Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a "rich club"-a high-cost, highcapacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical-subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants.connectome | brain development | tractography | preterm birth T o understand the functional properties of a complex network it is necessary to examine its structural organization and topological properties. In the human brain this can be achieved at a macroscale by tracing white matter connections between brain regions with diffusion MRI; this enables the interrogation of structural network topology in vivo with millimeter-scale spatial resolution, providing complementary evidence to experimental studies (1, 2).Network analysis of the adult human structural connectome has revealed a set of highly connected cortical "hubs" predominantly located in heteromodal association cortex, that provide a foundation for coherent neuronal activation across distal cortical regions (3-5). Further, some hub regions tend to be densely connected to each other, forming a "rich club" comprised of frontal and parietal cortex, precuneus, cingulate and the insula, as well as the hippocampus, thalamus, and putamen (6). Rich-club organization has been identified in a number of complex networks (7) and represents an attractive feature for investigation in the brain because rich-club connections tend to dominate network topology (8). Rich-club architecture appears to be a fundamental feature of the mature mammalian brain with similar organization identified in animal models (9, 10).It has been suggested that the emergence of complex neurological function is associated with the integration of major hubs across the cortex (11,...

AIDS Acquired immunodeficiency syndrome ART Antiretroviral therapy BINS Bayley Infant NeurodevelopmentalScreener HIV Human immunodeficiency virus NDI Neurodevelopmental impairment PMTCT Prevention of mother-to-child transmission AIM The aim of this article is to document the risk of neurodevelopmental impairment (NDI) among infants enrolled in a programme for the prevention of mother-to-child transmission of HIV (human immunodeficiency virus) in Zimbabwe using the Bayley Infant Neurodevelopmental Screener (BINS).METHOD We prospectively followed up infants at three primary care clinics in Harare, Zimbabwe.Neurodevelopmental assessments using the BINS were conducted during the first 12 months of life. NDI risk category and associated risk factors were examined. RESULTSOf the 598 infants assessed, 305 (51%) were female and 293 (49%) were male. Sixty-five infants (11%) were infected with HIV, 188 (31%) were exposed but uninfected, 287 (48%) were unexposed, and 58 (10%) were of unknown status. The prevalence of a high risk of NDI was 9.4% (95% confidence interval [CI] 7.1-11.1%): 9.2% in males and 9.6% in females. Of the 598 infants, 549 (92%) had ever been breastfed, 49% of whom had mothers infected with HIV.

Enteral feeding, in particular with formula feeds, is associated with necrotizing enterocolitis (NEC). In this study, we have examined, in the systemic and mucosal immune compartments, for evidence of bovine milk antigen sensitization in infants with NEC. Eleven newborns with Bell’s staging 2–3 NEC [median post‐conceptional age 31 wk (range 27–41 wk)], 21 neonatal controls [33 (28–40) wk] and 15 infants undergoing intestinal resection or mucosal biopsy for non‐inflammatory conditions [39 (34–42) wk] were studied. Spontaneous and antigen or mitogen elicited interferon‐γ (IFN‐γ) [T‐helper type I (Th1)], interleukin (IL)‐4 and IL‐5 [T‐helper type II (Th2)] responses were enumerated using single‐cell enzyme‐linked immunospot (ELISPOT) assay in peripheral blood (PBMC) or lamina propria mononuclear cells. NEC infants, compared with controls, showed a significant elevation in baseline PBMC cytokine secreting cells, vigorous mitogen responses (20‐ to 120‐fold increase) for IFN‐γ, IL‐4 and IL‐5 (p < 0.001), strong responses to beta‐lactoglobulin (βlg) (IFN‐γ > IL‐4/IL‐5, p ≤ 0.001), and somewhat smaller casein responses. Similarly, in the lamina propria, a small but significant increase in spontaneous cytokine‐secreting cells was detected in NEC infants (p < 0.01), with an IFN‐γ/IL‐4 predominant phytohemagglutinin (PHA)/concanavalin‐A (ConA) response. Three of nine NEC infants (but no controls) also showed a positive ELISPOT response to βlg (IFN‐γ only) but none to casein. We have thus demonstrated significant cow’s milk protein (CMP) sensitization in NEC, at least in the systemic compartment (mixed Th1/Th2), with minimal mucosal activation in some cases. These novel findings provide a potential mechanism for a direct contributory role of CMP in the pathogenesis of NEC.

In this study, healthy women and those at high-risk of adverse pregnancy outcomes (pre-eclampsia, fetal growth restriction, gestational diabetes) were selected to assess the effect of fatty acid supplementation. The purpose of this paper is to report two novel findings (i) at recruitment the receiver operating characteristic (ROC) for erythrocyte oleic acid predicted spontaneous delivery at 34 weeks gestation (ROC=0.926 n=296) for all women entering the study. Further analysis revealed oleic and all monounsaturated fatty acids were similarly predictive with or without a supplement during the pregnancy. (ii) At delivery, we observed a biomagnification of saturated fatty acids from mother to fetus with the reverse for monounsaturates. The major conclusions are (i) the status of the mother in the months prior to conception is a stronger predictor of preterm delivery than the events during the pregnancy. (ii) Saturated fats may be playing an important function in supporting fetal membrane growth.