early child development upon school entry. Understanding which combination of factors influences Aboriginal child neurodevelopment is important to inform policy and practice.Objective: The primary objective was to use latent class analysis (LCA) to model AEDC profiles and identify the highest need profiles. The secondary objective was to determine the associations of these high need profiles on the likelihood of a child becoming developmentally vulnerable.Methods: We designed a prospective population-based birth cohort study (n = 2715) using linked data sets with information on Aboriginal cohort children, and their mothers and siblings in Western Australia. Specific developmental indicators in the 2009 and 2012 AEDC were used to assess developmental vulnerability. LCA methods were used to determine need profiles and their association with developmental vulnerability.Results: 49.3% of Aboriginal children were vulnerable on at least one developmental domain, and 37.5% were vulnerable on two or more domains. LCA found six unique profiles. High needs family, High needs young mother, and Preterm infant comprised 42% of the cohort and were considered to have high need configurations. These groups were at least 1.7 times as likely to have children who had at least one or two developmental vulnerabilities compared with the Healthy family group.Conclusion: Many Aboriginal children in Western Australia enter school with at least one developmental vulnerability. This study highlights a range of unique profiles that can be used to empower Aboriginal families for change and develop targeted programmes for improving the early development of young Aboriginal children. [ABSTRACT FROM AUTHOR]

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This follow-up to the STOP-BPD randomized clinical trial, which investigated the efficacy and safety of systemic hydrocortisone treatment initiated 7 to 14 days after birth in ventilator-dependent, very preterm infants in the Netherlands and Belgium at 36 weeks' postmenstrual age, examines the prespecified composite of death and neurodevelopmental impairment among these infants at 2 years' corrected age. [ABSTRACT FROM AUTHOR]

Background/Objective: In this study, the behavior problems of healthy preterm and full term children will be compared. The effect of environmental and neonatal conditions on the rate of behavior problems, paying special attention to maternal depression and parental stress, will also be studied. Previous studies found significantly higher prevalence rates of total problems in preterm children. Most of these studies were carried out with pre-term children under 32 weeks of gestational age. In contrast, some studies carried out with moderately pre-term children found no significant difference. Method: We assessed 108 low risk preterm children and 33 full-term children through the Child Behavior Checklist when they were 5 years-old. Their mothers' stress and depression were also assessed. Results: No significant difference was found between the preterm and the full-term groups for overall internalizing or externalizing behavior problems, or for more fine grained behavior problems such as anxiety, attention or aggression. No effect of gestational age was found on the rate of behavior problems. In contrast maternal stress, but not maternal depression, was a strong predictor of behavior problems. Conclusions. These results indicate that behavior problems are not characteristic of preterm children as a group, but only of very or extremely preterm children. [ABSTRACT FROM AUTHOR]

Objective: Preterm infants' body composition at term-corrected age differs from that of term infants but appears to be similar at the age of 3 months. The aim of this study was to compare the metabolomic pattern of preterm infants at term and at 3 months with that of term infants and to determine its association with body composition development. Method: We designed a pilot study. Growth and body composition were evaluated by an air displacement plethysmography system in 13 preterm infants and seven term newborns at term and at 3 months of corrected age. Urine samples were collected at the same time points and analysed by nuclear magnetic resonance. Results: At term-corrected age, preterm infants showed a higher fat mass percentage compared with that of term newborns, whereas at 3 months of corrected age, the body composition parameters were similar between the groups. At the first time point, nuclear magnetic resonance analysis showed a urinary increase in choline/phosphocholine, betaine and glucose in preterm infants. At the second time point, the preterm group exhibited a urinary increase in choline/phosphocholine and a decrease in betaine. Conclusions: The increased urinary excretion of choline, a betaine precursor, could reflect a potential altered metabolism in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are still at an increased risk for suboptimal neurodevelopmental outcomes when compared with term born infants. The development of a child born preterm can be jeopardized by suboptimal conditions during pregnancy, in addition to the suboptimal growth environment postnatally compared to the normal in utero environment. This review summarizes the literature on the role of chorioamnionitis, placental insufficiency, and maternal smoking on the developmental outcomes of preterm infants. Methods: A systematic database search was performed to identify all original articles published on or before September 12, 2018 that evaluated the impact of clinical or histological chorioamnionitis, abnormal prenatal fetal and placental blood flow, and prenatal smoking exposure on the neuropsychological and cognitive outcomes of preterm infants. We identified a total of 54 studies. Thirty five original articles evaluated the effects of clinical or histological chorioamnionitis; 15 studies evaluated the effects of abnormal blood flow patterns; and four studies evaluated the effects of maternal smoking during pregnancy. Results: The studies on prenatal risk factors showed conflicting results about the impact on the neurodevelopment of preterm infants. The majority of the studies did not show that chorioamnionitis poses a direct risk to the development of preterm infants. The role of abnormal prenatal placental and fetal blood flow on the development of preterm infants remained inconclusive because the sample sizes were often small and methodological problems complicated the interpretation of the data. Maternal smoking during pregnancy was assessed only in one cohort which showed that maternal smoking is a risk for suboptimal cognitive and neuropsychological development in preterm infants. Conclusions: This review summarizes the data on several prenatal risk factors which play a role in the developmental outcomes of preterm infants. To optimize the developmental outcomes, we need to first optimize the fetal wellbeing before birth. More research that extends from the fetal life to long-term developmental outcomes is needed. [ABSTRACT FROM AUTHOR]

The early period of postnatal development of premature infants is often complicated by bacterial infections, in particular respiratory infections, which in adverse course can be transformed into generalized forms (sepsis), leading to life-threatening conditions. The development of these complications may be associated with delayed diagnosis and delayed start of targeted therapy. Thus, the development of new approaches to the diagnosis of inflammatory pathological processes, especially in the first hours of life, is an important area of research in modern neonatology. In this work the profiling of blood plasma lipids from newborn premature babies was performed in order to identify potential markers of inflammatory processes. The study involved three groups of patients who were diagnosed with pneumonia, pneumonia complicated by sepsis, or respiratory distress syndrome in the early postnatal period. As a result of HPLC-MS analysis of blood plasma lipid extracts, characteristic molecular profiles were obtained, which revealed significant differences between the groups under study. Analysis of the molecular composition showed differential representation of lipid classes such as phosphatidylcholines, phosphatidylethanolamines, di- and triglycerides, sphingolipids and lysophospholipids. Our results may indicate that the inflammatory processes at the local and systemic levels affect lipid metabolism and their composition in blood plasma. Moreover, each pathology—sepsis, pneumonia or RDS—has its own specific lipid profile, which may be useful not only to detect inflammation but also to differentiate inflammation-associated diseases from each other. [ABSTRACT FROM AUTHOR]

Abstract During the 3rd trimester, large-scale neural circuits are formed in the human brain, resulting in a highly efficient and segregated connectome at birth. Despite recent findings identifying important preterm human brain network properties such as rich-club organization, how the structural network develops differentially across brain regions and among different types of connections in this period is not yet known. Here, using high resolution diffusion MRI of 77 preterm-born and full-term neonates scanned at 31.9–41.7 postmenstrual weeks (PMW), we constructed structural connectivity matrices and performed graph-theory-based analyses. Faster increases of nodal efficiency were mainly located at the brain hubs distributed in primary sensorimotor regions, superior-middle frontal, and precuneus regions during 31.9–41.7PMW. Higher rates of edge strength increases were found in the rich-club and within-module connections, compared to other connections. The edge strength of short-range connections increased faster than that of long-range connections. Nodal efficiencies of the hubs predicted individual postmenstrual ages more accurately than those of non-hubs. Collectively, these findings revealed more rapid efficiency increases of the hub and rich-club connections as well as higher developmental rates of edge strength in short-range and within-module connections. These jointly underlie network segregation and differentiated emergence of brain functions. [ABSTRACT FROM AUTHOR]

Abstract Background Preterm birth is associated with altered brain development, with younger gestational age (GA) at birth often associated with greater brain volume reduction. Such volume alterations at term equivalent age (TEA) have been found with differing magnitude across different brain regions, although this has mostly been investigated with regards to whole tissue volumes and large-scale subdivisions. In addition to degree of prematurity, many other perinatal factors have been found to influence brain structure and development in infants born preterm. We aimed to clarify the relationships between degree of prematurity and regional brain volumes at TEA, and between perinatal factors and regional brain volumes at TEA, in finer spatial detail. Methods 285 preterm and term-born infants (GA at birth 24.6–42.1 weeks; 145 female; 59 born at term) were scanned at TEA. Data on perinatal factors were obtained by chart review, including sex, multiple birth, birthweight standard deviation (SD) score, postnatal growth and social risk. The Melbourne Children's Regional Infant Brain (M-CRIB) atlas was registered to the current sample, then 100 brain regions were labelled for volumetric analyses. Linear regressions with generalised estimating equations and likelihood ratio tests were performed to investigate whether GA at birth or perinatal factors were associated with regional volumes at TEA. Results Younger GA at birth was associated with smaller volumes at TEA in some regions including bilateral cerebral white matter, middle temporal gyri, amygdalae, pallidum and brainstem. In other regions, younger GA at birth was associated with larger volumes, including in primary visual, motor and somatosensory cortices. Positive associations between perinatal factors and regional volumes at TEA were found in many brain regions for birthweight SD score, and male sex, independent of GA at birth. These associations were seen on both univariable analyses, and multivariable analyses controlling for other perinatal factors. Social risk and multiple birth were generally not associated with regional brain volumes, and postnatal growth was associated with volume in many regions only after adjusting for other perinatal factors. Conclusions These results elucidate regional brain volume differences associated with preterm birth and perinatal factors at a more detailed parcellated level than previously reported, and contribute to understanding of the complex array of correlates of preterm birth. Highlights • Preterm birth was associated with regional volume changes at term equivalent age. • Of 100 regions measured, many were smaller with younger gestational age at birth. • Unexpectedly, some regions were larger in infants born more preterm. • Birthweight and male sex were strongly associated with larger regional volumes. [ABSTRACT FROM AUTHOR]

Abstract Resting-state functional MRI (rs-fMRI) is one of the most prevalent brain functional imaging modalities. Previous rs-fMRI studies have mainly focused on adults and elderly subjects. Recently, infant rs-fMRI studies have become an area of active research. After a decade of gap filling studies, many facets of the brain functional development from early infancy to toddler has been uncovered. However, infant rs-fMRI is still in its infancy. The image analysis tools for neonates and young infants can be quite different from those for adults. From data analysis to result interpretation, more questions and issues have been raised, and new hypotheses have been formed. With the anticipated availability of unprecedented high-resolution rs-fMRI and dedicated analysis pipelines from the Baby Connectome Project (BCP), it is important now to revisit previous findings and hypotheses, discuss and comment existing issues and problems, and make a "to-do-list" for the future studies. This review article aims to comprehensively review a decade of the findings, unveiling hidden jewels of the fields of developmental neuroscience and neuroimage computing. Emphases will be given to early infancy, particularly the first few years of life. In this review, an end-to-end summary, from infant rs-fMRI experimental design to data processing, and from the development of individual functional systems to large-scale brain functional networks, is provided. A comprehensive summary of the rs-fMRI findings in developmental patterns is highlighted. Furthermore, an extensive summary of the neurodevelopmental disorders and the effects of other hazardous factors is provided. Finally, future research trends focusing on emerging dynamic functional connectivity and state-of-the-art functional connectome analysis are summarized. In next decade, early infant rs-fMRI and developmental connectome study could be one of the shining research topics. Graphical abstract Image 1 Highlights • Comprehensive review of early brain developmental studies using rs-fMRI. • Outlining practical and end-to-end neonate/infant rs-fMRI pipelines. • Highlighting future research trends for early development studies. • Summarizing consistent findings in the literature regarding early brain developmental patterns. • Providing up-to-date neonate/infant (<5 years old) functional network literature review. [ABSTRACT FROM AUTHOR]

Abstract During the 3rd trimester, dramatic structural changes take place in the human brain, underlying the neural circuit formation. The survival rate of premature infants has increased significantly in recent years. The large morphological differences of the preterm brain at 33 or 36 postmenstrual weeks (PMW) from the brain at 40PMW (full term) make it necessary to establish age-specific atlases for preterm brains. In this study, with high quality (1.5 × 1.5 × 1.6 mm3 imaging resolution) diffusion tensor imaging (DTI) data obtained from 84 healthy preterm and term-born neonates, we established age-specific preterm and term-born brain templates and atlases at 33, 36 and 39PMW. Age-specific DTI templates include a single-subject template, a population-averaged template with linear transformation and a population-averaged template with nonlinear transformation. Each of the age-specific DTI atlases includes comprehensive labeling of 126 major gray matter (GM) and white matter (WM) structures, specifically 52 cerebral cortical structures, 40 cerebral WM structures, 22 brainstem and cerebellar structures and 12 subcortical GM structures. From 33 to 39 PMW, dramatic morphological changes of delineated individual neural structures such as ganglionic eminence and uncinate fasciculus were revealed. The evaluation based on measurements of Dice ratio and L1 error suggested reliable and reproducible automated labels from the age-matched atlases compared to labels from manual delineation. Applying these atlases to automatically and effectively delineate microstructural changes of major WM tracts during the 3rd trimester was demonstrated. The established age-specific DTI templates and atlases of 33, 36 and 39 PMW brains may be used for not only understanding normal functional and structural maturational processes but also detecting biomarkers of neural disorders in the preterm brains. Highlights • Dramatic structural changes during 3rd trimester require setup of age-specific atlas. • Age-specific DTI templates were established with 84 preterm and term-born datasets. • Age-specific DTI atlases at 33, 36 and 39 postmenstrual weeks were established. • Each age-specific DTI atlas includes 126 comprehensive gray and white matter labels. • The atlases can be used to measure the tract-based microstructures automatically. [ABSTRACT FROM AUTHOR]

Abstract The human brain undergoes explosive growth during the prenatal period and the first few postnatal years, establishing an early infrastructure for the later development of behaviors and cognitions. Revealing the developmental rules during the early phase is essential for understanding the emergence of brain functions and the origin of developmental disorders. Graph-theoretical network modeling in combination with multiple neuroimaging probes provides an important research framework to explore the early development of the topological wiring and organizational paradigms of the brain. Here, we reviewed studies that employed neuroimaging and graph-theoretical modeling to investigate brain network development from approximately 20 gestational weeks to 2 years of age. Specifically, the structural and functional brain networks have evolved to highly efficient topological architectures in the early stage; where the structural network remains ahead and paves the way for the development of the functional network. The brain network develops in a heterogeneous order, from primary to higher-order systems and from a tendency of network segregation to network integration in the prenatal and postnatal periods. The early brain network topologies show abilities in predicting certain cognitive and behavior performance in later life, and their impairments are likely to continue into childhood and even adulthood. These macroscopic topological changes may be associated with possible microstructural maturations, such as axonal growth and myelinations. Collectively, this review provides a detailed delineation of the early changes in the baby brains in a graph-theoretical modeling framework, which opens up a new avenue for understanding the developmental principles of the connectome. Highlights • Small-world, modules and hubs are present during the mid-gestation period. • Baby structural network maturates more quickly than functional network. • Network development is more segregated before birth and more integrated after birth. • Early brain network topology can predict later behavioral and cognitive performance. • Early brain network impairment is likely to continue into adulthood. [ABSTRACT FROM AUTHOR]

Abstract Premature birth has been associated with poor neurodevelopmental outcomes. However, the relation between such outcomes and brain growth in the neonatal period has not yet been fully elucidated. This study investigates longitudinal brain development between birth and term-equivalent age (TEA) by quantitative imaging in a cohort of premature infants born between 26 and 36 weeks gestational age (GA), to provide insight into the relation of brain growth with later neurodevelopmental outcomes. Longitudinal T2-weighted magnetic resonance images (MRI) of 84 prematurely born infants acquired shortly after birth and TEA were automatically segmented into cortical gray matter (CGM), unmyelinated white matter (UWM), subcortical gray matter (SGM), cerebellum (CB) and cerebrospinal fluid (CSF). General linear models and correlation analysis were used to study the relation between brain volumes and their growth, and perinatal variables. To investigate the ability of the brain volumes to predict children's neurodevelopmental outcome at 18–24 months and at 5 years of age, a linear discriminant analysis classifier was tested and several general linear models were fitted and compared by statistical tests. From birth to TEA, relative volumes of CGM, CB and CSF with respect to total intracranial volume increased, while relative volumes of UWM and SGM decreased. The fastest growing tissues between birth and TEA were found to be the CB and the CGM. Lower GA at birth was associated with lower growth rates of CGM, CB and total tissue. Among perinatal factors, persistent ductus arteriosus was associated with lower SGM, CB and IC growth rates, while sepsis was associated with lower CSF and intracranial volume growth rates. Model comparisons showed that brain tissue volumes at birth and at TEA contributed to the prediction of motor outcomes at 18–24 months, while volumes at TEA and volume growth rates contributed to the prediction of cognitive scores at 5 years of age. The family socio-economic status (SES) was not correlated with brain volumes at birth or at TEA, but was strongly associated with the cognitive outcomes at 18–24 months and 5 years of age. This study provides information about brain growth between birth and TEA in premature children with no focal brain lesions, and investigates their association with subsequent neurodevelopmental outcome. Parental SES was found to be a major determinant of neurodevelopmental outcome, unrelated to brain growth. However, further research is necessary in order to fully explain the variability of neurodevelopmental outcomes in this population. Highlights • Preterm infant longitudinal brain growth from birth to term age was investigated. • Infant brain MRIs were automatically segmented and tissue volumes measured. • Perinatal factors and gestational age affected tissue volumes and their growth. • Volumes and growth rates were associated with later cognitive and motor outcomes. • Family socio-economic status was a major determinant of neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Abstract Human cortical development during the third trimester is characterised by macro- and microstructural changes which are reflected in alterations in diffusion MRI (dMRI) measures, with significant decreases in cortical mean diffusivity (MD) and fractional anisotropy (FA). This has been interpreted as reflecting increased cellular density and dendritic arborisation. However, the fall in FA stops abruptly at 38 weeks post-menstrual age (PMA), and then tends to plateau, while MD continues to fall, suggesting a more complex picture and raising the hypothesis that after this age development is dominated by continuing increase in neural and organelle density rather than alterations in the geometry of dendritic trees. To test this, we used neurite orientation dispersion and density imaging (NODDI), acquiring multi-shell, high angular resolution dMRI and measures of cortical volume and mean curvature in 99 preterm infants scanned between 25 and 47 weeks PMA. We predicted that increased neurite and organelle density would be reflected in increases in neurite density index (NDI), while a relatively unchanging geometrical structure would be associated with constant orientation dispersion index (ODI). As dendritic arborisation is likely to be one of the drivers of gyrification, we also predicted that measures of cortical volume and curvature would correlate with ODI and show slower growth after 38 weeks. We observed a decrease of MD throughout the period, while cortical FA decreased from 25 to 38 weeks PMA and then increased. ODI increased up to 38 weeks and then plateaued, while NDI rose after 38 weeks. The evolution of ODI correlated with cortical volume and curvature. Regional analysis of cortical microstructure revealed a heterogenous pattern with increases in FA and NDI after 38 weeks confined to primary motor and sensory regions. These results support the interpretation that cortical development between 25 and 38 weeks PMA shows a predominant increase in dendritic arborisation and neurite growth, while between 38 and 47 weeks PMA it is dominated by increasing cellular and organelle density. Graphical abstract Image 1 Highlights • DTI and NODDI cortical measures between 25 and 47 weeks GA • Early cortical changes consistent with dendritic arborisation and neurite growth • After 38 weeks cortical changes consistent with increasing cellular density • Cortical curvature evolves in parallel with dendritic arborisation [ABSTRACT FROM AUTHOR]

Abstract Background It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32–33 weeks' GA) and late (LP; 34–36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38–44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT). Methods Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing. Results Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values. Conclusion Early life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum. Highlights • Early life factors affect regional brain volume and microstructural development. • Effects of early life factors on brain development differ by gestational age. • Males have higher brain volumes but less organised microstructure than females. • Poor prenatal growth is associated with lower volume and less mature white matter. • Multiple birth and social risk may also affect brain development. [ABSTRACT FROM AUTHOR]

Introduction: Despite recent advances in respiratory support, the wide use of antenatal steroids and surfactant-replacement therapy, respiratory problems continue to represent the leading cause of mortality in premature infants during the neonatal period. In the last few years, HHHFNC has been widely adopted as a mode of noninvasive respiratory support for infants with respiratory difficulties. However, data of the safety and efficacy of HHHFNC use in extremely premature infants are scarce. This study will aid in bridging the knowledge gap and sheds light on the efficacy and, more importantly, the safety of HHHFNC as noninvasive respiratory support for extremely premature infants.Methods: This is a retrospective comparative study conducted at neonatal intensive care unit (NICU), Norfolk and Norwich University Hospital between 1 October 2010 and 31 December 2014. Data were collected from the medical notes and electronic records of the eligible patients. Participants' total number was 26, 9 patients in nCPAP group while HHHFNC group consisted of 17 patients. The participants' gestational age was ranging between 24 to 29 + 9 weeks who were supported by either nCPAP or HHHFNC after first extubation. Primary outcome was defined as the need for reintubation within 72-hour immediately postextubation, i.e. failure of noninvasive respiratory support.Results: Study showed no statistically significant differences in either primary (nCPAP (9/2 [22%]), HHHFNC (17/2 [12%]; p = .59)) or secondary outcomes (Constant need for O2 in the first 4 weeks of life (p = .62), pneumothorax (p = 1.0), nasal injury (p = .35)). p Value for spontaneous bowel perforation was not computed, as there were no affected patients.Conclusions: The study demonstrates that HHHFNC is similarly safe and efficacious in comparison to nCPAP as noninvasive respiratory support for extremely premature infants' postextubation. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the relationship between corticotropin-releasing hormone (CRH) expression in the placenta and the risk of school-related dysfunctions at the age of 10 years among children born extremely preterm (EP).Methods: Corticotropin-releasing hormone expression was measured in the placenta of 761 EP children, who had the following assessments at the age of 10 years: Differential Ability Scales, Oral and Written Language Scales, the Wechsler Individual Achievement Test-III, NEPSY-II and the Child Symptom Inventory-4. We evaluated whether lowest and highest quartiles of CRH mRNA were associated with undesirable scores on these assessments. With 272 evaluations, we would expect 14 to be significant at p < 0.05.Results: Only 16 associations were statistically significant. On the other hand, seven of these were social limitations among girls whose placenta CRH mRNA was in the top quartile. Adjusting for delivery indication or restricting the sample to one delivery indication group resulted in few differences.Conclusion: Overall, placenta CRH mRNA concentrations in the top or bottom quartiles were not associated with increased risks of dysfunctions 10 years later. Girls whose placenta CRH expression was in the top quartile, however, were at increased risk of seven indicators/correlates of social limitations. [ABSTRACT FROM AUTHOR]

Background: Due to the importance of sleep in brain development of infants, this study was designed to compare the effects of environmental and behavioral Interventions on sleep cycle of preterm infants in NICU. Methods: In this prospective crossover clinical trial, 40 preterm infants with fetal age of 32 to 36 weeks hospitalized in NICU were selected. Infants were randomly divided into the two groups of environmental-behavioral intervention and behavioral -environmental intervention, based on the order of the performed interventions. The study included three courses of control, first intervention and second intervention each held for 2 hours. Sleep states were assessed by Prechtl sleeping and waking assessment tool. Results: Mean of quiet sleep time in three different courses showed significant differences and in behavioral intervention course was more in comparison to the two other courses (p<0.05). Mean of active sleep time in the behavioral course was significantly less than that in other courses. But, there was no significant difference between the control and environmental courses. Conclusions: Both behavioral and environmental interventions can increase total time of sleep and quiet sleep but behavioral intervention has more effect on quiet sleep. Therefore, infants sleep in NICU can be improved by behavioral interventions. [ABSTRACT FROM AUTHOR]

The aim of this study is to examine the effect of age correction on the developmental assessment scores of preterm infants, using for the first time, the Mullen scales of early learning (MSEL) test. Participants included 110 preterm infants (born at a gestational age of ≤ 34 weeks) at ages 1, 4, 8, 12, 18, 24 and 36 months. The corrected age-based MSEL composite score and each of the five MSEL scale scores were significantly higher than chronological age-based scores at all ages. These corrected scores were significantly higher than the chronological scores regardless of gestational age whether weight was, or adequate or small for gestational age. Larger differences between corrected and chronological age-based scores significantly correlated with earlier gestational age and with lower birth weight between 1 and 24 months but not at 36 months. Using chronological age-based scores yielded significantly more infants identified with developmental delays than using corrected age-based scores. The findings indicate that clinicians and researchers, as well as family members, should be aware of and acknowledge the distinction between corrected and chronological ages when evaluating preterm infants in research and clinical practices. [ABSTRACT FROM AUTHOR]

Background: Premature infants are vulnerable to destructive brain injury and disturbed neurological development. Prematurity may alter maturation of the central autonomic nervous system (ANS).Aims: To compare ANS function (using heart rate variability; HRV) between preterm infants with normal neuroimaging at term equivalent age and low-risk term controls. Study design, subjects. We performed a case-control study of preterm infants born ≤28 weeks gestational age that had normal brain imaging and archived continuous EKG data at term equivalent age. We documented other factors thought to influence ANS maturation (e.g. infection, ventilation days, and postnatal steroids). Controls were low-risk term gestational age newborns from uncomplicated pregnancies/deliveries. We characterized HRV metrics using frequency-(Welch periodogram) and time-domain (detrended fluctuation) analyses. Sympathetic tone was characterized by α1, root mean square analysis (RMS1 and RMS2), low-frequency (LF) power, and normalized LF (nLF) and parasympathetic tone was characterized by high-frequency (HF) power and normalized HF (nHF). α2 characterized ultraslow changes in heart rate. We used ANCOVA to compare HRV metrics between groups. Outcome measures, results. HRV from 26 preterm infants were compared to 55 controls. Analyzed HRV data for preterm infants were recorded at median (range) gestational age of 39 (36-39) weeks and for controls at 39 (37-41) weeks gestational age. α1, RMS2, LF and HF were significantly higher in control infants and remained significant after controlling for infection, ventilator days, and postnatal steroids (P < .005).Conclusions: Autonomic maturation is impaired in a premature extrauterine environment. In the absence of destructive brain injury, our data suggest an important role for disturbed programming in this impaired autonomic development. [ABSTRACT FROM AUTHOR]

Postpartum depression, a common complication in childbearing women, is of great public health concern. Previous screening tools have focused on depressed mood, with less attention paid to postpartum anxiety and suicidal ideation. This study developed and validated a tool to measure postpartum depression among mothers of preterm babies. From the clinical interviews and a pilot survey (n = 121) the Mothers of Preterm Babies Postpartum Depression Scale was developed. The Mothers of Preterm Babies Postpartum Depression Scale and the Edinburgh Postnatal Depression Scale questionnaires were completed by 152 mothers who delivered preterm babies at Massey Street Children's Hospital, Lagos. Data were analyzed with use of confirmatory factor analysis, principal component analysis, and Cronbach's alpha at the P ≤ 0.05 level of significance. The new scale demonstrated a reliability (α) of 0.91. Construct validity with exploratory factor analysis (Kaiser-Meyer-Olkin measure 0.70) yielded three dimensions of cognitive and emotional difficulty (α = 0.92), hopelessness and suicidal ideation (α = 0.93), and physiological distress (α = 0.71). Confirmatory factor analysis demonstrated a good fit: 18 degrees of freedom; goodness of fit index 0.97; adjusted goodness of fit index 0.93; and root mean square error of approximation 0.04. Convergent validity was established with the Edinburgh Postnatal Depression Scale (r = 0.66, P = 0.00). The new screening tool was demonstrated to have meritorious validity, faster and easier to administer to the obstetric population. [ABSTRACT FROM AUTHOR]

Background: The quality of mother-preterm infant interaction has been identified as a key factor in influencing the infant's later development and language acquisition. The relationship between mother-infant responsiveness and later development may be evident early in infancy, a time period which has been understudied.Aim: Describe the relationship between mother-infant mutual dyadic responsiveness and premature infant development.Design: This study employed a secondary analysis of data from the 6-week corrected age (CA) follow-up visit of the Hospital-Home Transition: Optimizing Prematures' Environment (H-HOPE) study, a randomized clinical trial testing the efficacy of a mother- and infant- focused intervention for improving outcomes among premature infants.Subjects: Premature infants born between 29 and 34 weeks gestational age and their mothers who had social-environmental risks.Outcome Measures: At 6-weeks corrected age, a play session was coded for the quality of mutual responsiveness (Dyadic Mutuality Code). Development was assessed via the Bayley Scales of Infant and Toddler Development, 3rd edition.Results: Of 137 mother-infant dyads, high, medium and low mutual responsiveness was observed for 35.8%, 34.3% and 29.9%, respectively. Overall motor, language and cognitive scores were 115.8 (SD = 8.2), 108.0 (7.7) and 109.3 (7.9). Multivariable linear models showed infants in dyads with high versus low mutual responsiveness had higher scores on the motor (β = 3.07, p = 0.06) and language (β = 4.47, p = 0.006) scales.Conclusion: High mutual responsiveness in mother-premature infant dyads is associated with significantly better language development and marginally better motor development. [ABSTRACT FROM AUTHOR]

Background: Clinicians' interest in the long-term effects of early postnatal growth (EPG) is growing. There is compelling evidence linking rapid EPG with later cardiovascular risk, but its neurodevelopmental benefits still remain hypothetical in individuals born moderately preterm (MP) or small for gestational at term (SGAT).Methods: The objective was to perform a systematic review of the relationship between EPG before age 3 years and neurodevelopmental outcome for individuals born MP (32-36 weeks' gestational age) or SGAT. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, 3 independent investigators searched for articles published on this topic in the Web of Science, EMBASE and PubMed from database inception to July 1, 2017. A detailed quality scale was used to evaluate articles.Results: We selected 19 articles relying on 12 distinct study populations; 7 articles from 3 study populations were considered at moderate or high quality. The lack of standardisation of growth analysis methods prevented performing a meta-analysis. Overall, EPG was positively associated with neurodevelopmental outcome, especially Intelligence Quotient (IQ) when available. In this relationship, the first 6 months of life might be a critical period. Analysis of the few articles investigating the shape of the relationships revealed a non-linear association, with a plateau for IQ with higher weight gain, which suggests a possible ceiling effect.Conclusions: A positive association was generally found between EPG and neurodevelopmental outcome for individuals born MP or SGAT. Strategies for future epidemiological studies are suggested to improve the characterisation of this relationship. [ABSTRACT FROM AUTHOR]

Aim: An important variable that influences breastfeeding outcomes is how confident a woman feels about her ability to breastfeed successfully at an early stage. We investigated breastfeeding self-efficacy in the mothers of late preterm infants.Methods: This was a prospective, comparative study that focused on mothers who had delivered babies at 34 + 0 to 36 + 6 weeks and were recruited in 2012-2015 from a neonatal intensive care unit and a postnatal ward at a Swedish university hospital. The Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) was used to psychometrically assess the mothers at 40 weeks of postmenstrual age (n = 148) and at three months of corrected age (n = 114).Results: The BSES-SF scores were higher in the 87% of mothers that exclusively breastfed when their babies reached 40 weeks (57.1 out of 70) than those who did not (41.4, p < 0.001), indicating better self-efficacy. The figures remained higher in the 68% of exclusive breastfeeding mothers at three months of corrected age (60.9 versus 51.7).Conclusion: Self-efficacy was an important predictor of the length of breastfeeding in mothers of late preterm infants, and the BSES-SF can be used to detect low self-efficacy that could lead to early breastfeeding cessation. [ABSTRACT FROM AUTHOR]

Aim: This Italian study evaluated whether painful procedures during the first four weeks of life were related to subsequent weight gain, head circumference (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated the number of invasive procedures that infants born at less than 32 weeks of gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi Hospital, Florence, from January to December 2015. Weight and HC were recorded at birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler Development - Third Edition.Results: We studied 83 preterm infants with a GA of 28 ± 2 weeks and birth weight of 1098 ± 340 g. A higher number of invasive painful procedures were related to a lower HC standard deviation score at 36 weeks of PMA and six and 12 months of CA and with lower cognitive scores at six months. At 12 months, the relationship only remained significant for infants born at less than 28 weeks (p < 0.001).Conclusion: Invasive painful procedures affected regular HC growth and short-term cognitive scores in preterm infants in the first year of life. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO2 ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden.Methods: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO2 targets were 88-92% and 142 in 2015-2016 when they were 91-95%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool.Results: The 2011-2012 infants who needed ROP treatment (12.6%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5% in 2011-12 to 48% in 2015-2016.Conclusion: After the SpO2 target range was increased from 88-92% to 91-95%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability to predict ROP requiring treatment. Risk factors clearly change as neonatal care develops. [ABSTRACT FROM AUTHOR]

Background: Amplitude-integrated electroencephalography (aEEG) is used increasingly in neonatal intensive care and seems helpful in predicting outcomes at the age of 2 years. Objectives: To determine whether early aEEG patterns in preterm infants are equally useful in predicting outcomes at early school age. Methods: We recorded aEEG in 41 preterms (gestational age 26.0–32.9 weeks) at a median postnatal age of 9.7 h (IQR 7.0–25.3) and in 43 preterms on median day 8 (IQR 7–9). We assessed aEEG by pattern recognition and calculated the means of the aEEG amplitude centiles. At a median of 7.39 years, i.e., early school age, we assessed their motor, cognitive, and behavioral outcomes. Results: Depressed aEEG patterns were not associated with poorer outcomes. Cyclicity directly after birth was associated with a higher total IQ (mean 104 vs. 97, p = 0.05) and higher scores on visual perception (mean percentile 57.1 vs. 40.1, p = 0.049) and visual memory (mean percentile 34.5 vs. 19.1, p = 0.090). We found some associations between the aEEG amplitude centiles and cognitive outcomes, but none for motor or behavioral outcomes. There was an increased risk of abnormal scores on long-term verbal memory in cases of the lower 5th and 50th aEEG amplitude centiles directly after birth. The odds ratios were 0.65 (95% CI 0.42–0.99, p = 0.040) and 0.71 (95% CI 0.52–0.96, p = 0.025), respectively. Conclusions: In relatively healthy preterm infants the value of aEEG in predicting neuropsychological outcomes at early school age is limited. The presence of cyclicity directly after birth tends to be associated with better cognition. [ABSTRACT FROM AUTHOR]

Emerging evidence has demonstrated that vitamin D plays an important role in many adult neurologic disorders, but is also critical in neuronal development and pruning in the neonatal and pediatric populations. Neonates are at a particularly high risk of vitamin D deficiency, in part due to the high prevalence of maternal deficiency during pregnancy. Several preclinical studies have demonstrated that infants born to vitamin D-deficient mothers are at a high risk of developing neonatal brain injury, and recent clinical studies have shown that neonates with hypoxic-ischemic encephalopathy (HIE) tend to be vitamin D-deficient. There are limited data, however, on whether additional prenatal or postnatal supplementation may alter the prevalence or severity of neonatal HIE. This review examines the current data supporting the neuroprotective role of vitamin D, with a focus on how these findings may be translated to neonates with HIE. [ABSTRACT FROM AUTHOR]

Aim: The neonatal intensive care unit (NICU) provides life-saving medical care for an increasing number of newborn infants each year. NICU care, while lifesaving, does have attendant consequences which can include repeated activation of the stress response and reduced maternal interaction, with possible negative long-term impacts on brain development. Here we present a neuroscientific framework for considering the impact of music on neurodevelopment in the NICU of infants born preterm and evaluate current literature on the use of music with this population to determine what is most reliably known of the physiological effects of music interventions.Method: Using online academic databases we collected relevant, experimental studies aimed at determining effects of music listening in infants in the NICU. These articles were evaluated for methodological rigor, ranking the 10 most experimentally stringent as a representative sample.Results: The selected literature seems to indicate that effects are present on the cardio-pulmonary system and behavior of neonates, although the relative effect size remains unclear.Interpretation: These findings indicate a need for more standardized longitudinal studies aimed at determining not only whether NICU music exposure has beneficial effects on the cardio-pulmonary system, but also on the hypothalamic-pituitary-adrenal axis, brain structures, and cognitive behavioral status of these children as well.What This Paper Adds: Provides a neuroscience framework for considering how music might attenuate stress in neonatal intensive care unit (NICU) infants. Considers how repeated stress may cause negative neurodevelopmental impacts in infants born preterm. Posits epigenetics can serve as a mechanistic pathway for music moderating the stress response. [ABSTRACT FROM AUTHOR]

Purpose To characterize and quantify early foveal development in preterm infants and to compare this development between eyes treated with intravitreal bevacizumab or laser photocoagulation (LPC) and untreated eyes. Design Observational case series. Participants One hundred thirty-one preterm infants undergoing retinopathy of prematurity (ROP) screenings. Methods Handheld OCT imaging was performed longitudinally on all patients. Thickness measurements of the inner and outer retinal layers were obtained at the foveal center and the nasal and temporal foveal rims. Comparisons between treated and untreated eyes were adjusted for age and other confounding variables. Main Outcome Measures Weekly change in inner and outer retinal thickness and presence of inner retinal layers, ellipsoid zone (EZ), and cystoid macular changes (CMCs). Results Outer retinal thickness at the foveal center increased by 3.1 μm/week in untreated eyes and 7.2 μm/week in bevacizumab-treated eyes ( P = 0.038). Eyes treated with LPC had a lower probability of having all inner retinal layers present at the foveal center (odds ratio, 0.04; P = 0.001) and a lower probability of having the EZ present at the foveal center (odds ratio, 0.07; P = 0.024) compared with untreated eyes. Cystoid macular changes were found in 53% of patients and 22% of imaging sessions. The age-adjusted incidence of CMCs was not correlated with bevacizumab or LPC treatment. Conclusions Intravitreal bevacizumab therapy for ROP is associated with more rapid outer retinal thickening at the foveal center, whereas LPC is associated with earlier extrusion of the inner retinal layers and delayed development of the EZ at the foveal center. Long-term follow-up is needed to determine the visual significance of these findings. [ABSTRACT FROM AUTHOR]

Highlights The kinematics of hand movements (spatial use, curvature, acceleration, and velocity) of infants with their mothers in an interactive setting are significantly associated with age in cohorts of typical and at-risk infants differ significantly at 5-6 months of age, depending on the context: relating either with an object or a person. Environmental and developmental factors shape the developmental trajectories of hand movements in different cohorts: environment for infants with VIMs; stage of development for premature infants and those with West syndrome; and both factors for infants with orality disorders. The curvature of hand movements specifically reflects atypical development in infants with West syndrome when developmental age is considered. We aimed to discriminate between typical and atypical developmental trajectory patterns of at-risk infants in an interactive setting in this observational and longitudinal study, with the assumption that hand movements (HM) reflect preverbal communication and its disorders. We examined the developmental trajectories of HM in five cohorts of at-risk infants and one control cohort, followed from ages 2 to 10 months: 25 West syndrome (WS), 13 preterm birth (PB), 16 orality disorder (OD), 14 with visually impaired mothers (VIM), 7 early hospitalization (EH), and 19 typically developing infants (TD). Video-recorded data were collected in three different structured interactive contexts. Descriptors of the hand motion were used to examine the extent to which HM were associated with age and cohort. We obtained four principal results: (i) the kinematics of HM (spatial use, curvature, acceleration, and velocity) were significantly associated with age in all cohorts; (ii) HM significantly differed at 5-6 months of age in TD infants, depending on the context; (iii) environmental and developmental factors shaped the developmental trajectories of HM in different cohorts: environment for VIM, development for PB and WS, and both factors for OD and; (iv) the curvatures of HM showed atypical development in WS infants when developmental age was considered. These findings support the importance of using kinematics of HM to identify very early developmental disorders in an interactive context and would allow early prevention and intervention for at-risk infants. [ABSTRACT FROM AUTHOR]

Aim: To examine the diagnostic ability of early magnetic resonance imaging (MRI; <36wks postmenstrual age) to detect later adverse motor outcomes or cerebral palsy (CP) in infants born preterm.Method: Studies of infants born preterm with MRI earlier than 36 weeks postmenstrual age and quantitative motor data or a diagnosis of CP at or beyond 1 year corrected age were identified. Study details were extracted and meta-analyses performed where possible. Quality of included studies was evaluated with the QUADAS-2 (a revised tool for the quality assessment of diagnostic accuracy studies).Results: Thirty-one articles met the inclusion criteria, five of which reported diagnostic accuracy and five reported data sufficient for calculation of diagnostic accuracy. Early structural MRI global scores detected a later diagnosis of CP with a pooled sensitivity of 100% (95% confidence interval [CI] 86-100) and a specificity of 93% (95% CI 59-100). Global structural MRI scores determined adverse motor outcomes with a pooled sensitivity of 89% (95% CI 44-100) and a specificity of 98% (95% CI 90-100). White matter scores determined adverse motor outcomes with a pooled sensitivity of 33% (95% CI 20-48) and a specificity of 83% (95% CI 78-88).Interpretation: Early structural MRI has reasonable sensitivity and specificity to determine adverse motor outcomes and CP in infants born preterm. Greater reporting of diagnostic accuracy in studies examining relationships with motor outcomes and CP is required to facilitate clinical utility of early MRI.What This Paper Adds: Early magnetic resonance imaging (MRI) has reasonable sensitivity and specificity to determine later adverse motor outcomes and cerebral palsy (CP). Detection of infants who progressed to CP was stronger than motor outcomes. Global MRI scores determined adverse motor outcomes more accurately than white matter scores. Few studies report diagnostic accuracy of early MRI findings. Diagnostic accuracy is required to draw clinically meaningful conclusions from early MRI studies. [ABSTRACT FROM AUTHOR]

Aim: There is a discrepancy between the amount of transitional milk produced by mothers of preterm infants and the low capacity of premature infants to consume it. This milk can be used in milk banks, but previous studies found that there are large variations in the level of host-defence proteins in individual samples of milk from mothers of premature infants, which implies that large individual variations in antioxidative defence composition are also possible.Methods: Milk samples were collected from 20 healthy mothers of preterm infants. We determined the values for non-enzymatic antioxidative capacity parameters (oxygen radical absorbance capacity (ORAC)), static oxidation-reduction potential (ORP), activities of antioxidant defence enzymes and the amount of vitamin C in whole milk, skim and whey fractions of transitional milk.Results: The main low-molecular-weight antioxidant in transitional milk is vitamin C and most of it is contained in whey. ORAC is higher in whole transitional milk than in skim milk and whey, and ORP is lower in whole transitional milk than that in skim milk and whey. Antioxidative enzyme activities are similar in all individual samples of transitional milk from mothers of preterm infants.Conclusions: Our results indicate that transitional milk of mothers of preterm infants shows slow individual variations in antioxidative defence composition; therefore, it can be used in human milk banks. [ABSTRACT FROM AUTHOR]

Very preterm birth influences brain development and may result in alterations of cortical morphometry. These structural alterations may interact with cognitive development. The aim of the present study was to investigate the structure-function relationship in school-aged very preterm and term-born control children. A comprehensive neuropsychological test battery was administered to 41 very preterm (<32 weeks of gestation) and 30 term-born control children aged seven to twelve years. The automated method FreeSurfer was used to obtain cortical thickness and cortical surface area measures from T1-weighted MRI images. Regional cortical thickness differed between groups but differences disappeared when controlling for age. Global cortical thickness differed between groups in the right hemisphere (very preterm children>controls). No group differences occurred for cortical surface area. The relationship between cortical morphometry and cognition differed between very preterm and control children. In very preterm children, some cognitive domains correlated positively and others negatively with regional cortical thickness and cortical surface area. Our findings contribute to the understanding of the structure-function relationship in very preterm children and their term-born peers. They add to the notion that this relationship varies depending on the brain region and the cognitive function in question and suggest developmental differences between very preterm and term-born children. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the extent to which children born preterm (< 37 weeks) and/or who have low birth weight (< 2,500 g) catch up with their full term peers in terms of their language abilities at early school age (= 5 to < 9 years). Method: A systematic literature search identified empirical studies that fit the inclusion criteria. Data from the tests/questionnaires used for meta-analysis spanned the following language categories: total language score, expressive language, receptive language, pragmatics, phonological awareness, and grammar. The means (standard deviations) were extracted from the studies and were converted to mean difference and 95% confidence intervals to test for overall effect. Results: Sixteen studies met the inclusionary criteria, for a total of 2,739 participants, of which 1,224 were born full term and 1,515 were born preterm. It is important to note that the preterm cohort represented very preterm infants who have a very low birth weight. The meta-analysis found that preterm infants scored significantly worse on total language (p < .001), receptive language (p < .001), expressive language (p < .001), phonological awareness (p < .001), and grammar (p = .03) than their full term peers. However, preterm infants did not score significantly worse than their peers on their pragmatics (p = .19). Conclusions: Children born VPT and who have VLBW perform worse than their peers on their total language, receptive language, expressive language, phonological awareness, and grammar abilities by early school age. This information is important for speech-language pathologists to consider as children born prematurely reach school age. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to determine if there is a specific association between motor delays and receptive and expressive language function, respectively, in prematurely born children. Method: Retrospective data review: 126 premature children = 1,250-g birthweight from English-speaking families were evaluated on motor development (normal, mild delay, and moderate-severe delay) and the cognitive and language scales of the Bayley Scales of Infant and Toddler Development- Third Edition (Bayley, 2006) at 18 months corrected age. Cognitive scores were categorized as normal, suspect, and abnormal. Gender, demographic, and perinatal variables were recorded and analyzed with respect to motor category. Results: Lower birthweight, chronic need for oxygen, severe intraventricular hemorrhage, and intestinal infection/inflammation were related to poorer motor development. On receptive language, the normal motor group attained significantly higher scores than the moderate-severe motor group but did not differ significantly from the mild delay motor group. On expressive language, the normal motor group had significantly higher scores than both the mild and moderate-severe groups. Girls performed better than boys on receptive and expressive language, but there was no significant interaction between gender and motor category on any of the Bayley scores. Cognitive, but not motor, category significantly contributed to variance of receptive language scores; cognitive and motor category each independently contributed to the variance in expressive language. Conclusion: Findings suggest that motor control areas of the brain may be implicated in expressive language development of premature children. Further research is needed to determine the underlying factors for the association between motor and expressive language function. [ABSTRACT FROM AUTHOR]

Background and Objectives: Human milk has nutritional, protective, and developmental advantages for premature infants. However, proteomic information of low abundant protein of donor milk is insufficient. The purpose of this study is to analyze and compare the proteome of low abundant protein of donor milk obtained at different postpartum ages other than the colostrum.Methods and Study Design: Donor breast milk from 12 healthy mothers was collected 15 days, 2 months and 6 months after delivery and stored by medically approved methods. The whey milk proteomes were analyzed by mass spectrometry and classified using bioinformatics analysis.Results: Human milk obtained 15 days and 2 months after delivery showed more abundant expression of whey proteins related to the generation of precursor metabolites and energy, metabolism, and catalytic activity, compared with milk collected at 3 months. Immune and transport-related proteins were abundant at all time points. Proteins involved in cellular movement, immune cell trafficking, and the carbohydrate metabolism network was more abundant in whey milk collected at 15 day and 2 months using a network analysis.Conclusions: We report proteomic information for human donor whey protein. As significant changes were found in whey proteome collected earlier than 2 months and 6 months after delivery, selecting human donor milk earlier than 2 months might be more helpful for early postnatal recipients. [ABSTRACT FROM AUTHOR]

Aim: Minimally aggressive and easily performed techniques that facilitate spontaneous respiratory stabilisation are required to reduce rescue intubation in extremely premature infants. This study evaluated the feasibility and safety of administering surfactant into the pharynx of infants born at <25 weeks immediately after birth.Methods: This study of 19 infants was conducted from January 2013 to June 2014 in a tertiary perinatal centre in Prague. We administered 1.5 mL of Curosurf as a bolus into the pharynx and simultaneously performed a sustained inflation manoeuvre (SIM). The extent of the interventions, death and severe neonatal morbidity in the study group were compared with 20 controls born before the study period and 20 born after it.Results: All infants received oropharyngeal surfactant within the median (interquartile range) time of 40 seconds (25-75) after cord camping. The surfactant had to be suctioned in one infant because of upper airway obstruction. Although more subsequent surfactant was administered in the study group, significantly fewer study period infants required intubation than the before and after controls (16% versus 75% and 58%, respectively, p < 0.01).Conclusion: Oropharyngeal surfactant with simultaneous SIM was feasible and safe and reduced the need for delivery room intubation in these fragile infants. [ABSTRACT FROM AUTHOR]

Aim: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery.Methods: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life.Results: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets.Conclusion: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice. [ABSTRACT FROM AUTHOR]

Background: The preferred timing of umbilical-cord clamping in preterm infants is unclear.Methods: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births.Results: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities.Conclusions: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .). [ABSTRACT FROM AUTHOR]

Background: Scientific evidence is insufficient to answer the question of whether premature birth causes altered tooth-crown dimensions. Objective: To evaluate permanent tooth-crown dimensions in prematurely born children and to compare the findings with full-term born controls. Subjects and Methods: Preterm children of 8-10 years of age were selected from the Swedish Medical Birth Register. One group consisted of 36 extremely preterm children (born before the 29th gestational week); the other group included 37 very preterm children (born during gestational weeks 29-32). The preterm children were compared with 41 matched full-term born children. Clinical examination and study casts were performed on all children. Permanent maxillary and mandibular first molars, central incisors, and laterals were measured with a digital sliding caliper on study casts. The tooth-crowns were measured both mesio-distal and bucco-lingual. Results: Both the mesio-distal and bucco-lingual measurements in the maxillary and mandibular first molars had a significantly smaller width in the extremely preterm group compared with the full-term group. The central incisors and lower laterals were significantly smaller mesio-distally in the extremely preterm group compared to the full-term group. A reduction in tooth size of 4-9% was found between the extremely preterm group and the full-term group for both boys and girls. The maxillary first molars and mandibular left first molar were also smaller mesio-distally in the extremely preterm group compared to the very preterm group. The results indicate that the more preterm the birth, the smaller the tooth-crown dimensions. Independent of gestational age girls had generally smaller teeth than boys. Conclusion: Premature birth is associated with reduced tooth-crown dimensions of permanent incisors and first molars. [ABSTRACT FROM AUTHOR]

Background: As care for preterm and low birth weight (LBW) infants improves in resource-limited settings, more infants are surviving the neonatal period. Preterm and (LBW) infants are at high-risk of nutritional and medical comorbidities, yet little is known about their developmental outcomes in low-income countries. This study evaluated the health, nutritional, and developmental status of preterm/LBW children at ages 1-3 years in Rwanda.Methods: Cross-sectional study of preterm/LBW infants discharged between October 2011 and October 2013 from a hospital neonatal unit in rural Rwanda. Gestational age and birth weight were gathered from hospital records to classify small for gestational age (SGA) at birth and prematurity. Children were located in the community for household assessments in November-December 2014. Caregivers reported demographics, health status, and child development using locally-adapted Ages and Stages Questionnaires (ASQ-3). Anthropometrics were measured. Bivariate associations with continuous ASQ-3 scores were conducted using Wilcoxon Rank Sum and Kruskal Wallis tests.Results: Of 158 eligible preterm/LBW children discharged from the neonatal unit, 86 (54.4%) were alive and located for follow-up. Median birth weight was 1650 grams, median gestational age was 33 weeks, and 50.5% were SGA at birth. At the time of household interviews, median age was 22.5 months, 46.5% of children had feeding difficulties and 39.5% reported signs of anemia. 78.3% of children were stunted and 8.8% wasted. 67.4% had abnormal developmental screening. Feeding difficulties (p = 0.008), anemia symptoms (p = 0.040), microcephaly (p = 0.004), stunting (p = 0.034), SGA (p = 0.023), very LBW (p = 0.043), lower caregiver education (p = 0.001), and more children in the household (p = 0.016) were associated with lower ASQ-3 scores.Conclusions: High levels of health, growth, and developmental abnormalities were seen in preterm/LBW children at age 1-3 years. As we achieve necessary gains in newborn survival in resource-limited settings, follow-up and early intervention services are critical for ensuring high-risk children reach their developmental potential. [ABSTRACT FROM AUTHOR]

Background Prematurity has been shown to be associated with an increased risk of intellectual disability (ID). Method The aim was to establish whether the prevalence of ID, defined as significant limitations in both intellectual (intelligence quotient below 70) and adaptive functioning among moderately preterm (MP; 32+0-33+6 weeks) and late preterm (LP; 34+0-36+6 weeks) infants, is increased compared with that in term infants (≥37+0 weeks). Antenatal and neonatal risk factors for ID among gestational age groups were sought. The national register study included all live-born infants in Finland in 1991-2008, excluding those who died before one year age, or had any major congenital anomaly or missing data. A total of 1 018 256 infants (98.0%) were analysed: very preterm (VP; <32+0 weeks, n = 6329), MP ( n = 6796), LP ( n = 39 928) and term ( n = 965 203). Results By the age of seven years, the prevalence of ID was 2.48% in the VP group, 0.81% in the MP group, 0.55% in the LP group and 0.35% in the term group. Intracranial haemorrhage increased the ID risk in all groups. Male sex and born small for gestational age predicted an increased risk in all but the MP group. Conclusions The prevalence of ID decreased with increasing gestational age. Prevention of intracranial haemorrhages may have a beneficial effect on the neurodevelopmental outcomes of neonates. [ABSTRACT FROM AUTHOR]

Background: Previous systematic reviews have examined preterm infants' long-term neurodevelopment after neonatal intensive care unit (NICU) discharge, although none have explored the effectiveness of interventions on preterm infants' neurodevelopment during NICU hospitalization. The aim of this review is to evaluate whether interventions, i.e., sensory stimulation, parental involvement, and control of environment, improve preterm infants' neurodevelopment during their NICU hospitalization. Methods: Experimental studies such as randomized controlled/clinical trials (RCTs) and cluster RCT will be included in this systematic review. Selected studies will be published in English or in French, in the past 15 years from 2002 to 2017. The following electronic databases will be searched to locate relevant studies: CINAHL, MEDLINE, PubMed, EMBASE (OVID), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. For all steps in selecting studies, agreement will be reached between two experts in neonatology. Data extraction will be performed independently by the two same experts and will then be compared. The Cochrane assessment tool will be used to screen the studies for risk of bias. A meta-analysis will be performed if the included studies are sufficiently homogeneous. Results will be analyzed using a standardized mean difference (with a 95% confidence interval). Statistical heterogeneity will be evaluated using the χ2 test at the significance level of 0.1 and the I2 with the classification suggested by PRISMA-P. If possible, subgroup analyses will be carried out considering preterm infants' gestational age, length of NICU hospitalization, and the characteristics of the intervention such as who delivered it, the type, the dose, the frequency, and the duration. Data synthesis will be performed using the RevMan 5.1 software. Publication bias and selection of variables in publication will be examined using the graphical method of funnel plot and with the statistical test of Egger. Quality of the evidence of all outcomes will be assessed using the Grades of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. Discussion: The results of this systematic review will highlight which interventions are effective for promoting preterm infants' neurodevelopment during NICU hospitalization and will contribute to the body of knowledge in neonatal care by providing guidance for NICU clinical practice and research. Systematic review registration: PROSPERO CRD42017047072. [ABSTRACT FROM AUTHOR]

Objective: Growth and development of preterm infants may be negatively affected by constant bright light in neonatal intensive care units ( NICUs ). It may also contribute to sleep pattern disorders commonly seen in in this group of infants. Reducing exposure to light by covering the incubators is recommended by guidelines of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP). Materials and Methods: This randomized clinical trial study was performed on 60 preterm infants with gestational age of 28-32 weeks admitted at NICU of Al-Zahra Teaching Hospital of Tabriz University of Medical Sciences in 2014. Preterm infants were divided randomly in 2 groups: In the first group (intervention), incubators were covered with a thick cover and the face was covered with a cloth (face cover). In the second group (observation), incubators were covered with a thick cover but the face was not covered. We darkened the environment of NICU by closing the curtain and turning off additional florescent lights from 19:30 pm till 7:30 am in both groups, then we compared sleep pattern in 2 groups of infants by using sleep diagram. Results: In the intervention group (face cover), the mean frequency of sleep during the 6 days increased by 2.96 times/ observations and the mean amount of sleep increased by 59 minutes. Conclusion: This study showed that light reduction with incubator covers and eye shield, increases the frequency and sleep duration in premature infants. [ABSTRACT FROM AUTHOR]

Background: Premature birth is often associated with neurodevelopmental difficulties throughout childhood. In the first three years of life, the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) constitute one of the most used tools for assessing child development. Since Bayley-III original norms are based on United States (US) population, it remains uncertain whether their use in other countries (e.g., European) is appropriate.Aims: This research aimed to examine neurodevelopment of preterm infants and full-term infants, using Bayley-III US norms in comparison to Italian (IT) norms. Patterns of developmental outcomes for both infant groups were also explored.Methods: 104 preterm and 58 full-term infants were included in the study. Bayley-III was used for neurodevelopmental assessment at 1year of corrected age, considering both IT and US norms for scores computation.Results: Comparing scores obtained with IT vs US norms, differences in means were all significant across five subscales (p<0.05 at least) for preterm infants, whereas for full-term peers significant differences were found only for Receptive Language and Fine Motor subscales (p<0.001). Effect size (η2) ranged from 0.22 to 0.94. Within each group, significant discrepancies across subscales were found. Moreover, Italian preterm infants had significantly lower performances than full-term peers, excepting for Expressive Language and Gross Motor subscales.Conclusions: As regards to Italian 1-year children, our study seems to provide evidence for the tendency of Bayley-III US norms to overestimate development compared to IT norms. These findings emphasize the need to early detect children at risk for developmental delay and to plan early intervention. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are exposed to a variety of sensory stimuli that they are not developmentally prepared to handle, which puts them at risk for developing a sensory processing disorder. However, the patterns and predictors of sensory processing disorder and their relationship to early behavior at term equivalent age are poorly understood.Objectives: The aims of the study are to: 1) describe the incidence of sensory processing disorder in preterm infants at four to six years of age, 2) define medical and sociodemographic factors that relate to sensory processing disorder, and 3) explore relationships between early neurobehavior at term equivalent age and sensory processing disorder at age four to six years.Methods: This study was a prospective longitudinal design. Thirty-two preterm infants born ≤30weeks gestation were enrolled. Infants had standardized neurobehavioral testing at term equivalent age with the NICU Network Neurobehavioral Scale. At four to six years of age, participants were assessed with the Sensory Processing Assessment for Young Children (SPA).Results: Sixteen children (50%) had at least one abnormal score on the SPA, indicating a sensory processing disorder. There were no identified relationships between medical and sociodemographic factors and sensory processing disorder. More sub-optimal reflexes (p=0.04) and more signs of stress (p=0.02) at term equivalent age were related to having a sensory processing disorder in early childhood.Conclusion: Preterm infants are at an increased risk for developing a sensory processing disorder. Medical and sociodemographic factors related to sensory processing disorder could not be isolated in this study, however relationships between sensory processing disorder and early neurobehavior were identified. [ABSTRACT FROM AUTHOR]