Underlying Disorders in Children With Infection-Related Acute Encephalopathy.

BACKGROUND: Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. METHODS: We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. RESULTS: The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. CONCLUSIONS: The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth.

Body composition and motor function in children born large for gestational age at term.

BACKGROUND: This cross-sectional study compared body composition and motor function between children who were born large for gestational age (LGA) and those born appropriate for gestational age (AGA) and to investigate the association between gait quality and other variables. METHODS: Body composition was determined using a bioelectrical impedance analyzer. Motor functions were assessed using one-leg standing time, timed up-and-go test, five times sit-to-stand test, and three-dimensional gait analysis. We compared the results between two groups. We performed multiple regression analysis to evaluate the association between gait deviation index and variables of LGA, fat mass index, and motor functions (adjusted for age and sex). RESULTS: Children aged 6-12 years who were born LGA at term (n = 23) and those who were born AGA at term (n = 147) were enrolled. The LGA group had a higher fat mass index (2.9 vs. 2.2, p = 0.006) and lower gait deviation index (91.4 vs. 95.4, p = 0.011) than the AGA group. On multiple regression analysis, gait deviation index was associated with being LGA and fat mass index. CONCLUSIONS: In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function. IMPACT: Children aged 6-12 years who were born large for gestational age (LGA) at term showed a higher fat mass index and lower gait deviation index than those who were born appropriate for gestational age at term. No significant differences in balance function or muscle strength were observed between groups. On multiple regression analysis, gait deviation index was associated with being LGA at birth and fat mass index. In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function.

Effect of levodopa on pathological gait in Dravet syndrome: A randomized crossover trial using three-dimensional gait analysis.

OBJECTIVE: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). METHODS: Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. RESULTS: Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. SIGNIFICANCE: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.

Three-Dimensional Gait Analysis as a Biomarker for GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia.

BACKGROUND: GTP-cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) typically presents in childhood with dystonic posture of the lower extremities, gait impairment, and a significant response to levodopa. We performed three-dimensional gait analysis (3DGA) to quantitatively assess the gait characteristics and changes associated with levodopa treatment in patients with GTPCH1-deficient DRD. METHODS: Three levodopa-treated patients with GTPCH1-deficient DRD underwent 3DGA twice, longitudinally. Changes were evaluated for cadence; gait speed; step length; gait deviation index; kinematic data of the pelvis, hip, knee, and ankle joints; and foot progression angle. RESULTS: Levodopa treatment increased the cadence and gait speed in one of three patients and increased the gait deviation index in two of three patients. The kinematic data for each joint exhibited different characteristics, with some improvement observed in each of the three patients. There was consistent marked improvement in the abnormal foot progression angle; one patient had excessive external rotation of one foot, another had excessive bilateral internal rotation, and the other had excessive internal rotation of one foot and excessive external rotation of the opposite foot, all of which improved. CONCLUSION: The 3DGA findings demonstrate that the gait pathology and recovery process in GTPCH1-deficient DRD vary from case to case. Changes in the foot progression angle and gait deviation index can enable the effects of treatment to be more easily evaluated.

Intrauterine exposure to chorioamnionitis and neuroanatomical alterations at term-equivalent age in preterm infants.

PURPOSE: Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. METHODS: A total of 58 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). RESULTS: The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. CONCLUSIONS: Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age.

Proteomic Analysis Reveals Novel Plasma Biomarkers for Neurological Complications in Patients With Congenital Cytomegalovirus Infection.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is a leading cause of nonhereditary neurological complications. When considering antiviral treatment, it is important to differentiate between symptomatic and asymptomatic patients. This study aimed to identify candidate plasma biomarkers for neurological complications of cCMV infection using proteomic analysis. METHODS: This study retrospectively enrolled five patients with symptomatic cCMV infection, four with asymptomatic cCMV infection with isolated sensorineural hearing loss (SNHL), and five with asymptomatic cCMV infection. The plasma samples were collected during neonatal period. The peptides were analyzed using liquid chromatography-mass spectrometry. The concentrations of differentially expressed proteins were validated using an enzyme-linked immunosorbent assay. RESULTS: A total of 456 proteins were identified and quantified. The levels of 80 proteins were significantly different between patients with and without cCMV-related symptoms including isolated SNHL. The levels of 31 proteins were significantly different between patients with and without neuroimaging abnormalities. The plasma concentrations of Fms-related receptor tyrosine kinase 4 in patients with cCMV-related symptoms were significantly higher than those in patients with asymptomatic cCMV infection. Moreover, plasma peptidylprolyl isomerase A levels were significantly higher in patients with neuroimaging abnormalities than in those without. CONCLUSIONS: Proteomic analysis of patients with cCMV infection showed that Fms-related receptor tyrosine kinase 4 and peptidylprolyl isomerase A could be novel diagnostic biomarkers for neurological complications of cCMV infection.

Two Cases of Juvenile Myelomonocytic Leukemia and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. METHODS: We investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. RESULTS: Patient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. CONCLUSION: We treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.

Gait performance and dual-task costs in school-aged children with Down syndrome.

OBJECTIVE: This cross-sectional observational study aimed to assess gait performance, its correlation with physical functions, and its dual-task costs in children with Down syndrome (DS), to investigate their gait adaptations. METHODS: Gait performance with or without movie-watching tasks was evaluated in 17 children with DS (age, 6-12 years) and 51 age- and sex-matched controls, using three-dimensional gait analysis. We compared participants' demographics, physical functions, and gait performance without tasks between the two groups. In the DS group, correlations between physical functions, the intelligence quotient, and gait variables were assessed. Dual-task costs for gait variables were also compared between the two groups. RESULTS: Children with DS showed poorer balance function and muscle strength and lower gait quality than the control group. In the DS group, there was a significant positive correlation between gait speed, step length, and intelligence quotient. There were no correlations between the balance function, muscle strength, intelligence quotient, and gait quality. Dual-task costs for gait speed, step length, and cadence were greater in the DS group; however, there was no significant difference in dual-task costs for gait quality between the two groups. CONCLUSION: These findings highlight the importance of providing appropriate interventions for motor functions in school-aged children with DS based on their gait performance in single- and dual-task conditions, as well as on their intelligence quotient.

Pathological gait in Rett syndrome: Quantitative evaluation using three-dimensional gait analysis.

OBJECTIVES: Ataxic-rigid gait is a characteristic gait pathology in patients with Rett syndrome (RTT). In the present study, we aimed to quantitatively evaluate gait pathology in patients with RTT using three-dimensional gait analysis (3DGA). METHODS: We performed 3DGA in 11 patients with RTT ranging from 5 to 18 years (median age, 9 years) and in 33 age-matched healthy female controls. We compared the results of 3DGA, including spatiotemporal gait parameters and comprehensive indices of gait kinematics, such as the Gait Deviation Index (GDI) and Gait Profile Score (GPS), between the two groups. The GPS consists of nine sub-indices called Gait Variable Scores (GVSs). Decline in GDI or elevation of GPS and GVS indicated greater abnormal gait pathology. RESULTS: The patients demonstrated significantly slower walking speed, lower step length/length of the lower extremities, lower cadence, wider step width, and higher coefficient of variation of step length than the controls. Moreover, the patients had a lower GDI and higher GPS than the controls. The patients also exhibited higher GVSs for eight out of nine gait kinematics, particularly the sagittal plane in the pelvis, hip, knee, and ankle joint; coronal plane in the pelvis and hip joint; and horizontal plane in the pelvis than the controls. CONCLUSIONS: Quantitative evaluation of gait pathology in patients with RTT is possible using 3DGA. We found that in addition to ataxic-rigid gait, abnormalities in the coronal plane of the pelvis and hip joint and the horizontal plane of the pelvis were prominent.

Impact of the Coronavirus Disease 2019 Pandemic on the Clinical Features of Pediatric Respiratory Syncytial Virus Infection in Japan.

Background: Mitigation measures implemented during the coronavirus disease 2019 (COVID-19) pandemic remarkably reduced the incidence of infectious diseases among children. However, a re-emergence of respiratory syncytial virus (RSV) infection was observed in 2021 in Japan. We compared the clinical characteristics of hospitalized patients with RSV infection before and during COVID-19. Methods: We retrospectively enrolled children aged <6 years who were hospitalized with RSV infection in 18 hospitals and compared their clinical characteristics before (January 2019 to April 2020, 1675 patients) and during COVID-19 (September 2020 to December 2021, 1297 patients). Results: The mean age of patients with RSV infection was significantly higher during COVID-19 than before (17.4 vs 13.7 months, P < .001). Compared with before COVID-19, a 2.6-fold increase in RSV cases in the 2-5 years age group was observed from sentinel surveillance during COVID-19, whereas a 1.2-fold increase was noted in the same age group among hospitalized patients. On average for all patients, consolidation shadows obtained on radiography were less frequently observed (26.1 vs 29.6%, P = .04), and reduced respiratory assistance (42.2% vs 48.7%, P < .001) and hospitalization stay (5.7 vs 6.0 days, P < .001) was required in patients with RSV infection during COVID-19. Conclusions: Coronavirus disease 2019 and social activity restriction caused epidemiological changes in pediatric RSV infections, and a majority of patients with RSV infection aged ≥2 years did not develop severe symptoms requiring hospitalization. The RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons.

Förster resonance energy transfer-based kinase mutation phenotyping reveals an aberrant facilitation of Ca2+/calmodulin-dependent CaMKIIα activity in de novo mutations related to intellectual disability.

CaMKIIα plays a fundamental role in learning and memory and is a key determinant of synaptic plasticity. Its kinase activity is regulated by the binding of Ca2+/CaM and by autophosphorylation that operates in an activity-dependent manner. Though many mutations in CAMK2A were linked to a variety of neurological disorders, the multiplicity of its functional substrates renders the systematic molecular phenotyping challenging. In this study, we report a new case of CAMK2A P212L, a recurrent mutation, in a patient with an intellectual disability. To quantify the effect of this mutation, we developed a FRET-based kinase phenotyping strategy and measured aberrance in Ca2+/CaM-dependent activation dynamics in vitro and in synaptically connected neurons. CaMKIIα P212L revealed a significantly facilitated Ca2+/CaM-dependent activation in vitro. Consistently, this mutant showed faster activation and more delayed inactivation in neurons. More prolonged kinase activation was also accompanied by a leftward shift in the CaMKIIα input frequency tuning curve. In keeping with this, molecular phenotyping of other reported CAMK2A de novo mutations linked to intellectual disability revealed aberrant facilitation of Ca2+/CaM-dependent activation of CaMKIIα in most cases. Finally, the pharmacological reversal of CAMK2A P212L phenotype in neurons was demonstrated using an FDA-approved NMDA receptor antagonist memantine, providing a basis for targeted therapeutics in CAMK2A-linked intellectual disability. Taken together, FRET-based kinase mutation phenotyping sheds light on the biological impact of CAMK2A mutations and provides a selective, sensitive, quantitative, and scalable strategy for gaining novel insights into the molecular etiology of intellectual disability.

Whole-exome analysis of 177 pediatric patients with undiagnosed diseases.

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24-35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

Quantitative Three-Dimensional Gait Evaluation in Patients With Glucose Transporter 1 Deficiency Syndrome.

BACKGROUND: Of the patients with glucose transporter 1 deficiency syndrome (GLUT1-DS), 90% have a pathologic gait. Ataxic-spastic and ataxic gaits are seen in 35% of patients each. A ketogenic diet and modified Atkins diet (MAD) are effective therapy in GLUT1-DS in terms of both the seizures and movement disorder. A three-dimensional gait analysis (3DGA) system can be used to evaluate gait quantitatively using spatiotemporal data and gait kinematics. We performed 3DGA in three ambulatory patients with GLUT1-DS to evaluate the characteristics of their gait pathology, and we compared the gait variables before and after enhancing the MAD in one patient. METHODS: After examination by pediatric neurologists and pediatric orthopedic surgeons, 3DGA was performed. We assessed walking speed, step length, step width, gait variability, Gait Deviation Index (GDI), Gait Profile Score (GPS), and Gait Variable Score (GVS). RESULTS: All three patients had a low GDI and high GPS, comprehensive indices of gait pathology. The unstable gait pattern featured a wide step width in one patient and high gait variability in two patients. In the sagittal plane, the patients had increased GVSs in the knee and ankle joints due to excessive knee flexion or extension and excessive ankle plantarflexion. In the horizontal plane, the patients had increased GVSs in the pelvis, hips, and foot due to excessive rotation during walking. After enhancing the MAD, GDI, GPS, and GVSs improved. CONCLUSIONS: 3DGA has potential for quantifying the characteristics of gait pathology and its improvement with dietary therapy in patients with GLUT1-DS.

Involvement of brain structures in childhood epilepsy with centrotemporal spikes.

BACKGROUND: We aimed to investigate electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) findings to elucidate the interictal epileptiform discharge (IED)-related functional alterations in deep brain structures and the neocortex in childhood epilepsy with centrotemporal spikes (CECTS). METHODS: Ten children with CECTS (median age 8.2 years), referred to our hospital within a year of onset, were eligible for inclusion. They underwent EEG-fMRI recording during sleep. Llongitudinal evaluations, including medical examinations, intelligence tests, and questionnaires about developmental disabilities, were performed. The initial evaluation was performed at the same time as the EEG-fMRI, and the second evaluation was performed over 2 years after the initial evaluation. RESULTS: Three children were unable to maintain sleep during the EEG-fMRI recording, and the remaining seven children were eligible for further assessment. All patients showed unilateral-dominant centrotemporal spikes during scans. One patient had only positive hemodynamic responses, while the others had both positive and negative hemodynamic responses. All patients showed IED-related hemodynamic responses in the bilateral neocortex. For deep brain structures, IED-related hemodynamic responses were observed in the cingulate gyrus (n = 4), basal ganglia (n = 3), thalamus (n = 2), and default mode network (n = 1). Seizure frequencies at the second evaluation were infrequent or absent, and the longitudinal results of intelligence tests and questionnaires were within normal ranges. CONCLUSIONS: We demonstrated that IEDs affect broad brain areas, including deep brain structures such as the cingulate gyrus, basal ganglia, and thalamus. Deep brain structures may play an important role in the pathophysiology of CECTS.

Acute encephalopathy with biphasic seizures and late reduced diffusion: Predictive EEG findings.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs. METHODS: We studied the electroencephalograms (EEGs) of children <6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep. RESULTS: The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035). CONCLUSIONS: EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

Effectiveness of lacosamide in children and young adults previously treated with other sodium channel blockers.

PURPOSE: This multicenter study examined the effectiveness and tolerability of lacosamide (LCM) for children and young adults with epilepsy, particularly in patients who had previously been treated with other sodium channel blockers (SCBs) and the difference in effectiveness and tolerability when using other concomitant SCBs. METHODS: We retrospectively studied the clinical information of patients aged <30 years given LCM to treat epilepsy. The effectiveness and adverse events (AEs) of LCM and the other SCBs were investigated. Factors related to the effectiveness and AEs of LCM, such as the number of antiepileptic drugs (AEDs) tried before LCM and concomitantly used SCBs, were also studied. RESULTS: We enrolled 112 patients (median age = 11 years). One year after starting LCM, 29% of the patients were seizure free, and 50% had a ≥50% seizure reduction. Of the patients, 17% experienced AEs, the most common being somnolence. A ≥50% seizure reduction was observed for LCM in 30% of patients in whom other SCBs had not been effective. Lacosamide produced a ≥50% seizure reduction in 35% of the patients taking one concomitant SCB. By contrast, no patients had ≥50% seizure reduction, and 33% developed AEs, when LCM was administered concomitantly with two SCBs. CONCLUSIONS: Lacosamide was effective in 30% of children and young adults in whom other SCBs had not been effective. The effectiveness of LCM may differ from that of other SCBs, and it is worth trying in patients with epilepsy resistant to other AEDs.

Hypertensive disorders of pregnancy and alterations in brain metabolites in preterm infants: A multi-voxel proton MR spectroscopy study.

BACKGROUND: Infants born to mothers with hypertensive disorders of pregnancy (HDP) have adverse neurodevelopmental consequences in later life. Magnetic resonance spectroscopy (MRS) is used to predict subsequent neurodevelopment in the field of perinatology. AIM: We aimed to determine whether exposure to HDP in utero leads to alterations in brain metabolites in preterm infants using multi-voxel proton MRS at term-equivalent age. STUDY DESIGN: Retrospective cohort study. SUBJECTS: A total of 103 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible. Twenty-seven infants were born to mothers with HDP (HDP group), and 76 were born to mothers without HDP (non-HDP group). OUTCOME MEASURES: The peak area ratios of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr were evaluated at 10 designated regions of interest (bilateral frontal lobes, basal ganglia, thalami, temporal lobes, and occipital lobes). RESULTS: The peak area ratios of NAA/Cho and NAA/Cr in the bilateral thalami were significantly higher in the HDP group than in the non-HDP group after adjustment for covariates (postmenstrual age at MRS assessment and infant sex). No significant differences were observed in other regions. Preeclampsia, abnormal umbilical artery blood flow, and fetal growth restrictions were significantly associated with increased NAA/Cho and NAA/Cr ratios in the thalami. CONCLUSIONS: Based on the evidence that NAA/Cho and NAA/Cr ratios constantly increase with postmenstrual age in normal brain development, exposure to maternal HDP in utero may accelerate brain maturation and increase neuronal activity in preterm infants.

Physical functions and gait performance in school-aged children born late preterm.

BACKGROUND: Children born late preterm (LP) have an increased risk of poor developmental motor outcomes. AIMS: This study aimed to assess physical functions and gait performance in school-aged children born LP. STUDY DESIGN: Cross-sectional study. SUBJECTS: Physical functions and gait performance were evaluated in 277 children aged 6-10 years born LP (n = 22) and full-term (FT) (n = 255). OUTCOME MEASURES: Physical function tests consisted of five times sit-to-stand test (FTSST), one-leg standing time, and grip strength. FTSST was used to assess the functional muscle strength of the lower limbs and dynamic balance function. Gait performance tests included gait quality, spatiotemporal gait parameters, and gait variability. Clinical data, physical functions, and gait performance were compared between two groups. Furthermore, logistic regression analysis was performed to assess the association between all variables and LP birth. RESULTS: In physical function tests, children born LP showed poorer FTSST than those born FT (p = 0.039). No significant difference in gait performance tests were identified between the two groups. Logistic regression analysis of FTSST for LP (adjusted for age at assessment) revealed that FTSST was significantly associated with LP birth (p = 0.004, odds ratio = 1.579, 95% confidence interval = 1.160-2.149). CONCLUSIONS: We demonstrated the physical functions and gait performance in school-aged children born LP. Our findings indicate that it is important to focus on the decreased functional muscle strength of the lower limbs and reduced dynamic balance function related to LP birth to improve functional mobility in children born LP.