Using nature to nurture: Breast milk analysis and fortification to improve growth and neurodevelopmental outcomes in preterm infants

Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth—particularly brain development—that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification—including targeted and adjusted fortification—show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants

Aberrant brain functional connectivity in newborns with congenital heart disease before cardiac surgery

Newborns with congenital heart disease (CHD) requiring open heart surgery are at increased risk for neurodevelopmental disabilities. Recent quantitative MRI studies have reported disrupted growth, microstructure, and metabolism in fetuses and newborns with complex CHD. To date, no study has examined whether functional brain connectivity is altered in this high-risk population after birth, before surgery. Our objective was to compare whole-brain functional connectivity of resting state networks in healthy, term newborns (n = 82) and in term neonates with CHD before surgery (n = 30) using graph theory and network-based statistics. We report for the first time intact global network topology – efficient and economic small world networks – but reduced regional functional connectivity involving critical brain regions (i.e. network hubs and/or rich club nodes) in newborns with CHD before surgery. These findings suggest the presence of early-life brain dysfunction in CHD which may be associated with neurodevelopmental impairments in the years following cardiac surgery. Additional studies are needed to evaluate the prognostic, diagnostic and surveillance potential of these findings

Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental perfusion imaging was performed using velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with whole-placenta coverage. In pregnancies with fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age; however, no such correlation was found in healthy pregnancies. Also, global placental perfusion was significantly higher in fetal CHD versus controls, in the lateral side-lying patient position versus supine, and in the posterior placental position versus anterior placental position. This study reports for the first time non-invasive whole-placenta perfusion imaging in utero. These data suggest that placental VSASL may serve as a potential biomarker of placental dysfunction in fetuses diagnosed with CHD

The long way to bilingualism: the peculiar case of multilingual South Tyrol

In the present contribution we discuss the challenges and the results of learning a second language in South Tyrol, the multilingual border region in northern Italy where the autochthonous German- and Ladinspeaking communities have cohabited with the Italian-speaking community since the end of the First World War. The picture resulting from the data collected in the Kolipsi project (Eurac/DiScoF), an extensive linguistic and psychosocial investigation about South Tyrolean secondary school pupils now in its second edition, gives precious inputs to all entities that intervene in the process of attitude formation and change, ranging from the family environment to politics.En el presente trabajo, debatimos los retos y los resultados del proceso de aprendizaje de segundas lenguas en el Tirol del Sur, la región fronteriza multilingüe del norte de Italia donde las comunidades autóctonas hablantes de alemán y ladino han convivido con la comunidad italohablante desde el fin de la Primera Guerra Mundial. La imagen resultante de los datos recogidos en el proyecto Kolipsi (Eurac/DiScoF), una investigación abarcadora tanto lingüística como psicosocial sobre alumnado de secundaria del Tirol del Sur, proporciona información muy valiosa a todas las entidades que intervienen en el proceso de la formación y el cambio de las actitudes, desde el entorno familiar hasta el ámbito de la política

Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI.

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental perfusion imaging was performed using velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with whole-placenta coverage. In pregnancies with fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age; however, no such correlation was found in healthy pregnancies. Also, global placental perfusion was significantly higher in fetal CHD versus controls, in the lateral side-lying patient position versus supine, and in the posterior placental position versus anterior placental position. This study reports for the first time non-invasive whole-placenta perfusion imaging in utero. These data suggest that placental VSASL may serve as a potential biomarker of placental dysfunction in fetuses diagnosed with CHD. © 2017 The Author(s)

Functional properties of resting state networks in healthy full-term newborns.

Objective, early, and non-invasive assessment of brain function in high-risk newborns is critical to initiate timely interventions and to minimize long-term neurodevelopmental disabilities. A prerequisite to identifying deviations from normal, however, is the availability of baseline measures of brain function derived from healthy, full-term newborns. Recent advances in functional MRI combined with graph theoretic techniques may provide important, currently unavailable, quantitative markers of normal neurodevelopment. In the current study, we describe important properties of resting state networks in 60 healthy, full-term, unsedated newborns. The neonate brain exhibited an efficient and economical small world topology: densely connected nearby regions, sparse, but well integrated, distant connections, a small world index greater than 1, and global/local efficiency greater than network cost. These networks showed a heavy-tailed degree distribution, suggesting the presence of regions that are more richly connected to others (\u27hubs\u27). These hubs, identified using degree and betweenness centrality measures, show a more mature hub organization than previously reported. Targeted attacks on hubs show that neonate networks are more resilient than simulated scale-free networks. Networks fragmented faster and global efficiency decreased faster when betweenness, as opposed to degree, hubs were attacked suggesting a more influential role of betweenness hub in the neonate network

Altered Cerebellar Biochemical Profiles in Infants Born Prematurely

This study aims to compare the cerebellar biochemical profiles in preterm (PT) infants evaluated at term equivalent age (TEA) and healthy full-term newborns using proton magnetic resonance spectroscopy (1H-MRS). We explore the associations between altered cerebellar metabolite profiles and brain injury topography, severity of injury, and prematurity-related clinical complications. We prospectively collected high quality 1H-MRS in 59 premature infants born ≤32 weeks and 61 healthy full term controls. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentration for N-acetyl-aspartate (NAA), choline (Cho) and creatine (Cr). PT infants had significantly lower cerebellar NAA (p \u3c 0.025) and higher Cho (p \u3c 0.001) at TEA when compared to healthy controls. Creatine was not different between the two groups. The presence of cerebellar injury was consistently associated with reduced concentrations for NAA, Cho, and Cr. Postnatal infection was negatively associated with NAA and Cr (p \u3c 005), while cerebral cortical brain injury severity was inversely associated with both Cho and Cr (p \u3c 0.01). We report for the first time that premature birth is associated with altered cerebellar metabolite profiles when compared to term born controls. Infection, cerebellar injury and supratentorial injury are important risk factors for impaired preterm cerebellar biochemistry

Regional microstructural organization of the cerebral cortex is affected by preterm birth.

Objectives: To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort. Study design: We prospectively enrolled very preterm infants (gestational age (GA) at birth\u3c32 \u3eweeks; birthweight\u3c1500 \u3eg) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI. Results: We studied 91 preterm infants at TEA and 69 full-term controls. Preterm infants demonstrated significantly higher diffusivity in the prefrontal, parietal, motor, somatosensory, and visual cortices suggesting delayed maturation of these cortical areas. Additionally, postnatal hydrocortisone treatment was related to accelerated microstructural organization in the prefrontal and somatosensory cortices. Conclusions: Preterm birth alters regional microstructural organization of the cerebral cortex in both neurocognitive brain regions and areas with primary sensory/motor functions. We also report for the first time a potential protective effect of postnatal hydrocortisone administration on cerebral cortical development in preterm infants

A Multidimensional Approach to Pain Assessment in Critically Ill Infants During a Painful Procedure

Objectives: Inferring the pain level of a critically ill infant is complex. The ability to accurately extract the appropriate pain cues from observations is often jeopardized when heavy sedation and muscular blocking agents are administered. Near-infrared spectroscopy is a noninvasive method that may provide the bridge between behavioral observational indicators and cortical pain processing. We aimed to describe regional cerebral and systemic hemodynamic changes, as well as behavioral reactions in critically ill infants with congenital heart defects during chest-drain removal after cardiac surgery. Methods: Our sample included 20 critically ill infants with congenital heart defects, less than 12 months of age, admitted to the cardiac intensive care unit after surgery. Results: Cerebral deoxygenated hemoglobin concentrations significantly differed across the epochs (ie, baseline, tactile stimulus, noxious stimulus) (P=0.01). Physiological systemic responses and Face Leg Activity Cry Consolability (FLACC) pain scores differed significantly across the events (P<0.01). The 3 outcome measures were not found to be associated with each other. Mean FLACC pain scores during the painful procedure was 7/10 despite administration of morphine. Midazolam administration accounted for 36% of the variance in pain scores. Discussion: We demonstrated with a multidimensional pain assessment approach that significant cerebral, physiological, and behavioral activity was present in response to a noxious procedure in critically ill infants despite the administration of analgesic treatment. Considering that the sedating agent significantly dampened pain behaviors, assessment of cerebral hemodynamic in the context of pain seems to be an important addition.National Institutes of Health (U.S.) (Grant R01EB001659)National Institutes of Health (U.S.) (Grant K24NS057568)National Institutes of Health (U.S.) (Grant R21HD056009)National Institute for Biomedical Imaging and Bioengineering (U.S.)National Institute of Neurological Disorders and Stroke (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.