Placental insufficiency with fetal intrauterine growth restriction (IUGR) is an important cause of perinatal mortality and morbidity and is subsequently associated with significant neurodevelopmental impairment in cognitive function, attention capacity, and school performance. The underlying biologic cause for this association is unclear. Twenty-eight preterm infants (gestational age 32.5 Ϯ 1.9 wk) were studied by early and term magnetic resonance imaging (MRI). An advanced quantitative volumetric three-dimensional MRI technique was used to measure brain tissue volumes in 14 premature infants with placental insufficiency, defined by abnormal antenatal Doppler measurements and mean birth weights Ͻ10 th percentile (1246 Ϯ 299 g) (IUGR) and in 14 preterm infants matched for gestational age with normal mean birth weights 1843 Ϯ 246 g (control). Functional outcome was measured at term in all infants by a specialized assessment scale of preterm infant behavior. Premature infants with IUGR had a significant reduction in intracranial volume (mean Ϯ SD: 253.7 Ϯ 29.9 versus 300.5 Ϯ 43.5 mL, p Ͻ 0.01) and in cerebral cortical gray matter (mean Ϯ SD: 77.2 Ϯ 16.3 versus 106.8 Ϯ 24.6 mL, p Ͻ 0.01) when measured within the first 2 wk of life compared with control premature infants. These findings persisted at term with intracranial volume (mean Ϯ SD: 429.3 Ϯ 47.9 versus 475.9 Ϯ 53.4 mL, p Ͻ 0.05) and cerebral cortical gray matter (mean Ϯ SD: 149.3 Ϯ 29.2 versus 189 Ϯ 34.2 mL, p Ͻ 0.01). Behavioral assessment at term showed a significantly less mature score in the subsystem of attention-interaction availability in IUGR infants (p Ͻ 0.01). Cerebral cortical gray matter volume at term correlated with attention-interaction capacity measured at term (r ϭ 0.45, p Ͻ 0.05). These results suggest that placental insufficiency with IUGR have specific structural and functional consequences on cerebral cortical brain development. These findings may provide insight into the structural-functional correlate for the developmental deficits associated with IUGR. An increasing number of developmental disorders (1, 2) and diseases (3, 4) in child and adult life are thought to have their origin in the fetal period. Central to this predisposition is fetal growth (5). The fetus receives its nutrients from the maternal/ uterine circulation via the placenta. Any disturbance in the placental-fetal circulation will therefore have severe consequences on the supply of important nutrients such as oxygen, glucose, and amino acids (6). The placenta itself is also an active endocrine organ and, therefore, changes in nutrient availability will also affect placental and, potentially, fetal endocrine function, in particular, the modification of the hypothalamo-pituitary-adrenal axis (7,8). Placental insufficiency, which is the most common cause of IUGR, has further been shown to be associated with a considerable perinatal mortality

ABSTRACT:The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency. O f the 4 million babies born annually in the United States, 12% (ϳ476,000) are born prematurely. Of these, 5-12% have additionally experienced intrauterine growth restriction (IUGR) and are born with inappropriately low birth weight (1). Preterm infants with additional IUGR are at highest risk for long-term morbidities, including developmental disabilities such as cerebral palsy, mental retardation, and a wide spectrum of learning disabilities and behavior disorders (2-7). The specific nature of these developmental disabilities and the underlying neuropathology are unknown. In vivo 3D magnetic resonance imaging (MRI) has recently opened up the possibility of determining the impact of prematurity on the structural development of the brain (8 -11). Brain structural changes after IUGR in the human have been described with an overall reduction of cortical gray matter volume in IUGR preterm infants throughout the neonatal period (12). Effects of prematurity on the structural development of specific brain regions have recently been described by similar 3D-MRI methods (13). Among different cortical brain regions, the hippocampus formation seems to be least genetically regulated (14,15) and most prone to developmental and environmental influences. The hippocampus is known for its crucial role in cognitive function such as memory and learning. It is vulnerable to hypoxia, stress hormones, undernutrition, and alteration of micronutrient supply, all likely to be present in pregnancies complicated by IUGR (16). IUGR, in an animal model was shown to induce a loss of neuronal volume and number in the cerebellum and hippocampus (17,18).With the ongoing i...

Preterm birth is associated with a higher prevalence of neurodevelopmental deficits. Indeed, preterm children are at increased risk for cognitive, behavioral, and socio-emotional difficulties. There is currently an increasing interest in introducing music intervention in neonatal intensive care unit (NICU) care. Several studies have shown short-term beneficial effects. A recent study has shown that listening to a familiar music (heard daily during the NICU stay) enhanced preterm infants’ functional connectivity between auditory cortices and subcortical brain regions at term-equivalent age. However, the long-term effects of music listening in the NICUs have never been explored. The aim of this study was to evaluate at 12 and 24 months the effects of music listening in the NICU on cognitive and emotional development in preterm children by comparing them to a preterm control group with no previous music exposure and to a full-term group. Participants were 44 children (17 full-term and 27 preterm). Preterm children were randomized to either music intervention or control condition (without music). The preterm-music group regularly listened to music from 33 weeks postconceptional age until hospital discharge or term-equivalent age. At 12 months, children were evaluated on the Bayley Scales of Infant and Toddler Development, Third Edition, then with 4 episodes of the Laboratory Temperament Assessment Battery (assessing expressions of joy, anger, and fear, and sustained attention). At 24 months, the children were evaluated with the same tests, and with 3 additional episodes of the Effortful Control Battery (assessing inhibition). Results showed that the scores of preterm children, music and control, differed from those of full-term children for fear reactivity at 12 months of age and for anger reactivity at 24 months of age. Interestingly, these significant differences were less important between the preterm-music and the full-term groups than between the preterm-control and the full-term groups. The present study provides preliminary, but promising, scientific findings on the beneficial long-term effects of music listening in the NICU on neurodevelopmental outcomes in preterm children, and more specifically on emotion mechanisms at 12 and 24 months of age. Our findings bring new insights for supporting early music intervention in the NICU.

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Predicting language performances after preterm birth is challenging. It is described in the literature that early exposure to the extrauterine environment can be either detrimental or advantageous for neurodevelopment. However, the emphasis mostly lies on the fact that preterm birth may have an unfavorable effect on numerous aspects of development such as cognition, language, and behavior. Various studies reported atypical language development in preterm born children in the preschool years but also in school-aged children and adolescents. This review gives an overview of the course of language development and examines how prematurity can lead to atypical linguistic performances. In this paper, we mainly focus on environmental and neurophysiological factors influencing preterm infant neuroplasticity with potential short- and long-term effects on language development. Further research, however, should focus on examining the possible benefits that early exposure might entail.