Neurodevelopmental and perinatal correlates of simple brain metrics in very preterm infants.

Objective: To explore perinatal correlates of 3 simple measures of brain size, known as metrics, in very preterm infants at term-equivalent age and their relationship to 2-year neurodevelopmental outcomes.

Design: Prospective cohort study of preterm infants born at a gestational age of less than 30 weeks or a weight of less than 1250 g between April 1, 2001, and December 31, 2003, and followed up at 2 years of corrected age.

Setting: The Royal Women's Hospital and the magnetic resonance imaging unit at the Royal Children's Hospital.

Biological and environmental factors as predictors of language skills in very preterm children at 5 years of age.

Objective: Language problems are thought to occur more frequently in very preterm children compared with healthy term born children. The primary aim of this study was to examine the contributions of biological and environmental risk factors to language outcomes in very preterm children at 5 years of age.

Methods: A cohort of 227 very preterm infants (birth weight <1250 g or gestational age <30 weeks) were recruited at birth and followed up at 2 and 5 years of age (corrected for prematurity) in a prospective, longitudinal study in Melbourne, Australia.

Neonatal white matter abnormalities predict global executive function impairment in children born very preterm.

Using prospective longitudinal data from 110 very preterm and 113 full term children, this article describes the executive functioning abilities of very preterm children at age 4, and examines relations between the extent of white matter abnormality on neonatal magnetic resonance imaging (MRI) and later executive function outcomes. Very preterm children performed less well than full term children on measures of planning ability, cognitive flexibility, selective attention, and inhibitory control. Executive impairments at age 4 were confined to preterm children with mild or moderate-severe white matter abnormalities on MRI.

Characterization of the corpus callosum in very preterm and full-term infants utilizing MRI.

The corpus callosum is the largest white matter tract, important for interhemispheric communication. The aim of this study was to investigate and compare corpus callosum size, shape and diffusion characteristics in 106 very preterm infants and 22 full-term infants. Structural and diffusion magnetic resonance images were obtained at term equivalent.

The effects of postnatal estrogen therapy on brain development in preterm baboons.

Objective: Estrogen receptors are present within the fetal brain, suggesting that estrogens may exert an influence on cerebral development. Loss of placentally derived estrogen in preterm birth may impair development.

Study Design: Baboons were delivered at 125 days of gestation (term approximately 185 days), randomly allocated to receive estradiol (n = 10) or placebo (n = 8), and ventilated for 14 days.

Caffeine and brain development in very preterm infants.

Objective: Caffeine improves neurological outcome in very preterm infants, but the mechanisms responsible for this neurological benefit are unknown. The objective of this study was to assess whether caffeine influenced brain macro- or microstructural development in preterm infants.

Methods: Seventy preterm infants <1,251 g birthweight randomly allocated to either caffeine (n = 33) or placebo (n = 37) underwent brain magnetic resonance imaging (MRI) at term-equivalent age; white and gray matter abnormalities were qualitatively scored, global and regional brain volumes were measured, and white matter microstructure was evaluated using diffusion-weighted imaging.

Neurosurgical treatment of progressive posthemorrhagic ventricular dilation in preterm infants: a 10-year single-institution study.

Object: Intraventricular hemorrhage (IVH) and progressive posthemorrhagic ventricular dilation (PPHVD) may result in significant neurological morbidity in preterm infants. At present, there is no consensus regarding the optimal timing or type of neurosurgical procedure to best treat PPHVD. Conflicting data exist regarding the relative risks and benefits of two commonly used temporizing neurosurgical procedures (TNPs), ventricular access devices ([VADs] or ventricular reservoirs) versus ventriculosubgaleal (VSG) shunts.

Neonatal status epilepticus.

Seizures are more prevalent during the neonatal period than at any other time in the human lifespan. During early development, neonates are developmentally predisposed to excitatory neuronal activity increasing their susceptibility to seizures. Status epilepticus is poorly defined in this subpopulation with a lack of a consensus definition.

Similar patterns of cortical expansion during human development and evolution.

The cerebral cortex of the human infant at term is complexly folded in a similar fashion to adult cortex but has only one third the total surface area. By comparing 12 healthy infants born at term with 12 healthy young adults, we demonstrate that postnatal cortical expansion is strikingly nonuniform: regions of lateral temporal, parietal, and frontal cortex expand nearly twice as much as other regions in the insular and medial occipital cortex. This differential postnatal expansion may reflect regional differences in the maturity of dendritic and synaptic architecture at birth and/or in the complexity of dendritic and synaptic architecture in adults.

Ibuprofen treatment for closure of patent ductus arteriosus is not associated with increased risk of neuropathology.

Ibuprofen is an effective pharmacological intervention for closure of a patent ductus arteriosus (PDA) in preterm infants and is an alternative to surgical ligation; however, it is not certain whether ibuprofen treatment is associated with adverse effects on the brain. Therefore, this study examined neuropathological outcomes of ibuprofen therapy for a PDA. Fetal baboons were delivered at 125 d of gestation (dg; term ∼185 dg) by caesarean section, given surfactant, and ventilated for 14 d with positive pressure ventilation (PPV).

Sodium bicarbonate administration and outcome in preterm infants.

The short-term outcomes of sodium bicarbonate therapy in preterm infants were investigated by retrospective analysis of 165 of 984 infants who received sodium bicarbonate. The infants treated with sodium bicarbonate were more immature and had greater severity of illness and more adverse outcomes. Sodium bicarbonate therapy did not improve the blood pH.

Preventive care at home for very preterm infants improves infant and caregiver outcomes at 2 years.

Objective: The objective of this study was to determine the effects of preventive care at home on child development and primary caregiver mental health at 2 years of age.

Methods: A total of 120 very preterm infants (<30 weeks) were assigned randomly to intervention (n = 61) or control (n = 59) groups. The intervention group received the preventive care program (9 home visits over the first year from a physiotherapist and a psychologist, focusing on the parent-infant relationship, the parents' mental health, and the infant's development); and the control group received standard care.

Sodium intake and intraventricular hemorrhage in the preterm infant.

Objective: Hypernatremia is associated with intracranial hemorrhage in term infants. The etiology of intraventricular hemorrhage in preterm infants is multifactorial. We aimed to characterize the associations between sodium intake, hypernatremia, and intraventricular hemorrhage in preterm infants.

Neonatal hemodynamic response to visual cortex activity: high-density near-infrared spectroscopy study.

The neurodevelopmental outcome of neonatal intensive care unit (NICU) infants is a major clinical concern with many infants displaying neurobehavioral deficits in childhood. Functional neuroimaging may provide early recognition of neural deficits in high-risk infants. Near-infrared spectroscopy (NIRS) has the advantage of providing functional neuroimaging in infants at the bedside.

Neuronal damage in the preterm baboon: impact of the mode of ventilatory support.

We evaluated the impact of randomized ventilatory strategies on specific neuronal populations of the cerebral cortex of preterm baboons. In the first series, baboons (n = 5) were delivered at 125 days of gestation (dg; term, 185 days) and exposed to 14 days of positive pressure ventilation (PPV) and compared with 140 dg controls (n = 6). In the second series, baboons were delivered at 125 dg and ventilated by either i) PPV for 1 day, followed by 27 days of nasal continuous positive airway pressure (early [EnCPAP]; n = 6) or ii) PPV for 5 days, followed by 23 days of CPAP (delayed [DnCPAP]; n = 4).

Longitudinal analysis of neural network development in preterm infants.

Application of resting state functional connectivity magnetic resonance imaging (fcMRI) to the study of prematurely born infants enables assessment of the earliest forms of cerebral connectivity and characterization of its early development in the human brain. We obtained 90 longitudinal fcMRI data sets from a cohort of preterm infants aged from 26 weeks postmenstrual age (PMA) through term equivalent age at PMA-specific time points. Utilizing seed-based correlation analysis, we identified resting state networks involving varied cortical regions, the thalamus, and cerebellum.

A surface-based analysis of hemispheric asymmetries and folding of cerebral cortex in term-born human infants.

We have established a population average surface-based atlas of human cerebral cortex at term gestation and used it to compare infant and adult cortical shape characteristics. Accurate cortical surface reconstructions for each hemisphere of 12 healthy term gestation infants were generated from structural magnetic resonance imaging data using a novel segmentation algorithm. Each surface was inflated, flattened, mapped to a standard spherical configuration, and registered to a target atlas sphere that reflected shape characteristics of all 24 contributing hemispheres using landmark constrained surface registration.

Understanding brain injury and neurodevelopmental disabilities in the preterm infant: the evolving role of advanced magnetic resonance imaging.

The high incidence of neurodevelopmental disability in premature infants requires continued efforts at understanding the underlying microstructural changes in the brain that cause this perturbation in normal development. Magnetic resonance imaging (MRI) methods offer great potential to fulfill this need. Serial MR imaging and the application of newer analysis techniques, such as diffusion tensor imaging (DTI), volumetric MR analysis, cortical surface analysis, functional connectivity MRI (fcMRI) and diffusion tractography, provide important insights into the trajectory of brain development in the premature infant and the impact of injury on this developmental trajectory.

Reduced cerebellar diameter in very preterm infants with abnormal general movements.

Background: Abnormal General Movements (GMs) early in life are predictive of later neuromotor deficits and are related to white matter abnormalities on magnetic resonance imaging (MRI). However, other structural correlates of abnormal GMs have not been defined.

Aims: The objective of this study was to explore brain-metrics (linear brain measurements on MRI representative of 3-D brain volumes) at term as a predictor of abnormal GMs at 1 and 3months' corrected age in preterm infants.

Parental mental health and early social-emotional development of children born very preterm.

Objective: The aims of this study were to describe the mental health of parents of children born very preterm and examine relations between parental mental health and early social-emotional development in very preterm and term born children.

Methods: Participants were 177 children born very preterm and 69 children term born and their parents. At 2 year's corrected age for the children, parental mental health was assessed using the General Health Questionnaire (GHQ-28), and child social-emotional development assessed using the Infant-Toddler Social-Emotional Assessment (ITSEA) and a structured parent-child interaction paradigm.

Improving the outcome of infants born at <30 weeks' gestation--a randomized controlled trial of preventative care at home.

Background: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems.

Methods/design: We have designed a randomized controlled trial to assess the effectiveness of a preventative care program delivered at home over the first 12 months of life for infants born very preterm (<30 weeks of gestational age) and their families, compared with standard medical follow-up.

Early sensitivity training for parents of preterm infants: impact on the developing brain.

After birth, preterm infants face a stressful environment, which may negatively impact early brain development and subsequent neurobehavioral outcomes. This randomized controlled trial involving 45 women with infants <30-wk gestation, assessed the effectiveness of training parents in reducing stressful experiences. Intervention consisted of 10 sessions in the Neonatal Intensive Care Unit (NICU).

In vivo MRI analysis of an inflammatory injury in the developing brain.

Cerebral periventricular white matter injury stands as a leading cause of cognitive, behavioral and motor impairment in preterm infants. There is epidemiological and histopathological evidence demonstrating the role of prenatal or neonatal inflammation in brain injury in preterm infants. In order to define the effect of an inflammatory insult in the developing brain on magnetic resonance (MR) imaging, we obtained high resolution conventional and diffusion MR images of the brain of rat pups after an inflammatory injury.

Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury.

The aim of the study was to determine the incidence of electrographic seizure activity in a prospective cohort of preterm infants and relate it to the presence of cerebral injury. Infants born <30-wk gestation received a median 74 h of continuous 2-channel EEG with amplitude-integrated EEG monitoring in the first week of life. Infants were classified in the abnormal outcome group if they died in the neonatal period and/or had grades 3-4 intraventricular hemorrhage and/or moderate or severe abnormalities on cerebral MRI.