[Neurodevelopmental follow-up of premature children in Lausanne and Geneva]. / Suivi neurodéveloppemental de l'enfant né prématuré dans l'Arc lémanique.

Preterm children born before 32 weeks of gestation represent 1% of the annual births in Switzerland, and are the most at risk of neurodevelopmental disabilities. A neurological surveillance is thus implemented in the neonatal units, and multidisciplinary neurodevelopmental follow-up is offered to all our preterm patients. The follow-up clinics of the University hospitals in Lausanne and Geneva follow the Swiss guidelines for follow-up. An extended history and neurological examination is taken at each appointment, and a standardized test of development is performed. These examinations, which take place between the ages of 3 months and 9 years old, allow the early identification and treatment of developmental disorders frequent in this population, such as motor, cognitive or behavioral disorders, as well as the monitoring of the quality of neonatal care.

[Erythropoietin and neuroprotection]. / Erythropoïétine et neuroprotection.

Erythropoietin (Epo) has long been recognised for its role in the control of erythropoiesis and therefore in the treatment of anemia including anemia of prematurity. The erythropoietin receptor (Epo-R) though is expressed in many other organs including the CNS. This review focuses on the role of erythropoietin during the development of the CNS and its potential role as a neuroprotective agent. Epo-R is expressed in many different cellules of the CNS during development including neural progenitor cells, neurons, astrocytes and oligodendrocytes. In the event of hypoxia CNS cells respond with increase of erythropoietin release with subsequent stimulation of neurogenesis through Epo-R on neural progenitor cells. In an Epo-R knock-out model therefore cerebral development is severely impaired. In models of hypoxia-ischemia exogenous Epo has been shown to reduce lesion size and improve structural and functional recovery. Human studies are emerging using Epo as a neuroprotective agent both for the term infant with hypoxia-ischemia as well as for the extremely preterm infant.

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).

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 factors.