Background and Objectives:Preterm birth is associated with altered white matter development and long-term neurodevelopmental impairments. Skin-to-skin care (kangaroo care) has well-documented benefits for physiological stability and bonding, but its association with neonatal brain structure remains unclear. This study explored the association between in-hospital skin-to-skin care and neonatal white matter microstructure in frontal and limbic pathways that are linked to stress regulation and socio-emotional development, processes potentially influenced by affective touch during skin-to-skin care. Methods:This retrospective study analyzed electronic medical records and diffusion MRI data collected from 86 preterm infants (<32 weeks gestational age) in a single NICU. Skin-to-skin care exposure was quantified as total duration (minutes/instance) and rate (minutes/day) of sessions. Diffusion MRI scans obtained before hospital discharge assessed mean diffusivity (MD) and fractional anisotropy (FA) in the cingulate, anterior thalamic radiations (ATR), and uncinate fasciculus. Hierarchical regression models examined associations between skin-to-skin care and white matter microstructure, adjusting for gestational age, health acuity, postmenstrual age at scan, and MRI coil type. Sensitivity analyses controlled for socioeconomic status and NICU visitation frequency. Results:Skin-to-skin care duration was positively associated with MD in the cingulate (B = 0.002, p = 0.016) and ATR (B = 0.002, p = 0.020). Skin-to-skin care rate was also positively linked to MD in the ATR (B = 0.040, p = 0.041). Skin-to-skin care duration and rate were not associated with FA in the cingulate but skin-to-skin duration and rate were negatively associated with FA in the ATR (duration: B = -0.001, p = 0.020; rate: B = -0.017, p = 0.008). No significant associations were found for the uncinate fasciculus. Findings remained robust after adjusting for socioeconomic status and visitation frequency. Discussion:This study provides novel evidence linking in-hospital experiences of skin-to-skin care to neonatal white matter development. These findings have important implications for understanding how family-centered neuroprotective practices, such as skin-to-skin care, may affect brain development to improve long-term developmental outcomes.

OBJECTIVE:To examine the relationship between inpatient skin-to-skin care rates and neurodevelopmental scores measured at 12 months in very preterm (VPT) infants. STUDY DESIGN:From a retrospective review of medical records of 181 VPT infants (<32 weeks gestational age [GA] at birth), we derived skin-to-skin care rate, ie, total minutes of skin-to-skin care each infant received over the number of days of hospital stay. We used scores on the Capute Scales from routine follow-up assessments at 12 months to measure neurodevelopmental outcomes. RESULTS:Families averaged approximately 17 minutes/day of skin-to-skin care (2 days/week, 70 minutes/session), although there was substantial variability. Variation in skin-to-skin rate was positively associated with outcomes at 12 months corrected age (r = 0.25, P < .001). Skin-to-skin rate significantly predicted 6.2% unique variance in 12-month neurodevelopmental outcomes, after adjusting for GA, socioeconomic status (SES), health acuity, and visitation frequency. A 20-minute increase in skin-to-skin care per day was associated with a 10-point increase (0.67 SDs) in neurodevelopmental outcomes at 12 months. GA and infant health acuity did not moderate these relations. CONCLUSION:VPT infants who experienced more skin-to-skin care during hospitalization demonstrated higher scores on 12-month neurodevelopmental assessments. Results provide evidence that skin-to-skin care confers extended benefits to VPT infants through the first year of life. Skin-to-skin care offers promise as a family-centered intervention designed to promote positive developmental outcomes in at-risk infants.

ABSTRACTBackgroundPostnatal steroids are used to prevent bronchopulmonary dysplasia in extremely preterm infants but may have adverse effects on brain development. This study assessed variation in connectivity metrics of major white matter pathways in the cerebrum and cerebellum at near-term gestational age among infants who did or did not receive a standardized regimen of hydrocortisone during the first 10 days of life.MethodsRetrospective cohort study. Participants: Infants born < 28 weeks, divided into 2 groups: Protocol group (n=33) received at least 50% of and not more than 150% of an intended standard dose of 0.5mg/kg hydrocortisone twice daily for 7 days, then 0.5 mg/kg per day for 3 days; versus Non-Protocol group (n=22), that did not receive protocol hydrocortisone or completed <50% of the protocol dose. We assessed group differences in near-term diffusion MRI mean fractional anisotropy (FA) and mean diffusivity (MD) across the corticospinal tract, inferior longitudinal fasciculus, corpus callosum and superior cerebellar peduncle.ResultsGroups were comparable in terms of gestational age, post-menstrual age at scan, medical complications, bronchopulmonary dysplasia, and necrotizing enterocolitis. No significant large-effect group differences were identified in mean FA or MD in any cerebral or cerebellar tract between the two groups.Conclusion(s)Low dose, early, postnatal hydrocortisone was not associated with significant differences in white matter tract microstructure at near term gestational age.ImpactThis study compared brain microstructural connectivity as a primary outcome among extremely preterm infants who did or did not receive early postnatal hydrocortisone.Low dose hydrocortisone in the first 10 days of life was not associated with significant differences in white matter microstructure in major cerebral and cerebellar pathwaysHydrocortisone did not have a significant effect on early brain white matter circuits.

To examine associations between maternal mental health and involvement in developmental care in the NICU. Mothers of infants born <32 weeks gestation (n = 135) were approached to complete mental health screening questionnaires at two weeks after admission. Mothers who completed screening (n = 55) were further classified as with (n = 19) and without (n = 36) elevated scores. Mothers’ frequency, rate, and duration of developmental care activities were documented in the electronic health record. 35% of screened mothers scored above the cutoff for clinical concern on ≥1 measure. No significant differences between the 3 groups were identified for rates, frequency, or amount of all developmental care, kangaroo care, and swaddled holding. Elevated scores on maternal mental health questionnaires did not relate to developmental care. Maternal developmental care engagement may not indicate mental health status. Universal screening for psychological distress is required to accurately detect symptoms in mothers of hospitalized preterm infants.

Objective Limited research links hospital-based experiences of skin-to-skin (STS) care to longer-term neurodevelopmental outcomes in preterm children. The present study examined relations between inpatient STS and neurodevelopmental scores measured at 12 months in a sample of very preterm (VPT) infants. Study Design and Methods From a retrospective study review of medical records of 181 VPT infants (<32 weeks gestational age (GA)) we derived the STS rate, i.e., the total minutes of STS each infant received/day of hospital stay. We used scores on the Capute Scales from routine follow-up care at 12 months as the measure of neurodevelopmental outcome (n=181). Results Families averaged approximately 17 minutes/day of STS care (2 days/week, 70 minutes/session), although there was substantial variability. Variation in STS rate was positively associated with outcomes at 12 months corrected age ( r = 0.25, p < .001). STS rate significantly predicted 6.2% unique variance in 12-month neurodevelopmental outcomes, after controlling for GA, socioeconomic status (SES), health acuity, and visitation frequency. A 20-minute increase in STS per day was associated with a 10-point increase (.67 SDs) in neurodevelopmental outcomes at 12 months. SES, GA, and infant health acuity did not moderate these relations. Conclusion VPT infants who experienced more STS during hospitalization demonstrated higher scores on 12-month assessments of neurodevelopment. Results provide evidence that STS care may confer extended neuroprotection on VPT infants through the first year of life.

Glucocorticoids (GC) are used in neonatal intensive care units to prevent or reduce the severity of chronic lung disease in preterm infants and have been implicated in impaired neurodevelopment. Our objective was to identify what is known about the effects of postnatal GC treatment in human preterm infants on structural brain development and to identify gaps in the literature. Following Arksey and O'Malley's scoping review methodological framework, we searched scientific literature databases for original research on human preterm infants, postnatal GCs, and brain structure. 11 studies assessed the effects of GCs on structural brain outcomes. 56 studies reported brain injury, but not structure. Dexamethasone was consistently associated with decreased total and regional brain volumes, including cerebellar volumes. Hydrocortisone was often, but not always associated with absence of brain volume differences. No studies examined the impact of inhaled GC on brain structure. Additional research on the effects of neonatal GCs after preterm birth on a variety of structural brain measures is required for understanding contributions to neurodevelopment and informing practice guidelines.

Many diffusion magnetic resonance imaging (dMRI) studies document associations between reading skills and fractional anisotropy (FA) within brain white matter, suggesting that efficient transfer of information across the brain contributes to individual differences in reading. Use of complementary imaging methods can determine if these associations relate to myelin content of white matter tracts. Compared to children born at term (FT), children born preterm (PT) are at risk for reading deficits. We used two MRI methods to calculate associations of reading and white matter properties in FT and PT children. Participants (N=79: 36 FT and 43 PT) were administered the Gray's Oral Reading Test at age 8. We segmented three dorsal (left arcuate and bilateral superior longitudinal fasciculus) and four ventral (bilateral inferior longitudinal fasciculus and bilateral uncinate) tracts and quantified (1) FA from dMRI and (2) R1 from quantitative T1 relaxometry. We examined correlations between reading scores and these metrics along the trajectories of the tracts. Reading positively correlated with FA in segments of left arcuate and bilateral superior longitudinal fasciculi in FT children; no FA associations were found in PT children. Reading positively correlated with R1 in segments of the left superior longitudinal, right uncinate, and left inferior longitudinal fasciculi in PT children; no R1 associations were found in FT children. Birth group significantly moderated the associations of reading and white matter metrics. Myelin content of white matter may contribute to individual differences in PT but not FT children.

This text, edited by nationally recognized leaders in trauma and development, brings together an interdisciplinary group of contributors from the fields of medicine, psychology, psychiatry, education, law, anthropology, and public health. The bold purpose of this book is to inform clinicians, educators, advocates, and policy makers at all levels about trauma and stressor-related disorders (TSRDs). The book summarizes up-to-date neuroscience and genetic research, treatment approaches, and information on the state of systems of care for children exposed to trauma. Trauma and stressor-related disorders are a heterogenous category of emotional and behavioral problems arising in response to real or perceived trauma. TSRDs form a new category in the Diagnostic and Statistical Manual (DSM-V), separating them from anxiety disorders, as they were classified in previous versions of the DSM. The field of trauma-related neurodevelopment is young, and evidence-based information to identify and care for children exposed to trauma and their caregivers is urgently needed. In this comprehensive yet readable book, the editors have provided a needed resource that synthesizes available research and treatment strategies for improving care for children who have experienced trauma. The volume moves logically from the neuroscience underpinnings of the effects of trauma on neurodevelopment to differential diagnosis of TSRDs to evidence-based treatments, focusing on young children. The latter half of the book examines TSRDs through the lenses of culture, education, and public health and reverses the construct to examine autism through the lens of health disparities and trauma. Because TSRD symptoms overlap with and may be mistaken for the core features of autism spectrum disorder (ASD), one of the aims of this book is to disentangle TSRDs from ASD. The editors review the history of ASD and cogently argue for the importance of differentiating ASD or related neurodevelopmental disorders from TSRDs. They acknowledge the barriers that may inhibit families from seeking effective and available treatments for TSRDs, including the implication of caregiver contribution to pathology and frequently concurrent poverty, chronic stress, or chaotic environment. The authors recognize that discussing TSRDs can be fraught for the family and clinician. This book aims to help the clinician avoid inappropriate referral, diagnosis, or treatment and to form therapeutic alliances with patients and clients to improve children's developmental trajectories and success in life. The authors provide tools, including sample dialogs, to work with families, schools, or other well-intentioned parties, who may clamor for an ASD diagnosis to access ASD-related support and therapy, even if they are inappropriate for symptoms that are secondary to trauma. The contributors use extensive, complex cases to highlight the challenges of this work. Through these highly readable passages, the authors describe pathology and the influence of the beliefs and values of the families, clinicians, and community providers. By not shying from detailed narrative, the authors bring life to the science. Other highlights include a thorough review of fetal alcohol spectrum disorders as they intersect with trauma, specific evidence-based treatment approaches, and systematic review of supporting research. The latter half of the book includes chapters on disparities, barriers, and cultural considerations in ASD diagnosis and treatment, transition to adulthood, public health, and education. These chapters include some repetition of the neuroscience and of diagnosis, making them amenable to reading as stand-alone chapters. Areas for improvement in a future edition include better annotation of tables and figures. The neurobiology chapter also presumes a level of knowledge about neuroanatomy and connectivity that may make it unapproachable for some readers. The traumatic effects of personal and societal violence, indifference, and adversity on children's development are increasingly recognized. Despite that knowledge, at times it seems we live in an era in which children's health and well-being are increasingly devalued. The authors describe the world as it is but also lay out a vision of the world as it should be. It is a timely and important addition to the bookshelves of anyone who works with children and especially those who are educating the next generation of doctors, psychologists, therapists, teachers, lawyers, and policy makers who work with children and their families.

ABSTRACT AIM Children born preterm (PT) experience perinatal white matter injury and later reading deficits at school age. We used two complementary neuroimaging modalities to determine if reading skills would be associated with contemporaneous white matter properties in school-aged PT children. METHOD In 8-year-old PT children (N=29), we measured diffusivity (fractional anisotropy, FA), from diffusion MRI, and myelin content (relaxation rate, R1) from quantitative relaxometry. We assessed reading (Gray’s Oral Reading Test, Fifth Edition) in each child. Whole-brain deterministic tractography coupled with automatic segmentation and quantification were applied to extract FA and R1 along four tracts and assess their statistical association with reading scores. RESULTS Reading-FA correlations were not significant along the four analyzed tracts. Reading-R1 correlations were significantly positive in portions of the left superior longitudinal fasciculus, right uncinate fasciculus, and left inferior longitudinal fasciculus. FA positively correlated with R1 in limited areas of reading-R1 associations, but did not contribute to the variance in reading scores. INTERPRETATION Combining complementary neuroimaging approaches identified relations between reading and white matter properties not found using a single MRI measure. Associations of reading skills and white matter properties may vary across white matter tracts and metrics in PT children. What this paper adds ▪ Preterm children’s reading was associated with white matter myelin content. ▪ Preterm children’s reading was not associated with white matter diffusivity.

Aim: To determine whether variability in diffusion MRI (dMRI) white matter tract metrics, obtained in a cohort of preterm infants prior to neonatal hospital discharge, would be associated with language outcomes at age 2 years, after consideration of age at scan and number of major neonatal complications. Method: 30 children, gestational age 28.9 (2.4) weeks, underwent dMRI at mean post menstrual age 36.4 (1.4) weeks and language assessment with the Bayley Scales of Infant Development-III at mean age 22.2 (1.7) months chronological age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 5 white matter tracts. Hierarchical linear regression assessed associations between tract FA, moderating variables, and language outcomes. Results: FA of the left inferior longitudinal fasciculus accounted for 17% (p = 0.03) of the variance in composite language and FA of the posterior corpus callosum accounted for 19% (p = 0.02) of the variance in composite language, beyond that accounted for by post-menstrual age at scan and neonatal medical complications. The number of neonatal medical complications moderated the relationship between language and posterior corpus callosum FA but did not moderate the association in the other tract. Conclusion: Language at age 2 is associated with white matter metrics in early infancy in preterm children. The different pattern of associations by fiber group may relate to the stage of brain maturation and/or the nature and timing of medical complications related to preterm birth. Future studies should replicate these findings with a larger sample size to assure reliability of the findings.

Background: Cognitive outcomes in preterm (PT) children have been associated with microstructural properties of white matter. PT children who experienced neonatal inflammatory conditions have poorer cognitive outcomes than those who did not. The goal of this study was to contrast white matter microstructure and cognitive outcomes after preterm birth in relation to the presence or absence of severe inflammatory conditions in the neonatal period. Methods: PT children (n = 35), born at gestational age 22-32 weeks, were classified as either PT + (n = 12) based on a neonatal history of inflammatory conditions, including bronchopulmonary dysplasia, necrotizing enterocolitis or culture positive sepsis, or PT- (n = 23) based on the absence of the three inflammatory conditions. Full term (FT) children (n = 43) served as controls. Participants underwent diffusion MRI and cognitive testing (intelligence, reading, and executive function) at age 6 years. The corpus callosum was segmented into 7 regions using deterministic tractography and based on the cortical projection zones of the callosal fibers. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for each segment. General linear models with planned contrasts assessed group differences in FA, MD and cognitive outcomes. Pearson correlations assessed associations of white matter metrics and cognitive outcome measures. Results: FA was significantly lower and MD was significantly higher in PT + compared to PT- or FT groups in multiple callosal segments, even after adjusting for gestational age. Executive function scores, but not intelligence or reading scores, were less favorable in PT + than in PT- groups. Among the entire sample, occipital FA was significantly correlated with IQ (r = 0.25, p < 0.05), reading (r = 0.32, p < 0.01), and executive function (r = -0.28, p < 0.05) measures. Anterior frontal FA and superior parietal FA were significantly correlated with executive function (r = -0.25, r = 0.23, respectively, p < 0.05). Conclusions: We observed differences in the white matter microstructure of the corpus callosum and in the cognitive skills of 6-year-old PT children based on their history of neonatal inflammation. Neonatal inflammation is one medical factor that may contribute to variation in long-term neurobiological and neuropsychological outcomes in PT samples.

Background & Aims: The impact of childhood Crohn's disease (CD) on volumetric bone mineral density (vBMD), bone structure, and muscle mass have not been established. The objective of this longitudinal study was to assess musculoskeletal outcomes in an incident cohort of children with CD using peripheral quantitative computed tomography (pQCT). Methods: Tibia pQCT was performed in 78 CD subjects (ages, 5-18 years) at diagnosis and in 67 over the subsequent year. pQCT outcomes were converted to sex- and race-specific z scores based on reference data in over 650 controls. Multivariable linear regression models identified factors associated with changes in bone outcomes. Results: At diagnosis, CD subjects had significant deficits in trabecular vBMD (z score, -1.32 +/- 1.32; P < .001), cortical section modulus (a measure of bone geometry and strength) (z score, -0.44 +/- 1.11; P < .01), and muscle (z score, -0.96 +/- 1.02; P < .001) compared with controls. Over the first 6 months, trabecular vBMD and muscle z scores improved significantly (both, P < .001); however, section modulus worsened (P = .0001), and all 3 parameters remained low after 1 year. Increases in muscle z scores were associated with less severe declines in cortical section modulus z scores. Improvements in trabecular vBMD z scores were greater in prepubertal subjects. Glucocorticoids were associated with increases in cortical vBMD. Conclusions: Substantial deficits in trabecular vBMD, cortical bone geometry, and muscle were observed at CD diagnosis. Trabecular vBMD improved incompletely; however, cortical deficits progressed despite improvements in muscle. Glucocorticoids were not associated with bone loss. Therapies to improve bone accrual in childhood CD are needed.

OBJECTIVE:To identify determinants of musculoskeletal deficits (muscle cross-sectional area [mCSA], trabecular volumetric bone mineral density [vBMD], and cortical bone strength [section modulus]) in patients with juvenile idiopathic arthritis (JIA) and to determine if cortical bone strength is appropriately adapted to muscle forces. METHODS:Peripheral quantitative computed tomography (pQCT) of the tibia was performed in 101 patients with JIA (79% female; 24 with oligoarticular JIA, 40 with polyarticular JIA, 18 with systemic JIA, and 19 with spondylarthritis [SpA]) and 830 healthy control subjects; all were ages 5-22 years. Outcomes of pQCT were expressed as sex- and race-specific Z scores. Multivariable linear regression models assessed mCSA and bone status in JIA patients compared with controls and identified factors associated with musculoskeletal deficits in JIA. RESULTS:The median duration of JIA was 40 months; 29% of the JIA patients had active arthritis, and 28% had received glucocorticoid therapy during the previous year. Compared with the controls, the mCSA and section modulus Z scores were significantly lower in patients with polyarticular JIA and those with SpA. Trabecular vBMD Z scores were significantly lower in patients with polyarticular JIA, those with systemic JIA, and those with SpA. Significant predictors of musculoskeletal deficits included active arthritis in the previous 6 months (mCSA), temporomandibular joint disease (mCSA and section modulus), functional disability (mCSA and vBMD), short stature (vBMD), infliximab exposure (vBMD), and JIA duration (section modulus). The section modulus was significantly reduced relative to mCSA in patients with JIA after adjustment for age and limb length. CONCLUSION:Marked deficits in vBMD and bone strength occur in JIA in association with severe and longstanding disease. Contrary to the findings of previous studies, bone deficits were greater than expected relative to the mCSA, which illustrates the importance of adjusting for age and bone length.

Although children with juvenile idiopathic arthritis (JIA) are at risk for vertebral fractures, recent conventional posterior-anterior (PA) spine dual-energy X-ray absorptiometry studies reported minimal areal bone mineral density (aBMD, g/cm2) deficits. Width-adjusted BMD (WA-BMD, g/cm3) represents the bone mineral content (BMC) from the lateral projection, excluding the dense cortical spinous processes, divided by the estimated vertebral body volume based on paired PA-lateral bone dimensions. Therefore, WA-BMD may be more sensitive to JIA effects on the predominantly trabecular vertebral body. Age- and sex-specific Z-scores for spine aBMD and WA-BMD were generated in 84 JIA subjects compared with healthy controls, aged 5-21 yr. JIA was associated with lower mean WA-BMD Z-scores (-0.78, 95% CI: -1.03, -0.53; p<0.001) and aBMD Z-scores (-0.26, 95% CI: -0.49, -0.02; p<0.05), compared with controls. WA-BMD Z-scores were significantly lower than aBMD Z-scores in JIA (p<0.001). A significant JIA by age interaction (p<0.001) indicated that the magnitude of the difference between WA-BMD and aBMD Z-scores was greater in younger subjects. In conclusion, WA-BMD may be more sensitive to disease effects in children because it selectively measures the trabecular-rich vertebral body and is independent of growth-related changes in BMC of the dense spinous processes.