Cortical Processing of Multimodal Sensory Learning in Human Neonates.

Following birth, infants must immediately process and rapidly adapt to the array of unknown sensory experiences associated with their new ex-utero environment. However, although it is known that unimodal stimuli induce activity in the corresponding primary sensory cortices of the newborn brain, it is unclear how multimodal stimuli are processed and integrated across modalities. The latter is essential for learning and understanding environmental contingencies through encoding relationships between sensory experiences; and ultimately likely subserves development of life-long skills such as speech and language. Here, for the first time, we map the intracerebral processing which underlies auditory-sensorimotor classical conditioning in a group of 13 neonates (median gestational age at birth: 38 weeks + 4 days, range: 32 weeks + 2 days to 41 weeks + 6 days; median postmenstrual age at scan: 40 weeks + 5 days, range: 38 weeks + 3 days to 42 weeks + 1 days) with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI) and magnetic resonance (MR) compatible robotics. We demonstrate that classical conditioning can induce crossmodal changes within putative unimodal sensory cortex even in the absence of its archetypal substrate. Our results also suggest that multimodal learning is associated with network wide activity within the conditioned neural system. These findings suggest that in early life, external multimodal sensory stimulation and integration shapes activity in the developing cortex and may influence its associated functional network architecture.

Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants.

Docosahexaenoic acid (DHA) and arachidonic acid (ArA) are essential brain specific fatty acids (BSFA) for mammalian central nervous system development. Human brains have accelerated growth with significant increase in cerebral content of ArA and DHA during the last trimester of pregnancy and first postnatal months. This randomized double blind placebo controlled single centre trial assessed the impact of BSFA supplementation in pregnancy on newborn infants' brain volumes. Eighty six infants born to study mothers had brain magnetic resonance imaging (MRI) scans soon after birth. Total and regional brain volumes were analyzed and related to maternal supplementation group. Males born to the BSFA supplemented mothers had significantly larger total brain volumes, total gray matter, corpus callosum and cortical volumes when compared to the placebo group. This is the first study to show maternal BSFA supplementation enhances newborn infants' brain size and suggests differential sex sensitivity of fetal brains to pregnancy BSFA status.

Increased osmolality of breast milk with therapeutic additives.

AIM: To evaluate the changes in the osmolality of expressed breast milk (EBM) after the addition of seven additives and four proprietary fortifiers commonly used during neonatal intensive care. METHODS: The osmolality of 5 ml EBM was measured with increasing doses of 6% NaCl, caffeine, sodium ironedetate, folic acid, and multivitamin drops. Sodium acid phosphate and chloral hydrate were added to 8 ml EBM, and the fortifiers were added to standard volumes of EBM. Dose-effect curves were plotted, and the volume of milk that must be added to the above additives to maintain osmolality below 400 mOsm/kg was calculated. RESULTS: The osmolality of the pure additives ranged from 242 to 951 mOsm/kg. There was a significant increase in the osmolality of EBM with increasing doses of all additives except caffeine. The osmolality of EBM with many additives in clinically used dosages potentially exceeded 400 mOsm/kg. The greatest increase occurred with sodium ironedetate syrup, where the osmolality of EBM increased to 951.57 (25.36) mOsm/kg. Proprietary fortifiers increased the osmolality of EBM to a maximum of 395 mOsm/kg. CONCLUSION: Routine additives can significantly increase the osmolality of EBM to levels that exceed current guidelines for premature infant feeding. A simple guide for clinical use is presented, which indicates the amount of milk required as diluent if hyperosmolality is to be avoided.

Characterization of cerebral white matter damage in preterm infants using 1H and 31P magnetic resonance spectroscopy.

The biochemical characteristics of white matter damage (WMD) in preterm infants were assessed using magnetic resonance spectroscopy (MRS). The authors hypothesized that preterm infants with WMD at term had a persisting cerebral lactic alkalosis and reduced N-acetyl aspartate (NAA)/ creatine plus phosphocreatine (Cr), similar to that previously documented in term infants weeks after perinatal hypoxiaischemia (HI). Thirty infants (gestational age 27.9 +/- 3.1 weeks, birth weight 1,122 +/- 445 g) were studied at postnatal age of 9.8 +/- 4.1 weeks (corrected age 40.3 +/- 3.9 weeks). Infants were grouped according to the presence or absence of WMD on magnetic resonance (MR) images. The peak area ratios of lactate/Cr, NAA/Cr, myo-inositol/Cr, and choline (Cho)/Cr were measured from an 8-cm3 voxel in the posterior periventricular white matter (WM) using proton MRS. Intracellular pH (pHi) was calculated using phosphorus MRS. Eighteen infants had normal WM on MR imaging; 12 had WMD. For infants with WMD, lactate/Cr and myo-inositol/Cr were related (P < 0.01); lactate/Cr and pHi were not (P = 0.8). In the WMD group, mean lactate/Cr and myo-inositol/Cr were higher (P < 0.001, P < 0.05, respectively) than the normal WM group. There was no difference in the NAA/Cr, Cho/Cr, or pHi between the two groups, although pHi was not measured in all infants. These findings suggest that WMD in the preterm infant at term has a different biochemical profile compared with the term infant after perinatal HI.

Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: The aim of this study was to establish whether abnormal signal intensity in the posterior limb of the internal capsule (PLIC) on magnetic resonance imaging is an accurate predictor of neurodevelopmental outcome at 1 year of age in infants with hypoxic-ischemic encephalopathy (HIE). METHODS: We have examined 73 term neonates with HIE between 1 and 17 days after birth with cranial magnetic resonance imaging and related the magnetic resonance imaging findings to neurodevelopmental outcome at 1 year of age. RESULTS: All infants with an abnormal signal intensity in the PLIC developed neurodevelopmental impairment although in 4 infants with very early scans the abnormal signal was not apparent until up to 4 days after birth. A normal signal intensity was associated with a normal outcome in all but 4 cases; 3 of these infants had minor impairments and all had persistent imaging changes within the white matter. The 4th infant with a normal signal intensity on day 2 died before a further image could be obtained. The absence of normal signal predicted abnormal outcome in term infants with HIE with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87. The test correctly predicted outcome in 93% of infants with grade II HIE, according to the Sarnat system. Applying a Bayesian approach, the predictive probability of the test (the probability that the test would predict an outcome correctly) was distributed with a mean of 0.94 and 95% confidence limits of 0.89 to 1.0. CONCLUSION: Abnormal signal intensity in the PLIC is an accurate predictor of neurodevelopmental outcome in term infants suffering HIE.

Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia and delayed cerebral energy failure in the newborn piglet.

Studies of the brains of severely birth-asphyxiated infants using proton (1H) magnetic resonance spectroscopy (MRS) have shown changes indicating a rise in cerebral lactate (Lac) and a fall in N-acetylaspartate (Naa). The aim of this study was to test two hypotheses: 1) that these changes can be reproduced in the newborn piglet after transient reversed cerebral hypoxiaischemia, and their time course determined; and 2) that changes in Lac peak-area ratios are related to changes in phosphorylation potential as determined by phosphorus (31P) MRS. Eighteen piglets aged < 24 h were anesthetized and ventilated. Twelve underwent temporary occlusion of the carotid arteries and hypoxemia, and six served as sham-operated controls. 1H and 31P spectra were acquired alternately, both during the insult and for the next 48 h, using a 7-tesla spectrometer. During hypoxiaischemia, the median Lac/total creatine (Cr) peak-area ratio rose from a baseline of 0.14 (interquartile range 0.07-0.27), to a maximum of 4.34 (3.33-7.45). After resuscitation, Lac/Cr fell to 0.75 (0.45-1.64) by 2 h, and then increased again to 2.43 (1.13-3.08) by 48 h. At all stages after resuscitation Lac/Cr remained significantly above baseline and control values. Naa/Cr was significantly reduced below baseline and control values by 48 h after resuscitation. The increases in the Lac peak-area ratios were concomitant with the falls in the [phosphocreatine (PCr)*]/ [inorganic phosphate (Pi)] ratio, during both acute hypoxiaischemia and delayed energy failure. The maximum Lac/Naa during delayed energy failure correlated strongly with the minimum [nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] (r = -0.94, p < 0.0001). We conclude that both hypotheses have been confirmed.