Structural network topology correlates of microstructural brain dysmaturation in term infants with congenital heart disease.

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject-specific white matter segmentation to investigate structural topology differences, as well as a voxel-based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost-dependent network inefficiencies in neonatal CHD in the pre- and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small-worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.

Fetuses with single ventricle congenital heart disease manifest impairment of regional brain growth.

OBJECTIVE: Anomalous neurological development associated with congenital heart disease (CHD) has been reported as early as third trimester of fetal development. While several studies have characterized variations in CHD neurodevelopmental outcomes in early childhood, these reports are often confounded by postnatal factors such as surgical outcome. Recent studies have focused on the comparing neurological variations between fetuses with CHD and normal controls. In this work, we present a comparison of in utero variations in brain development between fetuses with different types of CHD, by analyzing them under categories of single ventricle versus biventricular cardiac anatomy. METHODS: Using recent advances in fetal magnetic resonance imaging (MRI), we quantify the volumetric trajectories of various brain tissues (such as cortical plate, developing white matter, cerebrospinal fluid [CSF], and cerebellum). RESULTS: Our study is the first to differentiate between intraventricular and extra-axial CSF thereby allowing us to better identify variations in brain composition of the fetuses. CONCLUSIONS: Overall, our findings show that while total brain volume is similar between fetuses with single and biventricular anatomy, they exhibit statistically significant disparity in brain composition.

Clinical Factors Associated with Cerebral Metabolism in Term Neonates with Congenital Heart Disease.

OBJECTIVE: To determine associations between patient and clinical factors with postnatal brain metabolism in term neonates with congenital heart disease (CHD) via the use of quantitative magnetic resonance spectroscopy. STUDY DESIGN: Neonates with CHD were enrolled prospectively to undergo pre- and postoperative 3T brain magnetic resonance imaging. Short-echo single-voxel magnetic resonance spectroscopy of parietal white matter was used to quantify metabolites related to brain maturation (n-acetyl aspartate, choline, myo- inositol), neurotransmitters (glutamate and gamma-aminobutyric acid), energy metabolism (glutamine, citrate, glucose, and phosphocreatine), and injury/apoptosis (lactate and lipids). Multivariable regression was performed to search for associations between (1) patient-specific/prenatal/preoperative factors with concurrent brain metabolism and (2) intraoperative and postoperative factors with postoperative brain metabolism. RESULTS: A total of 83 magnetic resonance images were obtained on 55 subjects. No patient-specific, prenatal, or preoperative factors associated with concurrent metabolic brain dysmaturation or elevated lactate could be identified. Chromosome 22q11 microdeletion and age at surgery were predictive of altered concurrent white matter phosphocreatine (P < .0055). The only significant intraoperative association found was increased deep hypothermic circulatory arrest time with reduced postoperative white matter glutamate and gamma-aminobutyric acid (P < .0072). Multiple postoperative factors, including increased number of extracorporeal membrane oxygenation days (P < .0067), intensive care unit, length of stay (P < .0047), seizures in the intensive care unit (P < .0009), and home antiepileptic use (P < .0002), were associated with reduced postoperative white matter n-acetyl aspartate. CONCLUSION: Multiple postoperative factors were found to be associated with altered brain metabolism in term infants with CHD, but not patient-specific, preoperative, or intraoperative factors.

A comparison of activity patterns for captive Propithecus tattersalli and Propithecus coquereli.

The activity patterns and social interactions of two species of captive sifaka were observed during a 2-year period. Allogrooming was not observed in golden-crowned sifaka and they spent significantly more time resting than the Coquerel's sifaka. Females of both species were found to be dominant to males. The golden-crowned sifaka (Propithecus tattersalli) spent significantly less time feeding than the Coquerel's sifaka. Temperature, time of day, species, and interpair comparisons for the golden-crowned sifaka were found to affect activity and social interactions, while gender did not. Like the Coquerel's sifaka, the golden-crowned sifaka was found to be diurnal; however, they differed in that the golden-crowned sifaka did not descend to the ground.

Changes in mean arterial blood pressure during sildenafil use in neonates with meconium aspiration syndrome or sepsis.

The aim of this study was to evaluate changes in mean blood pressure (MBP) in late preterm and term newborns with meconium aspiration syndrome (MAS) or sepsis who, in addition to inhaled nitric oxide (iNO), received enteral sildenafil for treatment of persistent pulmonary hypertension of the newborn. Data on sildenafil dosing, MBP, and vasopressor/inotrope use were collected for 72 hours after initiation of sildenafil. Groups were compared between "low dose" (<3 mg·kg·d) versus "high dose" (≥ 3 mg·kg·d) and "early" (<7 postnatal days) versus "late" (≥ 7 postnatal days) administration of sildenafil. Seventeen patients were identified. Ten and 7 patients received "low-dose" and "high-dose" sildenafil, respectively, and 8 and 9 patients were started on sildenafil "early" and "late," respectively. At the doses used, sildenafil treatment of infants with MAS and sepsis was not associated with changes in MBP. In addition, vasopressor/inotropic support was weaned in all groups. During the first 72 hours of enteral sildenafil administration in neonates with pulmonary hypertension of the newborn secondary to MAS or sepsis, no significant decrease in MBP or increase in vasopressor/inotrope requirement occurred.

Congenital heart disease in low-birth-weight infants: effects of small for gestational age (SGA) status and maturity on postoperative outcomes.

Few studies have examined the role that small for gestational age (SGA) status plays in postoperative outcomes for low-birth-weight (LBW) infants with congenital heart disease (CHD). This study aimed to examine the effect of SGA status, gestational and chronologic age, and weight on differences in morbidities and mortalities during the immediate postoperative hospitalization period. The charts of infants with CHD weighing less than 2.5 kg who underwent operative repair during the neonatal period between 2004 and 2011 were reviewed. Infants with an isolated patent ductus arteriosus were excluded from the study. Data on hospital morbidities and mortality before discharge were collected. The study identified 136 LBW infants with a diagnosis of CHD. Among the 74 infants who underwent surgery and had complete chart records, the SGA infants had a higher gestational age at birth (36.8 vs. 32.3 weeks; p < 0.0001). The SGA and non-SGA infants did not differ in terms of survival to discharge or immediate postoperative outcomes. A lower weight at surgery was significantly associated with an increased risk of postoperative infection. In contradistinction, an older postnatal age at surgery was associated with an increased risk of preoperative infection (p < 0.0001). Additionally, lower gestational age at birth was associated with home oxygen use, higher tracheostomy rates, and discharge with a gastrostomy tube. Small for gestational age status played no protective role in the outcome for LBW infants after primary surgery for CHD. A weight of 2.4 kg or greater at the time of surgery was associated with lower rates of postoperative infections. Greater duration of time between birth and surgery was associated with a greater risk of preoperative infection. A gestational age of 32 weeks or more at birth was associated with decreased morbidities, which could influence obstetric management.

Abnormal development of thalamic microstructure in premature neonates with congenital heart disease.

Preterm birth is associated with alteration in corticothalamic development, which underlies poor neurodevelopmental outcomes. Our hypothesis was that preterm neonates with CHD would demonstrate abnormal thalamic microstructure when compared to critically ill neonates without CHD. A secondary aim was to identify any association between thalamic microstructural abnormalities and perioperative clinical variables. We compared thalamic DTI measurements in 21 preterm neonates with CHD to two cohorts of neonates without CHD: 28 term and 27 preterm neonates, identified from the same neonatal intensive care unit. Comparison was made with three other selected white matter regions using ROI manual-based measurements. Correlation was made with post-conceptional age and perioperative clinical variables. In preterm neonates with CHD, there were age-related differences in thalamic diffusivity (axial and radial) compared to the preterm and term non-CHD group, in contrast to no differences in anisotropy. Contrary to our hypothesis, abnormal thalamic and optic radiation microstructure was most strongly associated with an elevated first arterial blood gas pO2 and elevated preoperative arterial blood gas pH (p < 0.05). Age-related thalamic microstructural abnormalities were observed in preterm neonates with CHD. Perinatal hyperoxemia and increased perioperative serum pH were associated with abnormal thalamic microstructure in preterm neonates with CHD. This study emphasizes the vulnerability of thalamocortical development in the preterm neonate with CHD.

Magnetic resonance spectroscopy markers of axons and astrogliosis in relation to specific features of white matter injury in preterm infants.

INTRODUCTION: Punctate white matter lesions (pWMLs) and diffuse excessive high signal intensity (DEHSI) are commonly observed signal abnormalities on MRI scans of high-risk preterm infants near term-equivalent age. To establish whether these features are indicative abnormalities in axonal development or astroglia, we compared pWMLs and DEHSI to markers of axons and astrogliosis, derived from magnetic resonance spectroscopy (MRS). METHODS: Data from 108 preterm infants (gestational age at birth 31.0 weeks ± 4.3; age at scan 41.2 weeks ± 6.0) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses were used to test the effects of pWMLs and DEHSI on N-acetyl-aspartate (NAA) and myoinositol concentrations, respectively. RESULTS: Across the full sample, pWMLs were associated with a reduction in NAA whereas moderate to severe DEHSI altered the normal age-dependent changes in myoinositol such that myoinositol levels were lower at younger ages with no change during the perinatal period. Subgroup analyses indicated that the above associations were driven by the subgroup of neonates with both pWMLs and moderate to severe DEHSI. CONCLUSION: Overall, these findings suggest that pWMLs in conjunction with moderate/severe DEHSI may signify a population of infants at risk for long-term adverse neurodevelopmental outcome due to white matter injury and associated axonopathy. The loss of normal age-associated changes in myoinositol further suggests disrupted astroglial function and/or osmotic dysregulation.

Metabolic maturation of the human brain from birth through adolescence: insights from in vivo magnetic resonance spectroscopy.

Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease.

Neuroimaging biomarkers of preterm brain injury: toward developing the preterm connectome.

For typically developing infants, the last trimester of fetal development extending into the first post-natal months is a period of rapid brain development. Infants who are born premature face significant risk of brain injury (e.g., intraventricular or germinal matrix hemorrhage and periventricular leukomalacia) from complications in the perinatal period and also potential long-term neurodevelopmental disabilities because these early injuries can interrupt normal brain maturation. Neuroimaging has played an important role in the diagnosis and management of the preterm infant. Both cranial US and conventional MRI techniques are useful in diagnostic and prognostic evaluation of preterm brain development and injury. Cranial US is highly sensitive for intraventricular hemorrhage (IVH) and provides prognostic information regarding cerebral palsy. Data are limited regarding the utility of MRI as a routine screening instrument for brain injury for all preterm infants. However, MRI might provide diagnostic or prognostic information regarding PVL and other types of preterm brain injury in the setting of specific clinical indications and risk factors. Further development of advanced MR techniques like volumetric MR imaging, diffusion tensor imaging, metabolic imaging (MR spectroscopy) and functional connectivity are necessary to provide additional insight into the molecular, cellular and systems processes that underlie brain development and outcome in the preterm infant. The adult concept of the "connectome" is also relevant in understanding brain networks that underlie the preterm brain. Knowledge of the preterm connectome will provide a framework for understanding preterm brain function and dysfunction, and potentially even a roadmap for brain plasticity. By combining conventional imaging techniques with more advanced techniques, neuroimaging findings will likely be used not only as diagnostic and prognostic tools, but also as biomarkers for long-term neurodevelopmental outcomes, instruments to assess the efficacy of neuroprotective agents and maneuvers in the NICU, and as screening instruments to appropriately select infants for longitudinal developmental interventions.

Hydrographic magnetic resonance imaging of the fetal eye.

Previous work has shown that fetal hydrographic magnetic resonance imaging (MRI) provided additional information complementary to T2-weighted single-shot fast spin echo (ssFSE) images. The objective of this study was to determine if hydrographic MRI provides better conspicuity of fetal eye structures compared with ssFSE MRI. ssFSE and hydrographic images were retrospectively examined in 82 consecutive fetal studies with normal central nervous system without sensitivity encoding. Relative signal intensity values on ssFSE and hydrographic MRI were obtained for vitreous and sclera. Ratios of the signal intensity of vitreous to the signal intensity of sclera were calculated to determine conspicuity. Similar measurements were obtained in a smaller separate data set (n = 41) using hydrographic imaging with sensitivity encoding techniques. The hydrographic images significantly demonstrated greater conspicuity (ratio of vitreous to sclera) than ssFSE images. This was consistent for both sensitivity encoding and no-sensitivity encoding groups. The difference in conspicuity was on average approximately two times greater in the hydrographic images compared with ssFSE images. Hydrographic MRI of the fetal eye provides on average two times greater conspicuity of fetal eye structures than ssFSE imaging. This enhancement is not affected by gestational age or the use of sensitivity encoding parallel imaging techniques.

Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls.

OBJECTIVE: Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls. METHODS: We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting). RESULTS: Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (ß = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (ß = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (ß = -1.5; 95%CI = -2.95, -0.05; p = 0.04). CONCLUSION: CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.

Intrauterine exposure to mycophenolate mofetil and multiple congenital anomalies in a newborn: possible teratogenic effect.

There is very little data linking the use of immunomodulating agents following solid organ transplantation in pregnant women with specific congenital anomalies in the offspring. Here we report on a late preterm infant with multiple, nonsyndromic, congenital anomalies including microtia/anotia, cleft lip and palate, micrognathia, ocular hypertelorism, microphthalmia and cataracts, complex congenital heart disease, rib anomalies, and intestinal malrotation. The similarity of the complex anomalies in our case to other reported cases suggests that the abnormalities are likely due to mycophenolate mofetil alone or in combination with other immunosuppressive medications taken by the mother during pregnancy.

The clinical utility of esophageal manometry.

BACKGROUND AND AIMS: Esophageal manometry (EM) is performed to evaluate symptoms of chest pain and dysphagia, although its clinical utility is not known. The aim of this study was to evaluate the clinical utility of EM by determining whether EM provides new information, changes diagnoses, or alters patient management. METHODS: Before performing EM, referring providers noted indications for the test, symptoms, previous tests performed, and medication use. After EM was completed, a follow-up questionnaire ascertained whether EM provided new information or changed the patient's diagnosis or management plan. Patients provided demographic information. RESULTS: During a 12-month period, 569 EMs were performed and 444 were available for inclusion; 286 fully completed questionnaires were returned (64%) and are the basis for this analysis. The mean age (+/-SD) at the time of manometry was 52 (+/-15) years; 58% were women; 98% were white. EM was requested to assist placement of a pH measuring device (34%), and to evaluate symptoms of dysphagia (29%), chest pain (12%), or acid reflux (11%). Overall, 64% of EM were abnormal; 81% in gastroesophageal reflux disease patients, 74% in dysphagia, and 59% in chest pain. New information was obtained in 87% of patients, whereas a change in diagnosis occurred in 30% of patients, and management changed in 44% of patients. CONCLUSIONS: EM is a clinically useful test because it frequently provides new information and often changes patient diagnosis and management. The clinical utility of EM is greatest in patients with dysphagia.

Tolerability and clinical utility of the Bravo pH capsule in children.

GOALS: To prospectively evaluate the tolerability and clinical utility of the Bravo pH capsule in children. BACKGROUND: Acid reflux is common in children, and pH testing can be used to correlate acid exposure with symptom expression. The tolerability and clinical utility of the Bravo capsule in children has not been prospectively evaluated. METHODS: This was a prospective, open-label trial conducted at an academic medical center. Patient demographics, symptoms, and medication use were recorded in an outpatient setting. After Bravo capsule placement, patients were followed to determine whether the results of the Bravo capsule study changed clinical management. RESULTS: Fifty children (mean+/-SD=13+/-3 y; 52% female) were studied; no complications occurred. Reflux symptoms (40%), abdominal pain (18%), and nausea/vomiting (14%) were the 3 most common symptoms leading to Bravo capsule placement. Nearly all studies (96%) were performed off acid-suppressing medications. Results of the Bravo pH study changed clinical care in 88% of children; management changed more frequently in children with an abnormal study (94%) versus those with a normal study (78%; P<0.0001). CONCLUSIONS: The Bravo pH capsule is a safe, well-tolerated test to evaluate acid reflux symptoms in children, and the data obtained frequently changes patient management.

Association between Subcortical Morphology and Cerebral White Matter Energy Metabolism in Neonates with Congenital Heart Disease.

Complex congenital heart disease (CHD) is associated with neurodevelopmental impairment, the mechanism of which is unknown. Cerebral cortical dysmaturation in CHD is linked to white matter abnormalities, including developmental vulnerability of the subplate, in relation to oxygen delivery and metabolism deficits. In this study, we report associations between subcortical morphology and white matter metabolism in neonates with CHD using quantitative magnetic resonance imaging (MRI) and spectroscopy (MRS). Multi-modal brain imaging was performed in three groups of neonates close to term-equivalent age: (1) term CHD (n = 56); (2) preterm CHD (n = 37) and (3) preterm control group (n = 22). Thalamic volume and cerebellar transverse diameter were obtained in relation to cerebral metrics and white matter metabolism. Short echo single-voxel MRS of parietal and frontal white matter was used to quantitate metabolites related to brain maturation (n-acetyl aspartate [NAA], choline, myo-inositol), neurotransmitter (glutamate), and energy metabolism (glutamine, citrate, creatine and lactate). Multi-variate regression was performed to delineate associations between subcortical morphological measurements and white matter metabolism controlling for age and white matter injury. Reduced thalamic volume, most pronounced in the preterm control group, was associated with increased citrate levels in all three group in the parietal white matter. In contrast, reduced cerebellar volume, most pronounced in the preterm CHD group, was associated with reduced glutamine in parietal grey matter in both CHD groups. Single ventricle anatomy, aortic arch obstruction, and cyanotic lesion were predictive of the relationship between reduced subcortical morphometry and reduced GLX (particularly glutamine) in both CHD cohorts (frontal white matter and parietal grey matter). Subcortical morphological associations with brain metabolism were also distinct within each of the three groups, suggesting these relationships in the CHD groups were not directly related to prematurity or white matter injury alone. Taken together, these findings suggest that subplate vulnerability in CHD is likely relevant to understanding the mechanism of both cortical and subcortical dysmaturation in CHD infants. Future work is needed to link this potential pattern of encephalopathy of CHD (including the constellation of grey matter, white matter and brain metabolism deficits) to not only abnormal fetal substrate delivery and oxygen conformance, but also regional deficits in cerebral energy metabolism.

The Impact of Venoarterial and Venovenous Extracorporeal Membrane Oxygenation on Cerebral Metabolism in the Newborn Brain.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an effective therapy for supporting infants with reversible cardiopulmonary failure. Still, survivors are at risk for long-term neurodevelopmental impairments, the cause of which is not fully understood. OBJECTIVE: To elucidate the effects of ECMO on the newborn brain. We hypothesized that the cerebral metabolic profile of neonates who received ECMO would differ from neonates who did not receive ECMO. To address this, we used magnetic resonance spectroscopy (1H-MRS) to investigate the effects of venoarterial and venovenous ECMO on cerebral metabolism. METHODS: 41 neonates treated with ECMO were contrasted to 38 age-matched neonates. RESULTS: All 1H-MRS data were acquired from standardized grey matter and white matter regions of interest using a short-echo (TE = 35 milliseconds), point-resolved spectroscopy sequence (PRESS) and quantitated using LCModel. Metabolite concentrations (mmol/kg) were compared across groups using multivariate analysis of covariance. Elevated creatine (p = 0.002) and choline (p = 0.005) concentrations were observed in the grey matter among neonates treated with ECMO relative to the reference group. Likewise, choline concentrations were elevated in the white matter (p = 0.003) while glutamate was reduced (p = 0.03). Contrasts between ECMO groups revealed lower osmolite concentrations (e.g. myoinositol) among the venovenous ECMO group. CONCLUSION: Neonates who underwent ECMO were found to have an abnormal cerebral metabolic profile, with the pattern of abnormalities suggestive of an underlying inflammatory process. Additionally, neonates who underwent venovenous ECMO had low cerebral osmolite concentrations as seen in vasogenic edema.

Developmental synergy between thalamic structure and interhemispheric connectivity in the visual system of preterm infants.

Thalamic structural co-variation with cortical regions has been demonstrated in preterm infants, but its relationship to cortical function and severity of non-cystic white matter injury (non-cystic WMI) is unclear. The relationship between thalamic morphology and both cortical network synchronization and cortical structural connectivity has not been established. We tested the hypothesis that in preterm neonates, thalamic volume would correlate with primary cortical visual function and microstructural integrity of cortico-cortical visual association pathways. A total of 80 term-equivalent preterm and 44 term-born infants underwent high-resolution structural imaging coupled with visual functional magnetic resonance imaging or diffusion tensor imaging. There was a strong correlation between thalamic volume and primary visual cortical activation in preterms with non-cystic WMI (r = 0.81, p-value = 0.001). Thalamic volume also correlated strongly with interhemispheric cortico-cortical connectivity (splenium) in preterm neonates with a relatively higher severity of non-cystic WMI (p-value < 0.001). In contrast, there was lower correlation between thalamic volume and intrahemispheric cortico-cortical connectivity, including the inferior longitudinal fasciculus and inferior frontal orbital fasciculus. This study shows distinct temporal overlap in the disruption of thalamo-cortical and interhemispheric cortico-cortical connectivity in preterm infants suggesting developmental synergy between thalamic morphology and the emergence of cortical networks in the last trimester.

Metabolic maturation of white matter is altered in preterm infants.

Significant physiological switches occur at birth such as the transition from fetal parallel blood flow to a two-circuit serial system with increased arterial oxygenation of blood delivered to all organs including the brain. In addition, the extra-uterine environment exposes premature infants to a host of stimuli. These events could conceivably alter the trajectory of brain development in premature infants. We used in vivo magnetic resonance spectroscopy to measure absolute brain metabolite concentrations in term and premature-born infants without evidence of brain injury at equivalent post-conceptional age. Prematurity altered the developmental time courses of N-acetyl-aspartate, a marker for axonal and neuronal development, creatine, an energy metabolite, and choline, a membrane metabolite, in parietal white matter. Specifically, at term-equivalency, metabolic maturation in preterm infants preceded development in term infants, but then progressed at a slower pace and trajectories merged at ≈340-370 post-conceptional days. In parieto/occipital grey matter similar trends were noticed but statistical significance was not reached. The timing of white matter development and synchronization of white matter and grey matter maturation in premature-born infants is disturbed. This may contribute to the greater risk of long-term neurological problems of premature infants and to their higher risk for white matter injury.