Abstract Background Among preterm infants, higher morbidities of neurological disturbances and developmental delays are critical issues. Resting-state networks (RSNs) in the brain are suitable measures for assessing higher-level neurocognition. Since investigating task-related brain activity is difficult in neonates, assessment of RSNs provides invaluable insight into their neurocognitive development. Methods The participants, 32 term and 71 preterm neonates, were divided into three groups based on gestational age (GA) at birth. Cerebral hemodynamic activity of RSNs was measured using functional near-infrared spectroscopy in the temporal, frontal, and parietal regions. Results High-GA preterm infants (GA ≥ 30 weeks) had a significantly stronger RSN than low-GA preterm infants and term infants. Regression analyses of RSNs as a function of postnatal age (PNA) revealed a steeper regression line in the high-GA preterm and term infants than in the low-GA infants, particularly for inter-area brain connectivity between the frontal and left temporal areas. Conclusions Slower PNA-dependent development of the frontal–temporal network found only in the low-GA group suggests that significant brain growth optimal in the intrauterine environment takes place before 30 weeks of gestation. The present study suggests a likely reason for the high incidence of neurodevelopmental impairment in early preterm infants. Impact Resting-state fNIRS measurements in three neonate groups differing in gestational age (GA) showed stronger networks in the high-GA preterm infants than in the term and low-GA infants, which was partly explained by postnatal age (PNA). Regression analyses revealed a similar PNA-dependence in the development of the inter-area networks in the frontal and temporal lobes in the high-GA and term infants, and significantly slower development in the low-GA infants. These results suggest that optimal intrauterine brain growth takes place before 30 weeks of gestation. This explains one of the reasons for the high incidence of neurodevelopmental impairment in early preterm infants.
Several cut-off points for 25-hydroxyvitamin D (25(OH)D) levels have been proposed to determine vitamin D deficiency or insufficiency. However, the level for 25(OH)D deficiency in early infancy remains unclear. The serum 25(OH)D value at which parathyroid hormone level plateaus, called the "inflection point," is considered the most appropriate criterion for defining an adequate vitamin D status.This was a single-center retrospective study involving 305 1-month-old and 252 2-month-old Japanese infants. Nonlinear segmented regression analysis was performed based on the correlation between 25(OH)D and parathyroid hormone levels to determine vitamin D deficiency cut-off points.Inflection points were 7.90 ng/mL for 1-month-old (95% confidence interval, 6.31-9.49) and 6.74 ng/mL for 2-month-old (95% confidence interval, 5.80-7.68) Japanese infants, which were lower than previously reported. Cut-off values were also lower in the high-body mass index (BMI) group than in the low-BMI group for both 1-month and 2-month-old infants.These results imply the need for nutritional rickets prevention via policy recommendations in most full-term newborns in Japan. Although validation studies are required, these results can still be used to guide vitamin D insufficiency treatment options in early infancy.
Abstract Pre-babbling infants can track nonadjacent dependencies (NADs) in the auditory domain. While this forms a crucial prerequisite for language acquisition, the neurodevelopmental origins of this ability remain unknown. We applied functional near- infrared spectroscopy in neonates and 6-7-month-old infants to investigate the neural substrate supporting NAD learning using tone sequences in an artificial grammar learning paradigm. Detection of NADs was indicated by left prefrontal activation in neonates while by left supramarginal gyrus (SMG), superior temporal gyrus (STG), and inferior frontal gyrus activation in 6-7-month-olds. Functional connectivity analyses further indicated that the neonate activation pattern during the test phase benefited from a brain network consisting of prefrontal regions, left SMG and STG during the rest and learning phases. These findings suggest a left-hemispheric learning-related functional brain network may emerge at birth and be strengthened by complex auditory input across the first half year of life, providing a neural basis for language acquisition.
Background Early diagnosis of bacterial infections in extremely low birth weight (ELBW) infants is difficult and these infections easily progress rapidly to become systemic, suggesting the need for an objective, sensitive indicator for early treatment. The evanescent wave immunoassay enables the most sensitive measurement of C-reactive protein (CRP) in only 50 μl of whole blood in 10 minutes. In this study, we measured CRP in ELBW infants up to 7 days old using the evanescent wave immunoassay, and compared their normative standards with those of term infants. Subjects and Methods The subjects were 102 ELBW infants born in our neonatal intensive care unit between 1 January 2002 and 31 December 2007. Blood was collected daily between days 0 and 5 from the term infants, and between days 0 and 7 from the ELBW infants. CRP in ELBW infants was measured using EV20, and the 90 percentile values were compared with the normative standards of the term infants. Results A transient, physiological increase in CRP was observed in the ELBW infants as in the normal newborns. However, the term infants and ELBW infants differed in the level and timing of the physiological increase in CRP: 3768.34 μg/dl on day 1 in the term infants and 637.5 μg/dl on day 2 in the ELBW infants. Discussion We speculate that the difference in postnatal changes in CRP levels is due to a milder and slower response to delivery stress in ELBW than that in term infants. The results obtained are useful for the early detection of infections and avoidance of unnecessary antibiotic therapy in ELBW infants.
Background: Strict glycemic control is important to prevent perinatal complications in patients with gestational diabetes mellitus (GDM). Patients often require insulin injection, and frequent hospital visits are necessary to adjust the dose of insulin, which is considered burdensome for pregnant patients. Telemedicine may reduce the burden of hospital visits, and previous studies have reported its safety in GDM patients. This study aimed to evaluate the efficacy of telemedicine in GDM patients, focusing on patient satisfaction and health economic indicators.Methods: This is a single-center, two-arm, randomized, open-label parallel-group study. Subjects will be selected from the patient population attending the Department of Endocrinology, Metabolism, and Nephrology, Keio University School of Medicine, Japan. Patients diagnosed with GDM by an oral glucose tolerance test (OGTT) by 29 weeks and 6 days of gestation who have undergone self-monitoring of blood glucose (SMBG) and insulin injection are eligible for inclusion. In the intervention group, telemedicine will be administered using the MeDaCa telemedicine system developed by the Medical Data Card, Inc., Tokyo, Japan. Subjects in the control group will be examined face-to-face every 2-3 weeks, as usual. We set health economic indicators and patient satisfaction as the primary endpoints, and will perform a cost-consequence analysis. Glycemic control indicators and perinatal outcomes will be evaluated as secondary endpoints.Conclusions: Eligible patients are currently being recruited. Recruitment will be completed when the expected number of patients are enrolled.
Although the effectiveness of glucocorticoids for the treatment of cerebral edema has been widely accepted in neurosurgical practice, but its mechanism is still obscure. Also the dose equivalent of various kinds of glucocorticoid preparation is still uncertain. Only the dose equivalent determined by the test examining an antiinflammatory effect on a growth of glanulation, has been applied for the treatment of brain edema. The authors attempted to establish the dose equivalent of each kinds of glucocorticoid for the treatment of cerebral edema. Cold induced cerebral edema was produced by touching a metal probe at the temperature of -90 degrees C for 3 minutes on the right parietal cortex of rat brain. Hydrocortisone (16 mg/kg), prednisolone (3.2 mg/kg), methylprednisolone (3.2 mg/kg), dexamethasone (0.8 mg/kg) and betamethasone (0.8 mg/kg) were administered at the time of 3 hours prior or after the cold injury. The animals were sacrificed 24 hours after injury and the grade of brain edema was determined by the changes of water content in the brain tissue. For this purpose, the authors developed a new method of measuring water content in the brain tissue using tritiated water and a liquid scintillation counter. In the group of animals which were treated with prednisolone, dexamethasone or betamethasone, the water content was significantly decreased compared to the value of non-treated animals. But in the animals treated with hydrocortisone or methylprednisolone, no significant changes of the water content was observed. But in the animals treated with double doses of hydrocortisone (32 mg/kg) or methylprednisolone (6.4 mg/kg), cerebral edema was improved significantly. From these results the authors concluded that the dose equivalent of each kinds of glucocorticoid for the treatment of the brain edema was as follows: hydrocortisone: prednisolone: methylprednisolone: dexamethasone: betamethasone = 40 : 4 : 8 : 1 : 1.
The biological and neurological processes during the lifespan are dynamic with significant alterations associated with different stages of life. The phase and coupling of oxy-hemoglobin (Δ[HbO]) and deoxy-hemoglobin concentration changes (Δ[Hb]) measured by functional near-infrared spectroscopy (fNIRS) are shown to characterize the neurovascular and metabolic development of infants. However, the changes in phase and coupling across the human lifespan remain mostly unknown. Here, fNIRS measurements of Δ[HbO] and Δ[Hb] conducted at two sites on different age populations (from newborns to elderly) were combined. Firstly, we assessed the influence of random noise on the calculation of the phase difference and phase-locking index (PLI) in fNIRS measurement. The results showed that the phase difference is close to π as the noise intensity approaches -8 dB, and the coupling strength (i.e., PLI) presents a u-shape curve as the noise increase. Secondly, phase difference and PLI in the frequency range 0.01-0.10 Hz were calculated after denoising. It showed that the phase difference increases from newborns to 3-4-month-olds babies. This phase difference persists throughout adulthood until finally being disrupted in the old age. The children's PLI is the highest, followed by that of adults. These two groups' PLI are significantly higher than those of infants and the elderly (p < 0.001). Lastly, a hemodynamic model was used to explain the observations and found close associations with cerebral autoregulation and speed of blood flow. These results demonstrate that the phase-related parameters measured by fNIRS can be used to study the brain and assess brain health throughout the lifespan.
Abstract Background The etiology of Bednar's aphthae remains unclear. Our aim was to investigate the incidence of, and factors associated with, Bednar's aphthae in a Japanese newborn cohort. Methods A retrospective cross‐sectional study was conducted on neonates discharged from the well‐baby nursery at Saitama City Hospital, Japan. The principal investigator carefully examined each neonate's oral cavity, up to and including the pharynx, with a light‐emitting diode (LED) headlight to determine the presence of Bednar's aphthae. Maternal and neonatal clinical characteristics were first compared between neonates with and those without Bednar's aphthae by univariate analysis. Variables with significant inter‐group differences upon univariate analysis were entered into a multivariable logistic‐regression model. Results This study enrolled 1996 infants. We observed Bednar's aphthae in 9.3% of the Japanese newborn infants who were included. When restricted to infants who were born via vaginal delivery, 13.2% of them had aphthae. Multivariable logistic regression analysis identified vaginal delivery (odds ratio = 6.19, p < 0.0001) in Model 1, and vaginal delivery (odds ratio = 6.73, p < 0.0001) and birth weight (odds ratio = 0.9995, p = 0.034) in Model 2 as independent risk factors for the disease. Conclusion This is the first report of the prevalence of Bednar's aphthae among Japanese neonates. Vaginal delivery was identified as the strongest risk factor. Although confounding between mode of delivery and mechanical stimuli associated with sucking was not found in this study, the findings pave the way for a better understanding of the etiology of Bednar's aphthae.
