Faculty Profiles - WASHIO Yousuke

Papers - WASHIO Yousuke

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A case of fetal myocardial calcification with hyperechoic area in fetal echocardiography. International journal

Takeshi Sato, Yosuke Washio, Hotaka Kawai, Kenji Baba, Eriko Eto, Hisashi Masuyama, Hirokazu Tsukahara

Pediatrics international : official journal of the Japan Pediatric Society 67 ( 1 ) e15868 2025

Long-term survival of an infant with complete tetraploidy: A case report. International journal

Tomoka Okamura, Junko Yoshimoto, Daisaku Morimoto, Hirokazu Wanatabe, Yosuke Washio

American journal of medical genetics. Part A e63717 2024.6

Language：English Publishing type：Research paper (scientific journal)

We present the case of a girl with complete tetraploidy who has survived to her present age of 4 years and 1 month. Infants with complete tetraploidy have been described to have a limited lifespan owing to complications. We report her characteristics, medical history, and development.

DOI： 10.1002/ajmg.a.63717

Machine Learning to Improve Accuracy of Transcutaneous Bilirubinometry. International journal

Daisaku Morimoto, Yosuke Washio, Kana Fukuda, Takeshi Sato, Tomoka Okamura, Hirokazu Watanabe, Junko Yoshimoto, Maki Tanioka, Hirokazu Tsukahara

Neonatology 1 - 8 2024.4

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: This study aimed to develop models for predicting total serum bilirubin by correcting errors of transcutaneous bilirubin using machine learning based on neonatal biomarkers that could affect spectrophotometric measurements of tissue bilirubin. METHODS: This retrospective study included infants born at our hospital (≥36 weeks old, ≥2,000 g) between January 2020 and December 2022. Infants without a phototherapy history were included. Robust linear regression, gradient boosting tree, and neural networks were used for machine learning models. A neural network, inspired by the structure of the human brain, was designed comprising three layers: input, intermediate, and output. RESULTS: Totally, 683 infants were included. The mean (minimum-maximum) gestational age, birth weight, participant age, total serum bilirubin, and transcutaneous bilirubin were 39.0 (36.0-42.0) weeks, 3,004 (2,004-4,484) g, 2.8 (1-6) days of age, 8.50 (2.67-18.12) mg/dL, and 7.8 (1.1-18.1) mg/dL, respectively. The neural network model had a root mean square error of 1.03 mg/dL and a mean absolute error of 0.80 mg/dL in cross-validation data. These values were 0.37 mg/dL and 0.28 mg/dL, smaller compared to transcutaneous bilirubin, respectively. The 95% limit of agreement between the neural network estimation and total serum bilirubin was -2.01 to 2.01 mg/dL. Unnecessary blood draws could be reduced by up to 78%. CONCLUSION: Using machine learning with transcutaneous bilirubin, total serum bilirubin estimation error was reduced by 25%. This integration could increase accuracy, lessen infant discomfort, and simplify procedures, offering a smart alternative to blood draws by accurately estimating phototherapy thresholds.

DOI： 10.1159/000535970

Short stature in small-for-gestational-age offspring born to mothers with hypertensive disorders of pregnancy. International journal

Sakurako Mishima, Takashi Mitsui, Kazumasa Tani, Jota Maki, Eriko Eto, Kei Hayata, Yosuke Washio, Junko Yoshimoto, Hirokazu Tsukahara, Hisashi Masuyama

Hypertension in pregnancy 42 ( 1 ) 2187623 - 2187623 2023.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To investigate the incidence and risk factors of small-for-gestational age (SGA) short stature at 2 and 3 years of age in SGA offspring born to women with hypertensive disorders of pregnancy (HDP). METHODS: We examined 226 women with HDP whose respective SGA offspring were delivered. RESULTS: Eighty offspring (41.2%) were diagnosed with SGA short stature. The prematurity before 32 weeks of gestation was the most significant factor for catch-up growth failure. CONCLUSION: In SGA offspring born to women with HDP, SGA short stature incidence was high, and the risk factor was prematurity before 32 weeks of gestation.

DOI： 10.1080/10641955.2023.2187623

A nationwide birth cohort in Japan showed increased risk of early childhood hospitalisation in infants born small for gestational age. International journal

Asami Ohyama, Naomi Matsumoto, Kei Tamai, Yosuke Washio, Junko Yoshimoto, Takashi Yorifuji, Hirokazu Tsukahara

Acta paediatrica (Oslo, Norway : 1992) 2023.11

Language：English Publishing type：Research paper (scientific journal)

AIM: To examine associations between children being born small for gestational age and childhood hospitalisation following term and preterm births. METHODS: This study included 34 564 children from a nationwide population-based longitudinal survey starting in 2010, comprising 32 603 term births and 1961 preterm births. Children's hospitalisation history was examined during two observational periods, 6-18 and 6-66 months of age. Logistic regression analysis was conducted, adjusting for child and parental confounders, with children born appropriate for gestational age as reference. RESULTS: Children born small for gestational age were more likely to be hospitalised during early childhood than those born appropriate for gestational age. The odds ratio (95% confidence interval) for hospitalisation from 6 to 66 months of age was 1.19 (1.05-1.34) in term children born small for gestational age and 1.47 (1.05-2.06) for preterm children born small for gestational age, compared with those born appropriate for gestational age. The risk of hospitalisation from 6 to 66 months of age in children born small for gestational age was observed for bronchitis/pneumonia. CONCLUSION: We observed the adverse effects of small for gestational age on hospitalisation during early childhood in both term and preterm births, particularly for bronchitis and pneumonia.

DOI： 10.1111/apa.17032

Postnatal longitudinal analysis of serum Nitric oxide and eosinophil counts in extremely preterm infants. International journal

Hirokazu Watanabe, Yosuke Washio, Kei Tamai, Daisaku Morimoto, Tomoka Okamura, Junko Yoshimoto, Hidehiko Nakanishi, Misao Kageyama, Atsushi Uchiyama, Hirokazu Tsukahara, Satoshi Kusuda

Pediatrics and neonatology 2023.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. METHODS: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. RESULTS: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 μmol/L, 51.2 ± 23.7 μmol/L, 42.4 ± 15.2 μmol/L, and 33.8 ± 9.4 μmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/μL, 613 ± 625/μL, 466 ± 375/μL, and 292 ± 228/μL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. CONCLUSION: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age.

DOI： 10.1016/j.pedneo.2023.08.006

Three Cases of Down Syndrome with Transient Abnormal Myelopoiesis who Underwent Liver Biopsy before Induction of Low-Dose Cytarabine.

Kana Washio, Kosuke Tamefusa, Motoharu Ochi, Kiichiro Kanamitsu, Hisashi Ishida, Kaori Fujiwara, Kenji Nishida, Kei Tamai, Yosuke Washio, Junko Yoshimoto, Takuo Noda, Hirokazu Tsukahara

Acta medica Okayama 77 ( 2 ) 215 - 220 2023.4

Language：English

Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.

DOI： 10.18926/AMO/65153

Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study. International journal

Daisaku Morimoto, Yosuke Washio, Kei Tamai, Takeshi Sato, Tomoka Okamura, Hirokazu Watanabe, Yu Fukushima, Junko Yoshimoto, Misao Kageyama, Kenji Baba, Hirokazu Tsukahara

Biomedicines 11 ( 1 ) 2023.1

Language：English Publishing type：Research paper (scientific journal)

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.

DOI： 10.3390/biomedicines11010212

Prediction model for nonopiate-induced neonatal abstinence syndrome. International journal

Daisaku Morimoto, Yosuke Washio, Takeshi Sato, Tomoka Okamura, Hirokazu Watanabe, Junko Yoshimoto, Hirokazu Tsukahara

Pediatrics international : official journal of the Japan Pediatric Society 65 ( 1 ) e15435 2022.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Neonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. While psychiatric drugs are a more common cause of NAS in Japan, infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate-induced NAS using variables available at birth. METHODS: In this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents. RESULTS: A total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z-score and Apgar score at 5 minutes < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C-statistics were 0.747 (95% CI: 0.638-0.856), and 0.795 (95% CI: 0.683-0.907), respectively, indicating good predictive accuracy of NAS onset for the models. CONCLUSIONS: This study developed models that predicted nonopiate-induced NAS with good accuracy, which may be further improved through the use of drug indices.

DOI： 10.1111/ped.15435

【ケアの介入・搬送・報告のタイミングが変わる!新生児の生理・徴候と代表的疾患まるごとガイド】(第3章)新生児の代表的疾患その他、押さえておくべき疾患新生児薬物離脱症候群

森本大作, 鷲尾洋介

with NEO ( 2022秋季増刊 ) 289 - 292 2022.9

Sports participation and preterm birth: a nationwide birth cohort in Japan. International journal

Kei Tamai, Naomi Matsumoto, Akihito Takeuchi, Makoto Nakamura, Kazue Nakamura, Misao Kageyama, Yosuke Washio, Hirokazu Tsukahara, Takashi Yorifuji

Pediatric research 92 ( 2 ) 572 - 579 2021.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Children born preterm may be less physically active than children born term because of neurocognitive problems, reduced lung function, and poor physical fitness. We evaluated sports participation of children and adolescents who had been born preterm (<37 weeks) and early term (37-38 weeks) in 2001. METHODS: Data from a nationwide longitudinal survey (n = 47,015, including 2375 children born preterm) were analyzed. As indicators of sports participation, we used responses to questions about participation in sports clubs at 7 and 10 years old and in extracurricular school sports at 15 years old. RESULTS: Children born very preterm (25-31 weeks) and moderately to late preterm (32-36 weeks) were less likely to participate in sports clubs at 7, 10, and 15 years old than children born full term (39-41 weeks). Compared with children born full term, the adjusted risk ratios for participation in extracurricular school sports at 15 years old were 0.86 (95% confidence interval: 0.75-0.98) for children born very preterm, 0.92 (0.88-0.97) for children born moderately to late preterm, and 1.00 (0.98-1.02) for children born early term. CONCLUSIONS: Our findings suggest that preterm birth is associated with less participation in organized sports during childhood and adolescence than full-term birth. IMPACT: Research investigating associations between preterm birth and physical activity among children born in the 2000s is limited. This study shows that preterm birth was associated with less participation in organized sports during childhood and adolescence than full-term birth, especially in boys, and the participation in organized sports of children born preterm decreased as gestation shortened. During childhood, boys born early term were also less likely to participate in organized sports than boys born full term, suggesting a continuum with preterm births. These findings offer important additional insights into the limited evidence available for predicting future health outcomes for preterm infants.

DOI： 10.1038/s41390-021-01808-9

Head circumference in infants with nonopiate-induced neonatal abstinence syndrome. International journal

Daisaku Morimoto, Yosuke Washio, Kazuki Hatayama, Tomoka Okamura, Hirokazu Watanabe, Junko Yoshimoto, Hirokazu Tsukahara

CNS spectrums 26 ( 5 ) 509 - 512 2021.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: No relationship has been reported between nonopiate neonatal abstinence syndrome (NAS) and anthropometric indices, including head circumference (HC). The purpose of this study was to determine the relationship between maternal nonopioid drug use and HC at birth in neonates with NAS. METHODS: This retrospective observational study included neonates born between January 1, 2010 and March 31, 2019, whose mothers had been taking antipsychotic, antidepressant, sedative, or anticonvulsant medications. The outcome measures were HCs of NAS infants and controls. RESULTS: Of 159 infants, 33 (21%) were diagnosed with NAS. There was no maternal opioid use among mothers during pregnancy. The HCs in the NAS group were significantly smaller than those in the control group. The median z-scores for HC at birth were -0.20 and 0.29 in the NAS group and the control group, respectively (P = .011). The median HCs at birth were 33.0 and 33.5 cm in the NAS group and the control group, respectively. Multivariate analysis revealed that maternal antipsychotic drug use and selective serotonin reuptake inhibitors were independently associated with NAS (P < .001 and P = .004, respectively). Notably, benzodiazepine use and smoking were not independent risk factors. CONCLUSIONS: The results suggest an association between maternal antipsychotic drug use and NAS, which was further associated with decreased HC. Careful monitoring of maternal drug use should be considered to improve fetal outcomes.

DOI： 10.1017/S1092852920001522

Association Between Eosinophilia and Late-onset Circulatory Collapse in Preterm Infants: A case-Control Study.

Tomoka Okamura, Yosuke Washio, Hirokazu Watanabe, Hidehiko Nakanishi, Atsushi Uchiyama, Hirokazu Tsukahara, Satoshi Kusuda

Acta medica Okayama 75 ( 4 ) 505 - 509 2021.8

Language：English Publishing type：Research paper (scientific journal)

Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks' gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency.

DOI： 10.18926/AMO/62403

Associations of Birth Weight for Gestational Age with Child Health and Neurodevelopment among Term Infants: A Nationwide Japanese Population-Based Study. International journal

Kei Tamai, Takashi Yorifuji, Akihito Takeuchi, Yu Fukushima, Makoto Nakamura, Naomi Matsumoto, Yosuke Washio, Misao Kageyama, Hirokazu Tsukahara

The Journal of pediatrics 226 135 - 141 2020.11

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To examine the association of specific Z-score categories of birth weight for gestational age with child health and neurodevelopment using a large nationwide survey in Japan, focusing on term infants. STUDY DESIGN: We included 36 321 children born in 2010. Hospitalization up to 66 months of age was used as an indicator of health status, and responses to questions about age-appropriate behaviors at 30 and 66 months of age were used to indicate neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for child and parental variables. A restricted cubic spline function was used to model the relationship. RESULTS: Compared with children with birth weight appropriate for gestational age (-1.28 to 1.28 SDs of expected birthweight for gestational age), children who were small for gestational age (SGA) (<-1.28 SD) had higher risks of hospitalization and unfavorable neurobehavioral development, and the risks increased as SGA status became more severe. Compared with the appropriate for gestational age group, the adjusted risk ratios for hospitalization for all causes were 2.5 (95% CI, 1.7-3.6), 1.3 (95% CI, 1.1-1.6), and 1.1 (95% CI, 1.0-1.2) for children who were severely, moderately, and mildly SGA and 1.0 (95% CI, 0.9-1.1), 1.1 (95% CI, 0.9-1.2), and 1.4 (95% CI, 0.9-2.1) for children who were mildly, moderately, and severely large for gestational age, respectively. Severely large for gestational age children also had higher risks of unfavorable neurobehavioral development. These results were supported by spline analyses. CONCLUSIONS: Among term infants, the risks of unfavorable child health and neurodevelopment increased with the severity of SGA.

DOI： 10.1016/j.jpeds.2020.06.075

Neonatal hemochromatosis associated with rupture of esophageal varices. International journal

Kazuki Hatayama, Yosuke Washio, Tomoka Okamura, Takuo Noda, Hirokazu Tsukahara

Pediatrics international : official journal of the Japan Pediatric Society 61 ( 7 ) 735 - 737 2019.7

A Case of Nager Syndrome Diagnosed Before Birth.

Kei Hayata, Hisashi Masuyama, Eriko Eto, Takashi Mitsui, Shoko Tamada, Takeshi Eguchi, Jota Maki, Kazumasa Tani, Akiko Ohira, Yosuke Washio, Junko Yoshimoto, Kosei Hasegawa

Acta medica Okayama 73 ( 3 ) 273 - 277 2019.6

Language：English

Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly.

DOI： 10.18926/AMO/56872

Exchange Transfusion and Cytarabine for Transient Abnormal Myelopoiesis in Hydrops Fetalis.

Tomoka Okamura, Yousuke Washio, Junko Yoshimoto, Kazumasa Tani, Hirokazu Tsukahara, Akira Shimada

Acta medica Okayama 73 ( 2 ) 181 - 188 2019.4

Language：English

Most cases of transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) resolve spontaneously; however, DS-TAM neonates with hydrops fetalis (HF) show poor clinical outcomes. We report three infants with DS-TAM and HF who were treated with exchange transfusion (ET) followed by low-dose cytarabine (LD-CA). All of them survived without developing liver failure, acute leukemia, or other serious adverse events. Our results suggest that this combination treatment with ET and LD-CA would be safe, tolerable and effective as an novel approach for DS-TAM patients with HF.

DOI： 10.18926/AMO/56655

Population-based longitudinal study showed that children born small for gestational age faced a higher risk of hospitalisation during early childhood. International journal

Junko Yoshimoto, Takashi Yorifuji, Yosuke Washio, Tomoka Okamura, Hirokazu Watanabe, Hiroyuki Doi, Hirokazu Tsukahara

Acta paediatrica (Oslo, Norway : 1992) 108 ( 3 ) 473 - 478 2019.3

Language：English Publishing type：Research paper (scientific journal)

AIM: We examined the effects of being born small for gestational age (SGA) on the risk of being hospitalised for common diseases during childhood. METHODS: This Japanese nationwide, population-based longitudinal survey followed babies born before 42 weeks of gestation from 10 to 17 January and from 10 to 17 July 2001, using data from the Government's Longitudinal Survey of Babies in the 21st Century. Our study followed 41 268 children until 5.5 years of age: 39 107 full term (8.7% SGA) and 2161 preterm (15.5% SGA). We evaluated the relationship between SGA status and hospitalisation using their history of hospitalisation for common diseases and comparing full-term or preterm births. Logistic regression analysis, adjusted for potential confounders, estimated the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The full-term and preterm children who were born SGA were more likely to be hospitalised during infancy and early childhood than those born non SGA. The ORs for hospitalisation from six months to 18 months of age were 1.23 (95% CI: 1.10-1.37) for full-term and 1.67 (95% CI: 1.23-2.25) for preterm subjects. Higher risks of hospitalisation due to bronchitis, pneumonia, bronchial asthma and diarrhoea were also observed. CONCLUSION: Being born SGA was associated with all-cause and cause-specific hospitalisation in early childhood, particularly for term infants.

DOI： 10.1111/apa.14507

Associations of gestational age with child health and neurodevelopment among twins: A nationwide Japanese population-based study. International journal

Kei Tamai, Takashi Yorifuji, Akihito Takeuchi, Makoto Nakamura, Yosuke Washio, Hirokazu Tsukahara, Hiroyuki Doi, Misao Kageyama

Early human development 128 41 - 47 2019.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear. AIMS: To examine the association of gestational age with child health and neurological development in early childhood among twins. STUDY DESIGN: Population-based longitudinal study. SUBJECTS: We included 947 children from 479 pairs of twins with information on gestational age. OUTCOME MEASURES: Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations. RESULTS: The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (<37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (<32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children. CONCLUSION: We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.

DOI： 10.1016/j.earlhumdev.2018.11.005

Pregnancy with Anti-MuSK-Positive Myasthenia Gravis That Was Diagnosed During Pregnancy A Case Report

Hisashi Masuyama, Izumi Suzui, Kei Hayata, Yosuke Washio, Junko Yoshimoto, Yuji Hiramatsu

JOURNAL OF REPRODUCTIVE MEDICINE 64 ( 1-2 ) 71 - 73 2019.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SCI PRINTERS & PUBL INC

BACKGROUND: Anti-muscle-specific tyrosine kinase (MuSK)-positive myasthenia gravis (MG) has a late onset in the 4th decade of life and a poor response to medical treatment. Few cases of pregnancy with anti-MuSK-positive MG have been described. We report a case of pregnancy with anti-MuSK-positive MG that was diagnosed during pregnancy.CASE: A 46-year-old healthy primiparous woman was referred to Okayama University Hospital at 23 weeks' gestation because of antiMuSK-positive MG that was diagnosed during pregnancy in the first trimester. Emergent cesarean section was performed at 30 weeks' gestation because of severe preeclampsia and pre-crisis of MG. She received medication and plasmapheresis for hypertension and severe MG symptoms and was discharged on day 35 after delivery. The neonate had no symptoms of transient neonatal MG, and anti-MuSK antibody was positive at birth and then decreased to the normal range at 5 months old.CONCLUSION: Our case and previous reports indicate that pregnancy with anti-MuSK-positive MG might have the same or a relatively higher risk for the mother and neonate as compared with anti-AChR-positive MG. Multidisciplinary management throughout the perinatal period should be provided for pregnancy with anti-MuSK-positive MG.

Epidemiology of Pediatric Acute Encephalitis/Encephalopathy in Japan.

Shinichiro Goto, Nobuyuki Nosaka, Takashi Yorifuji, Tomoaki Wada, Yosuke Fujii, Masato Yashiro, Yosuke Washio, Kosei Hasegawa, Hirokazu Tsukahara, Tsuneo Morishima

Acta medica Okayama 72 ( 4 ) 351 - 357 2018.8

Language：English Publishing type：Research paper (scientific journal)

We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan.

DOI： 10.18926/AMO/56170

全前脳胞症に22q11.2欠失症候群を合併した1例

谷和祐, 牧尉太, 江口武志, 玉田祥子, 岡村朋香, 光井崇, 衛藤英理子, 早田桂, 鷲尾洋介, 吉本順子, 増山寿

日本周産期・新生児医学会雑誌 54 ( 2 ) 720 - 720 2018.6

Cover Image, Volume 176A, Number 3, March 2018. International journal

Kei Tamai, Katsuhiko Tada, Akihito Takeuchi, Makoto Nakamura, Hidenori Marunaka, Yosuke Washio, Hiroyuki Tanaka, Fuyuki Miya, Nobuhiko Okamoto, Misao Kageyama

American journal of medical genetics. Part A 176 ( 3 ) i 2018.3

Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non-lethal form of Raine syndrome. International journal

Kei Tamai, Katsuhiko Tada, Akihito Takeuchi, Makoto Nakamura, Hidenori Marunaka, Yosuke Washio, Hiroyuki Tanaka, Fuyuki Miya, Nobuhiko Okamoto, Misao Kageyama

American journal of medical genetics. Part A 176 ( 3 ) 682 - 686 2018.3

Language：English Publishing type：Research paper (scientific journal)

Raine syndrome is a rare osteosclerotic bone dysplasia characterized by craniofacial anomalies and intracranial calcification. Most patients with Raine syndrome are of Arab ancestry and die during the neonatal period. We herein report a Japanese patient with non-lethal Raine syndrome who presented with characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis. Craniofacial abnormalities, intracranial calcification, osteosclerosis, chondrodysplasia punctata, and a mutation of FAM20C was identified. She was subsequently discharged without surgical intervention and is now 2 years old with mild neurodevelopmental delays. Images of cerebral hyperechogenicity by fetal ultrasonography in a non-lethal case were described herein for the first time. This patient represents a rare occurrence of a child with Raine syndrome born to Japanese parents and confirms that this syndrome is not always lethal. Even if Raine syndrome is suspected in a fetus due to cerebral hyperechogenicity and a hypoplastic nose, cerebral hyperechogenicity without pulmonary hypoplasia does not always predict lethality or severe neurodevelopmental delays. The information provided herein will be useful for prenatal counseling.

DOI： 10.1002/ajmg.a.38598

Emergency Caesarean Section Saved Both an Anti-MuSK Antibody-positive Myasthenia Gravis Mother with Pregnancy-induced Hypertension and Her Premature Baby.

Yoshiaki Takahashi, Toru Yamashita, Ryuta Morihara, Yumiko Nakano, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Kei Hayata, Hisashi Masuyama, Tomoka Okamura, Yosuke Washio, Koji Abe

Internal medicine (Tokyo, Japan) 56 ( 24 ) 3361 - 3364 2017.12

Language：English Publishing type：Research paper (scientific journal)

We herein report the case of a 46-year-old pregnant woman with anti-muscle specific kinase (MuSK) antibody-positive myasthenia gravis (MG) who showed pregnancy-induced hypertension and developed respiratory failure at 30 weeks and 5 days of pregnancy, and who underwent an emergency caesarean section (CS). Her MG symptoms gradually improved in the subsequent weeks. The premature baby with positive MuSK antibodies was successfully delivered, but the male baby required temporary artificial ventilation. However, his condition also gradually improved over time. The present case suggests that an emergency CS could rescue both the mother, who was in critical condition, and the prematurely born baby, even when suffering from acute respiratory insufficiency.

DOI： 10.2169/internalmedicine.8636-16

羊水過多をきたし出生直後に気管切開を必要としたNager症候群の1例

江口武志, 谷和祐, 岡村朋香, 鷲尾洋介, 吉本順子, 増山寿, 平松祐司, 塚原宏一

日本周産期・新生児医学会雑誌 53 ( 2 ) 754 - 754 2017.6

当院で経験した気管無形成の3症例

谷和祐, 甲斐憲治, 清時毅典, 牧尉太, 岡本和浩, 江口武志, 玉田祥子, 岡村朋香, 光井崇, 衛藤英理子, 早田桂, 鷲尾洋介, 吉本順子, 増山寿, 平松祐司

日本周産期・新生児医学会雑誌 53 ( 2 ) 529 - 529 2017.6

Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models. International journal

Yoshiharu Nagaoka, Nobuyuki Nosaka, Mutsuko Yamada, Masato Yashiro, Yosuke Washio, Kenji Baba, Tsuneo Morishima, Hirokazu Tsukahara

Disease markers 2017 2594231 - 2594231 2017

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

DOI： 10.1155/2017/2594231

【周産期医学必修知識第8版】新生児編未熟児くる病

塚原宏一, 鷲尾洋介, 吉本順子

周産期医学 46 ( 増刊 ) 896 - 899 2016.12

出生後早期に気道確保を必要とした上顎体、舌奇形腫、舌裂を合併した唇顎口蓋裂の一例

江口武志, 牧尉太, 谷和祐, 岡本和浩, 玉田祥子, 光井崇, 衛藤英理子, 早田桂, 増山寿, 鷲尾洋介, 吉本順子, 飯田征二, 平松祐司

現代産婦人科 65 ( Suppl. ) S46 - S46 2016.9

体重差が少ないMD双胎の管理と母体・新生児予後の検討

江口武志, 柏原麻子, 牧尉太, 玉田祥子, 光井崇, 平野友美加, 衛藤英理子, 早田桂, 増山寿, 平松祐司, 鷲尾洋介, 吉本順子

日本周産期・新生児医学会雑誌 52 ( 2 ) 750 - 750 2016.6

Hemodynamic analysis in infants with late-onset circulatory collapse. International journal

Yosuke Washio, Atsushi Uchiyama, Hidehiko Nakanishi, Satsuki Totsu, Kenichi Masumoto, Satoshi Kusuda

Pediatrics international : official journal of the Japan Pediatric Society 55 ( 5 ) 582 - 8 2013.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Late-onset circulatory collapse (LCC) is a disorder in which blood pressure decreases and oliguria suddenly occurs in preterm infants who have survived the acute stage, leading to shock, without contributing underlying factors. In order to evaluate hemodynamic changes during LCC, the correlation between myocardial functions and organ blood flow was investigated with echography. METHODS: Seven very-low-birthweight infants were given a diagnosis of LCC during the study period. Cardiovascular and organ flow parameters of the infants were recorded prospectively, once a week, and compared with eight control very-low-birthweight infants with matching gestational age. Echographic study was performed before LCC, at the onset of LCC, and after LCC among infants with LCC. RESULTS: A significant increase in ejection fraction and a significant decrease in end systolic wall stress were observed in infants with the LCC condition. At the same time, the mean blood flow velocity increased significantly in the superior mesenteric artery, while it decreased in the anterior cerebral artery. Systolic blood flow velocity increased and mean velocity was maintained in the renal artery during LCC. CONCLUSION: LCC is a distributive shock, characterized by a hyperdynamic state and decreased afterload. Echographic examination of organ flow during LCC is useful in understanding the pathophysiology of the disorder.

DOI： 10.1111/ped.12114

Effect of Bifidobacterium administration on very-low-birthweight infants. International journal

Chika Yamasaki, Satsuki Totsu, Atushi Uchiyama, Hidehiko Nakanishi, Kenichi Masumoto, Yosuke Washio, Kyoko Shuri, Shuji Ishida, Ken Imai, Satoshi Kusuda

Pediatrics international : official journal of the Japan Pediatric Society 54 ( 5 ) 651 - 6 2012.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very-low-birthweight (VLBW) infants. METHODS: We conducted a single-center prospective pilot study. Thirty-six VLBW infants were randomly divided into two groups: group E, wherein B. bifidum was supplemented within 48 h of birth, and group L, wherein it was supplemented more than 48 h after birth. RESULTS: Group E and group L reached a total feeding volume of 100 mL/(kg/day) after 10 [7-13] days and 11 [10-15] days, respectively (median [quartile]). The daily bodyweight gain in group E was significantly higher (21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day, P < 0.02; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day, P < 0.04). No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real-time polymerase chain reaction assay at 1 and 4 weeks of age. However, the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth. The incidence of morbidities between the groups was similar. CONCLUSION: The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity. Furthermore, the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth.

DOI： 10.1111/j.1442-200X.2012.03649.x

Hydrocortisone and long-term outcomes in very-low-birthweight infants. International journal

Chika Yamasaki, Atsushi Uchiyama, Hidehiko Nakanishi, Kenichi Masumoto, Hiroyuki Aoyagi, Yosuke Washio, Satsuki Totsu, Ken Imai, Satoshi Kusuda

Pediatrics international : official journal of the Japan Pediatric Society 54 ( 4 ) 465 - 70 2012.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The long-term effects of hydrocortisone (HDC) used for very-low-birthweight (VLBW) infants with chronic lung disease (CLD) are not fully understood. The aim of this study was to examine the short-term clinical effects and long-term impact of a physiological replacement dose of HDC on acute deterioration of CLD in VLBW infants. METHODS: This prospective case-control study included 110 of the 174 VLBW infants admitted to our facility between 2003 and 2006 who were followed up to a corrected age of 18 months. Infant deaths and infants with congenital deformities were excluded from the study. The infants were classified into the following three groups: infants with CLD and treated with HDC (1-2 mg/kg/dose) due to progressive deterioration in oxygenation (CLD treatment group; n = 24); infants with CLD but not treated with HDC (CLD untreated group; n = 40); and infants without CLD (non-CLD group; n = 46). RESULTS: The fraction of inspired oxygen (F(I) O(2) ) in the CLD treatment group improved significantly after treatment (P < 0.01). There were no significant differences among the three groups in terms of growth and neurodevelopmental quotient at the corrected age of 18 months following adjustment for birthweight, sex, and presence of light-for-date infants. There were also no significant intergroup differences in all three areas of developmental quotient. CONCLUSIONS: Physiological doses of HDC replacement are effective in treating acute deterioration in oxygenation in VLBW infants with CLD. Furthermore, this treatment modality did not adversely affect the growth and development of infants at the corrected age of 18 months.

DOI： 10.1111/j.1442-200X.2012.03601.x

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