Term-equivalent Age Research Articles

Brain injury in preterm infants with surgical necrotizing enterocolitis: clinical and bowel pathological correlates.

The objective of this study was to determine the risk factors and outcomes of white matter brain injury (WMBI) on magnetic resonance imaging (MRI) at term-equivalent age in infants with surgical necrotizing enterocolitis (NEC). This retrospective study compared clinical/pathological information between infants with and those without WMBI. Out of 69 infants with surgical NEC, 17 (24.6%) had mild WMBI, 13 (18.8%) had moderate WMBI, and six (8.7%) had severe WMBI on the brain MRI. Several clinical factors (gestational age, more red blood cell (RBC) transfusions before NEC onset, pneumoperitoneum, earlier NEC onset age, postoperative ileus, acute kidney injury (AKI) by serum creatinine, postnatal steroids, hospital stay) and histopathological findings (necrosis, hemorrhage) had univariate associations with WMBI. Associations with RBC transfusion (odds ratio (OR) 23.6 [95% confidence interval (CI): 4.73-117.97]; p = 0.0001), age at NEC onset (OR 0.30 [95%CI: 0.11-0.84]; p = 0.021), necrosis (OR 0.10 [95%CI: 0.01-0.90]; p = 0.040), and bowel hemorrhage (OR 7.79 [95%CI: 2.19-27.72]; p = 0.002) persisted in multivariable association with grade 3-4 WMBI. The infants with WMBI had lower mean motor, cognitive, language scores, and higher ophthalmic morbidity at 2 years of age. The WMBI was most likely associated with earlier NEC onset, higher RBC transfusions, and less necrosis and greater hemorrhage lesions on intestinal pathology in preterm infants with surgical NEC. In preterm infants with surgical NEC, brain MRI showed injury in the white matter in 52%, gray matter in 10%, and cerebellar region in 30%. Preterm infants with severe WMBI (grade 3-4) had less necrosis and greater hemorrhagic lesions on histopathology of the bowel. Preterm infants with WMBI were more likely to have a more severe postoperative course, AKI, and longer length of hospitalization. Neuroprotective strategies to prevent brain injury in preterm infants with surgical NEC are needed with the goal of improving the neurodevelopmental outcomes.

Brain Development and Maternal Behavior in Relation to Cognitive and Language Outcomes in Preterm-Born Children

Background: Children born very preterm (<=32 weeks gestational age) show poorer cognitive and language development compared to their term-born peers. The importance of positive maternal-child interactions for promoting neurodevelopment is well-established. However, little is known about whether sensitive maternal behaviors can buffer the association of early brain dysmaturation with cognitive and language performance. Methods: Infants born very preterm were recruited from the neonatal intensive care unit for a prospective, observational cohort study. Chart review was conducted prospectively from birth to discharge. MRI was acquired at ~32 weeks postmenstrual age and again at term-equivalent age, including diffusion tensor imaging. Fractional anisotropy, a quantitative measure of brain maturation, was obtained from 11 bilateral regions of interest in the cortical gray matter. At 3 years corrected age, neurodevelopmental testing (Bayley Scales of Infant & Toddler Development, Third Edition [Bayley-III]) was administered, and parent-child interaction was filmed. One hundred and forty-six infants with neonatal brain imaging and follow-up data were included for analysis. We examined whether maternal sensitivity interacted with mean fractional anisotropy values to predict Cognitive and Language scores at 3 years corrected age. Findings: Higher maternal sensitivity significantly moderated cortical fractional anisotropy values at term-equivalent age to predict higher Bayley-III Cognitive (s=1.72, P=0.05, R2=0.23), and Language Scores (s=1.91, P=0.03, R2=0.25). Interpretation: This suggests that positive parenting following early brain dysmaturation may provide an opportunity to support more optimal neurodevelopment in children born very preterm. Funding Information: Canadian Institutes for Health Research operating grant MOP-79262 (SPM) and MOP-86489 (REG). Declaration of Interests: The authors have no competing interests to disclose. Ethics Approval Statement: This study was approved by the Clinical Research Ethics Board at the University of British Columbia and BC Children’s and Women’s Hospitals. Parent written informed consent was obtained according to the Declaration of Helsinki.

Endogenous erythropoietin concentrations and association with retinopathy of prematurity and brain injury in preterm infants.

BackgroundEndogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is also a potential neuroprotectant.MethodsIn a prospective study of 27 infants ≤ 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring.ResultsLower birth weight was associated with higher EPO concentrations throughout the first 2 weeks of life (r = -0.6, p < 0.01). Higher day 1 and week 1 EPO concentrations were associated with lower Apgar score at 1 minute (r = - 0.5) and 5 minutes (r = -0.7), respectively (p < 0.01). Higher day 1 EPO concentrations and 2-week area under the curve were associated with increased risk (p = 0.01) and severity (r = 0.5, p < 0.02) of retinopathy of prematurity. Higher EPO concentrations at 2 weeks were associated with increased total brain injury score (r = 0.5, p < 0.05).ConclusionElevated endogenous erythropoietin concentrations in the first two weeks of life are associated with lower birth weight and increased risk of adverse outcomes.

Lipid Intake and Neurodevelopment in Preterm Infants.

Preterm infants are born before the critical period of lipid accretion and brain development that occurs during the third trimester of pregnancy. Dietary lipids serve as an important source of energy and are involved in complex processes that are essential for normal central nervous system development. In addition to traditional neurodevelopmental testing, novel quantitative magnetic resonance imaging (MRI) techniques are now available to evaluate the impact of nutritional interventions on early preterm brain development. Trials of long-chain polyunsaturated fatty acid supplementation have yielded inconsistent effects on neurodevelopmental outcomes and quantitative MRI findings. Recent studies using quantitative MRI suggest a positive impact of early lipid intake on brain volumes and white matter microstructural organization by term-equivalent age.

Associations Between Neonatal Brain Structure, the Home Environment, and Childhood Outcomes Following Very Preterm Birth

BackgroundVery preterm birth is associated with an increased risk of childhood psychopathology and cognitive deficits. However, the extent to which these developmental problems associated with preterm birth are amenable to environmental factors or determined by neurobiology at birth remains unclear. MethodsWe derived neonatal brain structural covariance networks using non-negative matrix factorization in 384 very preterm infants (median gestational age [range], 30.29 [23.57–32.86] weeks) who underwent magnetic resonance imaging at term-equivalent age (median postmenstrual age, 42.57 [37.86–44.86] weeks). Principal component analysis was performed on 32 behavioral and cognitive measures assessed at preschool age (n = 206; median age, 4.65 [4.19–7.17] years) to identify components of childhood psychopathology and cognition. The Cognitively Stimulating Parenting Scale assessed the level of cognitively stimulating experiences available to the child at home. ResultsCognitively stimulating parenting was associated with reduced expression of a component reflecting developmental psychopathology and executive dysfunction consistent with the preterm phenotype (inattention-hyperactivity, autism spectrum behaviors, and lower executive function scores). In contrast, a component reflecting better general cognitive abilities was associated with larger neonatal gray matter volume in regions centered on key nodes of the salience network, but not with cognitively stimulating parenting. ConclusionsOur results suggest that while neonatal brain structure likely influences cognitive abilities in very preterm children, the severity of behavioral symptoms that are typically observed in these children is sensitive to a cognitively stimulating home environment. Very preterm children may derive meaningful mental health benefits from access to cognitively stimulating experiences during childhood.

Sex differences in postnatal weight gain trajectories of extremely preterm newborns

ObjectiveBoth postnatal growth and sex play a crucial role in long-term outcomes of extremely preterm newborns (EPNs), but the relationship between sex and postnatal growth is not clear. This study aims to assess sex differences in weight trajectories.Study designWeight data in the first 200 days of life from 4327 EPNs were used for generalized additive mixed modeling. We considered gestational age and sex as fixed-effects, and included random intercepts and random slopes for postnatal age. We assessed interactions between fixed-effects and postnatal age.ResultsMale EPNs had higher predicted weight trajectories than females. Weight z-score trajectories decreased in both sexes before term-equivalent age comparably, but females showed faster increases afterward. Although weight gain velocity was comparable between both sexes, weight gain velocity in male EPNs was lower compared to the corresponding reference values from the 2013 Fenton growth charts, which explained slower z-score rises.ConclusionSex disparity exists in postnatal weight gain trajectories of EPNs after reaching the term-equivalent age.

Duration of mechanical ventilation is more critical for brain growth than postnatal hydrocortisone in extremely preterm infants

Hydrocortisone is used in preterm infants. However, early disruption of growth velocities was observed in infants exposed to hydrocortisone. This retrospective study aimed to explore the postnatal brain growth of extremely preterm infants requiring hydrocortisone treatment as well as its association with perinatal factors. Extremely preterm infants exposed to hydrocortisone from 2011 to 2016 who survived up to 12 months were included. Each of them was matched with two infants not treated with hydrocortisone exhibiting similar gestational ages and nearly similar birth head circumferences. The outcome variables were brain tissue areas on MRIs performed at term-equivalent age and postnatal head circumference growth up to a corrected age of 12 months. Univariate and multiple regression analyses were performed. Infants treated with hydrocortisone (n=20) were matched with 40 infants not exposed to hydrocortisone. The infants exposed to hydrocortisone exhibited a lower birth weight (p=0.04) and a longer duration of mechanical ventilation (p<0.0001). Infants treated with hydrocortisone exhibited a smaller basal ganglia/thalamus area (p=0.04) at term-equivalent age and a smaller head circumference at a corrected age of 12 months (p=0.003). However, the basal ganglia/thalamus area and the postnatal brain growth were independently associated with the duration of mechanical ventilation and not with hydrocortisone. Interestingly, a significant interaction between hydrocortisone and sex was observed (p=0.04).Conclusion: This study supports previous data that indicated no obvious impact of hydrocortisone on brain growth and highlights the relationship between the severity of the neonatal course and postnatal brain growth in extremely preterm infants. What is Known: • Postnatal hydrocortisone disrupts transiently growth velocities including the head circumference growth. • Postnatal hydrocortisone has less impact on neurodevelopment than dexamethasone. What is New: •Hydrocortisone prescribed for infants in the most severe conditions did not show independent effect on brain growth up to the corrected age of 12 months.However, a different effect of hydrocortisone according to sex can't be excluded and needs further explorations. •Perinatal factors as birth weight and duration of mechanical ventilation were determinant for the subsequent brain growth.

Association between body composition at term equivalent age and Bayley scores at 2 years in preterm infants.

To evaluate whether in a historical cohort of preterm infants, body composition at term equivalent age (TEA) correlated with Bayley scores at 2 years of corrected age. Ninety-five preterm babies were admitted to our neonatal intensive unit and underwent air-displacement plethysmography assessment at TEA. Of these, 74 completed Bayley tests at 2 years. We used multiple linear regression analysis to assess the association of body composition with Bayley scores. Mean gestational age and birthweight of our population were respectively 29.8 (±2.2) weeks and 1150 (±330) grams. Higher fat-free mass (FFM) z-score was associated with higher language (adjusted r = 0.28, p = 0.03) and motor composite scores (adjusted r = 0.33, p = 0.03) in both univariate and multiple regression analysis including birth weight, sex, maternal university degree, mechanical ventilation, and bilingualism. In our study FFM at term equivalent age was associated with higher Bayley composite motor and language scores at 2 years.

Diffusion MRI Microstructural Abnormalities at Term-Equivalent Age Are Associated with Neurodevelopmental Outcomes at 3 Years of Age in Very Preterm Infants.

Microstructural white matter abnormalities on DTI using Tract-Based Spatial Statistics at term-equivalent age are associated with cognitive and motor outcomes at 2 years of age or younger. However, neurodevelopmental tests administered at such early time points are insufficiently predictive of mild-moderate motor and cognitive impairment at school age. Our objective was to evaluate the microstructural antecedents of cognitive and motor outcomes at 3 years' corrected age in a cohort of very preterm infants. We prospectively recruited 101 very preterm infants (<32 weeks' gestational age) and performed DTI at term-equivalent age. The Differential Ability Scales, 2nd ed, Verbal and Nonverbal subtests, and the Bayley Scales of Infant and Toddler Development, 3rd ed, Motor subtest, were administered at 3 years of age. We correlated DTI metrics from Tract-Based Spatial Statistics with the Bayley Scales of Infant and Toddler Development, 3rd ed, and the Differential Ability Scales, 2nd ed, scores with correction for multiple comparisons. Of the 101 subjects, 84 had high-quality DTI data, and of these, 69 returned for developmental testing (82%). Their mean (SD) gestational age was 28.4 (2.5) weeks, and birth weight was 1121.4 (394.1) g. DTI metrics were significantly associated with Nonverbal Ability in the corpus callosum, posterior thalamic radiations, fornix, and inferior longitudinal fasciculus and with Motor scores in the corpus callosum, internal and external capsules, posterior thalamic radiations, superior and inferior longitudinal fasciculi, cerebral peduncles, and corticospinal tracts. We identified widespread microstructural white matter abnormalities in very preterm infants at term that were significantly associated with cognitive and motor development at 3 years' corrected age.

Structural Changes in the Cortico-Ponto-Cerebellar Axis at Birth are Associated with Abnormal Neurological Outcomes in Childhood.

White matter lesions in hypoxic-ischemic encephalopathy (HIE) are considered to be the important substrate of frequent neurological consequences in preterm infants. The aim of the study was to analyze volumes and tractographic parameters of the cortico-ponto-cerebellar axis to assess alterations in the periventricular fiber system and crossroads, corticopontine and corticospinal pathways and prospective transsynaptic changes of the cerebellum.Term infants (control), premature infants without (normotypic) and with perinatal HIE (HIE) underwent brain magnetic resonance imaging at term-equivalent age (TEA) and at 2 years. Cerebrum, cerebellum, brainstem divisions and ventrodorsal compartments volumetric analysis were performed, as well as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of corticopontine, corticospinal pathways and middle cerebellar peduncles. Amiel-Tison scale at TEA and the Hempel test at 2 years were assessed.Cerebellum, brainstem and its compartments volumes were decreased in normotypic and HIE groups at TEA, while at 2 years volumes were significantly reduced in the HIE group, accompanied by decreased volume and FA and increased ADC of corticopontine and corticospinal pathways. Negative association of the brainstem, cerebellum, mesencephalon, pons, corticopontine volumes and corticospinal pathway FA at TEA with the neurological score at 2 years. Cerebellum and pons volumes presented as potential prognostic indicators of neurological outcomes.Our findings agree that these pathways, as a part of the periventricular fiber system and crossroads, exhibit lesion-induced reaction and vulnerability in HIE. Structural differences between normotypic and HIE group at the 2 years suggest a different developmental structural plasticity.

Safety and Efficacy of Early High Parenteral Lipid Supplementation in Preterm Infants: A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis was to summarize the effects of early initiation and achievement of a high dose of parenteral lipids (≥1.5 g/kg/day reached within the first 24 h of birth) on growth and adverse outcomes in preterm infants. PubMed, EMBASE, and Cochrane databases were utilized to search for publications for this meta-analysis. Randomized controlled trials were eligible if data on growth or clinical outcome was available. The search returned nine studies. The mean proportion of postnatal weight loss (%) was lower (mean difference [MD]: −2.73; 95% confidence interval [CI]: −3.69, −1.78), and the mean head circumference near the term equivalent age (cm) was higher in the early high lipid treatment group (MD: 0.67; 95% CI: 0.25, 1.09). There was a favorable association of early high lipid administration with the incidence of extrauterine growth restriction (relative risk [RR]: 0.27; 95% CI: 0.15, 0.48). Generally, there were no differences in morbidities or adverse outcomes with early high lipid administration. Early initiation of parenteral lipids and high dose achieved within the first 24 h of life appear to be safe and endurable and offer benefits in terms of growth.

White matter analysis of the extremely preterm born adult brain

The preterm brain has been analysed after birth by a large body of neuroimaging studies; however, few studies have focused on white matter alterations in preterm subjects beyond infancy, especially in individuals born at extremely low gestation age - before 28 completed weeks. Neuroimaging data of extremely preterm young adults are now available to investigate the long-term structural alterations of disrupted neurodevelopment. We examined white matter hierarchical organisation and microstructure in extremely preterm young adults. Specifically, we first identified the putative hubs and peripheral regions in 85 extremely preterm young adults and compared them with 53 socio-economically matched and full-term born peers. Moreover, we analysed Fractional Anisotropy (FA), Mean Diffusivity (MD), Neurite Density Index (NDI), and Orientation Dispersion Index (ODI) of white matter in hubs, peripheral regions, and over the whole brain. Our results suggest that the hierarchical organisation of the extremely preterm adult brain remains intact. However, there is evidence of significant alteration of white matter connectivity at both the macro- and microstructural level, with overall diminished connectivity, reduced FA and NDI, increased MD, and comparable ODI; suggesting that, although the spatial configuration of WM fibres is comparable, there are less WM fibres per voxel. These alterations are found throughout the brain and are more prevalent along the pathways between deep grey matter regions, frontal regions and cerebellum. This work provides evidence that white matter abnormalities associated with the premature exposure to the extrauterine environment not only are present at term equivalent age but persist into early adulthood.

Suppression of breathing by Gram‐positive bacterial proteins in neonatal Sprague Dawley rat pups

Preterm infants regularly present with immature and unstable respiratory control networks at birth leading to oxygen dysregulation in the newborn (Hofstetter et al., 2007). Sequentially, the requirement for prolonged medical support and hospital stays increases the risk of late-onset infection. Hypoxic stress during early life can alter central networks that control the cardiorespiratory system with profound autonomic dysregulation. We hypothesised that chronic neonatal exposure to intermittent hypoxia and hyperoxia (cIHH) with subsequent Gram-positive bacterial infection alters respiratory control. On postnatal day (PND) three, Sprague Dawley litters were exposed for 10 days to either cIHH or room air gas exposure. On PND13, pups were studied using whole body plethysmography at 30◦C. After an initial acclimatisation period, a baseline normoxic measurement was taken. Following intraperitoneal administration of lipoteichoic acid and peptidoglycan (LTA+PGN) or pyro-free saline (n=10 per group), animals were monitored for 3 hours under normoxic conditions. Oxygen dysregulation in early life in and of itself, did not alter breathing frequency (P=0.37) or minute ventilation (P=0.07). Administration of LTA+PGN suppressed breathing as shown by a decrease in frequency and minute ventilation (both P<0.05). Furthermore, administration of LTA+PGN on PND13 increased cytokine expression in both sexes as well as corticosterone concentration in male pups compared to relevant controls. Administration of LTA+PGN did not significantly alter rectal temperature compared to controls. Neonatal infection remains a significant challenge, with a paucity of studies investigating the response to Gram-positive bacterial proteins despite its clinical relevance. We report that Gram-positive bacterial proteins can quickly suppress breathing frequency and elicit both an inflammatory and stress response. Further studies are necessary to elucidate the mechanisms underlying aberrant respiratory control. References Hofstetter AO, Legnevall L & Ericherleniuskise EH (2007). Cardiorespiratory development in extremely preterm infants: vulnerability to infection and persistence of events beyond term-equivalent age. 285–292.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI–) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI– PWMLs.Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database.Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively).Conclusions: Our results suggest a nosological difference between SWI+ and SWI– PWMLs. Other prospective studies are warranted to corroborate these observations.

Secondary somatosensory cortex evoked responses and 6-year neurodevelopmental outcome in extremely preterm children

ObjectiveWe assessed in extremely preterm born (EPB) children whether secondary somatosensory cortex (SII) responses recorded with magnetoencephalography (MEG) at term-equivalent age (TEA) correlate with neurodevelopmental outcome at age 6 years. Secondly, we assessed whether SII responses differ between 6-year-old EPB and term-born (TB) children. Methods39 EPB children underwent MEG with tactile stimulation at TEA. At age 6 years, 32 EPB and 26 TB children underwent MEG including a sensorimotor task requiring attention and motor inhibition. SII responses to tactile stimulation were modeled with equivalent current dipoles. Neurological outcome, motor competence, and general cognitive ability were prospectively evaluated at age 6 years. ResultsUnilaterally absent SII response at TEA was associated with abnormal motor competence in 6-year-old EPB children (p = 0.03). At age 6 years, SII responses were bilaterally detectable in most EPB (88%) and TB (92%) children (group comparison, p = 0.69). Motor inhibition was associated with decreased SII peak latencies in TB children, but EPB children lacked this effect (p = 0.02). ConclusionsUnilateral absence of an SII response at TEA predicted poorer motor outcome in EPB children. SignificanceNeurophysiological methods may provide new means for outcome prognostication in EPB children.

Update on Calcium and Phosphorus Requirements of Preterm Infants and Recommendations for Enteral Mineral Intake

Background: With current Ca and P recommendations for enteral nutrition, preterm infants, especially VLBW, fail to achieve a bone mineral content (BMC) equivalent to term infants. During the first 3 years, most notably in light at term equivalent age (<−2 Z score) VLBW infants’ BMC does not catch up. In adults born preterm with VLBW or SGA, lower adult bone mass, lower peak bone mass, and higher frequency of osteopenia/osteoporosis have been found, implying an increased risk for future bone fractures. The aim of the present narrative review was to provide recommendation for enteral mineral intake for improving bone mineral accretion. Methods: Current preterm infant mineral recommendations together with fetal and preterm infant physiology of mineral accretion were reviewed to provide recommendations for improving bone mineral accretion. Results: Current Ca and P recommendations systematically underestimate the needs, especially for Ca. Conclusion: Higher enteral fortifier/formula mineral content or individual supplementation is required. Higher general mineral intake (especially Ca) will most likely improve bone mineralization in preterm infants and possibly the long-term bone health. However, the nephrocalcinosis risk may increase in infants with high Ca absorption. Therefore, individual additional enteral Ca and/or P supplementations are recommended to improve current fortifier/formula mineral intake.

Seizure burden in preterm infants and smaller brain volume at term-equivalent age.

Background:Seizures are underrecognized in preterm infants, and little is known about their impact on brain growth. We aimed to define the association between early seizures and subsequent brain growth.Methods:Infants <30 weeks’ gestation underwent 72h of prospective aEEG monitoring, term-equivalent age (TEA) MRI, and 2y neurodevelopmental testing.Seizures were defined as trains of sharp waves >10 seconds, evolving in frequency/amplitude/morphology, and identified using automated algorithms with manual review.Using T2-weighted images, cortical surface area (CSA) and gyrification index (GI) were calculated and volumes were segmented into five tissue classes: CSF, gray matter, white matter (WM), deep nuclear gray matter, and cerebellum. Correlations between total seizure burden and tissue-specific volumes were evaluated, controlling for clinical variables of interest.Results:Ninety-nine infants underwent aEEG/MRI assessments (mean GA=26.3 weeks, birthweight=899g). Seizure incidence was 55% with a median of two events; median length=66s and mean burden=285s.Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (R2=−0.603, p<.01), even after controlling for confounders. There was no association with GI.Conclusion:Seizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors.

Identifying Emergent Mesoscopic-Macroscopic Functional Brain Network Dynamics in Infants at Term-Equivalent Age with Electric Source Neuroimaging.

Aim: To identify and characterize the functional brain networks at the time when the brain is yet to develop higher order functions in term-born and preterm infants at term-equivalent age. Introduction: Although functional magnetic resonance imaging (fMRI) data have revealed the existence of spatially structured resting-state brain activity in infants, the temporal information of fMRI data limits the characterization of fast timescale brain oscillations. In this study, we use infants' high-density electroencephalography (EEG) to characterize spatiotemporal and spectral functional organizations of brain network dynamics. Methods: We used source-reconstructed EEG and graph theoretical analyses in 100 infants (84 preterm, 16 term born) to identify the rich-club topological organization, temporal dynamics, and spectral fingerprints of dynamic functional brain networks. Results: Five dynamic functional brain networks are identified, which have rich-club topological organizations, distinctive spectral fingerprints (in the delta and low-alpha frequency), and scale-invariant temporal dynamics (<0.1 Hz): The default mode, primary sensory-limbic system, thalamo-frontal, thalamo-sensorimotor, and visual-limbic system. The temporal dynamics of these networks are correlated in a hierarchically leading-following organization, showing that infant brain networks arise from long-range synchronization of band-limited cortical oscillation based on interacting fast- and slow-coherent cortical oscillations. Conclusion: Dynamic functional brain networks do not solely depend on the maturation of cognitive networks; instead, the brain network dynamics exist in infants at term age well before the childhood and adulthood, and hence, it offers a quantitative measurement of neurotypical development in infants. Clinical Trial Registration Number: ACTRN12615000591550. Impact statement Our work offers novel functional insights into the brain network characterization in infants, providing a new functional basis for future deployable prognostication approaches.

Exploring the relationship between maternal prenatal stress and brain structure in premature neonates.

Exposure to maternal stress in utero is associated with a range of adverse outcomes. We previously observed an association between maternal stress and white matter microstructure in a sample of infants born prematurely. In this study, we aimed to investigate the relationship between maternal trait anxiety, stressful life events and brain volumes. 221 infants (114 males, 107 females) born prematurely (median gestational age = 30.43 weeks [range 23.57-32.86]) underwent magnetic resonance imaging around term-equivalent age (mean = 42.20 weeks, SD = 1.60). Brain volumes were extracted for the following regions of interest: frontal lobe, temporal lobe, amygdala, hippocampus, thalamus and normalized to total brain volume. Multiple linear regressions were conducted to investigate the relationship between maternal anxiety/stress and brain volumes, controlling for gestational age at birth, postmenstrual age at scan, socioeconomic status, sex, days on total parenteral nutrition. Additional exploratory Tensor Based Morphometry analyses were performed to obtain voxel-wise brain volume changes from Jacobian determinant maps. In this large prospective study, we did not find evidence of a relationship between maternal prenatal stress or trait anxiety and brain volumes. This was the case for both the main analysis using a region-of-interest approach, and for the exploratory analysis using Jacobian determinant maps. We discuss these results in the context of conflicting evidence from previous studies and highlight the need for further research on premature infants, particularly including term-born controls.

Predicting the developmental outcomes of very premature infants via ultrasound classification: A CONSORT - clinical study.

Objective:This study aimed to assess the accuracy of ultrasonic grading in determining brain injury in very premature infants and analyze the affecting factors of these neonatal morbidity and mortality, and to investigate the relationship between serial cranial ultrasound (cUS) classification and Mental Developmental Index (MDI)/Psychomotor Developmental Index (PDI) in premature infants.Methods:A total of 129 very preterm infants (Gestational Age ≤ 28 weeks) were subjected to serial cUS until 6 months or older and classified into 3 degrees in accordance with classification standards. The MDI and PDI (Bayley test) of the infants were measured until the infants reached the age of 24 months or older. The consistency between Term Equivalent Age (TEA)-cUS and TEA- magnetic resonance imaging (MRI) was calculated. Ordinal regression was performed to analyze the relationship among severe disease, early cUS classifications, psychomotor and mental development, and death. Operating characteristic curve were used to analyze the relationship between serial cUS grades and MDI/PDI scores.Results:The mortality and survival rates of 129 very preterm infants were 32.8% and 67.3%, respectively. Among the 86 surviving infants, 20.9% developed mild cerebral palsy (CP) and 5.8% to 6.9% developed severe CP. The consistency between TEA-cUS and TEA-MRI was 88%. Grades 2 and 3 at first ultrasound were associated with adverse mental (OR = 3.2, OR = 3.78) and motor (OR = 2.25, OR = 2.59) development. cUS classification demonstrated high sensitivity (79%–96%). Among all cUS classifications, the specificity of the first cUS was the lowest and that of TEA-cUS was the highest (57% for PDI and 48% for MDI).Conclusions:Moderate and severe brain injury at first ultrasound is the most important factor affecting the survival rate and brain development of very premature infants. The cUS classification had high sensitivity and high specificity for the prediction of CP, especially in TEA-cUS.