Inpatient Skin-to-Skin Care Predicts 12-month Neurodevelopmental Outcomes in Very 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.

Early, low-dose hydrocortisone and near-term brain connectivity in extremely preterm infants.

BACKGROUND: Postnatal steroids are used to prevent bronchopulmonary dysplasia in extremely preterm infants but may have adverse effects on brain development. We assessed connectivity metrics of major cerebral and cerebellar white matter pathways 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. METHODS: Retrospective cohort study. PARTICIPANTS: Infants born <28 weeks: Protocol group (n = 33) received at least 50% and not more than 150% of an intended standard dose of 0.5 mg/kg hydrocortisone twice daily for 7 days, then 0.5 mg/kg per day for 3 days; Non-Protocol group (n = 22), 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. RESULTS: Groups were comparable in 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. CONCLUSION(S): Low dose, early, postnatal hydrocortisone was not associated with significant differences in white matter tract microstructure at near-term gestational age. IMPACT: This 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 pathways. Hydrocortisone did not have a significant effect on early brain white matter circuits.

Associations of behavioral problems with white matter circuits connecting to the frontal lobes in school-aged children born at term and preterm.

Introduction: This study investigated whether behavioral problems in children were associated with fractional anisotropy (FA) of white matter tracts connecting from other brain regions to right and left frontal lobes. We considered internalizing and externalizing behavioral problems separately and contrasted patterns of associations in children born at term and very preterm. Methods: Parents completed the Child Behavior Checklist/6-18 questionnaire to quantify behavioral problems when their children were age 8 years (N=36 FT and 37 PT). Diffusion magnetic resonance scans were collected at the same age and analyzed using probabilistic tractography. We used multiple linear regression to investigate the strength of association between age-adjusted T-scores of internalizing and externalizing problems and mean fractional anisotropy (mean-FA) of right and left uncinate, arcuate, and anterior thalamic radiations, controlling for birth group and sex. Results: Regression models predicting internalizing T-scores from mean-FA found significant group-by-tract interactions for the left and right arcuate and right uncinate. Internalizing scores were negatively associated with mean-FA of left and right arcuate only in children born at term (pleft AF =0.01, pright AF =0.01). Regression models predicting externalizing T-scores from mean-FA found significant group-by-tract interactions for the left arcuate and right uncinate. Externalizing scores were negatively associated with mean-FA of right uncinate in children born at term (pright UF =0.01) and positively associated in children born preterm (pright UF preterm =0.01). Other models were not significant. Conclusions: In this sample of children with scores for behavioral problems across the full range, internalizing and externalizing behavioral problems were negatively associated with mean-FA of white matter tracts connecting to frontal lobes in children born at term; externalizing behavioral problems were positively associated with mean-FA of the right uncinate in children born preterm. The different associations by birth group suggest that the neurobiology of behavioral problems differs in the two birth groups.

Maternal mental health and engagement in developmental care activities with preterm infants in the NICU.

OBJECTIVE: To examine associations between maternal mental health and involvement in developmental care in the NICU. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Effects of postnatal glucocorticoids on brain structure in preterm infants, a scoping review.

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.

Investigating Relations between the NICU Speech Environment and Weight Gain in Infants Born Very Preterm.

OBJECTIVE: Children born preterm, especially those born very preterm (<32 weeks of gestational age [GA]) are at risk for poor growth and adverse neurodevelopmental outcomes. Adverse growth and neurodevelopmental outcomes in preterm children have been attributed, in part, to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant to neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU. Our objective was to examine relations between the NICU speech environment and the rate of weight gain during hospitalization. STUDY DESIGN: Participants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32 to 36 weeks of postmenstrual age using an automatic speech-counting device. Average rates of weight gain (g/kg/d) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/d). Linear regressions examined caloric intake and speech counts as predictors of infant weight gain. RESULTS: Infant weight gain was significantly predicted by caloric intake and speech exposure, each uniquely accounting for approximately 27% variance (total R 2 = 60.2%; p < 0.001). Speech counts were uncorrelated with rates of family visitation, time in incubator, or health acuity. CONCLUSION: While future research should establish causality and direction of effects, enhancing speech exposure in the NICU may be beneficial for physical growth. NICU care plans should consider opportunities to increase speech exposure. KEY POINTS: · Preterm infants who experienced greater amounts of speech in the NICU gained significantly more weight than preterm infants who were exposed to lower amounts of speech during the same developmental period (32-36 weeks of postmenstrual age).. · Caloric intake and speech counts accounted for almost 60% of variance in infant weight gain between 32 and 36 weeks of postmenstrual age.. · Speech counts were not significantly correlated with family visitation, how long infants resided in incubators, or health acuity.. · Findings suggest that the NICU speech environment may play an important role in the physical health of preterm infants; however, more studies are needed to determine the directionality of the observed associations..

Associations of Behavioral Problems and White Matter Properties of the Cerebellar Peduncles in Boys and Girls Born Full Term and Preterm.

Accumulating evidence suggests that the role of cerebellum includes regulation of behaviors; cerebellar impairment may lead to behavioral problems. Behavioral problems differ by sex: internalizing problems are more common in girls, externalizing problems in boys. Behavioral problems are also elevated in children born preterm (PT) compared to children born full term (FT). The current study examined internalizing and externalizing problems in 8-year-old children in relation to sex, birth-group, fractional anisotropy (FA) of the three cerebellar peduncles (superior, middle, and inferior), and interactions among these predictor variables. Participants (N = 78) were 44 boys (28 PT) and 34 girls (15 PT). We assessed behavioral problems via standardized parent reports and FA of the cerebellar peduncles using deterministic tractography. Internalizing problems were higher in children born PT compared to children born FT (p = .032); the interaction of sex and birth-group was significant (p = .044). When considering the contribution of the mean-tract FA of cerebellar peduncles to behavioral problems, there was a significant interaction of sex and mean-tract FA of the inferior cerebellar peduncle (ICP) with internalizing problems; the slope was negative in girls (p = .020) but not in boys. In boys, internalizing problems were only associated with mean-tract FA ICP in those born preterm (p = .010). We found no other significant associations contributing to internalizing or externalizing problems. Thus, we found sexual dimorphism and birth-group differences in the association of white matter metrics of the ICP and internalizing problems in school-aged children. The findings inform theories of the origins of internalizing behavioral problems in middle childhood and may suggest approaches to treatment at school age.

White matter properties underlying reading abilities differ in 8-year-old children born full term and preterm: A multi-modal approach.

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.

Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome.

Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome. In this retrospective study, twenty-eight children with medulloblastoma (mean age 8.8 ± 3.8 years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy (FA) at 30 nodes along each tract. Thirteen patients developed cerebellar mutism syndrome. FA was significantly lower in the distal third of the left superior cerebellar peduncle pre-operatively in all patients compared to controls (FA in proximal third 0.228, middle and distal thirds 0.270, p = 0.01, Cohen's d = 0.927). Pre-operative differences in FA did not predict cerebellar mutism syndrome. However, post-operative reductions in FA were highly specific to the distal left superior cerebellar peduncle, and were most pronounced in children with cerebellar mutism syndrome compared to those without at the 1-4 month follow up (0.325 vs 0.512, p = 0.042, d = 1.36) and at the 1-year follow up (0.342, vs 0.484, p = 0.038, d = 1.12). High spatial resolution cerebellar profilometry indicated a site-specific alteration of the distal segment of the superior cerebellar peduncle seen in cerebellar mutism syndrome which may have important surgical implications in the treatment of these devastating tumours of childhood.

Disparities in Kangaroo Care for Premature Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: The aim of this study was to investigate whether preterm infants whose families have lower socioeconomic status (SES) or communicate with clinical staff in a language other than English experience differences in the rate, frequency, and duration of kangaroo care (KC) in the neonatal intensive care unit (NICU) compared with preterm infants of higher SES or primarily English-speaking families. METHODS: Participants were infants born <32 weeks' gestational age (GA), N = 116. We defined SES by the infants' health insurance (private/higher vs public/lower) and language by the language mothers used to communicate with clinical staff (English vs Other language). SES or language groups were compared on (1) rate of KC infants experienced during hospitalization per visitation days, (2) frequency of KC per visitation days, and (3) duration of KC events per day. RESULTS: Infants in the lower SES and Other language groups experienced KC in reduced amounts, lower frequencies, and shorter durations than infants in either the higher SES or English language groups. SES and language group differences remained significant after controlling for family visitation and GA at birth. After controlling for SES, language group differences in KC duration remained significant. CONCLUSION: Our findings revealed disparities in the rate, frequency, and duration of KC experienced in the NICU as a function of both SES and language. Such disparities reduced infants' access to this developmental care practice shown to stabilize clinical status and promote neurodevelopment. We recommend that hospital nurseries implement policies that minimize these disparities.

Impact of the COVID-19 pandemic on developmental care practices for infants born preterm.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on rates of hospital visitation and rates and durations of developmental care practices for infants born preterm. METHODS: We analyzed electronic medical record data from 129 infants born at less than 32 weeks gestational age (GA) cared for in the Lucile Packard Children's Hospital neonatal intensive care unit (NICU) in a COVID-19-affected period (March 8, 2020 to Nov 30, 2020, n = 67) and the analogous period in 2019 (n = 62). Rates of family visitation and of family- and clinical staff-delivered developmental care were compared across cohorts, adjusting for covariates. RESULTS: Families of infants visited the hospital at nearly half of the rate during 2020 as during 2019 (p = 0.001). Infants experienced developmental care less frequently in 2020 vs. 2019 (3.0 vs. 4.3 activities per day; p = 0.001), resulting in fewer minutes per day (77.5 vs. 130.0; p = 0.001). In 2020, developmental care activities were 5 min shorter, on average, than in 2019, p = 0.001. Similar reductions occurred in both family- and staff-delivered developmental care. Follow-up analyses indicated that effects persisted and even worsened as the pandemic continued through fall 2020, despite relaxation of hospital visitation policies. CONCLUSIONS: The COVID-19 pandemic has negatively impacted family visitation and preterm infant developmental care practices in the NICU, both experiences associated with positive health benefits. Hospitals should create programs to improve family visitation and engagement, while also increasing staff-delivered developmental care. Careful attention should be paid to long-term follow up of preterm infants and families.

Listening to Mom in the NICU: effects of increased maternal speech exposure on language outcomes and white matter development in infants born very preterm.

BACKGROUND: Infants born very preterm (< 32 weeks gestational age (GA)) are at risk for developmental language delays. Poor language outcomes in children born preterm have been linked to neurobiological factors, including impaired development of the brain's structural connectivity (white matter), and environmental factors, including decreased exposure to maternal speech in the neonatal intensive care unit (NICU). Interventions that enhance preterm infants' exposure to maternal speech show promise as potential strategies for improving short-term health outcomes. Intervention studies have yet to establish whether increased exposure to maternal speech in the NICU offers benefits beyond the newborn period for brain and language outcomes. METHODS: This randomized controlled trial assesses the long-term effects of increased maternal speech exposure on structural connectivity at 12 months of age (age adjusted for prematurity (AA)) and language outcomes between 12 and 18 months of age AA. Study participants (N = 42) will include infants born very preterm (24-31 weeks 6/7 days GA). Newborns are randomly assigned to the treatment (n = 21) or standard medical care (n = 21) group. Treatment consists of increased maternal speech exposure, accomplished by playing audio recordings of each baby's own mother reading a children's book via an iPod placed in their crib/incubator. Infants in the control group have the identical iPod setup but are not played recordings. The primary outcome will be measures of expressive and receptive language skills, obtained from a parent questionnaire collected at 12-18 months AA. The secondary outcome will be measures of white matter development, including the mean diffusivity and fractional anisotropy derived from diffusion magnetic resonance imaging scans performed at around 36 weeks postmenstrual age during the infants' routine brain imaging session before hospital discharge and 12 months AA. DISCUSSION: The proposed study is expected to establish the potential impact of increased maternal speech exposure on long-term language outcomes and white matter development in infants born very preterm. If successful, the findings of this study may help to guide NICU clinical practice for promoting language and brain development. This clinical trial has the potential to advance theoretical understanding of how early language exposure directly changes brain structure for later language learning. TRIAL REGISTRATION: NIH Clinical Trials (ClinicalTrials.gov) NCT04193579 . Retrospectively registered on 10 December 2019.

Impact of the COVID-19 pandemic on developmental care practices for infants born preterm.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on rates of hospital visitation and rates and durations of developmental care practices for infants born preterm delivered by both families and clinical staff. METHODS: We analyzed electronic medical record data from infants born at less than 32 weeks gestational age (GA) cared for in the Lucile Packard Children's Hospital neonatal intensive care unit (NICU) in a COVID-19-affected period (March 8, 2020 to May 31, 2020) and the analogous period in 2019. Our final sample consisted of 52 infants ( n =27, 2019 cohort; n =25, 2020 cohort). Rates of family visitation and of family- and clinical staff-delivered developmental care were compared across cohorts, adjusting for GA at start of study period. RESULTS: Results indicated that families of infants in the 2020 cohort visited less frequently (47% of available days) than those in the 2019 cohort (97%; p =0.001). Infants received developmental care activities less frequently in the 2020 cohort (3.51 vs. 4.72 activities per day; p =0.04), with a lower number of minutes per day (99.91 vs. 145.14; p =0.04) and a shorter duration per instance (23.41 vs. 29.65; p =0.03). Similar reductions occurred in both family- and staff-delivered developmental care activities. CONCLUSIONS: The COVID-19 pandemic has negatively impacted family visitation and preterm infant developmental care practices in the NICU, both experiences associated with positive health benefits. Hospitals should create programs to improve family visitation and engagement, while also increasing staff-delivered developmental care. Careful attention should be paid to long-term follow up of preterm infants and families.

Neonatal white matter tract microstructure and 2-year language outcomes after preterm birth.

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.

Associations of Reading Efficiency with White Matter Properties of the Cerebellar Peduncles in Children.

Reading in children has been associated with microstructural properties of the cerebellar peduncles, the white matter pathways connecting the cerebellum to the cerebrum. In this study, we used two independent neuroimaging modalities to assess which features of the cerebellar peduncles would be associated with reading. Twenty-three 8-year-old children were evaluated on word reading efficiency and imaged using diffusion MRI (dMRI) and quantitative T1 relaxometry (qT1). We segmented the superior (SCP), middle, and inferior cerebellar peduncles and extracted two metrics: fractional anisotropy (FA) from dMRI and R1 from qT1. Tract-FA was significantly correlated with tract-R1 in left and right SCPs (left: rP(21) = .63, right: rP(21) = .76, p ≤ .001) suggesting that FA of these peduncles, at least in part, indexed myelin content. Tract-FA and tract R1 were not correlated in the other cerebellar peduncles. Reading efficiency negatively correlated with tract-FA of the left (rP(21) = - .43, p = .040) and right SCP (rP(21) = - .37, p = .079). Reading efficiency did not correlate with tract-R1 in the SCPs. The negative association of reading efficiency with tract-FA and the lack of association of reading efficiency with tract-R1 implicate properties other than myelin content as relevant to the information flow between the cerebellum and the cerebrum for individual differences in reading skills in children.

Assessing speech exposure in the NICU: Implications for speech enrichment for preterm infants.

OBJECTIVE: Quantify NICU speech exposure over multiple days in relation to NICU care practices. METHODS: Continuous measures of speech exposure were obtained for preterm infants (n = 21; 12 M) born <34 weeks gestational age in incubators (n = 12) or open cribs (n = 9) for 5-14 days. Periods of care (routine, developmental) and delivery source (family, medical staff, cuddler) were determined through chart review. RESULTS: Infants spent 13% of their time in Care, with >75% of care time reflecting developmental care. Speech counts were higher during care than no care, for mature vs. immature infants, and for infants in open cribs vs. incubators. Family participation in care ranged widely, with the highest speech counts occurring during periods of intentional voice exposure. CONCLUSIONS: Care activities represent a small portion of NICU experiences. Speech exposure during Developmental Care, especially with intentional voice exposure, may be an important source of stimulation. Implications for care practices are discussed.

The Atypical Patient With Slipped Capital Femoral Epiphyses May Be at Increased Risk for a Missed Contralateral Slip.

Slipped capital femoral epiphysis (SCFE) is a commonly encountered hip disorder. The goal of this study was to describe the incidence of missed contra-lateral SCFE as well as to identify risk factors. The authors hypothesized that contralateral slips are more often missed in patients with severe involvement of the treated side. After institutional review board approval was obtained, a retrospective chart review was performed of all pediatric patients who were treated for sequential and bilateral SCFE at a single institution during an 18-year period. Medical records were reviewed for demographic features and attending surgeon. Radiographs were reviewed for skeletal maturity, Klein's line, and severity of the treated slip. All radiographs were reviewed by 3 pediatric orthopedists. Contralateral SCFE was deemed present when consensus was achieved. Comparisons were made with Fisher's exact test, and P<.05 was considered significant. Of the records that were reviewed, 56 patients met the study criteria. Of these, 19 patients had bilateral involvement and 5 missed slips were identified (8.9%). The patients with missed disease tended to be younger (mean age, 10.8 vs 11.4 years), with a lower body mass index. Fellowship-trained pediatric surgeons were more likely to identify bilateral disease compared with orthopedists without pediatric training (P=.0065). A contralateral slip was more likely to be present in patients who had a positive finding for Klein's line (P<.0001). Severity of the treated slip did not increase the likelihood of missing a contralateral slip. Although Klein's line is a useful tool in the diagnosis of SCFE, a false-negative rate of 40% was observed. The authors recommend increased vigilance when an "atypical" patient with SCFE presents with unilateral disease. [Orthopedics. 2020;43(2):e114-e118.].

White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm.

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.

White Matter Plasticity in Reading-Related Pathways Differs in Children Born Preterm and at Term: A Longitudinal Analysis.

Children born preterm (PT) are at risk for white matter injuries based on complications of prematurity. They learn to read but on average perform below peers born full term (FT). Studies have yet to establish whether properties of white matter pathways at the onset of learning to read are associated with individual variation later in reading development in PT children. Here, we asked whether fractional anisotropy (FA) at age 6 years is associated with reading outcome at age 8 years in PT children in the same pathways as previously demonstrated in a sample of FT children. PT (n = 34, mean gestational age = 29.5 weeks) and FT children (n = 37) completed diffusion MRI and standardized measures of non-verbal IQ, language, and phonological awareness at age 6 years. Reading skills were assessed at age 8 years. Mean tract-FA was extracted from pathways that predicted reading outcome in children born FT: left arcuate fasciculus (Arc), bilateral superior longitudinal fasciculus (SLF), and left inferior cerebellar peduncle (ICP). We explored associations in additional pathways in the PT children: bilateral inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. Linear regression models examined whether the prediction of reading outcome at age 8 years based on mean tract-FA at age 6 years was moderated by birth group. Children born PT and FT did not differ significantly in tract-FA at age 6 years or in reading at age 8 years. Sex, socioeconomic status, and non-verbal IQ at age 6 years were associated with reading outcome and were included as covariates in all models. Birth group status significantly moderated associations between reading outcome and mean tract-FA only in the left Arc, right SLF, and left ICP, before and after consideration of pre-literacy skills. Microstructural properties of these cerebral and cerebellar pathways predicted later reading outcome in FT but not in PT children. Children born PT may rely on alternative pathways to achieve fluent reading. These findings have implications for plasticity of neural organization after early white matter injury.

More than myelin: Probing white matter differences in prematurity with quantitative T1 and diffusion MRI.

OBJECTIVE: We combined diffusion MRI (dMRI) with quantitative T1 (qT1) relaxometry in a sample of school-aged children born preterm and full term to determine whether reduced fractional anisotropy (FA) within the corpus callosum of the preterm group could be explained by a reduction in myelin content, as indexed by R1 (1/T1) from qT1 scans. METHODS: 8-year-old children born preterm (n = 29; GA 22-32 weeks) and full term (n = 24) underwent dMRI and qT1 scans. Four subdivisions of the corpus callosum were segmented in individual native space according to cortical projection zones (occipital, temporal, motor and anterior-frontal). Fractional anisotropy (FA) and R1 were quantified along the tract trajectory of each subdivision and compared across two birth groups. RESULTS: Compared to controls, preterm children demonstrated significantly decreased FA in 3 of 4 analyzed corpus callosum subdivisions (temporal, motor, and anterior frontal segments) and decreased R1 in only 2 of 4 corpus callosum subdivisions (temporal and motor segments). FA and RD were significantly associated with R1 within temporal but not anterior frontal subdivisions of the corpus callosum in the term group; RD correlated with R1 in the anterior subdivision in the preterm group only. CONCLUSIONS: Myelin content, as indexed by R1, drives some but not all of the differences in white matter between preterm and term born children. Other factors, such as axonal diameter and directional coherence, likely contributed to FA differences in the anterior frontal segment of the corpus callosum that were not well explained by R1.