Brain Maturation In Infants Research Articles

Longitudinal Analysis of Sleep-Wake States in Neonatal Rats Subjected to Hypoxia-Ischemia.

ObjectiveSleep is necessary for brain maturation in infants. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of chronic neurological disease in infants. Although the developmental changes of electroencephalogram (EEG) in human newborns have been described, little is known about the EEG normal maturation characteristics in rodents and the changes in sleep-awake states caused by hypoxia-ischemia (HI). This study aimed to investigate the pathological response of sleep-wake states in neonatal rats with HIE.MethodsWe constructed HIE and sham models on postnatal day (P) 3 rats and continuously monitored them using electroencephalography and electromyography for up to P12. The distribution of sleep-wake states was analyzed to estimate the effects of HIE.ResultsCompared with the sham group, the HI group showed lower rapid eye movement (REM) sleep percentage, but wake percentage and frequency was higher during P4-P12. The frequency of REM and non-rapid eye movement (NREM) sleep increased and the duration of REM and NREM sleep decreased after HI induction. However, it gradually returned to the normal level with an increase in daytime.ConclusionHI damage alters the sleep-wake patterns during early neural development. The findings provide a comprehensive assessment of serial sleep-wake state recordings in neonatal rats from P4-P12.

Postoperative Improvement of Brain Maturation in Infants With Congenital Heart Disease

Children with severe congenital heart disease are at risk for neurodevelopmental impairments. We examined brain maturation in infants undergoing neonatal cardiopulmonary bypass surgery or hybrid procedure for hypoplastic left heart syndrome compared to controls. This is a prospective cohort study on term-born infants with congenital heart disease with cerebral MRI pre- and postoperatively. Healthy infants served as controls. Brain maturation was measured using a semiquantitative scoring system. The progress of brain maturation from the preoperative to postoperative MRI within patients was compared. Neurodevelopment was assessed at 1 year with the Bayley Scales of Infant and Toddler Development III. A total of 92 patients with congenital heart disease and 46 controls were studied. Median total maturation score in patients was 12 (interquartile range 10.6-13.0) preoperatively and 14 (12.0-15.0) postoperatively, in controls it was 14 (13.0-15.0). Median time interval between scans was 19 days (interquartile range 14-26). After correction for postmenstrual age at MRI, the pre- and postoperative maturation score was lower in patients compared to controls (preoperative P = 0.01, postoperative P = 0.03) and increased between pre- and postoperative assessment (P ≤ 0.001). Brain maturation scores did not correlate with neurodevelopmental outcome at 1 year, when corrected for socioeconomic status and postmenstrual age at MRI. This study confirms delayed brain maturation in children with congenital heart disease, and despite neonatal cardiac bypass surgery followed by postoperative intensive care medicine brain maturation is ongoing. We encourage further investigation in outcome prediction in this population, potentially by combining more advanced MRI measures with clinical methods.

A Mixed Lipid Emulsion Containing Fish Oil and Its Effect on Electrophysiological Brain Maturation in Infants of Extremely Low Birth Weight: A Secondary Analysis of a Randomized Clinical Trial

To assess whether parenteral nutrition for infants of extremely low birth weight using a mixed lipid emulsion that contains fish oil influences electrophysiological brain maturation. The study is a prespecified secondary outcome analysis of a randomized controlled trial of 230 infants of extremely low birth weight receiving a mixed (soybean oil, medium-chain triglycerides, olive oil, and fish oil; intervention) or a soybean oil-based lipid emulsion (control). The study was conducted at a single-level IV neonatal care unit (Medical University Vienna; June 2012 to October 2015). Electrophysiological brain maturation (background activity, sleep-wake cycling, and brain maturational scores) was assessed biweekly by amplitude-integrated electroencephalography (birth to discharge). A total of 317 amplitude-integrated electroencephalography measurements (intervention: n=165; control: n=152) from 121 (intervention: n=63; control: n=58) of 230 infants of the core study were available for analysis. Demographic characteristics were not significantly different. By 28weeks of postmenstrual age, infants receiving the intervention displayed significantly greater percentages of continuous background activity. Total maturational scores and individual scores for continuity, cycling, and bandwidth were significantly greater. Maximum maturational scores were reached 2weeks earlier in the intervention group (36.4weeks, 35.4-37.5) compared with the control group (38.4weeks, 37.1-42.4) (median, IQR; P<.001). Using a mixed parenteral lipid emulsion that contains fish oil, we found that electrophysiological brain maturation was accelerated in infants who were preterm. ClinicalTrials.gov: NCT01585935.

Estimating the age of healthy infants from quantitative myelin water fraction maps.

The trajectory of the developing brain is characterized by a sequence of complex, nonlinear patterns that occur at systematic stages of maturation. Although significant prior neuroimaging research has shed light on these patterns, the challenge of accurately characterizing brain maturation, and identifying areas of accelerated or delayed development, remains. Altered brain development, particularly during the earliest stages of life, is believed to be associated with many neurological and neuropsychiatric disorders. In this work, we develop a framework to construct voxel-wise estimates of brain age based on magnetic resonance imaging measures sensitive to myelin content. 198 myelin water fraction (VFM) maps were acquired from healthy male and female infants and toddlers, 3 to 48 months of age, and used to train a sigmoidal-based maturational model. The validity of the approach was then established by testing the model on 129 different VFM datasets. Results revealed the approach to have high accuracy, with a mean absolute percent error of 13% in males and 14% in females, and high predictive ability, with correlation coefficients between estimated and true ages of 0.945 in males and 0.94 in females. This work represents a new approach toward mapping brain maturity, and may provide a more faithful staging of brain maturation in infants beyond chronological or gestation-corrected age, allowing earlier identification of atypical regional brain development. Hum Brain Mapp 36:1233–1244, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Reference Values for Amplitude-Integrated EEGs in Infants From Preterm to 3.5 Months of Age

Amplitude-integrated electroencephalogram (aEEG) is a valuable tool for the continuous evaluation of functional brain maturation in infants. The amplitudes of the upper and lower margins of aEEGs are postulated to change with maturation and correlate with postmenstrual age (PMA). In this study we aimed to establish reliable reference values of aEEG amplitudes, which provide quantitative guidelines for assessing brain maturation as indicated by aEEG results in neonates and young infants. aEEGs from healthy infants (n = 274) with PMAs that ranged from 30 to 55 weeks were divided into 10 groups according to their PMAs. Two 5-minute segments were selected from each aEEG and were used to automatically calculate the upper and lower margins and bandwidths of the aEEG tracings. Interobserver agreement was achieved with an overall correlation of 0.99. The upper and lower margins of the aEEGs in both active and quiet sleep clearly rose in infants after the neonatal period. The bandwidth defined as the graphic distance decreased almost monotonically throughout the PMA range from 30 to 55 weeks. The lower margin of the aEEG was positively correlated with PMA, with a larger rank correlation coefficient during quiet sleep (r = 0.89) than during active sleep (r = 0.49). Reference values of aEEG amplitudes were obtained for infants with a wide range of PMAs and constituted the basis for the quantitative assessment of aEEG changes with maturation in neonates and young infants. The normative amplitudes of aEEG margins, especially of the lower margin in quiet sleep, are recommended as a source of reference data for the identification of potentially abnormal aEEG results.

Magnetic resonance imaging for quantitative flow measurement in infants with hydrocephalus: a prospective study

Raised intracranial pressure (ICP) that is associated with hydrocephalus may lead to alterations in cerebral hemodynamics and ischemic changes in the brain. In infants with hydrocephalus, defining the right moment for surgical intervention based on clinical signs alone can sometimes be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. Furthermore, when sutures are closed, ICP does not always correlate with the size of the ventricles or with the clinical signs or symptoms. In this study the authors investigated whether cerebral blood flow (CBF) can be measured by using quantitative MR angiography in infants with progressive hydrocephalus. In addition, the authors investigated the relationship between CBF and ICP, before and after cerebrospinal fluid (CSF) diversion. Fifteen infants with progressive hydrocephalus (age range 1 day-7 months) were examined. All patients underwent anterior fontanel pressure measurement, MR angiography, and mean arterial blood pressure measurements before and after CSF diversion. Brain volume was measured to compensate for the physiological increase in CBF during brain maturation in infants. The mean preoperative ICP was 19.1 +/- 8.4 cm H(2)O (+/- standard deviation). The mean postoperative ICP was 6.7 +/- 4.0 cm H(2)O (p < 0.005). The mean preoperative CBF was 25.7 +/- 11.3 ml/100 cm(3) brain/min. After CSF diversion, CBF increased to 50.1 +/- 12.1 ml/100 cm(3) brain/min (p < 0.005). The mean arterial blood pressure did not change after surgical intervention. Magnetic resonance imaging can be used to measure CBF in infants with hydrocephalus. Raised ICP was related to a decrease in CBF. After CSF diversion, CBF and ICP improved to values within the normal range.

The effects of repeated antenatal glucocorticoid therapy on the developing brain.

Antenatal glucocorticoid (GC) therapy improves infant outcome following preterm birth. As approximately 50% of women given a first course of antenatal GCs remain undelivered 7-14 d later, many clinicians administer further courses. GCs are known to be neurotoxic and there is concern that exposure during early development may have adverse effects on the immature brain. The aim of this investigation was to compare magnetic resonance (MR) indices of brain maturation in infants exposed to repeated antenatal GC therapy and born at or close to term, with non-GC exposed control infants. MR images were obtained during quiet sleep without sedation. T1 weighted volume images were obtained in the sagittal plane and T1, T2 weighted spin echo and inversion recovery images in the transverse plane. Brain volume and surface area were calculated from segmented image slices, and a measure of the complexity of cortical folding, the whole cortex convolution index (WCCI), from computerized analysis of a vector coded contour following algorithm. Analysis of covariance was used to compare the two groups after allowing for the effect of postmenstrual age. There were 10 infants in the GC group (range of antenatal GC exposure, 3-11 courses) and 6 controls. Each GC course comprised two 12-mg IM doses of betamethasone 24 h apart. GC exposed infants had a significantly lower WCCI (p = 0.001) and smaller surface area (p = 0.02), after allowing for postmenstrual age. There was no significant difference in brain volume (p = 0.5). Repeated antenatal GC exposure results in measurable differences in brain maturation when compared with gestational age matched non-GC exposed controls. The clinical relevance of these observations is not known.

Mapping of normal brain maturation in infants on phase-sensitive inversion-recovery MR images

It is illustrated that phase-sensitive inversion-recovery MR images are particularly well suited for the monitoring of brain maturation and myelination in the neonate and young infant. Provided appropriate timings are applied with the inversion-recovery MR pulse sequence, the myelinated areas show up as bright spots in the phase-sensitive images. The chronology of the appearance, and the location of these hyperintense zones correlate well with the chronology of brain maturation, as assessed by other means. In particular, the progressive functional capabilities of the infant correlate well with the progress of myelination, as exhibited by the MR images.