Validity of stress assessment using heart-rate variability in newborns.

BACKGROUND: The process of birth causes stress for neonates, but additional stressors for sick neonates are a matter of concern. As analysis of heart-rate variability (HRV), which reflects autonomic activity, has demonstrated that low-frequency (LF) activity reflects overall autonomic activity, high-frequency (HF) activity reflects parasympathetic activity, and the LF/HF ratio reflects sympathetic activity, HRV has been clinically applied as a non-invasive index of physical stress. In this study, we evaluated whether HRV is useful as a stress index for neonates by analyzing it in comparison with their salivary cortisol level. METHODS: We measured the salivary cortisol level and HRV in 12 healthy neonates and 37 neonates born during between 2014 and 2016 and admitted to the neonatal intensive care unit. These examinations were performed at birth and after approximately 1 week. The changes in parameters with time were examined. RESULTS: The LF and HF values in both groups exhibited significant negative correlations with the salivary cortisol level. In those admitted to the neonatal intensive care unit, the LF and HF values were correlated with gestational age and height. In the healthy neonates, a reduced salivary cortisol level and increase in the LF and HF values were observed approximately 1 week after birth compared with the values at birth, whereas the LF/HF ratio was not correlated with the salivary cortisol level and did not change over time. CONCLUSIONS: The LF and HF values were significantly correlated with the cortisol level, suggesting their usefulness as physiological indices of stress in clinical neonatal care.

Cerebellar peduncle injury predicts motor impairments in preterm infants: A quantitative tractography study at term-equivalent age.

PURPOSE: Cerebellar injury is well established as an important finding in preterm infants with cerebral palsy (CP). In this study, we investigated associations between injury to the cerebellar peduncles and motor impairments in preterm infants using quantitative tractography at term-equivalent age, which represents an early phase before the onset of motor impairments. METHODS: We studied 64 preterm infants who were born at <33 weeks gestational age. These infants were divided into three groups: CP, Non-CP (defined as infants with periventricular leukomalacia but having normal motor function), and a Normal group. Diffusion tensor imaging was performed at term-equivalent age and motor function was assessed no earlier than a corrected age of 2 years. Using tractography, we measured fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the superior cerebellar peduncles (SCP) and middle cerebellar peduncles (MCP), as well as the motor/sensory tracts. RESULTS: The infants in the CP group had significantly lower FA of the SCP and sensory tract than those in the other groups. There was no significant difference in FA and ADC of the motor tract among the three groups. Severity of CP had a significant correlation with FA of the MCP, but not with the FA of other white matter tracts. CONCLUSION: Our results suggested that the infants with CP had injuries of the ascending tracts (e.g. the SCP and sensory tract), and that additional MCP injury might increase the severity of CP. Quantitative tractography assessment at term-equivalent age may be useful for screening preterm infants for prediction of future motor impairments.

Longitudinal change in white matter in preterm infants without magnetic resonance imaging abnormalities: Assessment of serial diffusion tensor imaging and their relationship to neurodevelopmental outcomes.

PURPOSE: We used diffusion tensor imaging (DTI) to evaluate longitudinal changes in fractional anisotropy (FA) of white matter tracts in preterm infants without abnormal magnetic resonance imaging (MRI) findings. Imaging was conducted at term equivalent age (TEA) and 1year of corrected age. Furthermore, we assessed correlations between FA and neurodevelopmental outcomes at 3years of corrected age to investigate brain prematurity of preterm infants without MRI abnormalities. METHODS: Preterm infants underwent serial MRI at TEA and 1year of corrected age. Of these, 13 infants entered a retrospective study, undergoing neurodevelopmental assessment at 3years of corrected age. These infants were divided into two groups depending on gestational age (GA): <26weeks and ⩾26weeks. DTI-based tractography was performed to obtain the FA of the motor tract, sensory tract, superior cerebellar peduncle, middle cerebellar peduncle, and corpus callosum. FA was compared between two groups, and correlations between FA and neurodevelopmental outcomes were assessed. RESULTS: FA of the splenium at TEA was significantly different between the two groups divided according to GA. However, this difference was no longer observed at 1year of corrected age. There was no correlation between FA of the splenium at TEA and neurodevelopmental assessment scores at 3years of corrected age. CONCLUSIONS: At TEA, FA of the splenium was lower in younger GA infants without MRI abnormalities, but this may not affect subsequent neurodevelopmental outcomes.

Low-grade intraventricular hemorrhage disrupts cerebellar white matter in preterm infants: evidence from diffusion tensor imaging.

INTRODUCTION: Recent diffusion tensor imaging (DTI) studies have demonstrated that leakage of hemosiderin into cerebrospinal fluid (CSF), which is caused by high-grade intraventricular hemorrhage (IVH), can affect cerebellar development in preterm born infants. However, a direct effect of low-grade IVH on cerebellar development is unknown. Thus, we evaluated the cerebellar and cerebral white matter (WM) of preterm infants with low-grade IVH. METHODS: Using DTI tractography performed at term-equivalent age, we analyzed 42 infants who were born less than 30 weeks gestational age (GA) at birth (22 with low-grade IVH, 20 without). These infants were divided into two birth groups depending on GA, and we then compared the presence and absence of IVH which was diagnosed by cerebral ultrasound (CUS) within 10 days after birth or conventional magnetic resonance imaging (MRI) at term-equivalent age in each group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at the superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP), motor tract, and sensory tract were measured. RESULTS: In the SCP, preterm born infants with IVH had lower FA values compared with infants without IVH. In particular, younger preterm birth with IVH had lower FA values in the SCP and motor tract and higher ADC values in the MCP. CONCLUSION: Low-grade IVH impaired cerebellar and cerebral WM, especially in the SCP. Moreover, younger preterm infants exhibited greater disruptions to cerebellar WM and the motor tract than infants of older preterm birth.

Development of corpus callosum in preterm infants is affected by the prematurity: in vivo assessment of diffusion tensor imaging at term-equivalent age.

Callosal injury in preterm infants is a key factor affecting neurodevelopmental outcome. We investigated the characteristics of corpus callosum (CC) in preterm infants without apparent white matter lesions. We studied 58 preterm infants divided into three groups of 23-25, 26-29, and 30-33 wk GA. Diffusion tensor imaging (DTI) was obtained at term-equivalent age. The CC was parcellated into the genu, body, isthmus, and splenium. We measured fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of each CC subdivision using tractography and manual region of interest analysis. The cross-sectional areas were also measured. At the isthmus and splenium in the 23-25 GA group, the FA was significantly lower and the size was also significantly reduced. Furthermore, the FA and cross-sectional areas in the posterior CC decreased linearly with decreasing GA. There were no differences in FA and cross-sectional areas in other CC subdivisions, and no differences in ADC in any CC subdivisions, among the GA groups. We demonstrated that preterm infants without apparent white matter lesions affect development of the posterior CC depending on the degree of prematurity.

HCO(-3)-dependent pHi recovery and overacidification induced by NH+4 pulse in rat lung alveolar type II cells: HCO(-3)-dependent NH3 excretion from lungs?

Intracellular pH (pHi) after the NH+4 pulse addition and its removal were measured in isolated alveolar type II cells (ATII cells) using BCECF fluorescence. In the absence of HCO(-3), the NH+4 pulse addition increased pHi (alkali jump) and its removal decreased pH(i) (acid jump) to the control level (no overacidification). This pHi change was induced by reaction 1 (NH3 + H+ <--> NH+4). However, in the presence of HCO(-3), the NH+4 pulse removal decreased pHi (acid jump) with overacidification. The extent of overacidification was decreased by acetazolamide (a carbonic anhydrase inhibitor), bumetanide (an inhibitor of Na+/K+/2Cl(-) cotransporter [NKCC]), and NPPB (an inhibitor of Cl(-) channel). The NH+4 pulse addition led to the accumulation of NH+4 in ATII cells via reaction 1 and NKCC, and the NH+4 pulse removal induced reaction 2 (NH+4 + HCO(-3) --> NH3 + H+ HCO(-3)) in addition to the reversal of reaction 1. Thus, NH+4 that entered via NKCC reacts with HCO(-3) (reaction 2) to produce H+, which induces overacidification in the acid jump. After the overacidification, the pH(i) recovery consisted of a rapid recovery (first phase) followed by a slow recovery (second phase). The first phase was inhibited by NPPB, glybenclamide, amiloride, and an Na+-free solution, and the second phase was inhibited by DIDS, MIA, and an Na+-free solution. Both phases were accelerated by a high extracellular HCO(-3) concentration. These observations indicate that the first phase was induced by HCO(-3) entry via Cl(-) channels coupled with Na+ channels activities, and that the second phase was induced by H+ extrusion via Na+/H+ exchanger and by HCO(-3) entry via HCO(-3) cotransporter. Thus, in ATII cells, HCO(-3) entry via Cl(-) channels is essential for recovering pHi after overacidification during the acid jump and for removing NH+4 that entered via NKCC from ATII cells, suggesting HCO(-3)-dependent NH3 excretion from lungs.

Successful treatment of congenital systemic juvenile xanthogranuloma with Langerhans cell histiocytosis-based chemotherapy.

Juvenile xanthogranuloma (JXG), one of the most common forms of non-Langerhans cell histiocytosis (LCH), usually presents in young children as spontaneously regressing cutaneous lesions. However, the systemic type of JXG is difficult to treat in newborn infants, and fatal cases have been reported. In the patient described here, solid masses were discovered by fetal sonography during the 38th gestational week. At birth she had multiple tumors on the back, cheek, and hip as well as marked hepatosplenomegaly accompanied by respiratory failure. Laboratory results indicated pancytopenia, obstructive liver dysfunction, and coagulopathy. Brain magnetic resonance imaging revealed a tumor at the left pontine angle, and dysmorphic histiocytes were present in her spinal fluid. She was diagnosed with systemic JXG by histopathologic findings of the hip mass. The LCH-based multiagent chemotherapy including cytarabine, vincristine, methotrexate, and prednisolone ameliorated the symptoms rapidly. She was treated for 12 months and is currently doing well as a normally developing 2-year-old.