A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an inphase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants.irth is a drastic event for the developing brain, because this is when the oxygen supply switches from the fetal-placental circulation to an autonomous system. In addition, the extrauterine environment begins to provide the neonate with a tremendous flow of stimuli. Earlier exposure to the extrauterine environment is thought to influence the developmental trajectory of the brain. It has long been known that preterm birth affects brain development and is associated with a higher rate of neurodevelopmental impairment (1). A growing number of MRI studies have shown that preterm-born neonates and infants have brain structures with aberrant volumes, morphologies, and networks at term equivalent (2, 3) and school age (4, 5). Studies of resting-state fMRI have also shown that the functional connectivity of the cortex is different in term and preterm infants (6). However, it is a matter of controversy whether neonatal MRI of the brain can predict long-term adverse outcomes, such as minor neurological dysfunction (7,8). Given the fact that preterm birth before 37 wk of gestation accounts for more than 10% of all live births (9), we need a practical and safe method to detect the status of brain development in newborns.The development of the brain involves underlying hemodynamic and metabolic changes (10). Near-infrared spectroscopy (NIRS) has been used to measure cerebral blood concentrations of oxygenated Hb (oxy-Hb) and deoxygenated Hb (deoxy-Hb) at the bedside and estimate cerebral blood volume, oxygen saturation (SO 2 ), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO 2 ) in neonates (11,12). Previous studies in pr...

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Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the 'molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

Infants with Down Syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM is characterised by increased circulating blast cells but usually self-limiting. DS patients with TAM sometimes show fetal hydrops and effusion in body cavities, but the mechanism remains unclear. We report here a case of infant with DS who had pericardial effusion, TAM, and eosinophilia. In her pericardial effusion, white blood cell count was 6.0 × 10 3 /µL, 41% of which were eosinophils. After administration of prednisolone, pericardial effusion gradually decreased, and TAM and eosinophilia improved. In order to elucidate the immunological mechanism, we measured the levels of 17 cytokines in her pericardial effusion fluid and serum. In her pericardial fluid, there were high levels of 12 cytokines, and they were higher than those in her serum. In particular, IL-6 (44,573 pg/mL), IL-8 (4,865 pg/mL), and IL-13 (579.41 pg/mL) were at extremely high levels in her pericardial fluid. After administration of prednisolone, the levels of 8 of the 12 elevated cytokines in her pericardial fluid decreased and all of the elevated cytokines decreased in her serum. Corticosteroids can be effective to reduce cytokine levels and the amount of effusion in patients with DS. It is presumed that effusion seen in DS with TAM could be related to an abnormal production of cytokines at the effusion site.

Background: The risk factors for anemia of prematurity (AOP) among late preterm infants are unelucidated. We identified risk factors for declining hemoglobin (Hb) concentration and triggering factors for AOP treatment in infants born at 30-35 gestational weeks. Methods: From 2012 to 2020, we conducted a single-center retrospective study of infants born at 30-35 weeks of gestation without congenital anomalies or severe hemorrhage. The primary outcome was AOP development, defined by initiation of treatments including red blood cell transfusion, subcutaneous injections of erythropoietin, and iron supplementation. A multivariable logistic regression model was used to investigate potential risk factors for AOP. Results: A total of 358 infants were included. Lower gestational age (odds ratio, 0.19; 95% confidence interval 0.11-0.32), small for gestational age (SGA; 7.17, 2.15-23.9), low maternal Hb level before birth (0.66, 0.49-0.87), low Hb at birth (0.71, 0.57-0.89), and multiple large blood samplings (1.79; 1.40-2.29) showed significantly higher odds for AOP development. Conclusions: Gestational age, SGA, low maternal Hb before birth, Hb at birth, and high number of large blood samplings were positively associated with AOP development in infants born at 30-35 gestational weeks.