Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Ochiai Masayuki Last modified date:2022.04.06

Post-doctoral Fellow / Pediatrics /

1. Sonoda M, Ishimura M, Eguchi K, Shiraishi A, Kanno S, Kaku N, Inoue H, Motomura Y, Ochiai M, Sakai Y, Nakayama M, Ohara O, Ohga S., Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis, Int J Hematol, 10.1007/s12185-019-02738-3, 111, 1, 131-136, 2020.01.
2. Ryoji Taira, Hirosuke Inoue, Toru Sawano, Junko Fujiyoshi, Yuko Ichimiya, Michiko Torio, Masafumi Sanefuji, Masayuki Ochiai, Yasunari Sakai, Shouichi Ohga, Management of apnea in infants with trisomy 18, Developmental Medicine and Child Neurology, 10.1111/dmcn.14403, 62, 7, 874-878, 2020.07, This case series aimed to characterize the clinical features, management, and outcomes of apnea in infants with trisomy 18. Participants in this study were infants with trisomy 18 who were born alive and admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2018. Retrospective analysis was performed on clinical data recorded in our department. Twenty-seven infants with trisomy 18 were admitted to our hospital during the study period, of which 25 (nine males, 16 females) were enrolled as eligible participants in this study. Among them, 14 started presenting with apnea from median 3.5 days of age (range 0–47d). In these infants with apnea, eight received respiratory support of positive pressure ventilation (PPV). The 1-year survival rate of infants in the PPV group was higher than that of non-PPV-supported infants (5 out of 8 vs 0 out of 6 infants). Five PPV-supported infants received a diagnosis of epilepsy, which was controlled by antiepileptic drugs. Postnatal respiratory intervention provides better prognosis in infants with trisomy 18. Improved survival leads to accurate diagnosis and treatment of apneic events in association with epilepsy. What this paper adds: Respiratory support is effective against apnea in infants with trisomy 18. Intervention with ventilation provides a higher chance of prolonged survival. Improved survival leads to the accurate diagnosis and treatment of epilepsy-associated apnea..
3. Masayuki Ochiai, Hiroaki Kurata, Hirosuke Inoue, Masako Ichiyama, Junko Fujiyoshi, Shinichi Watabe, Takehiko Hiroma, Tomohiko Nakamura, Shouichi Ohga, Transcutaneous blood gas monitoring among neonatal intensive care units in Japan, Pediatrics International, 10.1111/ped.14107, 62, 2, 169-174, 2020.02, Background: This study aimed to investigate the utility of transcutaneous (tc) measurements of partial pressure of oxygen (tcPO2) and carbon dioxide (tcPCO2) monitoring in neonatal intensive care units (NICUs) in Japan. Methods: At the end of 2016,we sent a survey questionnaire on tc monitoring to all 106 NICUs registered with the Japanese Neonatologist Association. The questions included usage, subjects, methods, management, and the practical usefulness of tc monitoring. Results: The questionnaire was returned by 69 NICUs (65.1% of response rate). Seventeen institutions (24.6%) measured both tcPCO2 and tcPO2, and 42 (60.9%) measured tcPCO2 alone. Transcutaneous PCO2 or tcPO2 monitoring was applied for “pre-viable” infants born at 22–23 weeks’ gestational age (18.6% vs 23.5%), and infants of <500 g birthweight (30.5% vs 17.6%). The tcPCO2 and tcPO2 monitoring was started at birth in 49.2% and 70.6% of the newborn infants, respectively. The temperature of the sensor was set at <38°C for tcPCO2 in 54.3% and >42°C for tcPO2 in 58.9% of NICUs. The accuracy for tcPO2 was rated as good in 35.3% or moderate in 64.7%, of institutions but or for tcPCO2 as 1.7% or 93.2%of institutions, respectively. Conclusion: Transcutaneous monitoring was widely, but limitedly, used for preterm infants. The lower temperature of the tcPCO2 sensor compared to that reported in other developed countries might compromise the accuracy but increase the feasibility of tc monitoring in Japan..
4. Motoshi Sonoda, Masataka Ishimura, Katsuhide Eguchi, Akira Shiraishi, Shunsuke Kanno, Noriyuki Kaku, Hirosuke Inoue, Yoshitomo Motomura, Masayuki Ochiai, Yasunari Sakai, Manabu Nakayama, Osamu Ohara, Shouichi Ohga, Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis, International journal of hematology, 10.1007/s12185-019-02738-3, 111, 1, 131-136, 2020.01, Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 109/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH..
5. Mitsuru Arima, Masato Akiyama, Kohta Fujiwara, Yujiro Mori, Hirosuke Inoue, Eiko Seki, Takahito Nakama, Shoko Tsukamoto, Masayuki Ochiai, Shouichi Ohga, Koh Hei Sonoda, Neurodevelopmental outcomes following intravitreal bevacizumab injection in Japanese preterm infants with type 1 retinopathy of prematurity, PloS one, 10.1371/journal.pone.0230678, 15, 3, 2020, Purpose The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP). Methods In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis. Results Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03). Conclusions Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood..
6. , Yuki Matsushita, Yasunari Sakai, Michiko Torio, Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Hiroaki Kurata, Junko Fujiyoshi, Masako Ichiyama, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan, Journal of Perinatology, 10.1038/s41372-019-0494-7, 39, 11, 1472-1479, 2019.11, Objective: To determine clinical features of very low birth weight infants (VLBWIs) who had developed epilepsy by age 3 years. Study design: Multicenter cohort study using the Neonatal Research Network of Japan database. We analyzed clinical variables of 8431 VLBWIs who had recorded data of neurological sequelae at age 3 years. Logistic regression identified the association between variables and development of epilepsy. Result: One hundred and forty-three (1.7%) infants developed epilepsy, 683 (8.1%) showed cerebral palsy (CP), and 1114 (13.2%) had psychomotor delay. Epilepsy was associated with history of sepsis [adjusted odds ratio (AOR) 3.23], severe intraventricular hemorrhage (IVH; AOR 5.13), and cystic periventricular leukomalacia (PVL; AOR 12.7). Severe IVH and cystic PVL were also frequently associated with CP and psychomotor delay. Conclusion: Severe IVH and cystic PVL are strongly associated with development of epilepsy, as well as other neurological sequelae, and are potential critical therapeutic targets..
7. Hiroaki Kurata, Masayuki Ochiai, Hirosuke Inoue, Takeshi Kusuda, Junko Fujiyoshi, Masako Ichiyama, Yoshifumi Wakata, Hidetoshi Takada, Inflammation in the neonatal period and intrauterine growth restriction aggravate bronchopulmonary dysplasia, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.11.007, 60, 5, 496-503, 2019.10, Background: To investigate the hematological features of infants with bronchopulmonary dysplasia (BPD) and their relationships with clinical severity. Methods: This prospective observational study enrolled 73 BPD patients from a total of 331 infants with a birth weight of <1500 g from 2005 to 2013. The clinical severity of BPD was defined by the duration of oxygen supplementation and positive pressure ventilation (PPV) in line with the diagnostic criteria of BPD. The hematological status and cytokine levels were surveyed from blood samples at birth and at 2 and 4 weeks of life. Results: Thirty-four (46.6%) cases were classified as “moderate-to-severe” BPD. Small-for-gestational-age (SGA) was associated with the severity of BPD (OR: 5.05; 95% CI: 1.45 to 17.2). The CRP level at 2 weeks (partial regression coefficient [rc]: 21.8; 4.01 to 39.7) and the neutrophil count at 4 weeks (0.005; 0.001 to 0.007) were positively correlated with the oxygenation period. The PPV period was found to be correlated with the CRP level at 2 weeks (27.2; 14.9 to 39.5), and the neutrophil count (0.003; 0.001 to 0.004) at 4 weeks. Conclusion: The aggravation of BPD was associated with both SGA at birth and inflammation during neonatal period..
8. Kazuaki Yasuoka, Hirosuke Inoue, N. Egami, Masayuki Ochiai, Koichi Tanaka, Toru Sawano, Hiroaki Kurata, Masako Ichiyama, J. Fujiyoshi, Yuki Matsushita, Yasunari Sakai, Shouichi Ohga, Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants, Journal of Pediatrics, 10.1016/j.jpeds.2019.05.033, 212, 117-123.e4, 2019.09, Objective: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants. Methods: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse. Results: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P < .01). In multivariable logistic analysis, late-onset circulatory collapse was independently associated with CP (aOR, 1.52; 95% CI, 1.13-2.04) and developmental quotient score of <50 (OR, 1.83; 95% CI, 1.23-2.72). Conclusions: Late-onset circulatory collapse may be a relatively common event occurring in extremely preterm infants and an independent risk factor for CP at 3 years of age..
9. Tadamune Kinjo, Hirosuke Inoue, Takeshi Kusuda, J. Fujiyoshi, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Y. Koga, Toshiro Hara, Shouichi Ohga, Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.09.005, 60, 4, 382-388, 2019.08, Background: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. Methods: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into “progression group” (n = 7) that required any therapy and “spontaneous resolution group” (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. Results: Three patients developed leukemia during the study period (median, 1147 days; range, 33–3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = −0.46, p = 0.02). Conclusion: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants..
10. Shinya Iwasawa, Kumiko Yanagi, Atsuo Kikuchi, Yasuko Kobayashi, Kazuhiro Haginoya, Hiroshi Matsumoto, Kenji Kurosawa, Masayuki Ochiai, Yasunari Sakai, Atsushi Fujita, Noriko Miyake, Tetsuya Niihori, Matsuyuki Shirota, Ryo Funayama, Shigeaki Nonoyama, Shouichi Ohga, Hiroshi Kawame, Keiko Nakayama, Yoko Aoki, Naomichi Matsumoto, Tadashi Kaname, Yoichi Matsubara, Wataru Shoji, Shigeo Kure, Recurrent de novo MAPK8IP3 variants cause neurological phenotypes, Annals of Neurology, 10.1002/ana.25481, 85, 6, 927-933, 2019.06, c-Jun-amino-terminal kinase-interacting protein 3 (JIP3), encoded by MAPK8IP3, is an adaptor protein of the kinesin-1 complex and essential for axonal transport in neurons. However, an association between MAPK8IP3 variants and human disease has not been established. We identified 5 individuals from four families with recurrent de novo variants c.1732C>T (p.Arg578Cys) and c.3436C>T (p.Arg1146Cys) in MAPK8IP3. The core phenotype includes spastic diplegia, intellectual disability, cerebral atrophy, and corpus callosum hypoplasia. Zebrafish embryos overexpressing human mutant JIP3 showed axon varicosities of the posterior lateral line nerve, suggesting an adverse effect on the developing axons. Our results suggest that MAPK8IP3 variants cause a neurodevelopmental disease. ANN NEUROL 2019;85:927–933..
11. Masako Ichiyama, Hirosuke Inoue, Masayuki Ochiai, Masataka Ishimura, Akira Shiraishi, Junko Fujiyoshi, Hironori Yamashita, Kazuo Sato, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Shouichi Ohga, Diagnostic challenge of the newborn patients with heritable protein C deficiency, Journal of Perinatology, 10.1038/s41372-018-0262-0, 39, 2, 212-219, 2019.02, Objective: The diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan. Study design: We determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry. Result: Physiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s). Conclusion: The PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population..
12. , Hiroaki Kurata, Masayuki Ochiai, Hirosuke Inoue, Masako Ichiyama, Kazuaki Yasuoka, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Yasunari Sakai, Shouichi Ohga, A nationwide survey on tracheostomy for very-low-birth-weight infants in Japan, Pediatric Pulmonology, 10.1002/ppul.24200, 54, 1, 53-60, 2019.01, Objectives: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan. Methods: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined. Results: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P < 0.01) and longer hospitalization (229 days vs 83 days, P < 0.01) than non-tracheostomized infants. Tracheostomized patients showed higher comorbidities with hypoxic ischemic encephalopathy (odds ratio [OR] 10.98, P < 0.01), muscular disease (OR 10.95, P < 0.01), severe or moderate BPD (OR 7.79, P < 0.01), chromosomal abnormality (OR 4.43, P < 0.01) or sepsis (OR 1.78, P < 0.05) at hospital discharge than non-tracheostomized patients. Conclusion: We demonstrated the non-increasing rate in tracheostomy for VLBWIs and such cases were associated with an excellent survival in Japan. These data provide evidence that more attentive care must be practiced in order to reduce the pulmonary and neuromuscular burdens of VLBWIs at birth..
13. Masayuki Ochiai, Hazumu Nagata, Koichi Tanaka, Kenji Ihara, Shouichi Ohga, Critical association of Pallister–Hall syndrome and congenital heart disease, Pediatrics International, 10.1111/ped.13945, 61, 8, 827-828, 2019.
14. Hirosuke Inoue, Masayuki Ochiai, Yasunari Sakai, Kazuaki Yasuoka, Koichi Tanaka, Masako Ichiyama, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Neurodevelopmental outcomes in infants with birth weight ≤500 g at 3 years of age, Pediatrics, 10.1542/peds.2017-4286, 142, 6, 2018.12, OBJECTIVES: To determine neurodevelopmental outcomes at 3 years of age in children born with a birth weight (BW) of ≤500 g. METHODS: Infants who were born with a BW of ≤500 g from 2003 to 2012 in the Neonatal Research Network of Japan and survived to discharge from the NICU were eligible in this study. The study population consisted of 460 children (56.7% of 811 surviving infants) who were evaluated at 36 to 42 months of age. Neurodevelopmental impairment (NDI) was defined as having cerebral palsy, visual impairment, hearing impairment, or a developmental quotient score of <70. RESULTS: The overall proportion of NDI was 59.1% (95% confidence interval [CI]: 54.6%-63.5%). The trend revealed no significant change during the study period. In a multivariate modified Poisson regression analysis, NDI was associated with severe intraventricular hemorrhage (adjusted risk ratio [RR]: 1.42; 95% CI: 1.19-1.68; P <.01), cystic periventricular leukomalacia (adjusted RR: 1.40; 95% CI: 1.13-1.73; P <.01), severe necrotizing enterocolitis (adjusted RR: 1.31; 95% CI: 1.07-1.60; P <.01), surgical ligation for patent ductus arteriosus (adjusted RR: 1.29; 95% CI: 1.09-1.54; P <.01), and male sex (adjusted RR: 1.19; 95% CI: 1.01-2.40; P =.04). CONCLUSIONS: This cohort showed that neurodevelopmental outcomes of infants with a BW of ≤500 g have not improved from 2003 to 2012. Multivariate analysis revealed that severe intracranial hemorrhage and cystic periventricular leukomalacia were the strongest risk factors for NDIs. Our data suggested that measures aimed at reducing neurologic morbidities will be important for improving outcomes of infants with a BW of ≤500 g..
15. Yuka Matsunaga, Masataka Ishimura, Hazumu Nagata, Kiyoshi Uike, Tadamune Kinjo, Masayuki Ochiai, Kenichiro Yamamura, Hidetoshi Takada, Yoshihisa Tanoue, Masaki Hayakawa, Masanori Matsumoto, Toshiro Hara, Shouichi Ohga, Thrombotic microangiopathy in a very young infant with mitral valvuloplasty, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.02.002, 59, 6, 595-599, 2018.12, Background: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. Case presentation: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle. ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) activity was sustained (64%) with the undetectable inhibitor. Von Willebrand factor (VWF) multimer analyses showed absent high-molecular weight multimers. Echocardiography disclosed severe mitral regurgitation. The mitral valve repair 32 days after the initial valvuloplasty led to prompt resolution of TMA. These suggested that TMA occurred in association with valvulopathy-triggered turbulent shear flow, mechanical hemolysis and endothelial damage. The consumption of large VWF multimers might account for the vascular high shear stress shown in Heyde syndrome. Conclusion: The youngest case of post-operative TMA underscores the critical coagulopathy after the first surgical intervention for congenital heart disease..
16. Mamoru Muraoka, Hazumu Nagata, Yuichiro Hirata, Kiyoshi Uike, Eiko Terashi, Eiji Morihana, Masayuki Ochiai, Yasuyuki Fujita, Kiyoko Kato, Kenichiro Yamamura, Shouichi Ohga, High incidence of progressive stenosis in aberrant left subclavian artery with right aortic arch, Heart and Vessels, 10.1007/s00380-017-1056-6, 33, 3, 309-315, 2018.03, Right aortic arch with aberrant left subclavian artery (RAA/aLSCA) is a rare aortic arch anomaly. The clinical association of aLSCA stenosis with RAA/aLSCA has not yet been fully elucidated. The aim of this study was to investigate the diagnosis, incidence, management and outcome of aLSCA stenosis in infants with prenatally diagnosed RAA/aLSCA. Ten fetuses who were diagnosed as having RAA/aLSCA in Kyushu University Hospital between January 2011 and December 2014 were enrolled. The maternal and child medical records were reviewed to investigate sex, gestational age at the fetal diagnosis, gestational age and body weight at birth, the findings of computed tomography (CT), Doppler ultrasonography of the vertebral artery and angiography, and the complications and outcomes of aLSCA stenosis. In 8 of 10 patients, aLSCA stenosis was identified on the first CT examination after birth. No patients had dysphagia or respiratory distress. The stenosis spontaneously resolved in 3 patients. In 4 of the 5 remaining patients, aLSCA stenosis progressed, including one case in which complete occlusion occurred—the case was associated with retrograde flow from the left vertebral artery supplying the distal LSCA. Balloon angioplasty was successfully used to treat stenosis in two cases. The subclavian steal phenomenon and developmental problems were not observed in any patients. aLSCA stenosis was identified in 80% of patients with RAA/aLSCA after birth. The early detection and elective treatment of stenotic lesions may be required to prevent complete occlusion during the development of the cardiovascular and cerebrovascular systems..
17. Kanako Kojima-Ishii, Naoko Toda, Kazuhiro Okubo, Vlad Tocan, Noriko Ohyama, Mika Makimura, Terumichi Matsuo, Masayuki Ochiai, Shouichi Ohga, Kenji Ihara, Metabolic and immunological assessment of small-for-gestational-age children during one-year treatment with growth hormone
The clinical impact of apolipoproteins, Endocrine Journal, 10.1507/endocrj.EJ17-0485, 65, 4, 449-459, 2018, Children born small for gestational age (SGA) are at a higher risk for metabolic disorders later in life. In this study, we aimed to characterize young SGA children without catch-up growth and evaluate the effects of GH treatment on endocrinological, metabolic, and immunological parameters. Study design is a one-year single hospital-based study included prospective observation of SGA patients during 12 months of GH treatment. Clinical and laboratory profiles of SGA children at baseline were compared with controls born appropriate size for age. Twenty-six SGA children (median age, 3.4 years) and 26 control children (median age, 3.8 years) were enrolled. Anthropometric, hematologic, biochemical, immunological, and endocrinological parameters were assessed at baseline and 1, 3, 6, 9, and 12 months after the start of GH treatment. As a result, median height SD score (SDS) of SGA children increased by +0.42 with 12-month GH treatment. Body mass index SDS was lower in SGA children than in controls. Serum apolipoprotein A1 increased, whereas apolipoprotein B decreased during GH treatment. Serum leptin and resistin levels, which were lower in SGA children than in controls at baseline, did not change remarkably with GH treatment. Monocyte counts, which were lower in SGA patients at baseline, increased after GH treatment. Neutrophil counts significantly increased after GH treatment. Natural killer cell ratios, which were higher in SGA patients, decreased after GH treatment. In conclusion, there was no evidence suggesting metabolic abnormalities in SGA children. Serum apolipoprotein changes might predict the beneficial role of GH treatment in lowering cardiometabolic risk..
18. , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Koichi Tanaka, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Shutaro Suga, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Early Mortality and Morbidity in Infants with Birth Weight of 500 Grams or Less in Japan, Journal of Pediatrics, 10.1016/j.jpeds.2017.05.017, 190, 112-117.e3, 2017.11, Objective To assess the short-term prognosis of Japanese infants with a birth weight (BW) of ≤500 g. Study design Demographic and clinical data were reviewed for 1473 live born infants with a BW ≤500 g at gestational age ≥22 weeks who were treated in the 204 affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2012. Results Survival to hospital discharge occurred in 811 of 1473 infants (55%; 95% CI 53%-58%). The survival rates of BW ≤300 g, 301-400 g, and 401-500 g were 18% (95% CI 10%-31%), 41% (95% CI 36%-47%), and 60% (95% CI 57%-63%), respectively. In a multivariable Cox proportional hazards analysis, antenatal corticosteroid use (adjusted hazard ratio: 0.68; 95% CI 0.58-0.81; P <.01), cesarean delivery (0.69; 95% CI 0.56-0.85; P <.01), advanced gestational age per week (0.94; 95% CI 0.89-0.99; P =.02), BW per 100-g increase (0.55; 95% CI 0.49-0.64; P <.01), Apgar score ≥4 at 5 minutes (0.51; 95% CI 0.43-0.61; P <.01), and no major congenital abnormalities (0.38; 95% CI 0.29-0.51; P <.01) were associated with survival to discharge. Despite the improved survival rate over the 10-year study period (from 40% in 2003 [95% CI 30%-51%] to 68% in 2012 [95% CI 61%-75%]), at least 1 severe morbidity was present in 81%-89% of the survivors. Conclusions Improvements in perinatal-neonatal medicine have improved the survival, but not the rate of major morbidities, of infants with a BW ≤500 g in Japan..
19. Kazuaki Yasuoka, Hirosuke Inoue, Koichi Tanaka, Junko Fujiyoshi, Yuki Matsushita, Masayuki Ochiai, Yuhki Koga, Toshiharu Matsuura, Tomoaki Taguchi, Shouichi Ohga, Successful liver transplantation for transient abnormal myelopoiesis-associated liver failure, Neonatology, 10.1159/000474930, 112, 2, 159-162, 2017.08, Infants with Down syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM occasionally involves liver fibrosis, which can be fatal. The management of liver disease in TAM has not yet been established and is mainly supportive. We report an infant with DS and TAM who developed end-stage liver failure. Liver dysfunction progressed even after blast cells disappeared from the circulation. He underwent a living-donor liver transplantation at 56 days of life without surgical complications. The explanted liver showed atrophy and severe fibrosis without leukemic cell infiltration. The posttransplant course was favorable with no hematological abnormality. He is doing well 8 months after transplantation. To the best of our knowledge, this report is the first showing that liver transplantation might be a treatment option for TAM-related liver failure..
20. Naoko Toda, Kenji Ihara, Kanako Kojima-Ishii, Masayuki Ochiai, Kazuhiro Ohkubo, Yutaka Kawamoto, Yoshinori Kohno, Sakae Kumasaka, Akihiko Kawase, Yasuhisa Ueno, Takeshi Futatani, Tokuo Miyazawa, Yuko Nagaoki, Setsuko Nakata, Maiko Misaki, Hiroko Arai, Masahiko Kawai, Maki Sato, Yukari Yada, Nobuhiro Takahashi, Atsushi Komatsu, Kanemasa Maki, Shinichi Watabe, Yutaka Sumida, Makoto Kuwashima, Hiroshi Mizumoto, Kazuo Sato, Toshiro Hara, Hyperinsulinemic hypoglycemia in Beckwith–Wiedemann, Sotos, and Kabuki syndromes
A nationwide survey in Japan, American Journal of Medical Genetics, Part A, 10.1002/ajmg.a.38011, 173, 2, 360-367, 2017.02, Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period..
21. Masayuki Ochiai, Hiroaki Kurata, Hirosuke Inoue, Koichi Tanaka, Yuki Matsushita, Junko Fujiyoshi, Yoshifumi Wakata, Kiyoko Kato, Tomoaki Taguchi, Hidetoshi Takada, An Elevation of Serum Ferritin Level Might Increase Clinical Risk for the Persistence of Patent Ductus Arteriosus, Sepsis and Bronchopulmonary Dysplasia in Erythropoietin-Treated Very-Low-Birth-Weight Infants, Neonatology, 10.1159/000447991, 111, 1, 68-75, 2016.12, Background: The substantial risk of iron overload is not routinely monitored in most of the neonatal intensive care units (NICUs) in Japan; however, blood transfusion is an essential strategy for successfully treating preterm low-birth-weight infants. Objective: The aim of this study was to investigate the iron status and clinical features of infants with a birth weight of <1,500 g, i.e. very-low-birth-weight infants (VLBWIs). Methods: This prospective observational study enrolled 176 (82.6%) patients from a total of 213 VLBWIs admitted to our NICU from 2009 to 2014. Clinical information was collected including maternal records and infant morbidity and treatment. Management strategies including enteral iron supplementation, erythropoietin administration and blood transfusion were allowed according to the consensus in Japan. The hematological status was surveyed from birth to 12 postnatal weeks of age. The iron status was determined according to serum iron, unbound iron-binding capacity and serum ferritin. The definition of hyperferritinemia was set as a value of ≥500 ng/ml. Results: Twenty-four (13.6%) infants displayed hyperferritinemia. A multiple logistic analysis selected 3 associated factors of hyperferritinemia: surgical ligation for patent ductus arteriosus, sepsis and moderate or severe states of bronchopulmonary dysplasia. We also verified that the value of ferritin was significantly correlated with those of aspartate transaminase, creatine kinase and C-reactive protein according to a multilinear regression analysis. After excluding the ferritin data of these outliers, we did not observe any factors associated with hyperferritinemia. Conclusions: Hyperferritinemia might be associated with oxygen radical diseases and susceptibility to infection..
22. Masayuki Ochiai, Yuki Matsushita, Hirosuke Inoue, Takeshi Kusuda, Dongchon Kang, Kiyoshi Ichihara, Naoki Nakashima, Kenji Ihara, Shouichi Ohga, Toshiro Hara, Blood reference intervals for preterm low-birth-weight infants
A multicenter cohort study in Japan, PloS one, 10.1371/journal.pone.0161439, 11, 8, 2016.08, Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDRBW and SDRGA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDRGA and SDRBW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine..
23. Kimiaki Hashiguchi, Takato Morioka, Nobuya Murakami, Osamu Togao, Akio Hiwatashi, Masayuki Ochiai, Goki Eriguchi, Junji Kishimoto, Koji Iihara, Sequential morphological change of Chiari malformation type II following surgical repair of myelomeningocele, Child's Nervous System, 10.1007/s00381-016-3041-2, 32, 6, 1069-1078, 2016.06, Purpose: To document long-term morphological changes of Chiari type II malformation (CM-II) following closure of spina bifida manifesta (SBM). Methods: We retrospectively evaluated postnatal magnetic resonance images of the CM-II and posterior fossa (PF) in 28 consecutive cases. We measured changes in vertebral level and length of the cerebellar peg (CP), cerebrospinal fluid (CSF) spaces anterior and posterior to the cerebrospinal junction, PF area, and the anteroposterior diameters of the foramen magnum (FM) and C1 vertebra. We examined the morphological differences between the cases with and without ventriculoperitoneal (VP) shunting and derived predicted means by nonlinear mixed-effect modeling. Results: At birth, there were significant differences in CP length, PF area, and FM and C1 diameters between those who underwent VP shunting and those who did not. In cases with a CP below C1, VP shunting was required in every case but one. In those with visible CSF space at birth, VP shunts were not required. In 17 of 18 cases with a CP below C1, the vertebral level ascended by mean two vertebral levels (range 0–5 levels) within 4–6 months of delivery. In the remaining case, slowly progressive hydrocephalus and delayed CP descent required VP shunting at 8 months. Predicted mean CP length and FM and C1 diameters were greater in those who underwent VP shunting, but there was no difference in predicted mean PF area. Conclusion: The morphology of CM-II and the presence of hydrocephalus influence each other in children who have undergone postnatal SBM repair..
24. Hirosuke Inoue, Hisanori Nishio, Hidetoshi Takada, Yasunari Sakai, Etsuro Nanishi, Masayuki Ochiai, Mitsuho Onimaru, Si Jing Chen, Toshiro Matsui, Toshiro Hara, Activation of Nod1 signaling induces fetal growth restriction and death through fetal and maternal vasculopathy, Journal of Immunology, 10.4049/jimmunol.1500295, 196, 6, 2779-2787, 2016.03, Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface..
25. H. Yamamoto, M. Ishimura, M. Ochiai, H. Takada, K. Kusuhara, Y. Nakatsu, T. Tsuzuki, K. Mitani, T. Hara, BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector, Gene Therapy, 10.1038/gt.2015.91, 23, 2, 205-213, 2016.02, X-linked agammaglobulinemia (XLA) is one of the most common humoral immunodeficiencies, which is caused by mutations in Bruton's tyrosine kinase (BTK) gene. To examine the possibility of using gene therapy for XLA, we constructed a helper-dependent adenovirus/adeno-associated virus BTK targeting vector (HD-Ad.AAV BTK vector) composed of a genomic sequence containing BTK exons 6-19 and a green fluorescence protein-hygromycin cassette driven by a cytomegalovirus promoter. We first used NALM-6, a human male pre-B acute lymphoblastic leukemia cell line, as a recipient to measure the efficiency of gene targeting by homologous recombination. We identified 10 clones with the homologous recombination of the BTK gene among 107 hygromycin-resistant stable clones isolated from two independent experiments. We next used cord blood CD34+ cells as the recipient cells for the gene targeting. We isolated colonies grown in medium containing cytokines and hygromycin. We found that the targeting of the BTK gene occurred in four of the 755 hygromycin-resistant colonies. Importantly, the gene targeting was also observed in CD19+ lymphoid progenitor cells that were differentiated from the homologous recombinant CD34+ cells during growth in selection media. Our study shows the potential for the BTK gene therapy using the HD-Ad.AAV BTK vector via homologous recombination in hematopoietic stem cells..
26. Masako Ichiyama, Shouichi Ohga, Masayuki Ochiai, Kotaro Fukushima, Masataka Ishimura, Michiko Torio, Michiyo Urata, Taeko Hotta, Dongchon Kang, Toshiro Hara, Fetal hydrocephalus and neonatal stroke as the first presentation of protein C deficiency, Brain and Development, 10.1016/j.braindev.2015.07.004, 38, 2, 253-256, 2016.02, Severe protein C-deficiency is a rare heritable thrombophilia of the newborn. Infants with biallelic PROC mutations present purpura fulminans and intracranial thromboembolism, while the prenatal onset of mutated heterozygotes remains unclear. We herewith present the first case of fetal ventriculomegaly and neonatal stroke associated with heterozygous PROC mutation. The infant was born to a healthy mother at 38 gestational weeks. The fetal growth had been normal, but the routine ultrasound screening had indicated mild hydrocephalus at 28. weeks of gestation. He developed convulsions two days after birth. Computed tomography of the brain revealed multiple hemorrhagic infarctions and ventriculomegaly. Dissociated levels of the plasma activity between protein C (21%) and protein S (42%) reached to determine the heterozygote of PROC c.574_576delAAG, a common thrombophilic predisposition in Asian ancestries. PC-mutant heterozygotes may have a limited high risk of cerebral thromboembolism during the perinatal course..
27. Naoko Toda, Takayuki Hoshina, Yuhki Koga, Masayuki Ochiai, Noriyuki Kaku, Kenichiro Yamamura, Hiroyuki Torisu, Kenji Ihara, Hidetoshi Takada, Yoshihiko Maehara, Toshiro Hara, Analysis of death due to infectious diseases in patients hospitalized in the pediatric ward of a single Japanese tertiary medical facility, Japanese Journal of Infectious Diseases, 10.7883/yoken.JJID.2015.591, 69, 6, 464-470, 2016, SUMMARY: In developed countries,the infection related-mortality rates in children hospitalized in tertiary medical facilities,where many patients with underlying disease are also hospitalized,are uncertain. We investigated the characteristics of infectious diseases-related fatal cases in the pediatric ward of a Japanese tertiary medical facility. A total of 188 patients who died in the pediatric ward or intensive care unit at Kyushu University Hospital from 2002 to 2011 were enrolled. The patient characteristics were investigated based on their medical records. A total of 35 patients died of infections,31 of whom had underlying diseases. Most patients died of sepsis or pneumonia (n = 27). All 9 patients who died within 7 days of birth were premature. Nine of the 13 patients with malignancy or hematological disorders died of hematopoietic stem cell transplantation (HSCT)-associated infections. The ratio of infectious disease-related fatal cases to the total cases decreased in the latter half of the study period. In particular,the proportion of preterm infants who died of infections was significantly lower in the latter 5 years (p = 0.02). Many of the infectious disease-related fatal cases were in premature infants and HSCT or post-HSCT patients. However,the mortality due to infectious diseases decreased in these patient groups..
28. Prakesh S. Shah, Kei Lui, Gunnar Sjörs, Lucia Mirea, Brian Reichman, Mark Adams, Neena Modi, Brian A. Darlow, Satoshi Kusuda, Laura San Feliciano, Junmin Yang, Stellan Håkansson, Rintaro Mori, Dirk Bassler, Josep Figueras-Aloy, Shoo K. Lee, Nadia Badawi, Peter Marshall, Paul Craven, Karen Simmer, Jacqueline Stack, Dan Casalaz, Elizabeth Carse, Lucy Cooke, Vijay Shingde, David Cartwright, Rod Hunt, Charles Kilburn, Peter Dargaville, Kei Lui, Mary Paradisis, Ingrid Rieger, Carl Kuschel, Andrew Numa, Hazel Carlisle, Guan Koh, Chad Andersen, Melissa Luig, Nicola Austin, Roland Broadbent, Lindsay Mildenhall, Malcolm Battin, David Bourchier, Vaughan Richardson, Anne Synnes, Nicole Rouvinez-Bouali, Bruno Piedboeuf, Barbara Bulleid, Wendy Yee, Nalini Singhal, Adele Harrison, Cherrie Tan-Dy, Sandesh Shivananda, Kenneth Tan, Andrew James, Molly Seshia, Keith Barrington, Francine Lefebvre, Doug McMillan, Wayne Andrews, Lajos Kovacs, Kimberly Dow, Maxine Clarke, Patricia Riley, Prakesh Shah, Arne Ohlsson, Khalid Aziz, Abraham Peliowski, Zenon Cieslak, Todd Sorokan, Zarin Kalapesi, Abraham Ninan, Koravangattu Sankaran, Daniel Faucher, Keith Barrington, Gerarda Cronin, Roderick Canning, Orlando da Silva, David Lee, Cecil Ojah, Michael Dunn, Eli Heymann, Shmuel Zangen, Amir Kushnir, Francis Mimouni, David Bader, Avi Rothschild, Zipora Strauss, Clari Felszer, Jamalia Jeryes, Smadar Even Tov-Friedman, Benjamin Bar-Oz, Michael Feldman, Nizar Saad, Orna Flidel-Rimon, Meir Weisbrod, Daniel Lubin, Ita Litmanovitz, Shraga Blazer, Eric Shinwell, Leah Sirota, Yousif Nijim, Francis Mimouni, Agneta Golan, Dror Mandel, Vered Fleisher-Sheffer, David Kohelet, Lev Bakhrakh, Satoshi Hattori, Shohei Konishi, Takasuke Amizuka, Takeo Kasai, Ritsuko Takahasi, Hirokazu Arai, Maki Sato, Yayoi Miyazono, Junichi Shimizu, Hiroshi Suzumura, Yumi Kono, Takahiro Inoue, Hiroshi Miyabayashi, Hisanori Sobajima, Rika Ishiguro, Hiroyuki Sato, Satsuki Totsu, Nozomi Ishii, Shigeharu Hosono, Mika Shiraishi, Humihiro Miura, Atsushi Nakao, Hitoshi Yoda, Mitsumasa Shimizu, Kazuo Seki, Yasuhumi Itani, Keiji Suzuki, Atsushi Nemoto, Tomohiko Nakamura, Masaki Wada, Yoshihisa Nagayama, Osamu Numata, Takeshi Futatani, Yasuhisa Ueno, Kazuyuki Iwai, Yoshinori Kono, Shigeru Ooki, Yusuke Nakazawa, Chizuko Suzuki, Taihei Tanaka, Motoki Bonno, Kenji Nakamura, Minako Kihara, Hiroyuki Sano, Atsushi Shiraishi, Atsushi Ohashi, Hiroyuki Ichiba, Kiyoaki Sumi, Seiji Yoshimoto, Yukihiro Takahashi, Takahiro Okutani, Masumi Miura, Fumihide Kato, Shinichi Watabe, Misao Kageyama, Rie Fukuhara, Michiko Hayashitani, Keiko Hasegawa, Kosuke Koyano, Shoko Kobayashi, Shinosuke Akiyoshi, Yusei Nakata, Takeshi Kanda, Hisano Tadashi, Hiroshi Kanda, Masaki Nakamura, Naoko Matsumoto, Masayuki Ochiai, Mikihiro Aoki, Akihiko Kawase, Koichi Iida, Chie Ishihara, Moriyasu Kohama, Ma José Fernández Seara, José Ma Fraga Bermúdez, Andrés Martínez Gutiérrez, María Mercedes Martínez Ayúcar, Carolina Vizcaíno Díaz, José Luis Quiles Durá, María González Santacruz, Ma Anne Feret Siguile, Adela Rodríguez Fernández, Belén Fernández Colomer, Enrique García López, Josep Figuera Aloy, Francesc Botet Mussons, Israel Anquela Sanz, Gemma Ginovart Galiana, Elisenda Moliner Calderon, Antonio Natal Pujol, Alicia Mirada Vives, Martín Iriondo Sanz, Roser Porta, Eva Capdevila Cogul, Laura Castells Vilella, Álvarez Bruno Alonso, José María Montero Macarro, Ana R. Barrio Sacristán, Ma Jesús López Cuesta, Ortiz Tardío, Eugenia Valls Sánchez Puerta, Isabel Benavente Fernández, Juan Mena Romero, María Dolores Martinez Gimenez, Ramón Aguilera Olmos, Ricardo Tosca Segura, Juana Ma Guzmán Cabañas, Ma Dolores Huertas Muñoz, Alberto Trujillo, Luis Fidel Moltó Ripoll, José Antonio Hurtado Suazo, Ana Elena Aldea Romero, Luis Paisán Grisolía, Ana Isabel Garrido Ocana, Eduardo Garcia Soblechero, Ma Yolanda Ruiz del Prado, Inés Esteba Díez, Gema E. González-Luis, Fermín García-Muñoz Rodrigo, Emilio Álvaro Iglesias, Fernando Fernandez Calvo, Eduard Solé Mir, Jordi Garcia Martí, Roberto Ortiz Movilla, Lucía Cabanillas Vilaplana, Marta García San Miguel, Isabel Llana Martín, María Fernández Díaz, Jesús Pérez Rodríguez, Sofía Salas, Carmen Muñoz Labian, Carmen González Armengod, Laura Domingo Comeche, Tomás Sánchez Tamayo, Manuel García del Río, José Ángel Alonso Gallego, José María Lloreda Garcia, Javier Vilas González, Ocampo, Nieves Balado Insunza, Pilar García González, Mercedes Granero Asencio, Antonia López Sanz, Carmen Macías Díaz, Araceli Ferrari Cortés, Pedro Amadeo Fuster Jorge, Santiago López Mendoza, Sabina Romero Ramírez, Ma del Mar Albújar Font, Alicia de Ureta Huertas, Antonio Arroyos Plana, Javier Estañ Capell, Vicente Roqués, F. Morcillo, Sara Marín, María Fernanda Omaña, Gabriel Saitua Iturriaga, Jiri Kofron, Katarina Strand Brodd, Andreas Odlind, Lars Alberg, Sofia Arwehed, Eva Engström, Anna Kasemo, Charlotte Ekelund, Åhman Lars, Fredrik Ingemarsson, Österdahl Laura, Pernilla Thurn, Eva Albinsson, Bo Selander, Fredrik Lundberg, Ingela Heimdahl, Ola Hafström, Erik Wejryd, Johanna Kuusima-Löfbom, Ellen Elisabeth Lund, Annelie Thorén, Boubou Hallberg, Eva Berggren Broström, Torbjörn Hertzberg, Björn Stjernstedt, Johan Robinson, Aijaz Farooqi, Erik Normann, Magnus Fredriksson, Anders Palm, Åsa Hedblom, Kenneth Sjöberg, Leif Thorbjörnsson, Andreas Ohlin, Rein Florell, Agneta Smedsaas-Löfvenberg, Philipp Meyer, Claudia Anderegg, Sven Schulzke, Mathias Nelle, Bendicht Wagner, Walter Bär, Grégoire Kaczala, Riccardo E. Pfister, Jean François Tolsa, Matthias Roth, Thomas M. Berger, Bernhard Laubscher, Andreas Malzacher, John P. Micallef, Lukas Hegi, Dirk Bassler, Romaine Arlettaz, Vera Bernet, Santanu Bag, Jonathan Kefas, Oliver Rackham, Arumugavelu Thirumurgan, Bill Yoxall, Tim McBride, Delyth Webb, Laweh Amegavie, Ahmed Hassan, Priyadarshan Ambadkar, Mark Dyke, Seif Babiker, Susan Rubin, Amanda Ogilvy-Stuart, Nagesh Panasa, Paul Settle, Jonathan Moise, Ngozi Edi-Osagie, Carrie Heal, Jacqeline Birch, Abdul Hasib, Aung Soe, Niraj Kumar, Hamudi Kisat, Vimal Vasu, Meera Lama, Richa Gupta, Chris Rawlingson, Tim Wickham, Karin Schwarz, Van Sommen, Sara Watkin, Aashish Gupta, Narendra Aladangady, Imdad Ali, Lesley Alsford, Khalid Mannan, Ebel Rainer, Nicholas Wilson, Mark Thomas, Ramnik Mathur, Michele Cruwys, Sunit Godambe, Sunit Godambe, Timothy Watts, Jauro Kuna, John Chang, Jon Filkin, Charlotte Huddy, Ruth Shephard, Krzystof Zieba, Patti Rao, Andrew Currie, Andrew Currie, Azhar Manzoor, Munir Ahmed, Phil Simmons, Julie Nycyk, Phil Simmons, Andrew Gallagher, Chrisantha Halahakoon, Sanjeev Deshpande, Anand Mohite, Kate Palmer, Alan Gibson, Mehdi Garbash, Mithilesh Lal, Majd Abu-Harb, Mehdi Garbash, Róisín McKeon-Carter, Michael Selter, Paul Munyard, Vaughan Lewis, Mala Raman, Graham Whincup, Abdus Mallik, Philip Amess, Charles Godden, Philip Amess, Peter Reynolds, Indranil Misra, Naveen Shettihalli, Peter De Halpert, Sanjay Salgia, Rekha Sanghavi, Ruth Wigfield, Abby Deketelaere, Minesh Khashu, Michael Hall, Charlotte Groves, Nick Brown, Nick Brennan, Katia Vamvakiti, Mal Ratnayaka, Simon Pirie, Stephen Jones, Paul Mannix, David Harding, Megan Eaton, Karin Schwarz, David Gibson, Lawrence Miall, David Gibson, Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates
An International Comparison, Journal of Pediatrics, 10.1016/j.jpeds.2016.04.083, 177, 144-152.e6, 2016, Objective To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. Study design We included 58 004 infants born weighing <1500 g at 240–316 weeks' gestation from databases in Australia/New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the United Kingdom. We compared a composite outcome (mortality or any of grade ≥3 peri-intraventricular hemorrhage, periventricular echodensity/echolucency, bronchopulmonary dysplasia, or treated retinopathy of prematurity) between each country and all others by using standardized ratios and pairwise using logistic regression analyses. Results Despite differences in population coverage, included neonates were similar at baseline. Composite outcome rates varied from 26% to 42%. The overall mortality rate before discharge was 10% (range: 5% [Japan]-17% [Spain]). The standardized ratio (99% CIs) estimates for the composite outcome were significantly greater for Spain 1.09 (1.04-1.14) and the United Kingdom 1.16 (1.11-1.21), lower for Australia/New Zealand 0.93 (0.89-0.97), Japan 0.89 (0.86-0.93), Sweden 0.81 (0.73-0.90), and Switzerland 0.77 (0.69-0.87), and nonsignificant for Canada 1.04 (0.99-1.09) and Israel 1.00 (0.93-1.07). The adjusted odds of the composite outcome varied significantly in pairwise comparisons. Conclusions We identified marked variations in neonatal outcomes between countries. Further collaboration and exploration is needed to reduce variations in population coverage, data collection, and case definitions. The goal would be to identify care practices and health care organizational factors, which has the potential to improve neonatal outcomes..
29. Kimiaki Hashiguchi, Takato Morioka, Nobuya Murakami, Koji Yamashita, Akio Hiwatashi, Masayuki Ochiai, Seiichi Morokuma, Koji Iihara, Clinical Significance of Prenatal and Postnatal Heavily T2-Weighted Magnetic Resonance Images in Patients with Myelomeningocele, Pediatric Neurosurgery, 10.1159/000381746, 50, 6, 310-320, 2015.11, Purpose: To compare the utility and limitations of prenatal magnetic resonance (MR) imaging using half-Fourier acquisition single-shot turbo spin-echo (HASTE) with postnatal heavily T2-weighted imaging (hT2WI) for the evaluation of central nervous system abnormalities associated with myelomeningocele (MMC). Methods: Sixteen patients with MMC who had undergone pre- and postnatal MR imaging were included in this study. MR imaging, including HASTE, was undertaken in the 3rd trimester, and hT2WI was performed immediately after delivery. The precision with which each could distinguish MMC, hindbrain herniation and ventriculomegaly was compared retrospectively. Results: The skin defects and MMC sacs were clearly visible on prenatal HASTE images, although it was difficult to identify precisely the level of MMC compared with postnatal hT2WI, in which the detailed anatomical relationships of the spinal cord, neural placode and ventral nerve roots were evident in every case. Hindbrain herniation could be visualized on prenatal HASTE images, although its severity was difficult to evaluate because of the small size of the structures and neck flexion; again, the resolution was superior on postnatal hT2WI. For hydrocephalus, there were no significant differences in the diagnostic precision and ability to grade the severity between pre- and postnatal imaging. Conclusion: Prenatal HASTE imaging permits the diagnosis and understanding of the gross anatomy of MMC and associated hindbrain herniation and ventriculomegaly, but postnatal hT2WI is superior for evaluating detailed anatomy..
30. Reiko Inoue, Yasuo Yumoto, Yasuyuki Fujita, Masayuki Ochiai, Kotaro Fukushima, Kiyoko Kato, Placental chorioangioma presenting prenatal hemolytic anemia and consumption coagulopathy: a case report
A Case Report, Case Reports in Perinatal Medicine, 4, 2, 2015.09, Large placental chorioangioma is a rare but serious complication of pregnancy. To our knowledge, this case is the first reported diagnosis of consumption coagulopathy in a fetus using fetal blood sampling (FBS) during pregnancy complicated by placental chorioangioma. A 25-year-old woman, primigravida, was referred to our hospital at 29 weeks of gestation for placental chorioangioma. At 34+1 gestation, polyhydramnios and hyperdynamic circulation were observed in the fetus. FBS demonstrated microangiopathic hemolytic anemia and the presence of consumption coagulopathy. Cesarean section was performed at 34+4 gestation because fetal maturation was expected. A female infant weighing 2158 g was born, with Apgar scores of 6 and 8 at 1 and 5 min, respectively. Neonatal blood sampling results were similar to those of FBS. The infant was treated for hyperdynamic cardiac function, hemolytic anemia, and consumption coagulopathy on mechanical ventilation in the neonatal intensive care unit and recovered fully. When fetal anemia is suspected in a case of large placental chorioangioma, the possibility of developing consumption coagulopathy during the fetal period should be considered..
31. Yuka Otera, Yasuo Yumoto, Masayuki Ochiai, Koji Yamashita, Kiyoko Kato, Prenatal diagnosis of periventricular venous infarction in utero: a case with hereditary protein C deficiency
A Case Report, Case Reports in Perinatal Medicine, 4, 2, 2015.09, A 36-year-old primigravida woman with a normal pregnancy course presented with fetal unilateral focal ventriculomegaly on routine ultrasonography performed at 28 weeks of gestation. Periventricular venous infarction (PVI) in utero was diagnosed with fetal magnetic resonance imaging (MRI). The neonate was born at term uneventfully and in utero PVI was confirmed by MRI after birth. The neonate was diagnosed with hereditary protein C deficiency after coagulation laboratory studies. At 10 months of age, the infant presented with mild retardation of motor development. This is the first report about prenatally diagnosed PVI in utero by fetal MRI. When focal, unilateral enlargement of the ventricles is detected in utero by prenatal ultrasonography, it is important to consider PVI and perform confirmatory fetal MRI..
32. , Hidehiko Maruyama, Naohiro Yonemoto, Yumi Kono, Satoshi Kusuda, Masanori Fujimura, M. Fujimura, S. Kusuda, S. Hattori, S. Konishi, T. Amizuka, T. Kasai, R. Takahashi, H. Arai, M. Satoh, Y. Miyazono, Y. Kono, T. Fujiu, H. Sobajima, K. Kabe, S. Hosono, M. Shiraishi, Y. Kawakami, T. Watanabe, M. Hida, K. Seki, H. Itani, A. Nemoto, T. Nakamura, O. Numata, Y. Ueno, Y. Kawano, S. Oki, C. Suzuki, M. Bonno, K. Nakamura, T. Yamakawa, M. Kihara, H. Wada, J. Shiraishi, H. Minami, A. Ohashi, H. Ichiba, T. Okutani, M. Miura, S. Watabe, R. Fukuhara, S. Kobayashi, S. Akiyoshi, T. Hisano, M. Ochiai, Weight growth velocity and neurodevelopmental outcomes in extremely low birth weight infants, PloS one, 10.1371/journal.pone.0139014, 10, 9, 2015.09, Introduction This study aimed to assess whether weight growth velocity (WGV) predicts neurodevelopmental outcomes in extremely low birth weight infants (ELBWIs). Methods Subjects were infants who weighed 501-1000 g at birth and were included in the cohort of the Neonatal Research Network of Japan (2003-2007). Patel's exponential model (EM) method was used to calculate WGV between birth and discharge. Assessment of predictions of death or neurodevelopmental impairment (NDI) was performed at 3 years of age based on the WGV score, which was categorized by per one increase in WGV. Multivariate logistic regression analysis was used to calculate adjusted odds ratios and their 95% confidence intervals (95%CI). Results In the 2961 ELBWIs assessed, the median WGV was 10.5 g/kg/day (interquartile, 9.4- 11.9). With the categorical approach, the adjusted odds ratios for death or NDI with WGV scores of 6 and 7 were 2.41 (95%CI, 1.60-3.62) and 1.81 (95%CI, 1.18-2.75), respectively, relative to the reference WGV score of 10. WGV scores ≥8 did not predict death or NDI. Conclusions WGV scores <8 were significant predictors suggesting that values of WGV during hospitalization in a NICU are associated with neurodevelopmental outcomes. Further investigations is necessary to determine whether additional nutritional support may improve low WGV in ELBWIs..
33. Masayuki Ochiai, Masako Ichiyama, Mariko Iwayama, Yasuanri Sakai, Keiko Yoshida, Toshiro Hara, Longitudinal study of very low birth weight infants until 9years of age; attention deficit hyperactivity and autistic features are correlated with their cognitive functions, Early Human Development, 10.1016/j.earlhumdev.2015.09.005, 91, 12, 783-786, 2015, Background: Increasing attention has been given to neuro-developmental problems of very low birth weight infants (VLBWIs) at school age. However, it remains unknown whether their neuro-cognitive function and psychiatric symptoms are mutually associated. Aim: The aim of this study was to investigate the characteristics of neuro-cognitive functions in VLBWIs and their relationship with psychiatric symptoms. Methods: A total of 160 VLBWIs who were born at our institute between 2001 and 2005 were recruited consecutively and followed up until nine years of age. The developmental profiles were obtained from 77 children (45 males and 32 females) at six to nine years of age using the ADHD Rating Scale-Fourth edition (ADHD-RS), Autism Screening Questionnaire-Japanese version (ASQ-J) and the Wechsler Intelligence Scale for Children-Third edition (WISC-III). Results: The full-scale intelligence quotient did not significantly differ between the male and female VLBWIs (median: 91 vs. 99, p = 0.17). The males had higher total scores (median: 13 vs. 4, p. <. 0.01) and higher scores on the subscales of Inattention (8 vs. 2, p < 0.01) and Hyperactivity-Impulsivity (5 vs. 1, p < 0.01) of the ADHD-RS compared with the females. The Verbal Comprehension Index (VCI) of the WISC-III was inversely correlated with the total scores of the ASQ-J for all VLBWIs (n = 77, rc: - 0.32, 95% CI: - 0.19 to - 0.01, p = 0.04). We also observed that the Freedom from Distractibility Index (FDI) of the WISC-III was significantly correlated with the Inattentive scores of the ADHD-RS (n = 45, rc: - 0.18, 95% CI: - 0.35 to - 0.02, p = 0.03) in male, but not female VLBWIs. Conclusions: We herein report that the VCI and FDI of the WISC-III were correlated with the autism spectrum disorder and attention deficit hyperactivity disorder symptoms, respectively, in male VLBWIs..
34. Yuka Otera, Seiichi Morokuma, Kotaro Fukushima, Ai Anami, Yasuo Yumoto, Yushi Ito, Masayuki Ochiai, Kimiaki Hashiguchi, Norio Wake, Haruhiko Sago, Kiyoko Kato, Neurological outcomes in Chiari type II malformations and their correlation to morphological findings and fetal heart rate patterns
A retrospective study, BMC research notes, 10.1186/s13104-015-1014-2, 8, 1, 2015, Background: Correlations among Chiari type II malformation (CMII) morphological findings, the proportion of fetal heart rate patterns corresponding to the quiet phase (QP), and neurological outcomes have yet to be investigated. Findings: The correlations among the morphological findings (i.e., the degree of ventriculomegaly, myelomeningocele levels, and degree of cerebellar herniation), proportion of time spent in QP, and developmental quotients (DQs) were analyzed in 22 children. The proportion of time spent in QP was compared between children with poor neurological outcomes (n = 9) and those with good outcomes (n = 13). Pearson's correlations and the Mann-Whitney U-test were used to assess for statistical significance; P < 0.05 was considered statistically significant. No significant differences were observed between the DQs and morphological findings, but the DQs and the proportion of time spent in QP were significantly correlated (r = 0.287, P = 0.01). The proportion of time spent in QP was significantly different between children with poor outcomes and those with good outcomes (median, 11% [range, 0-32%] vs. 28% [range, 2-55%]; P = 0.006). Conclusions: The proportion of fetal heart rate patterns corresponding to the QP might be a useful predictor of neurological outcomes in 2-year-old children with CMII..
35. Naho Morisaki, Mandy B. Belfort, Marie C. McCormick, Rintaro Mori, Hisashi Noma, Satoshi Kusuda, Masanori Fujimura, M. Fujimura, S. Kusuda, S. Hattori, A. Noro, T. Amizuka, S. Chida, R. Takahashi, H. Arai, T. Imamura, N. Ujiie, Y. Miyazono, J. Shimizu, H. Suzumura, Y. Kono, M. Shimizu, T. Kunikata, T. Fujiu, H. Sato, T. Kondo, T. Watanabe, M. Aizawa, A. Uchiyama, M. Makimoto, J. Hoshi, H. Yoda, Y. Kawakami, N. Ishii, Y. Ito, H. Itani, K. Seki, M. Nomura, M. Nowatari, A. Nemoto, O. Nagata, Y. Nagayama, T. Nakamura, M. Okada, S. Nakata, E. Shimazaki, T. Yoda, T. Hutatani, Y. Ueno, K. Iwai, Y. Nakazawa, S. Oki, C. Suzuki, M. Bonno, Y. Kawano, K. Nakamura, N. Mitsufuji, J. Shiraishi, H. Ichiba, H. Minami, H. Wada, A. Ohashi, K. Sumi, Y. Takahashi, T. Okutani, S. Yoshimoto, I. Nagata, E. Kato, S. Watabe, M. Kageyama, R. Fukuhara, M. Hayashitani, K. Hasegawa, A. Ohta, T. Kuboi, S. Akiyoshi, K. Kikkawa, T. Saijo, S. Shimokawa, N. Matsumoto, H. Kanda, E. Oota, G. Kanda, M. Ochiai, M. Aoki, Y. Kondo, M. Iwai, K. Iida, T. Ikenoue, S. Ibara, M. Kohama, Brief parenteral nutrition accelerates weight gain, head growth even in healthy VLBWs, PloS one, 10.1371/journal.pone.0088392, 9, 2, 2014.02, Introduction: Whether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate. Methods: We studied 4005 hospitalized VLBW, very preterm (23-32 weeks' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003-2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement <10th percentile for postmenstrual age) at discharge. Results: 40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates. Discussion: Even in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants..
36. Yoko Fujita, Shoko Tsukamoto, Mika Tanabe, Kimiko Ishida, Yoshihisa Tahara, Masayuki Ochiai, Tatsuro Ishibashi, Experience of retinopathy of prematurity treated with intravitreal injection of bevacizumab and laser therapy, Folia Japonica de Ophthalmologica Clinica, 6, 4, 311-316, 2013.04.
37. Y. Matsunaga, S. Ohga, T. Kinjo, M. Ochiai, N. Ito, T. Doi, D. Kang, T. Hara, Neonatal asphyxia and renal failure as the presentation of non-inherited protein C deficiency, Journal of Perinatology, 10.1038/jp.2012.55, 33, 3, 239-241, 2013.03, Inherited or acquired protein C (PC) deficiency leads to thromboembolic events. Plasma PC activity in infancy is physiologically lower than in adults. We describe a case of neonatal asphyxia and acute renal failure associated with isolated PC deficiency. A full-term male infant was born to a healthy mother by caesarean section because of fetal distress. The small-for-gestational age infant showed 2 and 7 of Apgar scores at 1 and 5 minutes, respectively. Hypercoagulability required repeated infusions of fresh frozen plasma. Coagulation study revealed PC activity, 6%, protein S activity, 61%, and high D-dimer levels, along with normal factor VII activity and absent vitamin K deficiency. Anticoagulant and activated PC therapy improved coagulopathy and nephropathy. Imaging analyses indicated no visceral infarctions. Renal function and PC activity have been slowly normalized until 6 months of age. He had no PROC mutation or PC-deficient parents. Selective PC deficiency may occur as an acquired cause of hypercoagulable crisis in the stressed newborn..
38. Tetsuya Isayama, Shoo K. Lee, Rintaro Mori, Satoshi Kusuda, Masanori Fujimura, Xiang Y. Ye, Prakesh S. Shah, Wayne Andrews, Keith Barrington, Wendy Yee, Barbara Bullied, Rody Canning, Ruben Alvaro, Orlando Da Silva, Kimberly Dow, Michael Dunn, Adele Harrison, Andrew James, Zarin Kalapesi, Lajos Kovacs, Douglas D. McMillan, Arne Ohlsson, Cecil Ojah, Abraham Peliowski, Khalid Aziz, Bruno Piedboeuf, Patricia Riley, Daniel Faucher, Nicole Rouvinez-Bouali, Koravangattu Sankaran, Mary Seshia, Sandesh Shivananda, Zenon Cieslak, Anne Synnes, Herve Walti, S. Hattori, A. Noro, T. Amizuka, S. Chida, R. Takahashi, H. Arai, T. Imamura, N. Ujiie, Y. Miyazono, J. Shimizu, H. Suzumura, Y. Kono, M. Shimizu, T. Kunikata, T. Fujiu, H. Sato, T. Kondo, T. Watanabe, M. Aizawa, A. Uchiyama, M. Makimoto, J. Hoshi, H. Yoda, Y. Kawakami, N. Ishii, Y. Ito, H. Itani, K. Seki, M. Nomura, M. Nowatari, A. Nemoto, O. Nagata, Y. Nagayama, T. Nakamura, M. Okada, S. Nakata, E. Shimazaki, T. Yoda, T. Hutatani, Y. Ueno, K. Iwai, Y. Nakazawa, S. Oki, C. Suzuki, M. Bonno, Y. Kawano, K. Nakamura, N. Mitsufuji, J. Shiraishi, H. Ichiba, H. Minami, H. Wada, A. Ohashi, K. Sumi, Y. Takahashi, T. Okutani, S. Yoshimoto, I. Nagata, E. Kato, S. Watabe, M. Kageyama, R. Fukuhara, M. Hayashitani, K. Hasegawa, A. Ohta, T. Kuboi, S. Akiyoshi, K. Kikkawa, T. Saijo, S. Shimokawa, N. Matsumoto, H. Kanda, E. Oota, G. Kanda, M. Ochiai, M. Aoki, Y. Kondo, M. Iwai, K. Iida, T. Ikenoue, S. Ibara, M. Kohama, Comparison of mortality and morbidity of very low birth weight infants between Canada and Japan, Pediatrics, 10.1542/peds.2012-0336, 130, 4, e957-e965, 2012.10, OBJECTIVE: To compare neonatal outcomes of very low birth weight (VLBW) infants admitted to NICUs participating in the Canadian Neonatal Network and the Neonatal Research Network of Japan. METHODS: Secondary analyses of VLBW infants in both national databases between 2006 and 2008 were conducted. The primary outcome was a composite of mortality or any major morbidity defined as severe neurologic injury, bronchopulmonary dysplasia, necrotizing enterocolitis, or severe retinopathy of prematurity at discharge. Secondary outcomes included individual components of primary outcome and late-onset sepsis. Logistic regression adjusting for confounders was performed. RESULTS: A total of 5341 infants from the Canadian Neonatal Network and 9812 infants from the Neonatal Research Network of Japan were compared. There were higher rates of maternal hypertension, diabetes mellitus, outborn, prenatal steroid use, and multiples in Canada, whereas cesarean deliveries were higher in Japan. Composite primary outcome was better in Japan in comparison with Canada (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.79-0.96). The odds of mortality (AOR 0.40, 95% CI 0.34-0.47), severe neurologic injury (AOR 0.57, 95% CI 0.49-0.66), necrotizing enterocolitis (AOR 0.23, 95% CI 0.19-0.29), and late-onset sepsis (AOR 0.22, 95% CI 0.19-0.25) were lower in Japan; however, the odds of bronchopulmonary dysplasia (AOR 1.24, 95% CI 1.10-1.42) and severe retinopathy of prematurity (AOR 1.98, 95%CI 1.69-2.33) were higher in Japan. CONCLUSIONS: Composite outcome of mortality or major morbidity was significantly lower in Japan than Canada for VLBW infants. However, there were significant differences in various individual outcomes identifying areas for improvement for both networks..
39. Yoko Fujita, Shoko Tsukamoto, Kimiko Ishida, Yoshihisa Tahara, Tadamune Kinjo, Masayuki Ochiai, Hiroyuki Kondo, Tatsuro Ishibashi, Three cases of severe retinopathy of prematurity treated with intravitreal injection of bevacizumab and laser therapy, Folia Japonica de Ophthalmologica Clinica, 5, 4, 377-381, 2012.04.
40. Shunji Hikino, Shouichi Ohga, Tadamune Kinjo, Takeshi Kusuda, Masayuki Ochiai, Hirosuke Inoue, Satoshi Honjo, Kenji Ihara, Koichi Ohshima, Toshiro Hara, Tracheal aspirate gene expression in preterm newborns and development of bronchopulmonary dysplasia, Pediatrics International, 10.1111/j.1442-200X.2011.03510.x, 54, 2, 208-214, 2012.04, Background: Bronchopulmonary dysplasia (BPD) occurs in association with prenatal conditions predisposing infants to inflammation and remodeling of the premature lungs. Because of the lack of useful biomarkers for BPD, the gene expression of tracheal aspirate fluid (TAF) cells in premature infants was analyzed. Methods: Of 148 consecutive patients, 26 preterm infants (gestational age <34 weeks) were enrolled, who underwent assisted ventilation at birth for respiratory failure. Patients with congenital disorders were excluded. Half of these infants developed BPD. Interleukin (IL)-10, interferon (IFN)-γ, transforming growth factor (TGF)-β1, and platelet-derived growth factor (PDGF)-B mRNA of TAF cells were quantified on real-time polymerase chain reaction. Results: IL-10 (P < 0.01) and IFN-γ (P= 0.03) but not TGF-β1 or PDGF-B mRNA levels at birth were higher in BPD than in non-BPD infants. IL-10 expression differentiated BPD with the highest sensitivity (92%) and specificity (77%). IL-10 levels correlated with TGF-β1 (P= 0.03) and IFN-γ (P= 0.01), but not with PDGF-B levels. When BPD infants were classified according to comorbidity (group 1, six patients who suffered respiratory distress syndrome [RDS] but not chorioamnionitis [CAM]; group 2, five patients who had CAM but not RDS), PDGF-B levels were higher in group 2 (P= 0.01). High IL-10 expression was selected as a risk factor for BPD in infants who had CAM but not RDS (P= 0.01), although prolonged oxygen therapy was the most sensitive indicator for BPD (P < 0.01) on multivariate analysis. Conclusions: High IL-10 expression in TAF cells at birth could predict the evolution of BPD, but with less impact than oxygen requirement. PDGF might play a different role in the inflammatory process of premature lungs..
41. Kotaro Fukushima, Seiichi Morokuma, Yasuyuki Fujita, Kiyomi Tsukimori, Shoji Satoh, Masayuki Ochiai, Toshiro Hara, Tomoaki Taguchi, Norio Wake, Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis, Early Human Development, 10.1016/j.earlhumdev.2011.04.015, 87, 8, 571-575, 2011.08, Despite advances in diagnosis and management, non-immune hydrops fetalis (NIHF) has a high mortality rate. Perinatal survival depends on the underlying disorder and the gestational age at diagnosis. As prognostic information is limited, this study acquired data regarding the neurological development of perinatal survivors.We performed a retrospective chart review of 214 cases in which NIHF was diagnosed antenatally. We recorded maternal demographic characteristics and interventions and their effectiveness, as well as the short-term outcome (survival) and long-term outcome including developmental quotients. Among the affected fetuses, 91 (42.5%) survived the perinatal period. Fetuses with chylothorax, chyloascites, or meconium peritonitis, and those in whom therapy was effective, had high survival rates irrespective of the type of intrauterine intervention. The subsequent intact survival rate was 28/56 (50.0%), with intact defined as ratio of the number of infants with normal development to the number of all infants followed. In contrast to the perinatal survival rate, the intact survival rate decreased as gestational age at diagnosis advanced. These findings suggest that the long-term intact survival rate depends on the underlying cause of NIHF. Additionally, while survival was improved with intensive perinatal care during the perinatal period, aggressive perinatal intervention was not a prognostic factor for neurological outcome..
42. Tadamune Kinjo, Shouichi Ohga, Masayuki Ochiai, Satoshi Honjo, Tamami Tanaka, Yasushi Takahata, Kenji Ihara, Toshiro Hara, Serum chemokine levels and developmental outcome in preterm infants, Early Human Development, 10.1016/j.earlhumdev.2011.03.006, 87, 6, 439-443, 2011.06, Background: Cytokines and chemokines during perinatal period may involve the neurological development of newborns. Aims: We investigated the association of circulating chemokines during neonatal period with the outcome of premature infants. Study design: The prospective study enrolled 29 very low birth weight (< 1500. g) and appropriate-for-date infants having no underlying diseases. Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10 and CCL2) and cytokines at birth and 4. weeks postnatal age were measured. Developmental quotients (DQ) at 3. years of age by the Kyoto Scale of Psychological Development were studied for the association with chemokine/cytokine levels and clinical variables including chorioamnionitis, Apgar scores, ventilator treatment and supplemental oxygen. Results: CXCL8 levels at birth and days of ventilator treatment were negatively, CCL2 levels at 4. weeks after birth and 5-minute Apgar scores were positively correlated with the DQ of postural-motor [P-M] area at 3. years of age, respectively (CXCL8: correlation coefficient [CC] = -0.394, p = 0.037, ventilation: CC = -0.518, p = 0.006, CCL2: CC = 0.528, p = 0.013, and Apgar score: CC = 0.521, p = 0.005). Infants showing both ≥ 50. pg/ml of CXCL8 at birth and < 250. pg/ml of CCL2 4. weeks after birth had lower DQ of P-M than those who did not (p < 0.001). Multivariate analyses indicated that CCL2 levels at 4. weeks of age were higher in infants who attained normal DQ of P-M (≤ 85) (adjusted mean, 338.4 [95% confidence interval, 225.5-507.8]) than in those who did not (< 85) (159.0, [108.2-233.7]) (p = 0.019). Conclusion: Circulating patterns of CXCL8 (IL-8) and CCL2 (MCP-1) during the neonatal period might affect the neurological development of preterm infants..
43. T. Kusuda, S. Hikino, S. Ohga, T. Kinjo, M. Ochiai, Y. Takahata, S. Tokunaga, K. Ihara, Y. Hata, T. Hara, Genetic variation of vascular endothelial growth factor pathway does not correlate with the severity of retinopathy of prematurity, Journal of Perinatology, 10.1038/jp.2010.111, 31, 4, 246-250, 2011.04, Objective: The aim of this study was to assess the genetic effects of the vascular endothelial growth factor (VEGF) pathway on retinopathy of prematurity (ROP). Study Design: A prospective study from a tertiary center that enrolled 204 Japanese infants (<35 weeks of gestational age (GA)) having no anomalies. ROP developed in 127, but not in 77 infants. The relative severity was defined as non-severe, moderate and severe ROP for GA, based on the staging criteria. VEGF (g.-634G>C, g.+13553C>T) and VEGF-receptor (KDR g.+4422(AC)11 to 14, Flt-1 c.+6724(TG)13 to 23) gene polymorphisms and clinical variables were assessed by uni/multivariate analyses. Result: The frequency of polymorphisms did not differ between ROP and non-ROP patients. The TT genotype of g.+13553 showed a higher odds ratio for non-severe ROP than CC genotype (P=0.006). Multivariate analyses indicated that low birth weight, blood transfusion and respiratory distress syndrome, but not polymorphisms, were the risk factors of advanced ROP (≥stage 3). Conclusion: A genotype of the VEGF pathway weakly affects the severity of ROP compared with other clinical factors..
44. Xiangqun Li, Seiichi Morokuma, Kotaro Fukushima, Yuka Otera, Yasuo Yumoto, Kiyomi Tsukimori, Masayuki Ochiai, Toshiro Hara, Norio Wake, Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome, BMC Pregnancy and Childbirth, 10.1186/1471-2393-11-32, 11, 2011.04, Background: Amnioreduction remains a treatment option for pregnancies with twin-to-twin transfusion syndrome (TTTS) not meeting criteria for laser surgery or those in which it is not feasible. Amnioreduction is a relatively simple treatment which does not require sophisticated technical equipment. Previous reports of conservative management have indicated that major neurodevelopmental impairment occurs in 14.3-26% of survivors. The purpose of this study was to investigate long-term neurodevelopmental outcome in conservatively treated TTTS.Methods: During the nine-year study period from January 1996 to December 2004, all pregnancies with TTTS who were admitted to our center were investigated. TTTS was diagnosed by using standard prenatal ultrasound criteria, and staged according to the criteria of Quintero et al. We reviewed gestational age at diagnosis, gestational age at delivery, the stage of TTTS at diagnosis, and diagnosis to delivery interval. Neonatal cranial ultrasound findings were reviewed and the neurodevelopmental outcomes were evaluated.Results: Twenty-one pregnancies with TTTS were included. Thirteen pregnancies (62%) were treated with serial amnioreduction. The mean gestational age at delivery was 28 weeks (22 - 34 weeks). The perinatal mortality rate was 42.9%. Twenty survivors were followed up until at least 3 years of age. The mean age at follow-up was 6.3 years (3 - 12 years). Six children (30%) had neurodevelopmental impairment. Four children (20%) had major neurodevelopmental impairment and two children (10%) had minor neurodevelopmental impairment. Children with neurodevelopmental impairment were delivered before 29 weeks of gestation.Conclusions: Our study showed a high rate of perinatal mortality and a high rate of major neurodevelopmental impairment in conservatively treated TTTS. The long-term outcomes for the survivors with TTTS were good when survivors were delivered after 29 weeks of gestation..
45. Iron homeostasis and hepcidin in the neonates.
46. H. Inoue, K. Ihara, M. Ochiai, Y. Takahata, H. Kohno, T. Hara, Congenital multiple pituitary hormone deficiency associated with hyperammonemia
A case report with a short review of the literature, Journal of Perinatology, 10.1038/jp.2010.143, 31, 2, 146-148, 2011.02, We herein report a case study of a female newborn with multiple pituitary hormone deficiencies who presented with generalized seizures, hypoglycemia and hyperammonemia at 18 h after birth. In addition, we review the association of hyperammonemia in neonates with multiple pituitary hormone deficiencies reported in the previous literature. This unrecognized association should be taken into account for the early diagnosis and treatment of these patients..
47. Junko Kitajima, Shouichi Ohga, Tadamune Kinjo, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Toshiro Hara, Serum prohepcidin concentrations at birth and 1 month after birth in premature infants, Pediatric Blood and Cancer, 10.1002/pbc.22773, 56, 2, 267-272, 2011.02, Background: Premature newborns are vulnerable to iron imbalance, although the iron homeostasis during the perinatal period remains unclear. To clarify the iron metabolism of premature infants, we measured serum prohepcidin concentrations of preterm infants, and analyzed the association with iron parameters.Methods: Seventy-one (61 preterm and 10 term) infants were enrolled for the study, that had no underlying diseases including asphyxia, bleedings, infection, and anomalies. Serum concentrations of prohepcidin at birth and 1 month after birth were determined by enzyme-linked immunosorbent assay.Results: Prohepcidin levels at birth but not 1 month postnatal age positively correlated with gestational age (correlation coefficient [CC]:0.334, P-=-0.005) and birth weight (CC: 0.367, P-=-0.002). The levels at birth of preterm infants (median: 29.93-ng/ml, range: 4.0-110.6) were lower than those of full-term infants, and increased thereafter. On the other hand, the levels in small-for-gestational age infants were not associated with gestational age or birth weight. Prohepcidin levels at birth correlated positively with red cell counts (CC-=-0.487, P-=-0.025), unsaturated iron binding capacity (CC-=-0.755, P-=-0.001), total protein (CC-=-0.624, P-=-0.005), and serum albumin levels (CC-=-0.500, P-=-0.025), and negatively with serum iron levels (CC-=--0.688, P-=-0.003), but not ferritin levels. Multivariate analyses indicated that prohepcidin levels at birth were lower in infants with pregnancy-induced hypertension (P-=-0.03) or premature rupture of membrane (P-=-0.01).Conclusions: Prohepcidin production was physiologically low at birth of preterm infants according to the gestational age, and the levels might be susceptible to the in utero stress. The postnatal increase might reflect the maturation and/or adaptation of iron homeostasis..
48. Hirosuke Inoue, Hidetoshi Takada, Takeshi Kusuda, Takako Goto, Masayuki Ochiai, Tadamune Kinjo, Jun Muneuchi, Yasushi Takahata, Naomi Takahashi, Tomohiro Morio, Kenjiro Kosaki, Toshiro Hara, Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism, European Journal of Pediatrics, 10.1007/s00431-009-1126-6, 169, 7, 839-844, 2010.07, It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months..
49. Masayuki Ochiai, Hideki Nakayama, Kazuo Sato, Kouichi Iida, Shunji Hikino, Shouichi Ohga, Kiyomi Tsukimori, Norio Wake, Kouji Masumoto, Tomoaki Taguchi, Toshiro Hara, Head circumference and long-term outcome in small-for-gestational age infants, Journal of Perinatal Medicine, 10.1515/JPM.2008.042, 36, 4, 341-347, 2008.07, Objectives: To assess risk factors for the growth and development of small-for-gestational age (SGA) infants whose birth weight was less than the 10th percentile. Patients and methods: SGA infants who were admitted to the neonatal intensive care unit from 1995 to 1998 were enrolled in the study. Fifty-six SGA infants, having no chromosomal abnormalities, inherited diseases, TORCH infections, major anomaly and/or multiple birth, were divided into 34 asymmetrical and 22 symmetrical SGA infants by ≥ or <10 th percentile head circumference (HC) at birth. The physical growth including HC, and the developmental quotient (DQ) and intelligent quotient (IQ) scores were evaluated up to 6 years of age. Results: Symmetrical SGA infants had lower levels of weight, height and HC, but not of total DQ at 3 years or IQ scores at 6 years of age than asymmetrical SGA infants. The 21 SGA infants who had a HC less than the 10th percentile at 1 year of age (non-catch-up group) showed lower total DQ (mean 96 vs. 105) and IQ (82 vs. 102) scores than 34 SGA infants who had not (catch-up group). Conclusions: These results suggested that psychomotor development of SGA infants depended on the HC at 1 year of age rather than that at birth..
50. Taro Nagatomo, Koichiro Muta, Shouichi Ohga, Masayuki Ochiai, Koichi Ohshima, Toshiro Hara, Insulin-like growth factor-II
a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors, Experimental Hematology, 10.1016/j.exphem.2007.12.009, 36, 4, 401-411, 2008.04, Objective: To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells. Materials and Methods: Human CB-derived CD36+ erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO). Results: The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II) gene expression in CB-CD36+ erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36+ erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36+ erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab. Conclusions: These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion..
51. Masayuki Ochiai, Shunji Hikino, Hidetake Yabuuchi, Hideki Nakayama, Kazuo Sato, Shouichi Ohga, Toshiro Hara, A New Scoring System for Computed Tomography of the Chest for Assessing the Clinical Status of Bronchopulmonary Dysplasia, Journal of Pediatrics, 10.1016/j.jpeds.2007.05.043, 152, 1, 90-95.e3, 2008.01, Objective: To develop a new scoring system for computed tomography (CT) of the chest for assessing the clinical status of patients with bronchopulmonary dysplasia (BPD) in comparison with a modified Edwards roentgenographic scoring system. Study design: Preterm infants diagnosed with BPD (n = 42) were assessed prospectively by chest CT scan at the time of discharge. Three radiologists classified the CT findings into 1 of 3 categories-hyperexpansion, emphysema, or fibrous/interstitial abnormalities-and developed a new scoring system. We assessed interobserver reproducibility and investigated whether this classification system reflected the severity of BPD in these patients. Results: The CT scores had acceptable reproducibility (coefficient of correlation [cc] = 0.721 to 0.839). The subgroup with a more severe form of BPD had a higher CT score. The CT score correlated with the clinical score at 36 weeks of postmenstrual age (cc = 0.367) and the duration of oxygen therapy (cc = 0.537). Patients who were discharged home on oxygen had higher CT scores than patients who were not. Conclusions: The new chest CT scoring system may have higher objectivity and accuracy in terms of predischarge assessment of clinical status as well as prediction of the prognosis of patients with BPD..
52. 市山 正子, 落合 正行, Fetal hydrocephalus and neonatal stroke as the first presentation of protein C deficiency, Brain Dev, 2016.01.
53. 井上 普介, 落合 正行, Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy., J Immunol, 2016.03.
54. 落合 正行, Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan., PLoS One, 2016.08.
55. Masayuki Ochiai, BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector., Gene Ther., 2016.04.
56. Masayuki Ochiai, Longitudinal study of very low birth weight infants until 9years of age; attention deficit hyperactivity and autistic features are correlated with their cognitive functions., Early Hum Dev., 2015.12.
57. 山田 孝明, 落合 正行, Evaluation of teicoplanin concentrations and safety analysis in neonates, INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 10.1016/j.ijantimicag.2014.07.005, 44, 5, 458-462, 2014.11.
58. KENJI IHARA, Masayuki Ochiai, Hyperinsulinemic hypoglycemia of infancy in Sotos syndrome, AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 10.1002/ajmg.a.35657, 161A, 1, 34-37, 2013.01.
59. Shouichi Ohga, Masayuki Ochiai, Paediatric presentation and outcome of congenital protein C deficiency in Japan, HAEMOPHILIA, 10.1111/hae.12097, 19, 3, 378-384, 2013.05.
60. Hirosuke Inoue, Masayuki Ochiai, Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants, EARLY HUMAN DEVELOPMENT, 10.1016/j.earlhumdev.2012.12.011, 89, 6, 425-429, 2013.06.
61. Masayuki Ochiai, Survival and Neurodevelopmental Outcome of Preterm Infants Born at 22-24 Weeks of Gestational Age, NEONATOLOGY, 10.1159/000355818, 105, 2, 79-84, 2013.11, Background: The limits of viability in extremely premature infants are challenging for any neonatologists in developed countries. On the other hand, tThe neurological development and growth of extremely preterm infants have come to be the emerging issue in the next stage of following the management of in NICU.
Objective: To assess potential associations between changes in practice and survival/neurodevelopmental outcome, and clinical outcomes of extremely preterm infants born at the limit of viability were studied in a tertiary center.  
Study design: A retrospective study enrolled 51 infants who had no congenital disorders, and were born at 22-24 weeks of gestational age (GA) in 2000-2009 in our single institution. Clinical variables and interventions were studied with regard to one-year survival and developmental quotient (DQ) at 3 years of age.  
Results: The one-year survival rate of 24 preterm infants born in 2005-2009 (79%) was higher than that of the 27 those infants born in 2000-2004 (52%) (p=0.04). The iInfants born at or post-2005 underwent less and more frequently tocolysis (54% vs. 94%, p<0.01) and more frequently antenatal steroid therapy (32% vs. 6%, p=0.01) than those born at pre-20045, respectively. The post-2005 survivors (n=19) received more frequently indomethacin therapy (89% vs. 50%, p=0.03) and early parenteral nutrition (95% vs. 36%, p<0.01) than the pre-20045 survivors (n=14). There were no differences in the proportion of infants who attained a DQ of >50 at 3-years of age between pre-20045 (n=9/13=69%) and post-2005 groups (n=10/17=59%) (30% vs. 33%). Multivariate analysis indicated that extremely premature birth ity born at GA<24w was the sole critical factor for the development status with the a DQ of >50 in survivors.  
Conclusions: The perinatal care after 2005 could improved the overall survival rate, but not, the neurological outcomes of preterm survivors at the limit of viability. Neurodevelopmental impairments were associated with the extremely premature birth ity born at GA<24w.
62. 諸隈 誠一, 落合 正行, 和氣 徳夫, Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns, BRAIN & DEVELOPMENT, 10.1016/j.braindev.2012.01.007, 35, 1, 61-67, 2013.01.
63. 北島 順子, 落合 正行, 原 寿郎, Differential Transmission and Postnatal Outcomes in Triplets with Intrauterine Cytomegalovirus Infection, PEDIATRIC AND DEVELOPMENTAL PATHOLOGY, 10.2350/11-05-1034-CR.1, 15, 2, 151-155, 2012.03.
64. Kitajima J, Ohga S, Kinjo T, Ochiai M, Takahata Y, Honjo S, Hara T:, Serum prohepcidin concentrations at birth and 1 month after birth in premature infants., Pediatr Blood Cancer., 2011.02.
65. Inoue H, Ihara K, Ochiai M, Takahata Y, Kohno H, Hara T:, Congenital multiple pituitary hormone deficiency associated with hyperammonemia: a case report with a short review of the literature., J Perinatol., 2011.02.
66. Kitajima J, Inoue H, Ohga S, Kinjo T, Ochiai M, Yoshida T, Kusuhara K, Hara T:, Differential transmission and postnatal outcomes in triplets with intrauterine cytomegalovirus infection., Pediatr Dev Pathol., 2011.10.
67. Li X, Morokuma S, Fukushima K, Otera Y, Yumoto Y, Tsukimori K, Ochiai M, Hara T, Wake N:, Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome., BMC Pregnancy Childbirth. , 2011.04.
68. Fukushima K, Morokuma S, Fujita Y, Tsukimori K, Satoh S, Ochiai M, Hara T, Taguchi T, Wake N:, Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis., Early Hum Dev., 87, 8, 571-575, 2011.05.
69. Kusuda T, Hikino S, Ohga S, Kinjo T, Ochiai M, Takahata Y, Tokunaga S, Ihara K, Hata Y, Hara T:, Genetic variation of vascular endothelial growth factor pathway dose not correlate with the severity of retinopathy of prematurity., J Perinatol, 31, 4, 246-250, 2011.05.
70. Kinjo T, Ohga S, Ochiai M, Honjo S, Tanaka T, Takahata Y, Ihara K, Hara T, Serum chemokine levels and developmental outcome in preterm infants., Early Hum Dev., 2011.01.
71. Kinjo T, Ohga S, Ochiai M, Honjo S, Tanaka T, Takahata Y, Ihara K, Hara T, Serum chemokine levels and developmental outcome in preterm infants., Early Hum Dev., 2011.01.
72. Hikino S, Ohga S, Kinjo T, Kusuda T, Ochiai M, Inoue H, Honjo S, Ihara K, Ohshima K, Hara T, Tracheal aspirate gene expression of preterm newborns developing bronchopulmonary dysplasia., Pediatr Int, 2011.11.
73. Inoue H, Ihara K, Ochiai M, Takahata Y, Kohno H, Hara T:, Congenital multiple pituitary hormone deficiency associated with hyperammonemia: A case report with a short review of the literature., Journal of perinatology, 2011.02.
74. Inoue H, Takada H, Kusuda T, Goto T, Ochiai M, Kinjo T, Muneuchi J, Takahata Y, Takahashi N, Morio T, Kosaki K, Hara T:, Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism., Eur J Pediatr., 2010.06.
75. Kitajima J, Ohga S, Kinjo T, Ochiai M, Takahata Y, Honjo S, Hara T:, Serum prohepcidin concentrations at birth and one month after birth in premature infants., Pediatric Blood and Cancer, 2010.09.
76. Kusuda T, Hikino S, Ohga S, Kinjo T, Ochiai M, Takahata Y, Tokunaga S, Ihara K, Hata Y, Hara T:, Genetic variation of vascular endothelial growth factor pathway does not correlate with the severity of retinopathy of prematurity., J Perinatol, 2010.08.
77. Ochiai M, Hikino S, Nakayama H, Ohga S, Taguchi T, Hara T, Nonimmune hydrops fetalis due to generalized lymphatic dysplasia in an infant with Robertsonian trisomy 21., Am J Perinatol, 10.1055/s-2005-918892, 23, 1, 63-66, 23 (1): 63-66, 2005.05.
78. Nagatomo T, Muta K, Ohga S, Ochiai M, Ohshima K, Hara T, Insulin-like growth factor-II: a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors., Exp Hematol, 36 (4): 401-411, 2008.05.
79. Ochiai M, Nakayama H, Sato K, Iida K, Hikino S, Ohga S, Tsukimori K, Wake N, Masumoto K, Taguchi T, Hara T, Head circumference and long-term outcome in small-for-gestational age infants., J Perinat Med, J Perinat Med, 2008.05.
80. Ochiai M, Hikino S, Yabuuchi H, Nakayama H, Sato K, Ohga S, Hara T, A new scoring system for computed tomography of the chest for assessing the clinical status of bronchopulmonary dysplasia., J Pediatr, 130 (7): 2118-2119, 2008.01.