Mapping the Early Cortical Folding Process in the Preterm Newborn Brain

In the developing human brain, the cortical sulci formation is a complex process starting from 14 weeks of gestation onward. The potential influence of underlying mechanisms (genetic, epigenetic, mechanical or environmental) is still poorly understood, because reliable quantification in vivo of the early folding is lacking. In this study, we investigate the sulcal emergence noninvasively in 35 preterm newborns, by applying dedicated postprocessing tools to magnetic resonance images acquired shortly after birth over a developmental period critical for the human cortex maturation (26-36 weeks of age). Through the original three-dimensional reconstruction of the interface between developing cortex and white matter and correlation with volumetric measurements, we document early sulcation in vivo, and quantify changes with age, gender, and the presence of small white matter lesions. We observe a trend towards lower cortical surface, smaller cortex, and white matter volumes, but equivalent sulcation in females compared with males. By precisely mapping the sulci, we highlight interindividual variability in time appearance and interhemispherical asymmetries, with a larger right superior temporal sulcus than the left. Thus, such an approach, included in a longitudinal follow-up, may provide early indicators on the structural basis of cortical functional specialization and abnormalities induced by genetic and environmental factor

Primary cortical folding in the human newborn: an early marker of later functional development

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early ‘endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB

Global and Regional Differences in Brain Anatomy of Young Children Born Small for Gestational Age

In children who are born small for gestational age (SGA), an adverse intrauterine environment has led to underdevelopment of both the body and the brain. The delay in body growth is (partially) restored during the first two years in a majority of these children. In addition to a negative influence on these physical parameters, decreased levels of intelligence and cognitive impairments have been described in children born SGA. In this study, we used magnetic resonance imaging to examine brain anatomy in 4- to 7-year-old SGA children with and without complete bodily catch-up growth and compared them to healthy children born appropriate for gestational age. Our findings demonstrate that these children strongly differ on brain organisation when compared with healthy controls relating to both global and regional anatomical differences. Children born SGA displayed reduced cerebral and cerebellar grey and white matter volumes, smaller volumes of subcortical structures and reduced cortical surface area. Regional differences in prefrontal cortical thickness suggest a different development of the cerebral cortex. SGA children with bodily catch-up growth constitute an intermediate between those children without catch-up growth and healthy controls. Therefore, bodily catch-up growth in children born SGA does not implicate full catch-up growth of the brain

Avaliação longitudinal do desenvolvimento motor e da habilidade de sentar em crianças nascidas prematuras

Os bebês prematuros apresentam maior risco para atrasos na aquisição das habilidades neuromotoras. O objetivo do estudo foi detectar atrasos no desenvolvimento motor de crianças prematuras com baixo peso, analisar a evolução da habilidade do sentar e verificar a associação entre essa habilidade com outras aquisições motoras até os 8 meses de idade corrigida (IC). Foram avaliadas 10 crianças nascidas pré-termo, de ambos os sexos, dos 4 aos 8 meses de IC, pela escala motora infantil de Alberta AIMS (Alberta Infant Motor Scale). Cada criança foi avaliada três vezes, aos 4 para 5 meses, 5 para 6 meses, e 7 para 8 meses; os escores foram comparados para verificar alterações ao longo do tempo e identificação de possíveis atrasos no desenvolvimento motor. Os resultados mostram que, aos 7 para 8 meses, 30% das crianças apresentaram desenvolvimento motor atrasado e foram encaminhadas para tratamento fisioterapêutico. A habilidade de sentar foi melhorando progressiva e significativamente com a idade, tendo se mostrado fortemente correlacionada com outras posturas do desenvolvimento motor e com o escore total na AIMS.Preterm-born infants present higher risks of delayed neuromotor development. This study aimed at detecting delayed motor development in preterm, low-birthweight infants, by analysing development of the sitting skill in association to other motor development acquisitions until corrected age (CA) of 8 months. Ten preterm infants of both sexes were assessed by the AIMS - Alberta Infant Motor Scale from ages 4 to 8 months. Each child was evaluated three times, at 4-to-5 months, 5-to-6 months, and at 7-to-8 months CA; their scores were compared to verify changes over time and identify possible delays in motor development. Results show that at the age of 7-to-8 months, 30% of the children had delayed motor development and were referred for physical therapy treatment. The pace of sitting skill development increased gradually and significantly along the age; and strong correlations were found between the ability to sit and other motor development postures, and the total AIMS score

La naissance, un moment particulier à haut risque

This reflective practice paper looks at how reporting, a component of monitoring and evaluation, contributes to organizational learning and decision-making at the Aga Khan Foundation U.S.A (AKF USA). The scope is a monetization grant that sells nonfat dry milk powder donated by the U.S. Department of Agriculture (USDA) to fund an Education Dairy and Nutrition Program (EDNP) in Tajikistan. I found out that learning and action in response to learning occur at AKF USA by exchanging with the grant manager, one of its coordinator and a representative from USDA, the donor. AKF USA has made changes to the EDNP’s objectives and activities from learning from this program’s reports to improve its operations, communication with donor, and implementing partners. It is a learning organization that is still working on better measuring the impact of this 5 year program, and improving its reporting system. The program design is congruent with the foundation’s integrated approach to development that combines activities to generate changes for the communities it serves. Congruence with its claimed participatory approach needs to be determined given the design process from the headquarters to the field, the impossibility to indicate whether the program recipients are fully involved in decision-making beyond implementation, and will be able to sustain it after graduating from the foundation’s assistance

A single dose of antenatal betamethasone enhances isoprenaline and prostaglandin E2-induced relaxation of preterm ovine pulmonary arteries

Beta-adrenergic agonists and prostaglandin E2 (PGE2) play an important role in perinatal pulmonary circulation. We have determined the effect of antenatal glucocorticoid treatment on isoprenaline- and PGE2-mediated relaxation of pulmonary arteries of newborn preterm lambs. Ovine fetuses (121 days of gestation; term = 150 days) received a single intramuscular dose of betamethasone (0.5 mg/kg) or saline. Fifteen hours after the injection, the lambs were delivered, ventilated for 3 h, and sacrificed. The fourth-generation pulmonary arteries were dissected and cut into rings for study. In endothelin-1-preconstricted vessels, isoprenaline, PGE2, and forskolin (an activator of adenylyl cyclase) induced greater relaxations of pulmonary arteries of betamethasone-treated lambs than those of controls. 8-Bromo-cyclic adenosine monophosphate, a cell membrane permeable analogue of cyclic adenosine monophosphate, caused similar relaxation of all vessels. When stimulated with isoprenaline and PGE2, the adenylyl cyclase activity of crude membrane preparations of pulmonary arteries treated with betamethasone was greater than that of controls. These results show that single-dose antenatal betamethasone treatment enhances relaxation of pulmonary arteries of preterm lambs induced by isoprenaline and PGE2 and that an enhanced adenylyl cyclase activity contributes to the effect of betamethasone on pulmonary arteries of preterm lambs

Role of protein kinase G in nitric oxide- and cGMP-induced relaxation of newborn ovine pulmonary veins

In a variety of systemic blood vessels, protein kinase G (PKG) plays a critical role in mediating relaxation induced by agents that elevate cGMP, such as nitric oxide. The role of PKG in nitric oxide- and cGMP-induced relaxation is less certain in the pulmonary circulation. In the present study, we examined the effects of inhibitors of PKG on the responses of isolated fourth-generation pulmonary veins of newborn lambs (10 +/- 1 days of age) to nitric oxide and cGMP. In vessels preconstricted with endothelin-1, nitric oxide and 8-bromo-cGMP (a cell-membrane-permeable cGMP analog) induced concentration-dependent relaxation. The relaxation was significantly attenuated by beta-phenyl-1, N(2)-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate (Rp-8-Br-PET-cGMPS; a PKG inhibitor) and N-[2-(methylamino)ethyl]5-isoquinolinesulfonamide [H-8; an inhibitor of PKG and protein kinase A (PKA)] but was not affected by KT-5720 (a PKA inhibitor). Biochemical study showed that PKG activity in newborn ovine pulmonary veins was inhibited by 8-Br-PET-cGMPS and H-8 but not by KT-5720. PKA activity was not affected by 8-Br-PET-cGMPS but was inhibited by H-8 and KT-5720. These results suggest that PKG is involved in relaxation of pulmonary veins of newborn lambs induced by nitric oxide and cGMP