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.

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.

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.

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.

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.

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.

Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn's disease.

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.

Bone density, structure, and strength in juvenile idiopathic arthritis: importance of disease severity and muscle deficits.

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.

Assessment of spine bone mineral density in juvenile idiopathic arthritis: impact of scan projection.

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.