Research activity information

• Dec. 2023 日本エンドトキシン・自然免疫研究会, 奨励賞（最優秀賞）


• 2019 International Pediatric Research Foundation (IPRF), Travel Award grant for Early Career Investigators

  FUJIOKA Kazumichi


• 2019 Kobe University Hospital, Best Teacher Award

  FUJIOKA Kazumichi


• 2018 20th Congress of the Federation of Asia and Oceania Perinatal Societies in Manila., Travel Grants


• 2018 The 2nd Taiwan-Korea-Japan Joint congress of neonatology, Travel Award


• 2017 Western Society For Clinical Investigation, WSCI Travel Award, HEME OXYGENASE-1 DEFICIENCY INCREASES THE SEVERITY OF SEPSIS IN A PRETERM MOUSE MODEL

  International society


• 2016 第４回神緑会 Young Investigator Award 発表会, 優秀賞, THE ROLE OF HEME OXYGENASE-1 IN NEONATAL SEPSIS USING A PRETERM MOUSE MODEL

  Japan society


• 2016 日本 Shock 学会, 会長賞, 早産児マウス敗血症モデルにおけるヘムオキシゲナーゼ-1の保護効果

  FUJIOKA KAZUMICHI

  Japan society


• 2016 The Asian Society for Pediatric Research 2016, Travel Grants Award, THE ROLE OF HEME OXYGENASE-1 IN NEONATAL SEPSIS USING A PRETERM MOUSE MODEL

  FUJIOKA KAZUMICHI

  International society


• 2015 WESTERN SOCIETY FOR PEDIATRIC RESEARCH, WSPR Mead Johnson Travel Award, HEME OXYGENASE-1 PROMOTER POLYMORPHISMS AND RISK OF SPINA BIFIDA.

  International society


• 2014 日本未熟児新生児学会, 学会賞, 日本人small-for-gestational age児における血管内皮増殖因子遺伝子多型の関与の検討

  Official journal


• 2014 Stanford 5th Annual Pediatrics Research Retreat, Outstanding Abstract Poster First Prize, THE SIZE OF MICROSATELLITE POLYMORPHISMS IN THE HEME OXYGENASE-1 PROMOTER AND NEURAL TUBE DEFECTS

  International society


• 2014 Asian Society for Pediatric Research, Best Research Award, The Effect of Hourly Feeding Intervals on Very Low Birth Weight Infants

  International society


• 2013 The Japan Foundation for Pediatric Research, Eli Lilly Fellowship, ヘムオキシゲナーゼ-1 制御に基づく新生児重症黄疸に起因する発達障害の予防


• 2013 ASPR-PSM 2013, YOUNG INVESTIGATOR AWARD, A Vascular Endothelial Growth Factor Polymorphism is Associated with The Development of Chronic Lung Disease in Japanese Premature Newborns

  International society


• 2011 The Japanese Society for Premature and Newborn Medicine, Sata King's College Fellowship

• Neonatal metabolic alkalosis and mild diuresis resulting from torasemide self-medication by the mother: a case report.

  Yumi Kitahiro, Mari Hashimoto, Yukako Sonda, Miki Yagi, Kotaro Itohara, Takumi Kido, Kazumichi Fujioka, Hitomi Imafuku, Tomohiro Omura, Ikuko Yano

  BACKGROUND: Torasemide, a loop diuretic, is rarely used for pregnant women because of the risk of reduced placental blood flow resulting from decreased circulating plasma volume. We experienced a case of a newborn with metabolic alkalosis and mild polyuria. The mother was suspected of self-medicating as we detected torasemide in the neonatal serum by LC-MS/MS method. CASE PRESENTATION: A Japanese pregnant woman in her 20s with mental illness, symptoms of panic and eating disorders, and a history of overdosing on over-the-counter medications, was referred to our hospital for birth control. She presented with vomiting following bulimia nervosa and hypokalemia. Her baby was delivered vaginally at 36 weeks and 4 days of gestation. The baby's blood gas analysis on day 0 revealed metabolic alkalosis (pH > 7.42, HCO3- > 28 mmHg). Up to 16 h after birth, mild polyuria and a urine output of 3.3 mL/kg/h were observed without the administration of diuretics. We suspected diuretic intake by the mother before delivery, because she had a history of taking torasemide before being referred to the hospital. As expected, torasemide was detected in the baby's serum. The serum concentration on the first day after delivery (4.80 ng/mL) gradually decreased to 0.45 ng/mL on day 5, whereas torasemide was not detected in the maternal serum. Neonatal metabolic alkalosis improved by day 3 following birth. CONCLUSIONS: This case suggests close counseling and monitoring of pregnant women before childbirth regarding their past and present use of drugs, particularly in those with mental illness.

  Apr. 2025, Journal of pharmaceutical health care and sciences, 11(1) (1), 31 - 31, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Three-year hearing outcomes in infants with congenital cytomegalovirus disease treated with oral valganciclovir: Interim results of a six-year follow-up study in Japan.

  Ichiro Morioka, Yasumasa Kakei, Takumi Imai, Kazumichi Fujioka, Naoto Takahashi, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito, Akira Oka

  OBJECTIVE: To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months. STUDY DESIGN: We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of "Improved hearing" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed. RESULTS: At 3 years, among 48 ears from 24 infants, the number of "improved hearing," which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including "maintaining normal hearing" or "maintaining normal hearing or the same degree of hearing impairment", the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period. CONCLUSION: Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.

  Mar. 2025, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 177, 105778 - 105778, English, International magazine

  Scientific journal


• Discrepancies in the Diagnosis of Congenital Toxoplasma gondii Infection Between B1 Gene Semi-Nested Polymerase Chain Reaction and Serological Analyses.

  Akiko Uchida, Kenji Tanimura, Keisuke Shirai, Mariko Ashina, Kazumichi Fujioka, Ichiro Morioka, Miwa Sasai, Masahiro Yamamoto, Hideto Yamada

  Congenital Toxoplasma gondii (T. gondii) infection, which can be caused by a primary T. gondii infection during pregnancy, results in severe neurological sequelae in affected children. We have been conducting a prospective cohort study since January 2019 on pregnant women who were suspected of having primary T. gondii infection based on serological tests. In this study, congenital infection was diagnosed using semi-nested polymerase chain reaction (PCR) to detect the B1 gene in the body fluids of newborns. Up until December 2023, forty-one newborns born to mothers suspected of having primary T. gondii infection during pregnancy underwent B1 gene semi-nested PCR tests and anti-T. gondii immunoglobulin (Ig) G and IgM measurements of their blood samples. Eight newborns showed no clinical symptoms of congenital T. gondii infection; however, they were diagnosed with congenital T. gondii infection according to positive PCR results. However, none of the eight infants eventually exhibited any sign of congenital infection, as their serum samples tested negative for anti-T. gondii IgM and IgG until 12 months of age. Therefore, clinicians should consider discrepancies in the diagnosis of congenital T. gondii infection between PCR tests using body fluids of newborns and serological tests during their infantile period.

  Mar. 2025, Microorganisms, 13(3) (3), English, International magazine

  Scientific journal


• Discrepancies in the Diagnosis of Congenital Toxoplasma gondii Infection Between B1 Gene Semi-Nested Polymerase Chain Reaction and Serological Analyses

  Akiko Uchida, Kenji Tanimura, Keisuke Shirai, Mariko Ashina, Kazumichi Fujioka, Ichiro Morioka, Miwa Sasai, Masahiro Yamamoto, Hideto Yamada

  Mar. 2025, Microorganisms, 13(3) (3)

  Scientific journal


• Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection.

  Kotaro Itohara, Kazuhiro Yamamoto, Shunsuke Fujinaka, Mari Hashimoto, Naoki Tamura, Yumi Kitahiro, Tomohiro Omura, Kazumichi Fujioka, Ikuko Yano

  BACKGROUND: Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed. METHODS: Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir. RESULTS: Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL-1 of ganciclovir was calculated. CONCLUSIONS: The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.

  Sep. 2024, Therapeutic drug monitoring, English, International magazine

  Scientific journal


• Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection in Japan 2023: Executive Summary.

  Yoshinori Ito, Ichiro Morioka, Naoto Takahashi, Kazumichi Fujioka, Kiyonori Miura, Hiroyuki Moriuchi, Noriko Morimoto, Tetsushi Yoshikawa, Mariko Ashina, Shinya Abe, Hitomi Imafuku, Akiko Uchida, Aya Okahashi, Satsuki Kakiuchi, Yu Kakimoto, Soichiro Kawata, Yoshiki Kawamura, Takumi Kido, Hiroyuki Kidokoro, Kei Kozawa, Tomohiro Samejima, Takako Suzuki, Kenji Tanimura, Chiharu Tomonaga, Yuka Torii, Megumi Nakanishi, Nobuhiko Nagano, Takeshi Nagamatsu, Hajime Narita, Koji Nishimura, Norie Nonobe, Yuri Hasegawa, Koichiro Hara, Midori Hijikata, Takuya Fukuda, Yusuke Funato, Nobuko Mimura, Nobuko Yamamoto, Ai Yoshitomi, Yasumasa Kakei, Tomoyuki Kodama, Akira Oka

  Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.

  Jul. 2024, The Pediatric infectious disease journal, English, International magazine

  Scientific journal


• Human post-implantation blastocyst-like characteristics of Muse cells isolated from human umbilical cord

  Yoshihiro Kushida, Yo Oguma, Kana Abe, Taichi Deguchi, Federico Girolamo Barbera, Noriyuki Nishimura, Kazumichi Fujioka, Sota Iwatani, Mari Dezawa

  Abstract Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine.

  Springer Science and Business Media LLC, Jul. 2024, Cellular and Molecular Life Sciences, 81(1) (1)

  Scientific journal


• Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant.

  Kaung Htet Nay Win, Yoshihiro Kushida, Keiji Yamana, Sota Iwatani, Makiko Yoshida, Nanako Nino, Cho Yee Mon, Hiroyuki Ohsaki, Shingo Kamoshida, Kazumichi Fujioka, Mari Dezawa, Noriyuki Nishimura

  BACKGROUND: Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model. METHODS: Rats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed. RESULTS: Rats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion. CONCLUSION: Preterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.

  May 2024, Stem cell research & therapy, 15(1) (1), 147 - 147, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Pharmacokinetics of Brexpiprazole, Quetiapine, Risperidone, and Its Active Metabolite Paliperidone in a Postpartum Woman and Her Baby.

  Toru Konishi, Yumi Kitahiro, Naoko Fujiwara, Kazuhiro Yamamoto, Mari Hashimoto, Takahiro Ito, Kotaro Itohara, Kazumichi Fujioka, Hitomi Imafuku, Ikuo Otsuka, Tomohiro Omura, Ikuko Yano

  BACKGROUND: Brexpiprazole is a second-generation antipsychotic approved in Japan in 2018; however, information on placental passage and breast milk transfer remains limited. In this report, the patient, a 30-year-old pregnant woman with schizophrenia, was medicated with brexpiprazole, risperidone, and quetiapine. METHODS: The study used high-performance liquid chromatography-tandem mass spectrometry to determine the concentrations of brexpiprazole, quetiapine, risperidone, and its active metabolite (paliperidone) in maternal and neonatal plasma, cord venous plasma, and breast milk. Maternal plasma samples were obtained approximately 2 and 8 hours after the last administration of antipsychotics on the day of delivery and at the estimated drugs' trough time on days 1, 3, and 5 after delivery. RESULTS: The maternal plasma concentrations of brexpiprazole, quetiapine, and paliperidone increased by approximately 3.5-fold on the fifth day compared with those on the day of delivery, whereas the risperidone concentration remained almost constant. Moreover, the neonatal plasma concentrations of the 4 drugs immediately after birth were indistinguishable from the umbilical cord concentrations and gradually decreased, except for risperidone. Relative infant doses of these compounds were below 1.1%. CONCLUSIONS: Pregnancy status notably alters the pharmacokinetic properties of antipsychotics. Therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. Although brexpiprazole is transferred to neonates through the placenta, breastfeeding is still possible because the relative infant dose value of this drug was much less than 10%.

  Apr. 2024, Therapeutic drug monitoring, English, International magazine

  Scientific journal


• Assessment of patients' characteristics associated with the efficacy and safety of oral valganciclovir treatment for infants with symptomatic congenital cytomegalovirus disease.

  Yasumasa Kakei, Ichiro Morioka, Takumi Imai, Kotaro Itohara, Ikuko Yano, Naoto Takahashi, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito, Kazumichi Fujioka, Akira Oka

  INTRODUCTION: Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing. MATERIALS AND METHODS: We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count. RESULTS: Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019). CONCLUSIONS: Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening.

  Mar. 2024, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, English, International magazine

  Scientific journal


• Range of protein induced by vitamin K absence or antagonist-II levels in neonates at birth.

  Tomohiro Sameshima, Mariko Ashina, Takuya Fukuda, Takumi Kido, Shinya Abe, Yuko Watanabe, Itsuko Sato, Yoshihiko Yano, Kenji Tanimura, Hiroaki Nagase, Kandai Nozu, Kazumichi Fujioka

  Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal blood at birth and the correlation between PIVKA-II and gestational age are unclear. We retrospectively analyzed infants admitted to our institution between June 1, 2018, and March 31, 2022, whose clinical and PIVKA-II data were available, and classified them into preterm and term infant groups. Overall incidence of PIVKA-II-positive cases (≥ 50 mAU/mL) was 42.8%, including 0.6% apparent VK deficiency (≥ 5000 mAU/mL), 3.1% experimental VK deficiency (1000-4999 mAU/mL), and 10.7% latent VK deficiency (200-999 mAU/mL) cases. Incidence of PIVKA-II-positive cases was significantly higher in the term group than in the preterm group (49.4% vs. 29.7%, p < 0.001). Gestational age correlated with PIVKA-II levels (r2 = 0.117, p < 0.0001). Median serum PIVKA-II levels and incidence of PIVKA-II-positive cases (≥ 50 mAU/mL, 16.4%) were lower at 5 days after birth than at birth, possibly reflecting the postnatal VK prophylaxis impact. Only one infant was diagnosed with VK deficiency bleeding (PIVKA-II levels, at birth: 10,567 mAU/mL; at day 5: 2418 mAU/mL). Thus, serum PIVKA-II levels after birth weakly correlated with gestational age. VK deficiency was more common in term infants than in preterm infants.

  Jan. 2024, Scientific reports, 14(1) (1), 921 - 921, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Cerebral venous sinus thrombosis in an infant with neonatal sepsis.

  Yu Masuda, Takumi Kido, Mariko Ashina, Kandai Nozu, Kazumichi Fujioka

  2024, Pediatrics international : official journal of the Japan Pediatric Society, 66(1) (1), e15725, English, International magazine


• Impact of peritoneal lavage temperature during laparotomy in a preterm peritonitis mouse model using cecal slurry

  Shohei Yoshimura, Yuichi Okata, Yoshitomo Samejima, Harunori Miyauchi, Masafumi Saito, Shigeaki Inoue, Kazumichi Fujioka, Serena Iwabuchi, Yasuyuki Kameoka, Aya Watanabe, Kotaro Uemura, Yuichiro Tomioka, Yuko Bitoh

  Jul. 2023, Journal of Pediatric Surgery Open

  Scientific journal


• サイトメガロウイルス既感染母体から出生し,尿濾紙スクリーニング検査を契機に診断に至った症候性サイトメガロウイルス感染症の1新生児例

  金 潔駿, 阿部 真也, 川村 葵, 垂井 智前, 城戸 拓海, 京野 由紀, 菅 秀太郎, 仲宗根 瑠花, 芦名 満理子, 藤岡 一路, 野津 寛大

  (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 618 - 618, Japanese


• Association of Neonatal Serum Creatinine Concentration with Maternal Serum Creatinine Concentration and Birth Weight.

  Atsushi Kiyoshige, Kayo Osawa, Yuko Watanabe, Yuki Watanabe, Itsuko Satou, Takamitsu Imanishi, Mariko Ashina, Kazumichi Fujioka, Yoshihiko Yano, Jun Saegusa

  BACKGROUND: The serum creatinine (SCr) concentration in neonates is generally high for its body size, compared to those of infants. The aim of the present study was to investigate the effect of maternal SCr on neonatal SCr through measurements of prenatal maternal SCr and neonatal SCr from birth to postnatal Day 5. In addition, postnatal changes in SCr were compared between term and preterm infants, given that few studies have addressed this topic. METHODS: The retrospective study subjects were 151 neonates whose Scr was measured consecutively from birth to postnatal Day 5 and 124 mothers whose SCr was measured prenatally. RESULTS: There were significant correlations between maternal SCr and neonatal SCr at birth (r = 0.858, p < 0.001) and on postnatal Day 1 (r = 0.235, p < 0. 001). The SCr of term infants (median 0.69 mg/dL, range 0.54 - 0.96 mg/ dL) were higher than those of preterm infants (median 0.63 mg/dL, range 0.43 - 1.23 mg/dL, p < 0.001) at birth; however, these values were reversed on postnatal Day 1 (Term: median 0.75 mg/dL, range 0.51 - 1.13 mg/dL, Pre-term: median 0.88 mg/dL, range 0.56 - 1.25 mg/dL, p < 0.001). There were differences in the timing of reaching to peak SCr between preterm and term neonates. In addition, birth weight might affect SCr concentrations after birth. CONCLUSIONS: The results of this study suggest that neonatal SCr is influenced by maternal SCr, although the effect disappears by postnatal Day 2. Moreover, glomerular filtration rate differs between term and preterm infants.

  Mar. 2023, Clinical laboratory, 69(3) (3), English, International magazine

  Scientific journal


• Vertical Transmission of Coxsackievirus A6 with Severe Congenital Pneumonia/Sepsis.

  Ruka Nakasone, Miki Ogi, Aoi Kawamura, Osamu Miyake, Takumi Kido, Shinya Abe, Naoto Takahashi, Kandai Nozu, Kazumichi Fujioka

  We report a case of vertical transmission of Coxsackievirus (CV)-A6 with severe congenital pneumonia/sepsis. A male infant presented with severe respiratory symptoms at birth and was treated with full cardiopulmonary support, including inhaled nitric oxide. Three days before delivery, his older brother was diagnosed with hand, foot, and mouth disease (HFMD). His mother developed transient fever 1 day before delivery and presented a blister on her thumb 2 days after delivery. A multiplex polymerase chain reaction test on day 2 was positive for human rhinovirus/enterovirus. CV-A6 was later detected in the serum, tracheal aspirate, and stool of the patient sampled on day 6, and in the maternal serum sampled on the day of delivery. He was diagnosed with congenital CV-A6 pneumonia/sepsis caused by vertical transmission, based on VP1 consensus sequences used for typing of the virus that demonstrated a 100% match between the mother and infant. Further, the strain was closely related to the lethal CV-A6-Changchun strains in the phylogenetic analysis of the P2 region, which contributes to the pathogenicity. In conclusion, congenital CV-A6 infection should be considered if a woman exhibits HFMD symptoms during the perinatal period. Detailed virologic examination is useful for understanding its pathogenesis.

  Feb. 2023, International journal of environmental research and public health, 20(4) (4), English, International magazine

  Link to Kobe Univ. Repository (Kernel)


• Physiologically-based pharmacokinetic model to investigate the effect of pregnancy on risperidone and paliperidone pharmacokinetics: Application to a pregnant woman and her neonate.

  Walaa Y B Mahdy, Kazuhiro Yamamoto, Takahiro Ito, Naoko Fujiwara, Kazumichi Fujioka, Tadasu Horai, Ikuo Otsuka, Hitomi Imafuku, Tomohiro Omura, Kazumoto Iijima, Ikuko Yano

  This study aimed to determine the effects of pregnancy and ontogeny on risperidone and paliperidone pharmacokinetics by assessing their serum concentrations in two subjects and constructing a customized physiologically-based pharmacokinetic (PBPK) model. Risperidone and paliperidone serum concentrations were determined in a pregnant woman and her newborn. PBPK models for risperidone and paliperidone in adults, pediatric, and pregnant populations were developed and verified using the Simcyp simulator. These models were then applied to our two subjects, generating their "virtual twins." Effects of pregnancy on both drugs were examined using models with fixed pharmacokinetic parameters. In the neonatal PBPK simulation, 10 different models for estimating the renal function of neonates were evaluated. Risperidone was not detected in the serum of both pregnant woman and her newborn. Maternal and neonatal serum paliperidone concentrations were between 2.05-3.80 and 0.82-1.03 ng/ml, respectively. Developed PBPK models accurately predicted paliperidone's pharmacokinetics, as shown by minimal bias and acceptable precision across populations. The individualized maternal model predicted all observed paliperidone concentrations within the 90% prediction interval. Fixed-parameter simulations showed that CYP2D6 activity largely affects risperidone and paliperidone pharmacokinetics during pregnancy. The Flanders metadata equation showed the lowest absolute bias (mean error: 22.3% ± 6.0%) and the greatest precision (root mean square error: 23.8%) in predicting paliperidone plasma concentration in the neonatal population. Our constructed PBPK model can predict risperidone and paliperidone pharmacokinetics in pregnant and neonatal populations, which could help with precision dosing using the PBPK model-informed approach in special populations.

  Jan. 2023, Clinical and translational science, 16(4) (4), 618 - 630, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Correlation of cytomegalovirus viral load between whole blood and plasma of congenital cytomegalovirus infection under valganciclovir treatment.

  Yuka Torii, Ichiro Morioka, Yasumasa Kakei, Kazumichi Fujioka, Yu Kakimoto, Naoto Takahashi, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Akira Oka, Yoshinori Ito

  BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases. METHODS: CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay. RESULTS: Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman's ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman's ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays. CONCLUSIONS: There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.

  Jan. 2023, BMC infectious diseases, 23(1) (1), 31 - 31, English, International magazine

  Scientific journal


• Fetal Ultrasound and Magnetic Resonance Imaging Abnormalities in Congenital Cytomegalovirus Infection Associated with and without Fetal Growth Restriction.

  Kenji Tanimura, Akiko Uchida, Mizuki Uenaka, Hitomi Imafuku, Shinya Tairaku, Hiromi Hashimura, Yoshiko Ueno, Takumi Kido, Kazumichi Fujioka

  Congenital cytomegalovirus infection (cCMV) can cause fetal growth restriction (FGR) and severe sequelae in affected infants. Clinicians generally suspect cCMV based on multiple ultrasound (US) findings associated with cCMV. However, no studies have assessed the diagnostic accuracy of fetal US for cCMV-associated abnormalities in FGR. Eight FGR and 10 non-FGR fetuses prenatally diagnosed with cCMV were examined by undergoing periodic detailed US examinations, as well as postnatal physical and imaging examinations. The diagnostic accuracy of prenatal US for cCMV-associated abnormalities was compared between FGR and non-FGR fetuses with cCMV. The diagnostic sensitivity rates of fetal US for cCMV-related abnormalities in FGR vs. non-FGR fetuses were as follows: ventriculomegaly, 66.7% vs. 88.9%; intracranial calcification, 20.0% vs. 20.0%; cysts and pseudocysts in the brain, 0% vs. 0%; ascites, 100.0% vs. 100.0%; hepatomegaly, 40.0% vs. 100.0%; splenomegaly, 0% vs. 0%. The diagnostic sensitivity of fetal US for hepatomegaly and ventriculomegaly in FGR fetuses with cCMV was lower than that in non-FGR fetuses with cCMV. The prevalence of severe long-term sequelae (e.g., bilateral hearing impairment, epilepsy, cerebral palsy, and severe developmental delay) in the CMV-infected fetuses with FGR was higher, albeit non-significantly. Clinicians should keep in mind the possibility of overlooking the symptoms of cCMV in assessing fetuses with FGR.

  Jan. 2023, Diagnostics (Basel, Switzerland), 13(2) (2), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Influence of UGT1A1 Genetic Variants on Free Bilirubin Levels in Japanese Newborns: A Preliminary Study.

  Hiroaki Hanafusa, Shinya Abe, Shohei Ohyama, Yuki Kyono, Takumi Kido, Ruka Nakasone, Mariko Ashina, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka

  BACKGROUND: Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two UGT1A1 genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between UGT1A1 variants and Bf levels in newborns has not been elucidated. METHODS: We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two UGT1A1 genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, n = 77) and a non-high Bf group (Bf < 1.0 µg/dL, n = 407), based on the peak Bf values. Logistic regression analysis was performed to calculate the odds ratios (ORs) for each variant allele compared to wild-type alleles. RESULTS: The frequencies of the A allele in rs4148323 and (TA)7 allele in rs3064744 in the high Bf group (29% and 4%, respectively) were significantly different from those in the non-high Bf group (16% and 12%, respectively). In logistic regression analysis, for rs4148323, the A allele was significantly associated with an increased risk of hyper-free bilirubinemia over the G allele (adjusted OR: 1.80, 95% confidence interval [CI]: 1.19-2.72, p < 0.01). However, for rs3064744, the (TA)7 allele was significantly associated with a decreased risk of hyper-free bilirubinemia over the (TA)6 allele (adjusted OR: 0.42, 95% CI: 0.18-0.95, p = 0.04). CONCLUSIONS: This study is the first to show that the A allele in rs4148323 is a risk factor and that the (TA)7 allele in rs3064744 is a protective factor for developing hyper-free bilirubinemia in Japanese newborns.

  Oct. 2022, International journal of environmental research and public health, 19(20) (20), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Neonatal Pseudohypoaldosteronism Type-1 in Japan.

  Kazumichi Fujioka, Ruka Nakasone, Kosuke Nishida, Mariko Ashina, Itsuko Sato, Kandai Nozu

  (1) Background: Pseudohypoaldosteronism type 1 (PHA-1) is a disorder caused by renal tubular resistance to aldosterone and is characterized by problems with sodium regulation. PHA-1 is typically divided into primary PHA-1, which is caused by genetic mutation, and secondary PHA-1, which is associated with urinary tract abnormality. However, data on the clinical features of PHA-1 among newborn infants are limited. (2) Methods: We conducted a nationwide prospective surveillance study of neonatal PHA in Japan from 1 April 2019 to 31 March 2022 as part of a rare disease surveillance project of the Japan Society for Neonatal Health and Development. (3) Results: Fifteen cases (male:female = 7:8), including four primary, four secondary, and seven non-classified cases, were reported during the study period. The median gestational age and birthweight were 34 weeks (28-41) and 1852 g (516-4610), respectively. At the onset, the median serum Na and K levels were 132 mEq/L (117-137) and 6.3 mEq/L (4.7-8.3), respectively. The median plasma renin activity was 45 ng/mL/h (3.1-310, n = 9), active renin concentration was 1017 pg/mL (123-2909, n = 6), and serum aldosterone concentration was 5310 pg/mL (3250-43,700). (4) Conclusions: Neonatal PHA-1 was more common among preterm infants with no male predominance. It developed immediately after birth in cases without genetic or renal complications.

  Aug. 2022, Journal of clinical medicine, 11(17) (17), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan.

  Ichiro Morioka, Yasumasa Kakei, Takashi Omori, Kandai Nozu, Kazumichi Fujioka, Naoto Takahashi, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito, Akira Oka

  Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was -246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease.

  Jun. 2022, Journal of clinical medicine, 11(13) (13), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 極低出生体重児の後天性サイトメガロウイルス感染症予防における冷凍母乳の有用性の検討

  阿部 真也, 京野 由紀, 城戸 拓海, 菅 秀太郎, 仲宗根 瑠花, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 256 - 256, Japanese


• 症候性先天性サイトメガロウイルス感染症における治療中ウイルス量変化と聴力障害の予測

  城戸 拓海, 京野 由紀, 菅 秀太郎, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 257 - 257, Japanese


• 同胞の手足口病罹患から母子感染に至った先天性コクサッキーウイルスA6肺炎・敗血症の1例

  仲宗根 瑠花, 福田 拓弥, 城戸 拓海, 京野 由紀, 菅 秀太郎, 阿部 真也, 芦名 満理子, 高橋 尚人, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 257 - 257, Japanese


• 新生仔マウス敗血症モデルにおける軽微な先行感染の致死的敗血症に対する保護効果の作用機序の検討

  仲宗根 瑠花, 福田 拓弥, 城戸 拓海, 京野 由紀, 菅 秀太郎, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 259 - 259, Japanese


• ご家族の希望のもと緩和医療としての在宅医療移行が成功した多発奇形の一例

  阿部 真也, 京野 由紀, 城戸 拓海, 菅 秀太郎, 仲宗根 瑠花, 芦名 満理子, 大方 祐一, 尾藤 祐子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 311 - 311, Japanese


• 先天性中枢性低換気症候群患者由来iPS細胞の樹立と神経細胞への分化誘導

  城戸 拓海, 京野 由紀, 菅 秀太郎, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 313 - 313, Japanese


• NICU研修医ラダーを用いた手技獲得状況とラダーの有用性の検討

  久野 春香, 仲宗根 瑠花, 福田 拓弥, 城戸 拓海, 京野 由紀, 菅 秀太郎, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2022, 日本周産期・新生児医学会雑誌, 58(Suppl.1) (Suppl.1), 328 - 328, Japanese


• Long use of continuous positive airway pressure protects against the development of treatment-requiring retinopathy of prematurity.

  Shutaro Suga, Yuki Kyono, Takumi Kido, Ruka Nakasone, Shinya Abe, Mariko Ashina, Kandai Nozu, Kazumichi Fujioka

  Although preterm infant mortality is low, the proportion of patients with treatment-requiring retinopathy of prematurity (TR-ROP) is high in Japan. Various multicenter studies have reported the risk factors for TR-ROP; however, no large-scale studies have been conducted in Japan. We retrospectively analyzed 13,645 infants born at < 28 weeks' gestation (January 1, 2009-December 31, 2018), and registered in the Neonatal Research Network of Japan database. TR-ROP was defined as ROP requiring retinal laser photocoagulation and/or intravitreal anti-vasoendothelial growth factor drugs. Multivariable logistic regression analysis was performed to identify factors associated with TR-ROP development. The median gestational age of enrolled infants was 26 weeks (interquartile range [IQR], 24-27 weeks), median birth weight was 760 g (IQR, 620-918 g). Proportion of patients with TR-ROP was 30.3%. TR-ROP was significantly associated with birth at < 26 weeks' gestational age (adjusted odds ratio [aOR] 1.54), blood transfusion (aOR 1.49), invasive ventilation ≥ 28 days (aOR 1.41), sepsis (aOR 1.29), birth weight < 750 g (aOR 1.28), intraventricular hemorrhage (aOR 1.33), delayed achievement of full enteral feeding > 14 days (aOR 1.28), and continuous positive airway pressure (CPAP) therapy ≥ 28 days (aOR 0.79). Supplemental oxygen ≥ 28 days was not associated with TR-ROP development. Lower gestational age at birth and birth weight, blood transfusion, prolonged invasive ventilation, sepsis, intraventricular hemorrhage, and delayed achievement of full enteral feeding were risk factors for TR-ROP, whereas CPAP use was protective against TR-ROP.

  May 2022, Scientific reports, 12(1) (1), 7799 - 7799, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A prospective cohort study of newborns born to mothers with serum Toxoplasma gondii immunoglobulin M positivity during pregnancy.

  Midori Hijikata, Ichiro Morioka, Aya Okahashi, Nobuhiko Nagano, Kaori Kawakami, Atsushi Komatsu, Kei Kawana, Shohei Ohyama, Kazumichi Fujioka, Kenji Tanimura, Masashi Deguchi, Miwa Sasai, Masahiro Yamamoto, Hideto Yamada

  INTRODUCTION: The aims were to investigate the clinical characteristics of Toxoplasma gondii (T. gondii) immunoglobulin (Ig) M-positive mothers and to clarify the incidences of serum T. gondii IgM or blood T. gondii DNA positivity in newborns born to the mothers and the actual congenital T. gondii infection. METHODS: Mothers with T. gondii IgM positivity and newborns born to the mothers from 2013 to 2020 were prospectively investigated. Serum T. gondii IgG and IgM were measured by enzyme-linked immunosorbent assay. Blood T. gondii DNA was detected by semi-nested polymerase chain reaction. Congenital T. gondii infection was diagnosed based on clinical characteristic manifestations with serum T. gondii IgG positivity at any age or T. gondii IgG positivity after 12 months of age. RESULTS: Among 71 T. gondii IgM-positive mothers, including one with triplets, 41% had low T. gondii IgG avidity index and 73% received maternal therapy. Among 73 newborns who were examined for serum T. gondii IgG and IgM at birth, none had clinical manifestations, and one (1.4%) had T. gondii IgM positivity. Among 32 newborns who were examined for blood T. gondii DNA at birth, two (6.3%) were positive. All patients with serum T. gondii IgM or blood T. gondii DNA positivity showed T. gondii IgG negativity within 12 months of age. CONCLUSIONS: A few newborns born to T. gondii IgM-positive mothers were suspected of having congenital T. gondii infection based on serum T. gondii IgM or blood T. gondii DNA testing at birth. However, none developed congenital T. gondii infection.

  Apr. 2022, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 28(4) (4), 486 - 491, English, International magazine

  Scientific journal


• 日齢8の監視培養で検出されたMRSAが、分娩後に鼻腔内MRSA保菌者であることが判明した母体の菌株と一致し、水平伝播と判断した超早産児の1例

  藤本 将史, 阿部 真也, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 仲宗根 瑠花, 菅 秀太郎, 福嶋 祥代, 芦名 満理子, 西田 浩輔, 藤岡 一路, 飯島 一誠

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 541 - 541, Japanese


• covid-19疑い母体から出生した児のNICU入院管理経験について

  轉馬 珠美, 仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 芦名 満理子, 福嶋 祥代, 西田 浩輔, 藤岡 一路

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 549 - 549, Japanese


• NICU研修医ラダーを用いた手技獲得状況とラダーの有用性の検討

  吉川 なつこ, 仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 芦名 満理子, 福嶋 祥代, 西田 浩輔, 藤岡 一路

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 552 - 552, Japanese


• 長期の塩酸イソプロテレノール持続静注により管理した先天性洞不全症候群を合併した超早産児の一例

  京野 由紀, 垂井 智前, 城戸 拓海, 仲宗根 瑠花, 菅 秀太郎, 阿部 真也, 芦名 満理子, 藤岡 一路, 野津 寛大

  (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 251 - 251, Japanese


• Sepsis causes neutrophil infiltration in muscle leading to muscle atrophy and weakness in mice.

  Nobuto Nakanishi, Yuko Ono, Yusuke Miyazaki, Naoki Moriyama, Kazumichi Fujioka, Kimihiro Yamashita, Shigeaki Inoue, Joji Kotani

  Background: Sepsis-induced muscle atrophy leads to prolonged physical dysfunction. Although the interaction of muscle atrophy and macrophage has been reported in sepsis, the role of neutrophils in muscle atrophy has not been thoroughly investigated. This study sought to investigate the long-term changes in muscle-localized neutrophils after sepsis induction and their possible role in sepsis. Methods: Sepsis was induced in seven-week-old male C57BL/6J mice 8-12 (cecal slurry [CS] model) via intraperitoneal injection of 1 mg/g cecal slurry. The percentage change in body weight and grip strength was evaluated. The tibialis anterior muscles were dissected for microscopic examination of the cross-sectional area of myofibers or Fluorescence-activated cell sorting (FACS) analysis of immune cells. These changes were evaluated in the following conditions: (1) Longitudinal change until day 61, (2) CS concentration-dependent change on day 14 at the low (0.3 mg/g), middle (1.0 mg/g), and high (2.0 mg/g) concentrations, and (3) CS mice on day 14 treated with an anti-Ly6G antibody that depletes neutrophils. Results: Body weight and grip strength were significantly lower in the CS model until day 61 (body weight: 123.1% ± 1.8% vs. 130.3% ± 2.5%, p = 0.04; grip strength: 104.5% ± 3.8% vs. 119.3% ± 5.3%, p = 0.04). Likewise, cross-sectional muscle area gradually decreased until day 61 from the CS induction (895.6 [606.0-1304.9] μm2 vs. 718.8 [536.2-937.0] μm2, p < 0.01). The number of muscle-localized neutrophils increased from 2.3 ± 0.6 cell/mg on day 0 to 22.2 ± 13.0 cell/mg on day 14, and decreased thereafter. In terms of CS concentration-dependent change, cross-sectional area was smaller (484.4 ± 221.2 vs. 825.8 ± 436.2 μm2 [p < 0.001]) and grip strength was lower (71.4% ± 12.8% vs. 116.3% ± 7.4%, p = 0.01) in the CS High group compared with the control, with increased neutrophils (p = 0.03). Ly6G-depleted mice demonstrated significant increase of muscle cross-sectional area and grip strength compared with control mice (p < 0.01). Conclusions: Sepsis causes infiltration of neutrophils in muscles, leading to muscle atrophy and weakness. Depletion of neutrophils in muscle reverses sepsis-induced muscle atrophy and weakness. These results suggest that neutrophils may play a critical role in sepsis-induced muscle atrophy and weakness.

  2022, Frontiers in immunology, 13, 950646 - 950646, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The Current Challenges in Developing Biological and Clinical Predictors of Congenital Cytomegalovirus Infection.

  Kenji Tanimura, Akiko Uchida, Hitomi Imafuku, Shinya Tairaku, Kazumichi Fujioka, Ichiro Morioka, Hideto Yamada

  Congenital cytomegalovirus (CMV) infection may cause severe long-term sequelae. Recent studies have demonstrated that early antiviral therapy for infants with symptomatic congenital CMV (cCMV) infection may improve neurological outcomes; thus, accurate identification of newborns at high risk of cCMV infection may contribute to improved outcomes in affected children. However, maternal serological screening for cCMV infection by diagnosing primary infection during pregnancy, which is a popular screening strategy, is inefficient, because the number of cCMV infections with nonprimary causes, including reactivation of or reinfection with CMV, is larger than that of cCMV infections with primary causes. Low levels of neutralizing antibodies against pentameric complex and potent CMV-specific T cell-mediated immune responses are associated with an increased risk of cCMV infection. Conversely, our prospective cohort studies revealed that the presence of maternal fever/flu-like symptoms, threatened miscarriage/premature delivery, or actual premature delivery are risk factors for cCMV infection among both women with normal pregnancies and those with high-risk ones, regardless of whether the infection is primary or nonprimary. This review focused on host immune responses to human CMV and current knowledge of potential biological and clinical factors that are predictive of cCMV infection.

  Dec. 2021, International journal of molecular sciences, 22(24) (24), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Change in Viral Load during Antiviral Therapy Is Not Useful for the Prediction of Hearing Dysfunction in Symptomatic Congenital Cytomegalovirus Infection.

  Takumi Kido, Yuki Kyono, Shutaro Suga, Ruka Nakasone, Shinya Abe, Mariko Ashina, Hisayuki Matsumoto, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka

  For symptomatic congenital cytomegalovirus infections (CCMVI), the usefulness of changes in viral load during valganciclovir (VGCV) treatment for the prediction of hearing dysfunction (HD) is unclear. To determine the utility of viral load change in the whole blood or urine for the prediction of HD, we performed a retrospective study to compare viral load changes during VGCV treatment between CCMVI infants with (n = 12) or without (n = 8) HD at six months of corrected age, whose blood and urine viral loads were measured continuously for eight weeks from April 2009 to December 2019. There was no significant difference in the changes in both the blood and urine viral loads after the initiation of VGCV treatment between CCMVI infants between the groups. Moreover, this negative result was maintained in the analysis for each six weeks or six months treatment period. In conclusion, the change in viral load during antiviral therapy is not useful for the prediction of HD at six months of corrected age in symptomatic CCMVI.

  Dec. 2021, Journal of clinical medicine, 10(24) (24), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Protective Role of an Initial Low-Dose Septic Challenge against Lethal Sepsis in Neonatal Mice: A Pilot Study.

  Ruka Nakasone, Mariko Ashina, Takumi Kido, Harunori Miyauchi, Masafumi Saito, Shigeaki Inoue, Masakazu Shinohara, Kandai Nozu, Kazumichi Fujioka

  Neonatal sepsis is characterized by systemic bacterial invasion followed by a massive inflammatory response. At present, no therapeutic strategy has been found that significantly reduces the mortality of neonatal sepsis. We aimed to investigate the protective role of an initial low-dose septic challenge for the prevention of subsequent lethal sepsis in a mouse model. A stock cecal slurry (CS) solution was prepared from adult ceca. The LD83 (1.5 mg CS/g) was used for all animals. An initial challenge of normal saline (NS) or 0.5 mg CS/g (non-lethal dose) was administered at four days of age, then 1.5 mg CS/g was administered intraperitoneally at seven days of age (72 h post-initial challenge), and survival was monitored. Initial exposure to NS (n = 10) resulted in 90% mortality following exposure to the LD83 CS dose in contrast to an initial exposure to CS (n = 16), which significantly decreased mortality to 6% (p < 0.0001), reduced blood bacterial counts, attenuated inflammatory responses, and suppressed lipid mediators. Initial exposure to a non-lethal CS dose prior to exposure to a lethal CS dose significantly reduces sepsis mortality, a protective effect that might be mediated by modulating abnormal systemic inflammatory responses.

  Dec. 2021, Journal of clinical medicine, 10(24) (24), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Correlation between Severity of Fetal Growth Restriction and Oxidative Stress in Severe Small-for-Gestational-Age Infants.

  Mariko Ashina, Takumi Kido, Yuki Kyono, Asumi Yoshida, Shutaro Suga, Ruka Nakasone, Shinya Abe, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka

  Severe small-for-gestational-age (sSGA) infants exhibit increased mortality and morbidity. Oxidative stress is suggested to be involved in intrauterine growth restriction. This retrospective study aimed to evaluate the oxidative stress level at birth in an sSGA population. Sera of 28 sSGA (sSGA group) and 31 non-sSGA (control group) infants, born at our hospital between March 2017 and March 2020, were evaluated. Oxidative stress (derivative of reactive oxidative metabolites: d-ROM level), biological antioxidant potential (BAP) level, and the ratio of d-ROM/BAP level (oxidative stress index: OSI) were measured. The sSGA group had a significantly lower birth weight (BW), BW z-score, head circumference, and height than the control group (all p < 0.05). No significant difference was noted in the BAP level; sSGA infants exhibited a significantly higher d-ROM level than control infants. sSGA infants showed a significantly increased OSI compared with control infants, and the BW z-score was inversely correlated with d-ROM levels and OSI in sSGA infants (R2 = 0.300; p < 0.01 and R2 = 0.319; p = 0.02, respectively) but not in controls. In conclusion, sSGA infants, including preterm infants, exhibited higher oxidative stress at birth. The severity of fetal growth restriction was significantly correlated with oxidative stress levels at birth in sSGA infants.

  Oct. 2021, International journal of environmental research and public health, 18(20) (20), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 新生児敗血症モデルマウスにおいて、軽微な先行感染は後の致死的敗血症罹患に対して保護効果を発揮する

  仲宗根 瑠花, 芦名 満理子, 城戸 拓海, 邱 智前, 曽根原 晶子, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 127 - 127, Japanese


• 症候性先天性サイトメガロウイルス感染症児における治療開始後ウイルス残存量と聴力障害との関連

  城戸 拓海, 邱 智前, 曽根原 晶子, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 129 - 129, Japanese


• 症候性先天性サイトメガロウイルス感染症に対するバルガンシクロビル治療中の好中球数推移

  阿部 真也, 邱 智前, 曽根原 晶子, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 仲宗根 瑠花, 芦名 満理子, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 145 - 145, Japanese


• 2012-2018年に産科外来を受診した妊婦の母子感染に関する認知度の変遷

  菅 秀太郎, 邱 智前, 曽根原 晶子, 京野 由紀, 吉田 阿寿美, 城戸 拓海, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 190 - 190, Japanese


• 2012-2018年における妊婦の代表的母子感染病原体に関する知識の変遷

  菅 秀太郎, 邱 智前, 曽根原 晶子, 京野 由紀, 吉田 阿寿美, 城戸 拓海, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 191 - 191, Japanese


• 新生児病棟におけるサルモネラ菌の水平感染の経験

  京野 由紀, 邱 智前, 曽根原 昌子, 城戸 拓海, 吉田 阿寿美, 菅 秀太郎, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 196 - 196, Japanese


• ヒト胎便懸濁液の腹腔内投与により作成した胎便性腹膜炎モデルマウスの病態生理

  芦名 満理子, 仲宗根 瑠花, 城戸 拓海, 邱 智前, 曽根原 晶子, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 藤岡 一路

  (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 197 - 197, Japanese


• Bilateral Renal Hypoplasia with High β2-Microglobulinuria in the Neonatal Period.

  Sadayuki Nagai, Kazumichi Fujioka, Shogo Minamikawa, Kandai Nozu, Kazumoto Iijima

  Urinary β2 microglobulin (β2-MG) is a low-molecular-weight protein that is filtered by the glomerular basement membrane and absorbed by the proximal tubule epithelial cells. In perinatal management, urinary β2-MG levels are used to assess intrauterine inflammation in newborns, since urinary excretion increases during inflammation. Furthermore, β2-MG levels in fetal blood and urine are also used for predicting fetal renal function because β2-MG is not transferred to the placenta. Herein, we reported a patient with persistent high urinary β2-MG levels since neonatal period, who was later diagnosed with bilateral renal hypoplasia. If a newborn presents persistent hyper β2-microglobulinuria even without hematuria or proteinuria, congenital renal malformations should be considered.

  Aug. 2021, The Kobe journal of medical sciences, 67(1) (1), E34-E37, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Assessment of catabolic state in infants with the use of urinary titin N-fragment.

  Sachiyo Fukushima, Nobuto Nakanishi, Kazumichi Fujioka, Kenichi Suga, Taku Shirakawa, Kayo Osawa, Kanako Hara, Rie Tsutsumi, Maki Urushihara, Ryuji Nakagawa, Hiroyuki Awano, Jun Oto, Hiroshi Sakaue, Kazumoto Iijima, Masafumi Matsuo

  BACKGROUND: Urinary titin N-fragment levels have been used to assess the catabolic state, and we used this biomarker to evaluate the catabolic state of infants. METHODS: We retrospectively measured urinary titin N-fragment levels of urinary samples. The primary outcome was its changes according to postmenstrual age. The secondary outcomes included differences between gestational age, longitudinal change after birth, influence on growth, and relationship with blood tests. RESULTS: This study included 219 patients with 414 measurements. Urinary titin N-fragment exponentially declined with postmenstrual age. These values were 12.5 (7.1-19.6), 8.1 (5.1-13.0), 12.8 (6.0-21.3), 26.4 (16.4-52.0), and 81.9 (63.3-106.4) pmol/mg creatinine in full, late, moderate, very, and extremely preterm infants, respectively (p < 0.01). After birth, urinary levels of titin N-fragment exponentially declined, and the maximum level within a week was associated with the time to return to birth weight in preterm infants (ρ = 0.39, p < 0.01). This was correlated with creatine kinase in full-term infants (ρ = 0.58, p < 0.01) and with blood urea nitrogen in preterm infants (ρ = 0.50, p < 0.01). CONCLUSIONS: The catabolic state was increased during the early course of the postmenstrual age and early preterm infants. IMPACT: Catabolic state in infants, especially in preterm infants, was expected to be increased, but no study has clearly verified this. In this retrospective study of 219 patients with 414 urinary titin measurements, the catabolic state was exponentially elevated during the early postmenstrual age. The use of the urinary titin N-fragment clarified catabolic state was prominently increased in very and extremely preterm infants.

  Jul. 2021, Pediatric research, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Administration of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection: A case series.

  Toshihiko Ikuta, Shinya Abe, Shutaro Suga, Ruka Nakasone, Mariko Ashina, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka

  The incidence of syphilis infection among pregnant women is persistently high in Japan and in several developed countries. Here, we report the utility of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection. Because the recommended treatment (intramuscular benzathine benzylpenicillin) is not available in Japan, we intravenously administered benzylpenicillin for 10 days, which is used for treatment in high-risk cases. The administration of benzylpenicillin in low-risk infants resulted in an extended duration of parent-to-infant separation and increased the infants' exposure to invasive procedures. Thus, establishing evidence of the adequacy of no-treatment follow-up in low-risk groups and introducing intramuscular injections of benzathine benzylpenicillin may improve the management of infants suspected with congenital syphilis in Japan.

  Jul. 2021, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 27(11) (11), 1662 - 1664, English, International magazine

  Scientific journal


• 当院において母乳バンクより提供されたドナーミルク(DHM)を使用した7症例の検討

  仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P156 - P156, Japanese


• ABPC耐性大腸菌による早発型敗血症をきたした超低出生体重児の1例

  浅井 麻由, 仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 福嶋 祥代, 阿部 真也, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P171 - P171, Japanese


• 細菌カウンタを用いた生後早期新生児の口腔内細菌数の変化に関する検討

  仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P175 - P175, Japanese


• 細菌カウンタを用いた生後早期新生児の口腔内細菌数測定における検体採取法に関する検討

  仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P175 - P175, Japanese


• 光線療法は在胎35週未満の早産児においてB/A比とUB値の相関関係を減弱させる

  阿部 真也, 京野 由紀, 城戸 拓海, 吉田 阿寿美, 菅 秀太郎, 福嶋 祥代, 仲宗根 瑠花, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P316 - P316, Japanese


• 光線療法後の検体においてB/A比をUB値の代替として用いてはならない

  阿部 真也, 京野 由紀, 城戸 拓海, 吉田 阿寿美, 菅 秀太郎, 福嶋 祥代, 仲宗根 瑠花, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P316 - P316, Japanese


• 光線療法がビリルビン・アルブミン結合に与える影響の検討

  阿部 真也, 京野 由紀, 城戸 拓海, 吉田 阿寿美, 菅 秀太郎, 福嶋 祥代, 仲宗根 瑠花, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P316 - P316, Japanese


• 高照度強化光線療法を行った2症例における酸化ストレス動態の検討

  阿部 真也, 京野 由紀, 城戸 拓海, 吉田 阿寿美, 菅 秀太郎, 福嶋 祥代, 仲宗根 瑠花, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P317 - P317, Japanese


• 正期産児の経腟分娩における小児科医立ち会いの必要性の後方視的検討

  藤本 将史, 阿部 真也, 京野 由紀, 城戸 拓海, 吉田 阿寿美, 菅 秀太郎, 福嶋 祥代, 仲宗根 瑠花, 芦名 満理子, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P323 - P323, Japanese


• ヒト胎便懸濁液の腹腔内投与による胎便性腹膜炎モデルマウスの病態解明

  芦名 満理子, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 仲宗根 瑠花, 菅 秀太郎, 阿部 真也, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P327 - P327, Japanese


• 早産児マウス敗血症モデルにおけるシベレスタットナトリウムの敗血症保護効果の検討

  芦名 満理子, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 仲宗根 瑠花, 菅 秀太郎, 福嶋 祥代, 阿部 真也, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P328 - P328, Japanese


• 非外科的マウス敗血症モデルにおけるエダラボンの保護効果の検討

  菅 秀太郎, 芦名 満理子, 城戸 拓海, 吉田 阿寿美, 京野 由紀, 福嶋 祥代, 仲宗根 瑠花, 阿部 真也, 西田 浩輔, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P328 - P328, Japanese


• 成獣敗血症モデルマウスに対するTrained Immunity誘導の保護効果の検討

  菅 秀太郎, 芦名 満理子, 仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 阿部 真也, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P328 - P328, Japanese


• 新生児敗血症モデルマウスに対するTrained Immunity誘導の保護効果の検討

  藤岡 一路, 仲宗根 瑠花, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 菅 秀太郎, 阿部 真也, 芦名 満理子

  (一社)日本周産期・新生児医学会, Jun. 2021, 日本周産期・新生児医学会雑誌, 57(Suppl.) (Suppl.), P328 - P328, Japanese


• Sepsis Induces Physical and Mental Impairments in a Mouse Model of Post-Intensive Care Syndrome.

  Yoshihisa Fujinami, Shigeaki Inoue, Yuko Ono, Yusuke Miyazaki, Kazumichi Fujioka, Kimihiro Yamashita, Joji Kotani

  Post-intensive care syndrome (PICS) is a physical, cognitive, and mental impairment observed in intensive care unit (ICU) survivors. Although this is an emerging problem in the ICU, how sepsis induces the characteristic symptoms of PICS remains unclear. To develop a model of PICS, we induced sepsis in male C57/B6 mice via sublethal cecum slurry injection and subsequently treated them using ICU-like interventions. At 1-2 weeks post-sepsis induction, we simultaneously evaluated the abilities of the surviving mice using the following behavioral tests: (1) a grip strength test (GST) and a treadmill test for physical assessment, (2) a novel object recognition test (NORT) for cognitive assessment, and (3) an open field test (OFT) and a marble burying test (MBT) for mental assessment. The surviving mice showed a range of deficits, including muscle weakness with significantly decreased grip strength in the GST; decreased total mileage during the treadmill test; anxiety and decreased activity, with significantly decreased time in the central area, and increased duration of immobility in the OFT; and an increased number of buried marbles in the MBT. Given these physical and mental impairments in the surviving mice, our model has the potential to elucidate mechanistic insights and to discover therapeutic targets and new interventions for PICS.

  Apr. 2021, Journal of clinical medicine, 10(8) (8), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 院内出生児における複数箇所の入院時培養検体採取の妥当性の検討

  菅 秀太郎, 仲宗根 瑠花, 近藤 淳, 阿部 真也, 芦名 満理子, 福嶋 祥代, 大山 正平, 生田 寿彦, 西田 浩輔, 藤岡 一路, 飯島 一誠, 楠木 まり

  (公社)日本新生児成育医学会, Apr. 2021, 日本新生児成育医学会雑誌, 33(2) (2), 321 - 321, Japanese


• 院外出生児の入院時培養として臍培養は重要である

  菅 秀太郎, 仲宗根 瑠花, 近藤 淳, 阿部 真也, 芦名 満理子, 福嶋 祥代, 大山 正平, 生田 寿彦, 西田 浩輔, 藤岡 一路, 飯島 一誠, 楠木 まり

  (公社)日本新生児成育医学会, Apr. 2021, 日本新生児成育医学会雑誌, 33(2) (2), 322 - 322, Japanese


• 重症黄疸またはIVHは在胎34/35週出生児における修正1歳半時点の神経学的予後予測因子である

  仲宗根 瑠花, 近藤 淳, 菅 秀太郎, 阿部 真也, 芦名 満理子, 福嶋 祥代, 大山 正平, 生田 寿彦, 西田 浩輔, 藤岡 一路, 飯島 一誠

  (公社)日本新生児成育医学会, Apr. 2021, 日本新生児成育医学会雑誌, 33(2) (2), 362 - 362, Japanese


• NICU研修医ラダーを用いた研修医の研修期間と手技習得状況の検討

  濱本 麻希, 仲宗根 瑠花, 近藤 淳, 菅 秀太郎, 阿部 真也, 芦名 満理子, 福嶋 祥代, 大山 正平, 生田 寿彦, 西田 浩輔, 藤岡 一路, 飯島 一誠

  (公社)日本新生児成育医学会, Apr. 2021, 日本新生児成育医学会雑誌, 33(2) (2), 377 - 377, Japanese


• The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease.

  Ruka Nakasone, Mariko Ashina, Shinya Abe, Kenji Tanimura, Hans Van Rostenberghe, Kazumichi Fujioka

  Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)n repeats based on transcriptional capacity should be further investigated.

  Mar. 2021, International journal of environmental research and public health, 18(7) (7), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Genetic Analysis of UGT1A1 Polymorphisms Using Preserved Dried Umbilical Cord for Assessing the Potential of Neonatal Jaundice as a Risk Factor for Autism Spectrum Disorder in Children.

  Tomoko Horinouchi, Kaori Maeyama, Masashi Nagai, Masami Mizobuchi, Yasuko Takagi, Yuka Okada, Takeshi Kato, Mio Nishimura, Yoko Kawasaki, Mieko Yoshioka, Satoshi Takada, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Sachiyo Fukushima, Kazumichi Fujioka, Kazumi Tomioka, Hiroaki Nagase, Kandai Nozu, Kazumoto Iijima, Noriyuki Nishimura

  Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for UGT1A1*28 (c.-41-40dup), UGT1A1*6 (c.211 G > A), and UGT1A1*27 (c.686 C > A). The allele frequency of UGT1A1*6 (OR = 1.34, p = 0.26) and UGT1A1*28 (OR = 0.80, p = 0.54) and the prevalence of UGT1A1*28/*6 diplotypes did not differ significantly from those in the control population. No UGT1A1*27 allele was detected in the subjects. ASD symptom assessment scores were not associated with UGT1A1*28/*6/*27 genotypes or UGT1A1*28/*6 diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.

  Mar. 2021, Journal of autism and developmental disorders, 52(2) (2), 483 - 489, English, International magazine

  Scientific journal


• Early career investigator highlight biocommentary.

  Kazumichi Fujioka

  Feb. 2021, Pediatric research, English, International magazine

  Scientific journal


• Fetal Goitrous Hyperthyroidism in a Pregnant Woman with Triiodothyronine-Predominant Graves' Disease.

  Keiichi Washio, Mizuki Uenaka, Kenji Tanimura, Masashi Deguchi, Kosuke Nishida, Kazumichi Fujioka, Hideto Yamada

  Triiodothyronine (T3)-predominant Graves' disease is characterized by increased serum free T3 (FT3) levels after free thyroxine (FT4) levels become normal or even low during antithyroid drug treatment. We encountered a 34-year-old pregnant woman, gravida 5 para 4, who was complicated by T3-predominant Graves' disease. She was diagnosed with Graves' disease at 20 years old, and had received methimazole. Methimazole was changed to potassium iodide to reduce the risk of congenital anomalies during the first trimester. The dose of antithyroid drugs was adjusted based on maternal FT4 levels, so that maternal Graves' disease deteriorated and fetal goitrous hyperthyroidism appeared during the second trimester. Since the fetus presented goiter and tachycardia at 27-28 gestational weeks, doses of methimazole and potassium iodide were increased. A male newborn weighing 2604 g was delivered by a cesarean section at 35 gestational weeks. The newborn was diagnosed with neonatal hyperthyroidism, and received methimazole for six months. He developed normally with normal thyroid function at 1 year old. In pregnancies complicated by T3-predominant Graves' disease, the kinds and doses of antithyroid drugs have to be carefully selected to maintain maternal levels of FT4 as well as FT3 within the normal range, considering trimesters of pregnancy, teratogenicity of medication, and maternal levels of thyroid-stimulating hormone receptor antibody.

  Feb. 2021, The Kobe journal of medical sciences, 66(4) (4), E153-E158, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A Preterm Case of Cow's Milk Allergy Presenting with Recurrent Ascites Treated with Donor Breast Milk.

  Ruka Nakasone, Kazumichi Fujioka, Shutaro Suga, Shinya Abe, Mariko Ashina, Kosuke Nishida, Motoichiro Sakurai, Katsumi Mizuno, Kandai Nozu, Kazumoto Iijima

  We report a case of a preterm infant who developed cow's milk allergy. This male infant presented with recurrent ascites and was successfully treated with donated breast milk. He was born at 24 weeks' gestation with a birthweight of 506 g. From day 20, infant formula, soy protein-based formula, and casein-hydrolyzed formula were used due to insufficient maternal lactation. This resulted in abdominal distention, generalized edema, and recurrent ascites. We diagnosed him with cow's milk allergy since these symptoms improved on exclusive breast milk feeding. No recurrence of symptoms occurred when donated breast milk was used in combination with the mother's own milk. Ascites should be regarded as a clinical symptom of neonatal cow's milk allergy. Donated breast milk may be effective in the treatment of the allergy if breastfeeding is not available.

  Jan. 2021, International journal of environmental research and public health, 18(3) (3), English, International magazine

  Link to Kobe Univ. Repository (Kernel)


• Bilirubin/albumin (B/A) ratios correlate with unbound bilirubin levels in preterm infants.

  Shinya Abe, Kazumichi Fujioka, Ruka Nakasone, Shutaro Suga, Mariko Ashina, Kosuke Nishida, Ronald J Wong, Kazumoto Iijima

  BACKGROUND: A strong correlation between the bilirubin/albumin (B/A) ratio and unbound bilirubin (UB) levels in newborns ≥35 weeks of gestation has been reported. However, in preterm infants, the usefulness of B/A ratios remains unclear. METHODS: We obtained serum from 381 newborns <35 weeks of gestation. UB levels were measured using the glucose oxidase-peroxidase method. Total serum bilirubin (TB) and albumin (Alb) concentrations were measured spectrophotometrically. Samples were then stratified into two groups based on the infant's phototherapy use. B/A ratios were calculated and correlated with UB levels. Samples taken from infants prior to or never receiving phototherapy (No PTx) were then stratified by gestational age (GA) epochs: 22-27, 28-29, 30-31, and 32-34 weeks and B/A ratios correlated with UB levels. RESULTS: B/A ratios significantly correlated with UB levels in samples from the No PTx cohort (n = 1250; y = 1.83x - 0.15, r2 = 0.93) when compared with samples from infants post-phototherapy (Post-PTx, n = 2039; y = 1.05x + 0.09, r2 = 0.69). Even when stratified by GA, the correlation remained. CONCLUSIONS: In preterm infants <35 weeks of gestation, B/A ratios correlated with UB levels better in infants prior to or never receiving phototherapy than in those infants receiving phototherapy. IMPACT: The bilirubin/albumin (B/A) ratio significantly correlates with unbound bilirubin (UB) levels in preterm infants <35 weeks of gestation. The B/A ratio can be used as an index of UB levels in preterm infants <35 weeks of gestation. The B/A ratio is useful, especially when UB measurements are not available, for managing hyperbilirubinemia in preterm infants.

  Jan. 2021, Pediatric research, English, International magazine

  Scientific journal


• Comparison of Two Hepatitis B Vaccination Strategies Targeting Vertical Transmission: A 10-Year Japanese Multicenter Prospective Cohort Study.

  Koji Nishimura, Keiji Yamana, Sachiyo Fukushima, Kazumichi Fujioka, Hiroshi Miyabayashi, Masao Murabayashi, Ken Masunaga, Aya Okahashi, Nobuhiko Nagano, Ichiro Morioka

  In 1985, a hepatitis B (HB) vaccination strategy against vertical HB virus transmission was introduced in Japan that recommended vaccination of infants at two, three, and five months of age (delayed strategy). This schedule was revised in 2013, recommending to vaccinate at birth and at 1 and 6 months of age (non-delayed strategy). We aimed to compare the vertical HB virus transmission rates and immunogenic responses between these two vaccination strategies. This Japanese multicenter prospective cohort study included 222 infants born between 2008 and 2017 to serum hepatitis B surface (HBs) antigen (HBsAg)-positive mothers. During the study period, 136 and 86 infants received delayed and non-delayed strategies, respectively. A positive vertical HB virus transmission was defined as a positive serum HBsAg status. Seropositive immunogenic response was defined as a serum anti-HBs titer of ≥10 mIU/mL. Post-vaccination serum HBsAg positivity rates did not differ significantly between the delayed (0/136 [0.0%, 95% confidence interval, 0.0-2.7%]) and non-delayed (2/86 [2.3%, 95% confidence interval, 0.3-8.1%]) strategy groups. Seropositive immunogenic response rates were 100.0% (136/136) and 97.7% (84/86), respectively. Although this study was under-powered to detect a statistically significant result, no vertical HB virus transmission was observed in the delayed strategy.

  Jan. 2021, Vaccines, 9(1) (1), English, International magazine

  Scientific journal


• Neurodevelopmental Outcomes at 18 Months of Corrected Age for Late Preterm Infants Born at 34 and 35 Gestational Weeks.

  Ruka Nakasone, Kazumichi Fujioka, Yuki Kyono, Asumi Yoshida, Takumi Kido, Shutaro Suga, Shinya Abe, Mariko Ashina, Kosuke Nishida, Kenji Tanimura, Hideto Yamada, Kandai Nozu, Kazumoto Iijima

  To date, the difference in neurodevelopmental outcomes between late preterm infants (LPI) born at 34 and 35 gestational weeks (LPI-34 and LPI-35, respectively) has not been elucidated. This retrospective study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age for LPI-34 and LPI-35, and to elucidate factors predicting neurodevelopmental impairment (NDI). Records of all LPI-34 (n = 93) and LPI-35 (n = 121) admitted to our facility from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the Kyoto Scale of Psychological Development at 18 months of corrected age. NDI was defined as DQ <80 or when severe neurodevelopmental problems made neurodevelopmental assessment impossible. We compared the clinical characteristics and DQ values between LPI-34 (n = 62) and LPI-35 (n = 73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared clinical factors between the NDI (n = 17) and non-NDI (n = 118) groups. No significant difference was observed in DQ values at 18 months of corrected age between the groups in each area and overall. Among clinical factors, male sex, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had a higher prevalence in the NDI group than in the non-NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI. Based on the results of this study, we can conclude that no significant difference in neurodevelopmental outcomes at 18 months of corrected age was observed between LPI-34 and LPI-35. Patients with severe hyperbilirubinemia and/or IVH should be considered to be at high risk for developing NDI.

  Jan. 2021, International journal of environmental research and public health, 18(2) (2), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Can exchange transfusion be replaced by double-LED phototherapy?

  Shinya Abe, Kazumichi Fujioka

  Phototherapy is a conventional treatment for neonatal jaundice and widely considered as a safe procedure. Recent developments in light-emitting diode (LED) phototherapy devices have made more effective treatments possible. Exchange transfusion (ET) is typically applied for cases of refractory severe hyperbilirubinemia despite its risk of various complications. Since the therapeutic effect of phototherapy is correlated with its irradiance, ET may be avoided by performing phototherapy with higher irradiation. Recently, we adopted double-LED phototherapy as a bridging treatment to ET to treat a case of severe hyperbilirubinemia. In this case, the continual increase of bilirubin levels was suppressed immediately after its administration, and ET was not required. Throughout the treatment, no complications or increase in oxidative stress was observed. In addition, neurodevelopment was appropriate for the patient's age at the 1-year follow-up, and no findings of kernicterus, including physical and magnetic resonance imaging findings, were observed. We hypothesized that double-LED phototherapy may be a good treatment strategy to replace ET for infants with severe hyperbilirubinemia; however, further investigations regarding safety issues including acute and long-term complications are needed before clinical adaptation.

  2021, Open medicine (Warsaw, Poland), 16(1) (1), 992 - 996, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Changes in awareness and knowledge concerning mother-to-child infections among Japanese pregnant women between 2012 and 2018.

  Shutaro Suga, Kazumichi Fujioka, Ruka Nakasone, Shinya Abe, Sachiyo Fukushima, Mariko Ashina, Kosuke Nishida, Kandai Nozu, Kazumoto Iijima, Kenji Tanimura, Hideto Yamada

  This study aimed to investigate the long-term changes in awareness of and knowledge about mother-to-child infections across 6 years in Japan. A questionnaire survey was conducted at our facility from October 2012 to January 2018, and the study periods were divided into 4 phases comprising 16 months each. A multiple-choice questionnaire assessed participants' awareness of the following 13 pathogens of mother-to-child infections: cytomegalovirus (CMV), Toxoplasma gondii (T. gondii), hepatitis B virus, rubella virus, herpes simplex virus, parvovirus B19, hepatitis C virus, human immunodeficiency virus, human T cell leukemia virus type-1, measles virus, varicella-zoster virus, Chlamydia trachomatis, and Treponema pallidum. For the selected four pathogens (i.e., CMV, rubella virus, T. gondii, and parvovirus B19), the questionnaire also evaluated participants' knowledge of transmission routes, the most susceptible time of infection that could yield severe fetal disease during pregnancy, the maximum frequency of fetal infection in cases of maternal infection, and methods to prevent maternal infection. In total, 1433 pregnant Japanese women were included in this study. There was no secular change in awareness of the pathogens concerning mother-to-child infections over time, and we also clarified that the detailed knowledge of the four pathogens of typical mother-to-child infections did not improve. Since knowledge about methods to prevent maternal infection is still insufficient for all pathogens, further advocacy is required to prevent mother-to-child infections.

  2021, PloS one, 16(1) (1), e0244945, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Clinical Factors Associated With Congenital Cytomegalovirus Infection: A Cohort Study of Pregnant Women and Newborns.

  Akiko Uchida, Kenji Tanimura, Mayumi Morizane, Kazumichi Fujioka, Ichiro Morioka, Masanobu Oohashi, Toshio Minematsu, Hideto Yamada

  BACKGROUND: The aim of this prospective cohort study was to determine clinical factors associated with the occurrence of congenital cytomegalovirus infection (cCMV) in pregnant women. METHODS: Between March 2009 and November 2017, newborns born at a primary maternity hospital received polymerase chain reaction (PCR) analyses for CMV DNA in their urine with informed consent of the mothers at a low risk. Clinical data, including age, gravidity, parity, body mass index, occupation, maternal fever/flulike symptoms, pregnancy complications, gestational weeks at delivery, birth weight, and automated auditory brainstem response, were collected. Logistic regression analyses were performed to determine clinical factors associated with cCMV. RESULTS: cCMV was diagnosed by positive PCR results of neonatal urine in 9 of 4125 pregnancies. Univariate and multivariable analyses revealed that the presence of fever/flulike symptoms (odds ratio [OR], 17.9; 95% confidence interval [CI], 3.7-86.7; P < .001) and threatened miscarriage/premature labor in the second trimester (OR, 6.0; 95% CI, 1.6-22.8; P < .01) were independent clinical factors associated with cCMV. Maternal fever/flulike symptoms or threatened miscarriage/premature labor in the second trimester had 100% sensitivity, 53.2% specificity, and a maximum Youden index of .85. CONCLUSIONS: This cohort study for the first time demonstrated that these clinical factors of pregnant women and newborns were associated with the occurrence of cCMV. This is useful information for targeted screening to assess risks of cCMV in low-risk mothers, irrespective of primary or nonprimary CMV infection.

  Dec. 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 71(11) (11), 2833 - 2839, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Immunoglobulin fetal therapy and neonatal therapy with antiviral drugs improve neurological outcome of infants with symptomatic congenital cytomegalovirus infection.

  Kenji Tanimura, Yutoku Shi, Akiko Uchida, Mizuki Uenaka, Hitomi Imafuku, Toshihiko Ikuta, Kazumichi Fujioka, Ichiro Morioka, Masashi Deguchi, Toshio Minematsu, Hideto Yamada

  Infants with symptomatic congenital cytomegalovirus infection (cCMV) suffer from long-term sequelae. This study aimed at evaluating the efficacy of combining immunoglobulin (Ig) fetal therapy (FT) and neonatal therapy (NT) with antiviral drugs to improve neurological outcomes of affected infants. Women whose fetuses had symptomatic cCMV received Ig injection into the fetal peritoneal cavity and/or maternal blood as FT, while affected newborns received oral valganciclovir or intravenous ganciclovir as NT. We compared the neurological outcomes at ≥18 months old between infants receiving FT with or without NT (FT group) and those receiving NT only (NT group). From 2009-2019, 15 women whose fetuses had symptomatic cCMV received FT, while 19 newborns received NT only. In FT group, two newborns died, and two were <18 months old. Neurological outcomes of the remaining 11 infants in FT group were as follows: normal 45.5 %, mild impairments 36.4 %, and severe impairments 18.2 %. In NT group, one newborn died, one's parents refused the follow-up, one was <18 months old, and two had only chorioretinitis as symptoms. Neurological outcomes of the remaining 14 infants in NT group were as follows: normal 21.4 %, mild impairments 14.3 %, and severe impairments 64.3 %. The proportion of infants with severe impairments in FT group was significantly lower than that in NT group (18.2 % vs 64.3 %, p < 0.05). This is the first trial demonstrating that the combination of Ig FT and NT with antiviral drugs may be more effective in improving neurological outcomes of newborns with symptomatic cCMV as compared to NT only.

  Dec. 2020, Journal of reproductive immunology, 143, 103263 - 103263, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Aggressive posterior retinopathy of prematurity in a preterm infant with congenital hyperinsulinemia without persistent hyperglycemia.

  Mariko Ashina, Kazumichi Fujioka, Kaori Ueda, Akiko Miki, Kazumoto Iijima

  Dec. 2020, Pediatrics and neonatology, 61(6) (6), 665 - 666, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of the CD44 Gene.

  Sachiyo Fukushima, Manal Farea, Kazuhiro Maeta, Abdul Qawee Mahyoob Rani, Kazumichi Fujioka, Hisahide Nishio, Masafumi Matsuo

  Splicing reporter minigenes are used in cell-based in vitro splicing studies. Exon skippable antisense oligonucleotide (ASO) has been identified using minigene splicing assays, but these assays include a time- and cost-consuming step of reverse transcription PCR amplification. To make in vitro splicing assay easier, a ready-made minigene (FMv2) amenable to quantitative splicing analysis by fluorescence microscopy was constructed. FMv2 was designed to encode two fluorescence proteins namely, mCherry, a transfection marker and split eGFP, a marker of splicing reaction. The split eGFP was intervened by an artificial intron containing a multicloning site sequence. Expectedly, FMv2 transfected HeLa cells produced not only red mCherry but also green eGFP signals. Transfection of FMv2CD44v8, a modified clone of FMv2 carrying an insertion of CD44 exon v8 in the multicloning site, that was applied to screen exon v8 skippable ASO, produced only red signals. Among seven different ASOs tested against exon v8, ASO#14 produced the highest index of green signal positive cells. Hence, ASO#14 was the most efficient exon v8 skippable ASO. Notably, the well containing ASO#14 was clearly identified among the 96 wells containing randomly added ASOs, enabling high throughput screening. A ready-made FMv2 is expected to contribute to identify exon skippable ASOs.

  Nov. 2020, International journal of molecular sciences, 21(23) (23), English, International magazine

  Scientific journal


• Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies.

  Hitomi Imafuku, Hideto Yamada, Akiko Uchida, Masashi Deguchi, Tokuro Shirakawa, Yuki Sasagawa, Yutoku Shi, Kazumichi Fujioka, Ichiro Morioka, Kenji Tanimura

  This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1-6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6-11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8-27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1-6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

  Nov. 2020, Scientific reports, 10(1) (1), 19706 - 19706, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Infiltrated regulatory T cells and Th2 cells in the brain contribute to attenuation of sepsis-associated encephalopathy and alleviation of mental impairments in mice with polymicrobial sepsis.

  Masafumi Saito, Yoshihisa Fujinami, Yuko Ono, Shohei Ohyama, Kazumichi Fujioka, Kimihiro Yamashita, Shigeaki Inoue, Joji Kotani

  Sepsis-associated encephalopathy (SAE) increases not only morbidity and mortality but has been associated with long-lasting mental impairment after hospital discharge in septic patients. Recently, studies have shown that these mental impairments are caused by infection-induced neuroinflammation. However, the role of T cells in the pathogenesis of SAE and mental impairments remains unclear. Thus, in this study, we aimed to clarify how immune cells, especially T cells, influence the development and recovery of these disorders. In the cecal slurry (CS)-induced septic mouse model, we performed three different kinds of behavioral tests, open-field test, marble burying test, and forced swimming test, and observed anxiety-like behavior in septic mice. Additionally, increased interleukin (IL)-1β and IL-6 expression levels, and infiltration of neutrophils and T cells were examined in the brain of septic mice, 10 days after sepsis onset. Twenty days after sepsis onset, the septic mice could recover the number of astrocytes. At day 30, expression levels of IL-1β and tumor necrosis factor (TNF)-α returned to normal levels in the cerebral cortex of septic mice. Interestingly, resolution of neuroinflammation and alleviation of depression were delayed in septic mice treated with FTY720, which inhibits sphingosine-1-phosphate (S1P)-dependent lymphocyte egress from lymph nodes. On analyzing the brain T cells with or without FTY720 in septic mice, the FTY720 untreated mice presented increased regulatory T cells (Treg) and Th2 cells in the brain, whereas the FTY720 treated mice demonstrated increased Th17 in the brain at day 30. Furthermore, in FTY720 treated septic mice, the number of astrocytes in the cerebral cortex remained reduced at day 30. These results suggest that infiltrated Treg and Th2 cells contribute to the attenuation SAE and alleviate SAE-induce mental disorder by resolving neuroinflammation in the chronic phase of sepsis.

  Nov. 2020, Brain, behavior, and immunity, 92, 25 - 38, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Incidence of hypospadias in severe small-for-gestational-age infants: A multicenter Asian population study.

  Mariko Ashina, Kazumichi Fujioka, Seiji Yoshimoto, Tomoaki Ioroi, Kazumoto Iijima

  Oct. 2020, Pediatrics and neonatology, 61(5) (5), 548 - 550, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Three cases of pseudohypoaldosteronism following ileostomy in preterm infants.

  Ruka Nakasone, Kazumichi Fujioka, Kosuke Nishida, Kandai Nozu, Kazumoto Iijima

  Sep. 2020, Pediatrics and neonatology, 62(1) (1), 119 - 121, English, International magazine

  Link to Kobe Univ. Repository (Kernel)


• False positive cases of elevated tetradecenoyl carnitine in newborn mass screening showed significant loss of body weight.

  Ryosuke Bo, Hiroyuki Awano, Kosuke Nishida, Kazumichi Fujioka, Atsushi Nishiyama, Osamu Miyake, Kazumoto Iijima

  Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, a condition in which the body is unable to break down long-chain fatty acids properly, is the most common fatty acid oxidation disorder in Japan. Tandem mass spectrometry has been used in newborn screening (NBS), allowing the detection of patients with VLCAD deficiency even before symptoms manifest. However, tandem mass spectrometry has a high false positive rate. We investigated the clinical characteristics of patients with false positive results for tetradecenoyl acylcarnitine (C14:1). This case-control study used data collected between the 1st of January 2014 and the 31st of March 2019. The case group was defined as patients having levels of both C14:1 and C14:1/C2 ratio higher than cut-off levels in the first newborn mass screening, who were eventually diagnosed as false positives by attending doctors at Kobe University Hospital, Palmore Hospital, or Kakogawa Central City Hospital in Japan. The control group comprised 100 patients randomly selected from the three facilities. The false positive group included 17 cases, and the control group contained 300 patients. The demographics of each group did not show any significant differences in sex, body weight at birth, Cesarean section rate, complete breastfeeding rate, or the number of feedings per day. However, the change in body weight at the sampling day of NBS in the false positive and control groups was -10.2%, and - 4.6%, respectively, showing a statistically significant difference (p < 0.01). In addition, body weight gain at the one-month medical checkup was 38.9 g/day in the false positive group and 44.1 g/day in the control group (p < 0.05). An elevation of C14:1 carnitine has been reported in situations involving the catalysis of fatty acid. Therefore, patients with severe body weight loss might be associated with poor sucking or poor milk supply, which might cause a false positive elevation of C14:1 and C14:1/C2. In suspected VLCAD deficiency, attending doctors should pay attention to body weight changes recorded during newborn mass screening.

  Sep. 2020, Molecular genetics and metabolism reports, 24, 100634 - 100634, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A cohort study of the universal neonatal urine screening for congenital cytomegalovirus infection.

  Hideto Yamada, Kenji Tanimura, Sachiyo Fukushima, Kazumichi Fujioka, Masashi Deguchi, Yuki Sasagawa, Shinya Tairaku, Toru Funakoshi, Ichiro Morioka

  OBJECTIVES: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae. METHODS: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age. RESULTS: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment. CONCLUSIONS: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries.

  Aug. 2020, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26(8) (8), 790 - 794, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Insulin therapy for hyperglycemia in neonatal sepsis using a preterm mouse model.

  Harunori Miyauchi, Kazumichi Fujioka, Saki Okubo, Kosuke Nishida, Mariko Ashina, Toshihiko Ikuta, Yuichi Okata, Kosaku Maeda, Kazumoto Iijima, Yuko Bitoh

  BACKGROUND: Stress-induced hyperglycemia is a frequent complication of neonatal sepsis. Hyperglycemia induces oxidative stress and immunosuppression. We investigated the glucose kinetics and effect of insulin administration during stress-induced hyperglycemia in a neonatal sepsis mouse model. METHODS: A stock cecal slurry (CS) solution was prepared from adult cecums and 3.0 mg of CS/g (LD40 ) was administered intraperitoneally to 4-day-old FVB mouse pups. Blood glucose levels were measured at 1.5, 3, 6, and 9 h post-sepsis induction and compared with basal levels. Two different doses of ultrafast-acting insulin were administered subcutaneously, and blood glucose levels and survival rates were monitored. RESULTS: Blood glucose levels were significantly higher than those of baseline levels with a peak at 3 h, which progressively decreased from 6 to 9 h post-sepsis induction. Insulin treatment reduced post-sepsis-induced hyperglycemia at 1.5 and 3 h. The mortality rate of CS-only pups (39%) was similar to that of CS + 1 U/kg insulin pups (60%). However, the mortality rate of CS + 5 U/kg insulin pups (82%) was significantly higher than that of CS-only pups. CONCLUSIONS: Marked hyperglycemia was induced immediately after post-sepsis induction, and the high-dose insulin treatment increased mortality post-induction. Stress-induced hyperglycemia could therefore be a physiological and protective response for preterm sepsis, and aggressive treatment of this hyperglycemia might be contraindicated.

  May 2020, Pediatrics international : official journal of the Japan Pediatric Society, 62(5) (5), 581 - 586, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Efficacy and safety of valganciclovir in patients with symptomatic congenital cytomegalovirus disease: Study Protocol Clinical Trial (SPIRIT Compliant).

  Ichiro Morioka, Yasumasa Kakei, Takashi Omori, Kandai Nozu, Kazumichi Fujioka, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito, Akira Oka

  BACKGROUND: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. METHODS: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age ≥32 weeks at birth and weighing ≥1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects. DISCUSSION: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan.

  Apr. 2020, Medicine, 99(17) (17), e19765, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Case report of eight pregnant women with syphilis.

  Yukiko Nakasuji, Kenji Tanimura, Yuki Sasagawa, Hitomi Imafuku, Mayumi Morizane, Kazumichi Fujioka, Goh Ohji, Hideto Yamada

  Congenital syphilis may lead to severe sequelae in affected infants. The prevalence of syphilis in women of childbearing age has increased worldwide. From 2015 to 2018, we encountered eight pregnant women with syphilis including six with late latent and two with early latent syphilis. Seven pregnant women with syphilis received antibiotic therapies of oral amoxicillin, intravenous penicillin G, or the both. The syphilotherapies in four cases were considered effective, because rapid plasma reagin titers decreased. None of the seven pregnant women who received syphilotherapies had congenital syphilis. The remaining one woman who did not undergo a maternity checkup or syphilotherapy delivered a stillbirth with congenital syphilis at 29 gestational weeks.

  Mar. 2020, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26(3) (3), 298 - 300, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Recombinant human thrombomodulin attenuated sepsis severity in a non-surgical preterm mouse model.

  Mariko Ashina, Kazumichi Fujioka, Kosuke Nishida, Saki Okubo, Toshihiko Ikuta, Masakazu Shinohara, Kazumoto Iijima

  Neonatal sepsis is characterised by dysregulated immune responses. Lipid mediators (LMs) are involved in the regulation of inflammation. Human recombinant thrombomodulin (rhTM), an anticoagulant, has anti-inflammatory effects and might be useful for sepsis treatment. A stock caecal slurry (CS) solution was prepared from adult caeca. To induce sepsis, 1.5 mg/g of CS was administered intraperitoneally to 4 d-old wild-type FVB mouse pups. Saline (Veh-CS) or rhTM (3 or 10 mg/kg; rhTM3-CS or rhTM10-CS) was administered subcutaneously 6 h prior to sepsis induction, and liver LM profiles at 3 and 6 h post-sepsis induction and survival up to 7 days were examined. Mortality was significantly lower (47%) in the rhTM3-CS group and significantly higher (100%) in the rhTM10-CS group, compared with the Veh-CS group (79%, p < 0.05). Eleven LMs (12-HEPE, EPA, 14-HDHA, DHA, PD1, PGD2, 15d-PGJ2, 12S-HHT, lipoxin B4, 12-HETE, AA) were significantly increased at 3 h, and five LMs (5-HEPE, 15-HEPE, 18-HEPE, 17-HDHA, PD1) were significantly increased at 6 h post-sepsis induction. Increased EPA, DHA, 12S-HHT, lipoxin B4, and AA were significantly suppressed by rhTM pre-treatment. rhTM was protective against neonatal sepsis. This protective effect might be mediated via LM modulation. Further post-sepsis studies are needed to determine clinical plausibility.

  Jan. 2020, Scientific reports, 10(1) (1), 333 - 333, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Prediction of Neurodevelopmental Impairment in Congenital Cytomegalovirus Infection by Early Postnatal Magnetic Resonance Imaging.

  Kosuke Nishida, Kazumichi Fujioka, Yusuke Sugioka, Shinya Abe, Mariko Ashina, Sachiyo Fukushima, Shohei Ohyama, Toshihiko Ikuta, Kenji Tanimura, Hideto Yamada, Kazumoto Iijima, Ichiro Morioka

  INTRODUCTION: Congenital cytomegalovirus infection (CCMVI) may result in neurodevelopmental impairments (NDIs) such as hearing loss, developmental delay, epilepsy, and cerebral palsy. We aimed to investigate the potential for brain magnetic resonance imaging (MRI) to predict NDI in patients with CCMVI. METHODS: We studied infants with CCMVI who were referred to our hospital from April 2010 to October 2018 and underwent a brain MRI within 3 months since birth. We screened for 6 classic presentations of CCMVI including ventriculomegaly, periventricular cysts, hippocampal dysplasia, cerebellar hypoplasia, migration disorders, and white matter abnormalities. Images were interpreted by a blinded pediatric radiologist. NDI was defined as having a developmental quotient <80, hearing dysfunction, blindness, or epilepsy requiring anti-epileptic drugs at approximately 18 months of corrected age. RESULTS: The study involved 42 infants with CCMVI (median gestational age 38 weeks, birthweight 2,516 g). At least one abnormal finding was detected in 28 (67%) infants. Abnormal findings consisted of 3 cerebellar hypoplasia (7%), 7 migration disorders (17%), 26 white matter abnormalities (62%), 12 periventricular cysts (28%), 1 hippocampal dysplasia (2%), and 20 ventriculomegaly (48%). Abnormal findings were significantly more prevalent in infants with clinical symptoms (21/24, 91%) than in those without (7/19, 37%, p < 0.01). For NDI prediction, having ≥2 of ventriculomegaly, periventricular cysts, and white matter abnormality produced the highest Youden index values (0.78). CONCLUSION: Infants with CCMVI with at least 2 of the abovementioned specific brain image abnormalities may be at high risk of developing NDI.

  2020, Neonatology, 117(4) (4), 460 - 466, English, International magazine

  [Refereed]

  Scientific journal


• A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study

  Masakazu Shinohara, Emma Tabe Eko Niba, Yogik Onky Silvana Wijaya, Izumi Takayama, Chisako Mitsuishi, Sakae Kumasaka, Yoichi Kondo, Akihiro Takatera, Isamu Hokuto, Ichiro Morioka, Kazutaka Ogiwara, Kimimasa Tobita, Atsuko Takeuchi, Hisahide Nishio, Kazumichi Fujioka, Kazumoto Iijima, Akihito Takahashi, Daisaku Morimoto, Yosuke Washio, Yasuhiko Takahashi, Junko Yamamoto, Yasushi Takahata, Nobuhiko Nagano, Hideto Nakao, Tomoyuki Yokota, Seiji Yoshimoto, Kuniko Ieda, Norioki Ohno, Kazutoshi Cho, Hideaki Shiraishi, Norihisa Koyama, Mari Sugimoto, Manabu Iwanaga, Muneaki Matsuo, Hitoshi Osaka, Hironori Shimozawa, Takanori Yamagata, Naoki Fukushima, Masaaki Ueda, Shinobu Yoshida, Hideki Shimomura, Yasuhiro Takeshima, Fumiko Kinoshita, Tatsuharu Sato, Shinichi Niijima, Noboru Yoshida, Ken Masunaga, Mikihiro Aoki, Takeshi Morisawa, Yoshihisa Nagayama, Kei Murayama, Tomoko Tsuruoka, Tomoyuki Miyamoto, Hiroaki Imamura, Jiro Ogawa, Hideomi Asanuma, Shuku Ishikawa, Masaki Kobayashi, Taihei Tanaka, Takaharu Yamada, Hiroyuki Adachi, Atsuko Noguchi, Tsutomu Takahashi, Yuko Sato, Koichi Nakanishi, Tomohide Yoshida, Masao Murabayashi, Masato Mizushima, Tatsuo Satomi, Shinya Hayashida, Yutaka Nishimura, Masato Kantake, Sasagu Kimura, Kazumasa Takahashi, Go Tajima

  Dec. 2019, INTERNATIONAL JOURNAL OF NEONATAL SCREENING, 5(4) (4), English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Pharmacokinetic assessment of alprazolam-induced neonatal abstinence syndrome using physiologically based pharmacokinetic model.

  Kazuhiro Yamamoto, Sachiyo Fukushima, Yui Mishima, Mari Hashimoto, Kei Yamakawa, Kazumichi Fujioka, Kazumoto Iijima, Ikuko Yano

  Sustained benzodiazepine use during pregnancy can induce neonatal abstinence syndrome (NAS). In this study, the association between NAS and plasma alprazolam concentration was examined using the measured neonatal concentrations in the time series as well as simulated plasma concentrations of pregnant woman and neonate by physiologically based pharmacokinetic (PBPK) modeling. A neonate born to a mother taking alprazolam daily throughout pregnancy exhibited symptoms such as apnea and vomiting from 9 h to 4 days after birth. Finnegan score was 7 at birth and decreased to 0 by day 4. Apnea improved by 24 h post-delivery and gastrointestinal symptoms disappeared by day 4. The plasma alprazolam concentration in the neonate was 15.2 ng/mL immediately after birth and gradually decreased over 3 days. Measured neonate and estimated maternal plasma alprazolam concentrations were within the 90% prediction intervals of each concentration by PBPK simulation using "pregnancy" and "pediatrics" population parameters including in Simcyp population-based ADME simulator. In conclusion, NAS symptoms such as apnea and digestive events disappeared in parallel with the decrease of the neonate's plasma alprazolam concentrations. Moreover, PBPK modeling and simulation is a useful methodology for toxicological assessment in special characteristics populations lacking specific experimental data.

  Dec. 2019, Drug metabolism and pharmacokinetics, 34(6) (6), 400 - 402, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Prediction of poor neurological development in patients with symptomatic congenital cytomegalovirus diseases after oral valganciclovir treatment.

  Sachiyo Fukushima, Ichiro Morioka, Shohei Ohyama, Kosuke Nishida, Sota Iwatani, Kazumichi Fujioka, Tsurue Mandai, Hisayuki Matsumoto, Yuji Nakamachi, Masashi Deguchi, Kenji Tanimura, Kazumoto Iijima, Hideto Yamada

  OBJECTIVE: This study aimed to evaluate the neurodevelopmental outcomes of infants with symptomatic congenital cytomegalovirus (SCCMV) disease after antiviral treatment and investigate the symptoms at birth associated with a developmental quotient (DQ) < 70. METHODS: In this prospective study conducted from 2009 to 2018, infants with SCCMV disease who received oral valganciclovir (VGCV; 32 mg/kg/day) for 6 weeks (November 2009 to June 2015) or 6 months (July 2015 to March 2018) were evaluated for their neurodevelopmental outcomes at around 18 months of corrected age. Sequelae were categorized as follows: no impairment with a DQ ≥ 80 and no hearing dysfunction; mild sequelae including unilateral hearing dysfunction or a DQ of 70-79; and severe sequelae with a DQ < 70, bilateral hearing dysfunction requiring hearing aids, blindness or epilepsy requiring anti-epileptic drugs. DQ was assessed using the Kyoto Scale of Psychological Development. Symptoms at birth associated with a DQ < 70 were determined using univariate and receiver operating characteristic curve analyses. RESULTS: Of the 24 treated infants, 21 reached > 18 months of corrected age. Six (29%) were no impairment, 4 (19%) had mild sequelae, and 11 (52%) developed severe sequelae. The symptoms at birth associated with a DQ < 70 were microcephaly and/or small for gestational age. CONCLUSION: In our cohort of infants with SCCMV disease after VGCV treatment, the incidence of severe sequelae at 18 months of corrected age was around 50%. When microcephaly and/or small for gestational age are seen at birth, a low DQ may appear even after oral VGCV treatment.

  Oct. 2019, Brain & development, 41(9) (9), 743 - 750, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Incidence and Neonatal Risk factors of Short Stature and Growth Hormone treatment in Japanese Preterm Infants Born Small for Gestational Age.

  Matsumoto M, Nagano N, Awano H, Ohyama S, Fujioka K, Iwatani S, Urakami T, Iijima K, Morioka I

  Aug. 2019, Scientific reports, 9(1) (1), 12238

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Diagnostic Value of Cytomegalovirus IgM Antibodies at Birth in PCR-Confirmed Congenital Cytomegalovirus Infection.

  Ohyama S, Fujioka K, Fukushima S, Abe S, Ashina M, Ikuta T, Nishida K, Matsumoto H, Nakamachi Y, Tanimura K, Yamada H, Iijima K

  Although cytomegalovirus (CMV) DNA detection in urine is the standard method for diagnosing congenital cytomegalovirus infection (CCMVI), polymerase chain reaction (PCR) is not comprehensively available. Currently, the efficacy of CMV-specific IgM (CMV-IgM) and CMV-specific IgG (CMV-IgG) detection remains unclear. To determine the sensitivity and specificity of CMV-specific antibodies at birth, we investigated CMV-IgM and CMV-IgG titers in CCMVI cases and non-CCMVI controls, with confirmed diagnoses by urine quantitative real-time PCR within 3 weeks after birth. We included 174 infants with suspected CCMVI in whom serological testing was performed within the first 2 weeks after birth during 2012-2018. We classified the participants into a CCMVI group (n = 32) and non-CCMVI group (n = 142) based on their urine PCR results. The CMV-IgM-positive rate was 27/32 (84.4%) in the CCMVI group, compared with 1/142 (0.7%) in the non-CCMVI group (p < 0.0001). The positive CMV-IgG rates were 32/32 (100%) in the CCMVI group and 141/142 (99.3%) in the non-CCMVI group. The positive predictive value for CMV-IgM was high at 96.4% (27/28). This value may be sufficient for clinical use, especially in settings with limited resources where PCR is unavailable. However, CCMVI screening by CMV-IgM alone appears insufficient because of the considerable number of false-negative cases.

  Jul. 2019, International journal of molecular sciences, 20(13) (13), English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Efficacy of Valganciclovir Treatment Depends on the Severity of Hearing Dysfunction in Symptomatic Infants with Congenital Cytomegalovirus Infection.

  Shohei Ohyama, Ichiro Morioka, Sachiyo Fukushima, Keiji Yamana, Kosuke Nishida, Sota Iwatani, Kazumichi Fujioka, Hisayuki Matsumoto, Takamitsu Imanishi, Yuji Nakamachi, Masashi Deguchi, Kenji Tanimura, Kazumoto Iijima, Hideto Yamada

  Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital cytomegalovirus (CMV) infection; its efficacy on the severity of hearing dysfunction is unclear. We conducted a prospective study among 26 infants with congenital CMV infections from 2009 to 2018. Oral VGCV (32 mg/kg/day) was administered for 6 weeks (November 2009 to June 2015; n = 20) or 6 months (July 2015 to March 2018, n = 6). Hearing function was evaluated by measuring the auditory brainstem response before VGCV treatment and at 6 months. Hearing dysfunction, defined as a V-wave threshold >40 dB, was categorized into: most severe, ≥91 dB; severe, 61⁻90 dB; and moderate, 41⁻60 dB. Hearing improvement was defined as a decrease of ≥20 dB from the pretreatment V-wave threshold. Of 52 ears in 26 infants with congenital CMV infection, 29 (56%) had hearing dysfunction, and of 29 ears, 16 (55%) improved after VGCV treatment. Although, 16 (84%) of 19 ears with moderate or severe hearing dysfunction improved after treatment (p < 0.001), 10 ears with the most severe form did not. In conclusion, VGCV treatment is effective in improving moderate and severe hearing dysfunction in infants with congenital CMV infection.

  Mar. 2019, International journal of molecular sciences, 20(6) (6), English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.

  Yinmon Htun, Shinji Nakamura, Yasuhiro Nakao, Tsutomu Mitsuie, Makoto Nakamura, Satoshi Yamato, Wataru Jinnai, Kosuke Koyano, Kenichi Ohta, Aya Morimoto, Takayuki Wakabayashi, Masashiro Sugino, Kazumichi Fujioka, Ikuko Kato, Sonoko Kondo, Saneyuki Yasuda, Takanori Miki, Masaki Ueno, Takashi Kusaka

  Despite its poor outcomes, therapeutic hypothermia (TH) is the current standard treatment for neonatal hypoxic-ischaemic encephalopathy (HIE). In this study, due to its antioxidant, anti-inflammatory, and antiapoptotic properties, the effectiveness of molecular hydrogen (H2) combined with TH was evaluated by means of neurological and histological assessments. Piglets were divided into three groups: hypoxic-ischaemic insult with normothermia (NT), insult with hypothermia (TH, 33.5 ± 0.5 °C), and insult with hypothermia with H2 ventilation (TH-H2, 2.1-2.7%). H2 ventilation and TH were administered for 24 h. After ventilator weaning, neurological assessment was performed every 6 h for 5 days. On day 5, the brains of the piglets were harvested for histopathological analysis. Regarding the neurological score, the piglets in the TH-H2 group consistently had the highest score from day 2 to 5 and showed a significantly higher neurological score from day 3 compared with the NT group. Most piglets in the TH-H2 group could walk at day 3 of recovery, whereas walking ability was delayed in the two other groups. The histological results revealed that TH-H2 tended to improve the status of cortical gray matter and subcortical white matter, with a considerable reduction in cell death. In this study, the combination of TH and H2 improved short-term neurological outcomes in neonatal hypoxic-ischaemic piglets.

  Mar. 2019, Scientific reports, 9(1) (1), 4088 - 4088, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Mesenchymal stem cell therapy for neonatal intraventricular hemorrhage: a long way to go?

  Abe S, Fujioka K

  Mar. 2019, Annals of translational medicine, 7(5) (5), 79

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Isolation and Characterization of Human Umbilical Cord-derived Mesenchymal Stem Cells from Preterm and Term Infants.

  Sota Iwatani, Makiko Yoshida, Keiji Yamana, Daisuke Kurokawa, Jumpei Kuroda, Khin Kyae Mon Thwin, Suguru Uemura, Satoru Takafuji, Nanako Nino, Tsubasa Koda, Masami Mizobuchi, Masahiro Nishiyama, Kazumichi Fujioka, Hiroaki Nagase, Ichiro Morioka, Kazumoto Iijima, Noriyuki Nishimura

  Mesenchymal stem cells (MSCs) have considerable therapeutic potential and attract increasing interest in the biomedical field. MSCs are originally isolated and characterized from bone marrow (BM), then acquired from tissues including adipose tissue, synovium, skin, dental pulp, and fetal appendages such as placenta, umbilical cord blood (UCB), and umbilical cord (UC). MSCs are a heterogeneous cell population with the capacity for (1) adherence to plastic in standard culture conditions, (2) surface marker expression of CD73+/CD90+/CD105+/CD45-/CD34-/CD14-/CD19-/HLA-DR- phenotypes, and (3) trilineage differentiation into adipocytes, osteocytes, and chondrocytes, as currently defined by the International Society for Cellular Therapy (ISCT). Although BM is the most widely used source of MSCs, the invasive nature of BM aspiration ethically limits its accessibility. Proliferation and differentiation capacity of MSCs obtained from BM generally decline with the age of the donor. In contrast, fetal MSCs obtained from UC have advantages such as vigorous proliferation and differentiation capacity. There is no ethical concern for UC sampling, as it is typically regarded as medical waste. Human UC starts to develop with continuing growth of the amniotic cavity at 4-8 weeks of gestation and keeps growing until reaching 50-60 cm in length, and it can be isolated during the whole newborn delivery period. To gain insight into the pathophysiology of intractable diseases, we have used UC-derived MSCs (UC-MSCs) from infants delivered at various gestational ages. In this protocol, we describe the isolation and characterization of UC-MSCs from fetuses/infants at 19-40 weeks of gestation.

  Jan. 2019, Journal of visualized experiments : JoVE, (143) (143), English, International magazine

  [Refereed]

  Scientific journal


• Fetal Primary Small Bowel Volvulus Associated with Acute Gastric Dilatation Detected by Ultrasonography.

  Sachiyo Fukushima, Kazumichi Fujioka, Mariko Ashina, Shohei Ohyama, Toshihiko Ikuta, Kosuke Nishida, Harunori Miyauchi, Yuichi Okata, Yuko Bitoh, Kenji Tanimura, Masashi Deguchi, Hideto Yamada, Kazumoto Iijima

  Fetal intestinal volvulus is a rare condition, and fetal diagnosis of this disease is still challenging, especially in primary cases not accompanied by other comorbidities, such as intestinal malformations. Herein, we report a case of fetal primary small bowel volvulus associated with acute gastric dilatation detected by ultrasonography. We speculate that the mechanism of acute gastric dilatation in our case was peristatic malfunction of the whole intestine caused by a strangulated ileus resulting from fetal intestinal volvulus. In conclusion, acute gastric dilatation detected by fetal ultrasound can indicate the fetal intestinal volvulus.

  Jan. 2019, The Kobe journal of medical sciences, 64(4) (4), E157-E159 - E159, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• DNA methylation of the Rtl1 promoter in the placentas with fetal growth restriction.

  Fujioka K, Nishida K, Ashina M, Abe S, Fukushima S, Ikuta T, Ohyama S, Morioka I, Iijima K

  BACKGROUND: Small for gestational age (SGA) babies experience fetal growth restriction because of placental insufficiency, and aberrant fetal growth has been linked to DNA methylation in the placenta. An imprinted gene encoding retrotransposon-like protein 1 (RTL1) is regulated by DNA methylation in the promoter region and plays a key role in placental development. We therefore investigated the DNA methylation status of RTL1 in the placenta of infants with severe SGA. METHODS: We extracted DNA from the placenta of appropriate for gestational age (AGA; gestational age 35 ± 6 weeks, birthweight 2292 ± 1006 g; n = 12), SGA (birthweight z-score ≤-2 SD, 33 ± 5 weeks, 1373 ± 580 g; n = 11), and severe SGA (birthweight z-score ≤-3 SD, 33 ± 4 weeks, 1145 g ± 423 g; n = 7) infants, and we determined the methylation rates of five CpG sites in the CG4 (82,275,427-82,275,737 in NT_026437 sequence, NCBI database) region of the RTL1 promoter by pyrosequencing. We defined hypermethylation (>75.5%) and hypomethylation (<45.6%) based on the average methylation rate exceeding ± two standard deviations (SD) in the AGA group, respectively, and compared these among groups. RESULTS: There was no significant difference in the average methylation of CpG1-5 (control 59%, SGA 60%, severe SGA 63%), but abnormal methylation (hyper-/hypo-methylation) in CpG1 differed significantly among the groups (control 0%, SGA 36%, severe SGA 71%). CONCLUSION: Infants with severe SGA have abnormal placental DNA methylation of CpG1 in the CG4 region of RTL1, suggesting the existence of disturbed epigenetic control in utero.

  Jan. 2019, Pediatrics and neonatology, 60(5) (5), 512 - 516, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Neonatal vitamin K deficiency in the son of a mother with short bowel syndrome.

  Ashina M, Fujioka K, Nishida K, Iijima K

  Oct. 2018, Pediatrics international : official journal of the Japan Pediatric Society, 60(10) (10), 991 - 992, English, International magazine

  [Refereed]

  Scientific journal


• Evaluation index for asymmetric ventricular size on brain magnetic resonance images in very low birth weight infants.

  Toshihiko Ikuta, Masami Mizobuchi, Yoshinori Katayama, Seiji Yoshimoto, Tomoaki Ioroi, Masayuki Yamane, Takeshi Morisawa, Akihiro Takatera, Masaaki Ueda, Akio Shibata, Kaori Maeyama, Tsurue Mandai, Kazumichi Fujioka, Noriyuki Nishimura, Kazumoto Iijima, Ichiro Morioka

  OBJECTIVE: Asymmetric ventriculomegaly is often evident on brain magnetic resonance imaging (MRI) in very low birth weight infants (VLBWI) and is interpreted as white matter injury. However, no evaluation index for asymmetric left-right and anterior-posterior ventricular sizes has been established. METHODS: In this retrospective multicenter cohort study, brain T2-weighted MRI was performed at term-equivalent ages in 294 VLBWI born between 2009 and 2011. The value of a lateral ventricular index (LVI) to evaluate asymmetric ventricular size, as well as the relationship between the LVI value and walking at a corrected age of 18 months was investigated. At the level of the foramen of Monro in a horizontal slice, asymmetry between the left and right sides and between the anterior and posterior horns was identified by the corrected width and was detected by a low concordance rate and κ statistic value. An LVI representing the sum of the widths of the four horns of the lateral ventricle corrected for cerebral diameter was devised. RESULTS: Asymmetric left-right and anterior-posterior ventricular sizes were confirmed. The LVI value was significantly higher in the non-walking VLBWI group (n = 39) than in the walking VLBWI group (n = 255; 18.2 vs. 15.8, p = 0.02). An LVI cut-off value of 21.5 was associated with non-walking. Multivariate analysis revealed that an LVI value >21.5 was an independent predictor of walking disability at the corrected age of 18 months (odds ratio 2.56, p = 0.008). CONCLUSIONS: The LVI value calculated via MRI may predict walking disability at a corrected age of 18 months in VLBWI.

  Oct. 2018, Brain & development, 40(9) (9), 753 - 759, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Hyperbilirubinemia in Term Newborns Needing Phototherapy within 48 Hours after Birth in a Japanese Birth Center.

  Tsujimae S, Yoshii K, Yamana K, Fujioka K, Iijima K, Morioka I

  Sep. 2018, The Kobe journal of medical sciences, 64(1) (1), E20 - E25

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Feeding interval and use of donor breast milk for very low birthweight infants: A nationwide survey in Japan.

  Ashina M, Fujioka K, Totsu S, Shoji H, Miyazawa T, Wada K, Iijima K, Morioka I

  BACKGROUND: Enteral feeding is critical for postnatal growth of very low birthweight infants (VLBWI); however, a standard feeding strategy has not been established in Japan. A 2- or 3-h feeding interval is generally used, but no clear evidence supports either approach. Additionally, there is no nationwide breast milk bank in Japan and no consensus exists on the use of donor breast milk (DBM). To clarify the current feeding strategies for VLBWI in Japan, we undertook a nationwide survey. METHODS: We sent a questionnaire to the 382 NICUs included in the Neonatal Research Network in Japan. We sought information on NICU size, number of admissions, necrotizing enterocolitis (NEC) incidence, feeding interval, and use of DBM. RESULTS: We received responses from 217 NICUs (56.8%), including 76 tertiary centers and 140 regional centers. We only analyzed data obtained from tertiary perinatal centers with a high response rate (77.6%) owing to the insufficient response rate of lower-level facilities (<50%). Most NICUs (71.1%) used a 3-h feeding interval. Only 9.2% used a 2-h interval for all VLBWI. Most NICUs (64.5%) never used DBM, which is not routinely pasteurized. DBM was used in 27 NICUs (35.5%), with and without limitations. Data from 14,233 VLBWI were analyzed; 258 infants (1.8%) were diagnosed with NEC from 2011 to 2015. The incidence of NEC was higher in NICUs that used a 2-h interval (2.7%) than in others. No association was found between NEC and the use of DBM. The NEC incidence did not differ between centers using the most common strategy of a 3-h interval without DBM and those using other strategies. CONCLUSION: Most NICUs in Japan use a 3-h feeding interval and do not use DBM for VLBWI. Further prospective studies including multiple confounders are required to clarify the relationship between feeding strategy and the incidence of NEC.

  Jul. 2018, Pediatrics and neonatology, 60(3) (3), 245 - 251, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Hepatitis B vaccine: Immunogenicity in an extremely low-birthweight infant

  Keiji Yamana, Sota Iwatani, Kazumichi Fujioka, Kazumoto Iijima, Ichiro Morioka

  Blackwell Publishing, May 2018, Pediatrics International, 60(5) (5), 489 - 490, English

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Heme oxygenase-1 deficiency promotes severity of sepsis in a non-surgical preterm mouse model.

  Fujioka K, Kalish F, Zhao H, Wong RJ, Stevenson DK

  May 2018, Pediatric research

  [Refereed]


• Nontypeable Haemophilus Influenzae Sepsis in a Term Neonate.

  Okubo S, Fujioka K, Yamane M, Ashina M, Fukushima S, Ikuta T, Ohyama S, Yamana K, Kobayashi A, Iijima K, Morioka I

  We reported a term newborn case of early onset sepsis caused by nontypeable Haemophilus Influenzae (NTHi) with massive bacterial invasion in the placenta. Based on the consistent results of maternal placental pathology and neonatal bacterial culture, we diagnosed this as vertical transmission of NTHi via vaginal delivery. In general, NTHi infections occur in preterm infants, and our term infant case is very unusual. In conclusion, clinicians should consider NTHi as a cause of neonatal sepsis, even in term infants.

  Apr. 2018, The Kobe journal of medical sciences, 63(4) (4), E105 - E108, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A Case of Congenital Complete Atrioventricular Block Treated with Transdermal Tulobuterol.

  Ikuta T, Fujioka K, Sato Y, Ashina M, Fukushima S, Ohyama S, Okubo S, Yamana K, Morizane M, Tanimura K, Deguchi M, Iijima K, Morioka I, Yamada H

  Congenital complete atrioventricular block (CCAVB) is a condition in which the atria and ventricles beat independently of each other. CCAVB cases require permanent pacemaker implantation until adulthood. Nevertheless, consensus regarding postnatal medical therapy for bradycardia has not been reached. Here we report the case of a newborn with CCAVB, whose intractable bradycardia was successfully treated with transdermal tulobuterol. Tulobuterol is a selective β2-adrenoceptor agonist, widely used safely as bronchodilator in children. It also has positive inotropic and chronotropic effect via β1-adrenoceptors. We believe the tulobuterol patch can be used as an optional therapy for CCAVB where pacemaker implantation is not available.

  Apr. 2018, The Kobe journal of medical sciences, 63(4) (4), E109 - E112, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth.

  Rappoport N, Toung J, Hadley D, Wong RJ, Fujioka K, Reuter J, Abbott CW, Oh S, Hu D, Eng C, Huntsman S, Bodian DL, Niederhuber JE, Hong X, Zhang G, Sikora-Wohfeld W, Gignoux CR, Wang H, Oehlert J, Jelliffe-Pawlowski LL, Gould JB, Darmstadt GL, Wang X, Bustamante CD, Snyder MP, Ziv E, Patsopoulos NA, Muglia LJ, Burchard E, Shaw GM, O'Brodovich HM, Stevenson DK, Butte AJ, Sirota M

  Jan. 2018, Scientific reports, 8(1) (1), 226

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Pulmonary Hypoplasia Caused by Fetal Ascites in Congenital Cytomegalovirus Infection Despite Fetal Therapy

  Kazumichi Fujioka, Ichiro Morioka, Kosuke Nishida, Mayumi Morizane, Kenji Tanimura, Masashi Deguchi, Kazumoto Iijima, Hideto Yamada

  Nov. 2017, FRONTIERS IN PEDIATRICS, 5, 241, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Loss of Surfacten((R)) during bolus administration with a feeding catheter

  Kazumichi Fujioka, Jumpei Kuroda, Keiji Yamana, Kazumoto Iijima, Ichiro Morioka

  Nov. 2017, PEDIATRICS INTERNATIONAL, 59(11) (11), 1174 - 1177, English

  [Refereed]

  Scientific journal


• Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns

  Keiji Yamana, Ichiro Morioka, Daisuke Kurokawa, Sachiyo Fukushima, Kosuke Nishida, Shohei Ohyama, Noriyuki Nishimura, Kandai Nozu, Mariko Taniguchi-Ikeda, Hiroaki Nagase, Kazumichi Fujioka, Sota Iwatani, Hajime Nakamura, Kazumoto Iijima

  Oct. 2017, PEDIATRICS INTERNATIONAL, 59(10) (10), 1058 - 1063, English

  [Refereed]

  Scientific journal


• Gestational Age-Dependent Increase of Survival Motor Neuron Protein in Umbilical Cord-Derived Mesenchymal Stem Cells

  Sota Iwatani, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Shinya Tairaku, Akemi Shono, Daisuke Kurokawa, Keiji Yamana, Khin Kyae Mon Thwin, Makiko Yoshida, Masami Mizobuchi, Tsubasa Koda, Kazumichi Fujioka, Mariko Taniguchi-Ikeda, Hideto Yamada, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura

  Sep. 2017, FRONTIERS IN PEDIATRICS, 5, 194, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• INDUCTION OF HEME OXYGENASE-1 ATTENUATES THE SEVERITY OF SEPSIS IN A NON-SURGICAL PRETERM MOUSE MODEL

  Kazumichi Fujioka, Flora Kalish, Hui Zhao, Sabrina Lu, Stephanie Wong, Ronald J. Wong, David K. Stevenson

  Feb. 2017, SHOCK, 47(2) (2), 242 - 250, English

  [Refereed]

  Scientific journal


• Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

  Sota Iwatani, Akemi Shono, Makiko Yoshida, Keiji Yamana, Khin Kyae Mon Thwin, Jumpei Kuroda, Daisuke Kurokawa, Tsubasa Koda, Kosuke Nishida, Toshihiko Ikuta, Kazumichi Fujioka, Masami Mizobuchi, Mariko Taniguchi-Ikeda, Ichiro Morioka, Kazumoto Iijima, Noriyuki Nishimura

  Hindawi Limited, 2017, Stem Cells International, 2017, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

  Sota Iwatani, Akemi Shono, Makiko Yoshida, Keiji Yamana, Khin Kyae Mon Thwin, Jumpei Kuroda, Daisuke Kurokawa, Tsubasa Koda, Kosuke Nishida, Toshihiko Ikuta, Kazumichi Fujioka, Masami Mizobuchi, Mariko Taniguchi-Ikeda, Ichiro Morioka, Kazumoto Iijima, Noriyuki Nishimura

  2017, STEM CELLS INTERNATIONAL, 2017, 8749751, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Intraventricular Hemorrhage Due to Coagulopathy After Vitamin K Administration in a Preterm Infant With Maternal Crohn Disease.

  Fujioka K, Fukushima S, Nishida K, Iijima K, Morioka I

  Intraventricular hemorrhage (IVH) is a devastating morbidity in preterm infants and can result in poor neurodevelopmental outcomes. Intraventricular hemorrhage usually occurs within 72 hours after birth; post-acute-phase IVH (>1 week after birth) is uncommon. Development of the hemostatic system in fetuses and neonates is an age-dependent evolving process, and the neonatal hemostatic system is characterized by low levels of vitamin K-dependent factors, with further reduction caused by prematurity. Importantly, a severe coagulation deficiency can be a major contributing factor of IVH. Active maternal Crohn disease (CD) during pregnancy causes malnutrition via enteral malabsorption; this may include vitamin K deficiency, resulting in fetal vitamin K deficiency. We herein describe a preterm infant who was born to a mother with CD and developed post-acute-phase IVH due to coagulopathy despite vitamin K administration.

  2017, Japanese clinical medicine, 8, 1179670717746333 - 1179670717746333, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Gestational age-dependency of height and body mass index trajectories during the first 3 years in Japanese small-for-gestational age children

  Kaori Maeyama, Ichiro Morioka, Sota Iwatani, Sachiyo Fukushima, Daisuke Kurokawa, Keiji Yamana, Kosuke Nishida, Shohei Ohyama, Kazumichi Fujioka, Hiroyuki Awano, Mariko Taniguchi-Ikeda, Kandai Nozu, Hiroaki Nagase, Noriyuki Nishimura, Chika Shirai, Kazumoto Iijima

  Dec. 2016, SCIENTIFIC REPORTS, 6, 38659, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Inhibition of heme oxygenase activity using a microparticle formulation of zinc protoporphyrin in an acute hemolytic newborn mouse model

  Kazumichi Fujioka, Flora Kalish, Ronald J. Wong, David K. Stevenson

  Feb. 2016, PEDIATRIC RESEARCH, 79(2) (2), 251 - 257, English

  [Refereed]

  Scientific journal


• Heme oxygenase-1 promoter polymorphisms and risk of spina bifida

  Kazumichi Fujioka, Wei Yang, Matthew B. Wallenstein, Hui Zhao, Ronald J. Wong, David K. Stevenson, Gary M. Shaw

  Sep. 2015, BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, 103(9) (9), 741 - 746, English

  [Refereed]

  Scientific journal


• Association of a vascular endothelial growth factor polymorphism with the development of bronchopulmonary dysplasia in Japanese premature newborns.

  Kazumichi Fujioka, Akio Shibata, Tomoyuki Yokota, Tsubasa Koda, Miwako Nagasaka, Mariko Yagi, Yasuhiro Takeshima, Hideto Yamada, Kazumoto Iijima, Ichiro Morioka

  Mar. 2014, Scientific reports, 4, 4459 - 4459, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• N-Terminal pro-brain natriuretic peptide levels in dichorionic diamniotic twins with selective intrauterine growth restriction.

  Kazumichi Fujioka, Masami Mizobuchi, Hitomi Sakai, Sota Iwatani, Keiko Wada, Seiji Yoshimoto, Hideto Nakao

  Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.

  Mar. 2014, The Kobe journal of medical sciences, 59(4) (4), E141-8 - 8, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• N-terminal pro-brain natriuretic peptide levels in monochorionic diamniotic twins with selective intrauterine growth restriction

  K. Fujioka, M. Mizobuchi, H. Sakai, S. Iwatani, K. Wada, S. Yoshimoto, H. Nakao

  Jan. 2014, JOURNAL OF PERINATOLOGY, 34(1) (1), 6 - 10, English

  [Refereed]

  Scientific journal


• N-Terminal pro-brain natriuretic peptide and cardiovascular adaptations in monochorionic diamniotic twins.

  Fujioka K, Nakao H

  2014, J Neonatal Biol, 3, 124

  [Refereed]


• Increased levels of interleukin-6 in tracheal aspirate fluid are indicative of fetal inflammation in ventilated extremely low gestational age newborn

  Sota Iwatani, Masami Mizobuchi, Satoshi Tanaka, Kazumichi Fujioka, Keiko Wada, Hitomi Sakai, Seiji Yoshimoto, Hideto Nakao

  Kobe University School of Medicine, 2014, Kobe Journal of Medical Sciences, 60(1) (1), E19 - E24, English

  [Refereed]

  Scientific journal


• Severe retinopathy of prematurity with retinal detachment in monozygotic twins.

  Kazumichi Fujioka, Ichiro Morioka, Shigeru Honda, Yasutomo Tsukahara, Akihiro Miwa, Akio Shibata, Kenji Tanimura, Naoki Yokoyama, Hideto Yamada, Kazumoto Iijima

  We report a monochorionic diamniotic twin pair born at 29 weeks of gestation in which both twins developed severe retinopathy of prematurity (ROP) with retinal detachment. The pregnancy was terminated due to reversal of donor-recipient phenotypes in possible TTTS. Both twins had unstable cardiopulmonary status during the first week, and developed chronic lung disease. The larger twin, born at 1372 g, developed stage 4a ROP in both eyes, and the smaller twin, born at 1168 g, developed stage 4a ROP in the left eye. Genetic analysis of NDP, FZD4, LRP5, TSPAN12 genes revealed no mutations; however, VEGF gene polymorphism analysis showed heterozygous carrier state of the VEGF 936T allele in both twins, which is a risk factor for threshold ROP in Japanese newborn infants. We speculate the synergistic effects of unstable perinatal cardiopulmonary status and genetic predisposition due to VEGF 936C>T polymorphism caused the development of severe ROP with retinal detachment.

  3, Jun. 2013, Pediatrics international : official journal of the Japan Pediatric Society, 55(3) (3), 366 - 8, English, International magazine

  [Refereed]


• N-terminal pro-brain natriuretic peptide levels in monochorionic diamniotic twins with twin-to-twin transfusion syndrome treated by fetoscopic laser photocoagulation.

  Kazumichi Fujioka, Hitomi Sakai, Satoshi Tanaka, Sota Iwatani, Keiko Wada, Masami Mizobuchi, Seiji Yoshimoto, Hideto Nakao

  Twin-to-twin transfusion syndrome (TTTS) affects 15% of monochorionic diamniotic (MD) twin pregnancies, and is associated with adverse perinatal outcome. Recently, fetoscopic laser photocoagulation (FLP) has been widely accepted as the most definitive therapy to treat TTTS. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a powerful diagnostic marker of cardiac dysfunction in neonates, and is elevated in MD twins with TTTS. However, there are no reports assessing the effect of FLP on neonatal cardiac overload in TTTS by measuring the serum NT-proBNP levels at birth. Here, we aimed to compare serum NT-proBNP levels at birth in MD twins with TTTS treated with FLP or not. Twelve MD twin pairs with TTTS admitted to our center between October 2007 and September 2012 were enrolled in this study. The MD twin pairs were separated into two groups: seven twins (12 newborn infants) with FLP (FLP group) and five twins (nine newborn infants) without FLP (non-FLP group). Gestational age, birthweight, and Apgar scores were significantly higher in the FLP group than that in the non-FLP group. Serum NT-proBNP levels at birth were significantly lower in the FLP group than in the non-FLP group [1425 pg/ml (range, 466-9560) vs. 29900 pg/ml (range, 7300-77900), respectively; p=0.0003]. The serum NT-proBNP levels of larger and smaller co-twins were significantly correlated with each other (r=0.750; p=0.026). In conclusion, serum NT-proBNP levels at birth are lower in MD twins with TTTS after FLP treatment than in those without FLP.

  Apr. 2013, The Kobe journal of medical sciences, 59(1) (1), E28-35 - 35, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Novel treatment strategy for Japanese newborns with high serum unbound bilirubin.

  Tomoyuki Yokota, Ichiro Morioka, Takayuki Kodera, Takeshi Morisawa, Itsuko Sato, Seiji Kawano, Tsubasa Koda, Kiyomi Matsuo, Kazumichi Fujioka, Satoru Morikawa, Akihiro Miwa, Akio Shibata, Naoki Yokoyama, Masahiko Yonetani, Hideto Yamada, Hajime Nakamura, Kazumoto Iijima

  BACKGROUND: Serum unbound bilirubin (UB) is a measure of bilirubin not bound to albumin, and has been reported to be better than total bilirubin level at identifying infants at risk of developing bilirubin-induced neurotoxicity, including auditory abnormalities. A detailed treatment strategy for newborns with high serum UB has not been established. The aim of this study was to assess auditory outcomes in newborns with serum UB ≥1.00 μg/dL who were treated according to a novel treatment protocol. METHODS: A prospective clinical study was conducted in newborns weighing >1500 g with serum UB ≥1.00 μg/dL who were admitted to Kobe University Hospital and Kakogawa Municipal Hospital, Japan from 2006 to 2011. Enrolled newborns were treated as follows: (i) if serum UB was 1.00-1.50 μg/dL, phototherapy and infusion were given with or without albumin or immunoglobulin therapy; and (ii) if serum UB was >1.50 μg/dL, exchange transfusion was performed immediately. Auditory brainstem responses were evaluated at the time of discharge. RESULTS: A total of 89 Japanese newborns with UB ≥1.00 μg/dL were enrolled at a median age of 4 days. Of these, 85 had UB 1.00-1.50 μg/dL and four had UB >1.50 μg/dL. After being treated according to the protocol, no newborns were diagnosed with auditory brainstem response abnormalities. CONCLUSIONS: The present treatment protocol for Japanese newborns with serum UB ≥1.00 μg/dL may be useful for the prevention of bilirubin-induced auditory abnormalities.

  1, Feb. 2013, Pediatrics international : official journal of the Japan Pediatric Society, 55(1) (1), 54 - 9, English, International magazine

  [Refereed]


• Successful Management of an Extremely Premature Infant with Congenital Candidiasis

  Iwatani Sota, Murakami Yuko, Mizobuchi Masami, Fujioka Kazumichi, Wada Keiko, Sakai Hitomi, Yoshimoto Seiji, Nakao Hidet

  Thieme Publishing Group, 2013, American Journal of Perinatology Reports, 4(1) (1), 5 - 8

  [Refereed]


• Renin is activated in monochorionic diamniotic twins with birthweight discordance who do not have twin-to-twin transfusion syndrome

  K. Fujioka, I. Morioka, A. Miwa, T. Yokota, K. Matsuo, S. Morikawa, M. Enomoto, A. Shibata, M. Morizane, N. Yokoyama, H. Yamada, M. Matsuo

  Jul. 2012, JOURNAL OF PERINATOLOGY, 32(7) (7), 514 - 519, English

  [Refereed]

  Scientific journal


• Is bilirubin/albumin ratio correlated with unbound bilirubin concentration?

  Yumi Sato, Ichiro Morioka, Akihiro Miwa, Tomoyuki Yokota, Kiyomi Matsuo, Tsubasa Koda, Kazumichi Fujioka, Satoru Morikawa, Akio Shibata, Naoki Yokoyama, Kaoru Takahashi, Hisahide Nishio, Masafumi Matsuo

  BACKGROUND: The American Academy of Pediatrics guidelines recommend that the total bilirubin (TB)/albumin (Alb) ratio (B/A ratio), instead of serum concentration of unbound bilirubin (UB), can be used with TB for determining treatment modality for jaundiced newborns ≥ 35 weeks of gestation. It is unknown, however, whether the B/A ratio is actually correlated with serum UB. METHODS: Four hundred and ninety-seven serum samples were obtained from 209 newborns ≥ 35 weeks of gestation, who were admitted to Kobe University Hospital. Serum UB concentration was measured using the glucose oxidase-peroxidase method. Serum TB and Alb concentrations were measured on spectrophotometry. B/A ratios were calculated and were linearly compared with serum UB. Furthermore, the accuracy of the B/A ratio was evaluated. RESULTS: The B/A ratio was significantly correlated with serum UB concentration. A serum UB concentration of 0.6 µg/dL was in agreement with a B/A ratio of 0.5. For comparison of the number of newborns who had serum UB concentrations ≥ or <0.6 µg/dL and B/A ratios ≥ or <0.5, we found the following characteristics: the concordance rate between serum UB concentrations and the B/A ratio was 94%, sensitivity was 51%, and specificity was 99%. CONCLUSIONS: The B/A ratio is significantly correlated with serum UB concentration in newborns ≥ 35 weeks of gestation. The B/A ratio, however, is underestimated when serum UB concentrations are >0.6 µg/dL.

  1, Feb. 2012, Pediatrics international : official journal of the Japan Pediatric Society, 54(1) (1), 81 - 5, English, International magazine

  [Refereed]


• Correlation and precision of serum free bilirubin concentrations determined by single and two peroxidase concentration methods in term or late-preterm newborn infants using a FDA-approved analyzer.

  Akihiro Miwa, Ichiro Morioka, Tomoyuki Yokota, Akio Shibata, Kiyomi Matsuo, Kazumichi Fujioka, Tsubasa Koda, Satoru Morikawa, Hisahide Nishio, Naoki Yokoyama, Hajime Nakamura, Masafumi Matsuo, Hideto Yamada

  BACKGROUND: Free bilirubin concentration (B(f)) is an index for identifying newborns at risk for developing bilirubin-induced neurotoxicity. It has been suggested that B(f) measured by a single peroxidase concentration (B(f-single)) does not equal the equilibrium concentration of B(f), which is confirmed by B(f) at two different peroxidase concentrations (B(f-two)). However, the differences between B(f-single) and B(f-two) are unknown in the serum of term or late-preterm newborn infants. Furthermore, to apply B(f-single) with savings on time and cost to the clinical setting, it is very important for us to clarify the differences between B(f-single) and B(f-two). METHODS: Forty serum samples were obtained from 21 term or late-preterm newborns who were admitted at Kobe University Hospital. Using a peroxidase method, B(f-single) was measured at one peroxidase concentration, and B(f-two) was determined at two different peroxidase concentrations (the manufacturer's recommended peroxidase concentration and half the manufacturer's recommended peroxidase concentration). To clarify the relationship between B(f-single) and peroxidase concentrations, B(f-single) was measured at five different concentrations of peroxidase reagent. Intra-day and inter-day analyses were performed to assess the precision of B(f-single) and B(f-two). RESULTS: 1/B(f-single) increased as peroxidase concentration increased. B(f-single) was significantly lower than B(f-two) (B(f-single): 0.50 microg/dL [0.13 - 1.22 microg/dL] versus B(f-two): 0.59 microg/dL [0.15 - 1.76 microg/dL], p < 0.001), but B(f-single) was significantly correlated with B(f-two) (r = 0.953, p < 0.0001). Intra-day analysis showed that the CV was 9.7% for B(f-two) and 3.3% for B(f-single), and the inter-day CV was 12.4% for B(f-two) and 3.2% for B(f-single). CONCLUSIONS: Although B(f-single) and B(f-two) are not identical, B(f-single) is significantly correlated with B(f-two) and it is more precise than B(f-two) in term or late-preterm newborns.

  5-6, 2012, Clinical laboratory, 58(5-6) (5-6), 507 - 14, English, International magazine

  [Refereed]


• A surviving case of papillorenal syndrome with the phenotype of Potter sequence.

  Kazumichi Fujioka, Ichiro Morioka, Kandai Nozu, Masashi Nishimoto, Mariko Amano, Mizuki Tagami, Shigeru Honda, Naoki Yokoyama, Hideto Yamada, Kazumoto Iijima, Masafumi Matsuo

  3, Jun. 2011, Pediatrics international : official journal of the Japan Pediatric Society, 53(3) (3), 406 - 8, English, International magazine

  [Refereed]

  Scientific journal


• Hypoalbuminemia following abdominal surgery leads to high serum unbound bilirubin concentrations in newborns soon after birth.

  Akihiro Miwa, Ichiro Morioka, Chieko Hisamatsu, Kazumichi Fujioka, Satoru Morikawa, Akio Shibata, Masao Yasufuku, Naoki Yokoyama, Masafumi Matsuo

  BACKGROUND: The serum concentration of unbound bilirubin (UB), which is bilirubin not bound to albumin (Alb), is a better index than total bilirubin concentration (TB) for identifying infants at risk for developing bilirubin neurotoxicity. The degree to which the hypoalbuminemia following abdominal surgery in jaundiced newborns affects bilirubin binding is unknown. OBJECTIVE: To determine whether lower Alb occurring in newborns undergoing abdominal surgery shortly after birth results in significantly higher UB in serum versus nonsurgical patients at comparable serum TB. METHODS: A matched case-control study was conducted with term and late-preterm newborns. The surgery group included 15 newborns who underwent abdominal operation within 3 days after birth. Clinical and laboratory data (serum UB, TB, and Alb concentrations, UB/TB ratio, and binding constant) in the surgery group were collected and compared with those of 30 control newborns who did not undergo abdominal surgery (control group). RESULTS: Serum UB and the UB/TB ratio in the surgery group were significantly higher than those in the control group (p < 0.02, p < 0.001, respectively), whereas there were no significant differences in serum TB and binding constant between the groups. Serum Alb concentrations in the surgery group were significantly lower than those in the control group (p < 0.001). When pre- and postoperative serum Alb concentrations were compared, there was a significant decrease from 3.4 to 2.7 g/dl (p < 0.001). CONCLUSIONS: Our study suggests that hypoalbuminemia following abdominal surgery causes a higher serum UB at comparable serum TB in newborns.

  3, 2011, Neonatology, 99(3) (3), 202 - 7, English, International magazine

  [Refereed]


• Does thrombocytopenia contribute to patent ductus arteriosus?

  Kazumichi Fujioka, Ichiro Morioka, Akihiro Miwa, Satoru Morikawa, Akio Shibata, Naoki Yokoyama, Masafumi Matsuo

  1, Jan. 2011, Nature medicine, 17(1) (1), 29 - 30, English, International magazine

  [Refereed]


• The lowest surviving birth weight infant delivered from a systemic lupus erythematosus mother with antiphospholipid syndrome.

  Kazumichi Fujioka, Ichiro Morioka, Takeshi Urade, Kaho Suzuki, Mayumi Morizane, Naoki Yokoyama, Masafumi Matsuo

  We report the intact surviving case of a newborn with a birth weight of 412 g delivered from an active systemic lupus erythematosus (SLE) mother with antiphospholipid syndrome. A review of the literature revealed that our infant is the lowest surviving birth weight in newborns from SLE mothers to date.

  9, Sep. 2010, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 23(9) (9), 1050 - 2, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)

• 【数値からみる周産期医療 新生児編】栄養 栄養摂取量

  芦名 満理子, 藤岡 一路

  (株)東京医学社, Sep. 2023, 周産期医学, 53(9) (9), 1347 - 1351, Japanese


• MRSA保菌母体から母児接触により児へ水平伝播をきたした超早産児の1例

  藤本 将史, 阿部 真也, 城戸 拓海, 京野 由紀, 吉田 阿寿美, 仲宗根 瑠花, 菅 秀太郎, 芦名 満理子, 藤岡 一路

  (株)東京医学社, Jun. 2023, 周産期医学, 53(6) (6), 992 - 995, Japanese


• 【論文の書き方・査読の仕方】症例報告の書き方

  藤岡 一路

  (公社)日本新生児成育医学会, Jun. 2023, 日本新生児成育医学会雑誌, 35(2) (2), 176 - 180, Japanese


• 【研修医として今知りたい新生児の診療に必要な手技】治療手技 交換輸血,部分交換輸血

  芦名 満理子, 藤岡 一路

  (株)診断と治療社, May 2023, 小児科診療, 86(5) (5), 565 - 569, Japanese


• 【小児の治療方針】新生児 新生児黄疸

  鮫島 智大, 藤岡 一路

  (株)診断と治療社, Apr. 2023, 小児科診療, 86(春増刊) (春増刊), 912 - 914, Japanese


• 周産期感染症の最前線 先天性サイトメガロウイルス感染

  谷村 憲司, 内田 明子, 今福 仁美, 平久 進也, 藤岡 一路, 森岡 一朗, 峰松 俊夫, 山田 秀人

  日本産婦人科・新生児血液学会, Mar. 2023, 日本産婦人科・新生児血液学会誌, 32(2) (2), 27 - 33, Japanese


• 一絨毛膜一羊膜双胎第一子のみに発症した脳室上衣下異所性灰白質の1例

  白井 佳祐, 芦名 満理子, 福田 拓弥, 鮫島 智大, 城戸 拓海, 阿部 真也, 野津 寛大, 藤岡 一路

  (株)総合医学社, Feb. 2023, 小児科臨床, 76(1) (1), 61 - 65, Japanese


• 手足口病に伴う急性壊死性脳症の小児例

  今川 幸人, 藤岡 一路, 森沢 猛

  (株)総合医学社, Feb. 2023, 小児科臨床, 76(1) (1), 99 - 103, Japanese


• 重症患者における咬合不全のインパクトを探る

  藤浪好寿, 斎藤雅史, 大野雄康, 岡崎智哉, 篠原奈都代, 一二三亨, 黒田泰弘, 大山正平, 藤岡一路, 山田勇, 井上茂亮, 小谷穣治

  2023, 日本臨床栄養代謝学会学術集会(Web), 38th


• 【Controversies in perinatology 2023 新生児編】新生児黄疸に対する治療開始基準 森岡の基準(新神戸基準)を使う

  阿部 真也, 藤岡 一路

  (株)東京医学社, Jan. 2023, 周産期医学, 53(1) (1), 55 - 57, Japanese


• 【191の疑問に答える 周産期の栄養】小児科編Q&A ハイリスク(Question 69) 経管栄養は2時間ごとか3時間ごとのどちらがよいですか?

  京野 由紀, 芦名 満理子, 藤岡 一路

  (株)東京医学社, Nov. 2022, 周産期医学, 52(増刊) (増刊), 488 - 490, Japanese


• 【191の疑問に答える 周産期の栄養】小児科編Q&A ハイリスク(Question 85) 早産児の経口哺乳開始の目安と注意点は何ですか?

  川村 葵, 京野 由紀, 藤岡 一路

  (株)東京医学社, Nov. 2022, 周産期医学, 52(増刊) (増刊), 523 - 525, Japanese


• 【191の疑問に答える 周産期の栄養】新生児・乳児の栄養 早産児の栄養 経腸栄養の実践方法

  仲宗根 瑠花, 藤岡 一路

  (株)東京医学社, Nov. 2022, 周産期医学, 52(増刊) (増刊), 624 - 627, Japanese


• 【191の疑問に答える 周産期の栄養】小児科編Q&A ハイリスク(Question 69) 経管栄養は2時間ごとか3時間ごとのどちらがよいですか?

  京野 由紀, 芦名 満理子, 藤岡 一路

  (株)東京医学社, Nov. 2022, 周産期医学, 52(増刊) (増刊), 488 - 490, Japanese


• 【191の疑問に答える 周産期の栄養】小児科編Q&A ハイリスク(Question 85) 早産児の経口哺乳開始の目安と注意点は何ですか?

  川村 葵, 京野 由紀, 藤岡 一路

  (株)東京医学社, Nov. 2022, 周産期医学, 52(増刊) (増刊), 523 - 525, Japanese


• 【191の疑問に答える 周産期の栄養】新生児・乳児の栄養 早産児の栄養 経腸栄養の実践方法

  仲宗根 瑠花, 藤岡 一路

  (株)東京医学社, Nov. 2022, 周産期医学, 52(増刊) (増刊), 624 - 627, Japanese


• 過去に国内で報告された新生児偽性低アルドステロン症75例の文献レビュー

  市川 裕太, 藤岡 一路, 福田 拓弥, 川村 あおい, 鮫島 智大, 城戸 拓海, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 野津 寛大

  (株)総合医学社, Oct. 2022, 小児科臨床, 75(5) (5), 773 - 793, Japanese


• 【ケアの介入・搬送・報告のタイミングが変わる!新生児の生理・徴候と代表的疾患まるごとガイド】(第2章)新生児の主な徴候 黄疸

  福田 拓弥, 藤岡 一路

  (株)メディカ出版, Sep. 2022, with NEO, (2022秋季増刊) (2022秋季増刊), 81 - 88, Japanese


• 【新生児の症状・所見・検査値 見きわめドリル 見逃してはいけない赤ちゃんのコモントラブル】《検査編》ビリルビン値

  福田 拓弥, 藤岡 一路

  (株)メディカ出版, Jun. 2022, ペリネイタルケア, 41(6) (6), 564 - 569, Japanese


• 母体低栄養により、出生後にPIVKA-II高値を認め潜在的ビタミンK欠乏と診断した一例

  垂井 智前, 阿部 真也, 京野 由紀, 仲宗根 瑠花, 芦名 満理子, 藤岡 一路

  日本産婦人科・新生児血液学会, May 2022, 日本産婦人科・新生児血液学会誌, 32(1) (1), 5 - 6, Japanese


• 十二指腸空腸バイパス術既往のある母体から出生し、新生児ビタミンK欠乏性出血症をきたした一例

  金 潔駿, 阿部 真也, 垂井 智前, 京野 由紀, 仲宗根 瑠花, 芦名 満理子, 藤岡 一路

  日本産婦人科・新生児血液学会, May 2022, 日本産婦人科・新生児血液学会誌, 32(1) (1), 7 - 8, Japanese


• 出生時から先天性胆道拡張症の顕在化まで経時的にPIVKA-IIを測定し得た新生児例

  京野 由紀, 垂井 智前, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  日本産婦人科・新生児血液学会, May 2022, 日本産婦人科・新生児血液学会誌, 32(1) (1), 9 - 10, Japanese


• 精神疾患合併妊婦から出生した児の自宅退院困難に関連する要因の検討

  京野 由紀, 城戸 拓海, 菅 秀太郎, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Dec. 2021, 日本周産期・新生児医学会雑誌, 57(3) (3), 494 - 498, Japanese


• 【家族へ説明できる!新生児の脳 発達と注意すべきサイン】核黄疸と脳

  阿部 真也, 藤岡 一路

  (株)メディカ出版, Oct. 2021, with NEO, 34(5) (5), 760 - 767, Japanese


• バルガンシクロビル内服により著明な好中球減少をきたした先天性サイトメガロウイルス感染症の一例

  京野 由紀, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  日本産婦人科・新生児血液学会, May 2021, 日本産婦人科・新生児血液学会誌, 31(1) (1), 31 - 32, Japanese


• 新生児偽性低アルドステロン症

  藤岡 一路

  (公社)日本新生児成育医学会, Apr. 2021, 日本新生児成育医学会雑誌, 33(2) (2), 224 - 224, Japanese


• 【ドクター&ナースが使える 新生児のエコーと画像検査】胸部X線

  芦名 満理子, 藤岡 一路

  (株)メディカ出版, Feb. 2021, with NEO, 34(1) (1), 117 - 122, Japanese


• 【ドクター&ナースが使える 新生児のエコーと画像検査】胸部X線

  芦名 満理子, 藤岡 一路

  (株)メディカ出版, Feb. 2021, with NEO, 34(1) (1), 117 - 122, Japanese


• 胎児治療と新生児治療の併用は先天性サイトメガロウイルス感染症児の予後を改善する

  谷村憲司, 施裕徳, 内田明子, 今福仁美, 藤岡一路, 森岡一朗, 出口雅士, 峰松俊夫, 寺井義人, 山田秀人

  2021, 日本周産期・新生児医学会雑誌(Web), 57(Suppl) (Suppl)


• 非初感染母体から出生した重篤な症候性先天性サイトメガロウイルス感染症児の一例

  今福仁美, 谷村憲司, 益子尚久, 内田明子, 藤本将史, 京野由紀, 藤岡一路, 出口雅士, 寺井義人

  2021, 日本周産期・新生児医学会雑誌(Web), 57(Suppl) (Suppl)


• The association between development and past seizure history in a health check-up at 3 years of age

  西山将広, 京野由紀, 徳元翔一, 山口宏, 冨岡和美, 藤岡一路, 三品浩基, 飯島一誠, 永瀬裕朗

  2021, 日本小児科学会雑誌, 125(2) (2)


• Perinatal Factors Affecting Failure of Discharge to Home in Infants Born to Mothers with Mental Illness

  京野由紀, 城戸拓海, 菅秀太郎, 仲宗根瑠花, 阿部真也, 芦名満理子, 藤岡一路

  2021, 日本周産期・新生児医学会雑誌(Web), 57(3) (3)


• Neonatal hyperbilirubinemia

  京野由紀, 藤岡一路

  (株)東京医学社, 2021, 小児内科, 53(増刊) (増刊), 146 - 149, Japanese


• 出生時に好中球減少が見られたが、G-CSFが有効であった先天性サイトメガロウィルス感染症の一例

  生田 寿彦, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 藤岡 一路

  日本産婦人科・新生児血液学会, Dec. 2020, 日本産婦人科・新生児血液学会誌, 30(1) (1), 19 - 20, Japanese


• 出生時の超音波スクリーニングで発見した右頭頂葉出血の1例

  仲宗根 瑠花, 阿部 真也, 芦名 満理子, 生田 寿彦, 藤岡 一路

  日本産婦人科・新生児血液学会, Dec. 2020, 日本産婦人科・新生児血液学会誌, 30(1) (1), 45 - 46, Japanese


• 亜鉛投与によって改善した皮膚症状に先行して腸瘻からの出血が遷延した低亜鉛血症を呈する極低出生体重児の一例

  阿部 真也, 仲宗根 瑠花, 芦名 満理子, 生田 寿彦, 藤岡 一路

  日本産婦人科・新生児血液学会, Dec. 2020, 日本産婦人科・新生児血液学会誌, 30(1) (1), 47 - 48, Japanese


• 高感度PIVKA II測定法を用いたハイリスク新生児における潜在性ビタミンK欠乏症のスクリーニング

  芦名 満理子, 仲宗根 瑠花, 阿部 真也, 生田 寿彦, 藤岡 一路

  日本産婦人科・新生児血液学会, Dec. 2020, 日本産婦人科・新生児血液学会誌, 30(1) (1), 51 - 52, Japanese


• 切迫早産から妊娠29週未満で早産となった児の予後に関連する因子の検討

  澤田 茉美子, 谷村 憲司, 施 裕徳, 内田 明子, 笹川 勇樹, 白川 得朗, 森實 真由美, 藤岡 一路, 山田 秀人

  「産婦人科の進歩」編集室, Oct. 2020, 産婦人科の進歩, 72(4) (4), 392 - 394, Japanese


• エンドトキシン研究:ベンチサイドとベッドサイドからのメッセージ 糞便懸濁液投与法を用いた早産児マウス敗血症モデルの作成と臨床課題への応用

  藤岡 一路

  日本エンドトキシン・自然免疫研究会, Oct. 2020, エンドトキシン・自然免疫研究, 23, 16 - 21, Japanese


• 【NICU卒業生の予後と診療のポイント】先天性感染症 トキソプラズマ

  菅 秀太郎, 藤岡 一路

  (株)診断と治療社, Sep. 2020, 小児科診療, 83(9) (9), 1235 - 1238, Japanese


• 【パーフェクト版 新生児のフィジカルアセスメント 正期産児からLate preterm児、早産児まで】(第3章)新生児の症状別アセスメント:正常からの逸脱を見抜く チアノーゼ

  芦名 満理子, 藤岡 一路

  (株)メディカ出版, Sep. 2020, with NEO, (2020秋季増刊) (2020秋季増刊), 128 - 131, Japanese


• 【パーフェクト版 新生児のフィジカルアセスメント 正期産児からLate preterm児、早産児まで】(第3章)新生児の症状別アセスメント:正常からの逸脱を見抜く 黄疸(皮膚/眼球結膜)

  阿部 真也, 藤岡 一路

  (株)メディカ出版, Sep. 2020, with NEO, (2020秋季増刊) (2020秋季増刊), 132 - 136, Japanese


• 【チャートで極める!母体疾患別 新生児の病態生理とケア 家族説明シートつき】重症筋無力症の母親と児

  近藤 淳, 藤岡 一路

  (株)メディカ出版, Jun. 2020, with NEO, 33(3) (3), 367 - 373, Japanese


• 免疫性血小板減少症母体より出生し血小板減少症を呈した姉妹例

  三上 華奈, 藤岡 一路, 福嶋 祥代, 阿部 真也, 芦名 満理子, 生田 寿彦, 大山 正平, 西田 浩輔, 飯島 一誠

  (株)東京医学社, May 2020, 周産期医学, 50(5) (5), 872 - 876, Japanese


• 【[必携]専攻医と指導医のための新生児診療到達目標】疾患別到達目標 新生児黄疸

  仲宗根 瑠花, 藤岡 一路

  (株)東京医学社, Apr. 2020, 周産期医学, 50(4) (4), 698 - 700, Japanese


• 【新生児の生理と対応のポイント 生後すぐから1ヵ月健診まで助産師・お母さんの悩みもスッキリ解決】《出生直後〜生後72時間の症状》黄疸

  芦名 満理子, 藤岡 一路

  (株)メディカ出版, Apr. 2020, ペリネイタルケア, 39(4) (4), 366 - 370, Japanese


• 病理組織学的に異所性唾液腺を認めた,瘻孔を伴う先天性頸部嚢胞の1例

  會田洋輔, 尾藤祐子, 大片祐一, 宮内玄徳, 中谷太一, 冨岡雄一郎, 橘木由美子, 中井優美子, 芦名満理子, 藤岡一路, 飯島一誠

  2020, 日本小児科学会雑誌, 124(6) (6)


• 第2子に偽性低アルドステロン症を認め、第1子にも高レニン・高アルドステロン血症を認めた二絨毛膜二羊膜双胎例

  市川 裕太, 藤岡 一路, 阿部 真也, 芦名 満理子, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠

  (株)東京医学社, Dec. 2019, 周産期医学, 49(12) (12), 1675 - 1678, Japanese


• 第2子に偽性低アルドステロン症を認め、第1子にも高レニン・高アルドステロン血症を認めた二絨毛膜二羊膜双胎例

  市川 裕太, 藤岡 一路, 阿部 真也, 芦名 満理子, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠

  (株)東京医学社, Dec. 2019, 周産期医学, 49(12) (12), 1675 - 1678, Japanese


• 後方視的研究を英文論文として採択させるために

  藤岡 一路

  (公社)日本新生児成育医学会, Oct. 2019, 日本新生児成育医学会雑誌, 31(3) (3), 684 - 684, Japanese


• 症候性先天性サイトメガロウイルス感染症に対する胎児治療と新生児治療の有効性

  谷村 憲司, 内田 明子, 今福 仁美, 森實 真由美, 出口 雅士, 藤岡 一路, 森岡 一朗, 峰松 俊夫, 山田 秀人

  (一社)日本産婦人科感染症学会, Sep. 2019, 日本産婦人科感染症学会誌, 3(1) (1), 87 - 87, Japanese


• 母体の尾骨突出を認めた新生児頭蓋骨陥没骨折の2例

  西田 浩輔, 藤岡 一路, 森沢 猛, 米谷 昌彦, 飯島 一誠

  (一社)日本周産期・新生児医学会, Sep. 2019, 日本周産期・新生児医学会雑誌, 55(3) (3), 848 - 851, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 【新生児医療67の臨床手技とケア タイミング、流れ&コツ、評価まで見える】(第2章)治療・検査の手技 (5節)検査【エコー、生理機能検査】聴性脳幹反応 ABRとaABR

  西田 浩輔, 森本 紗代, 藤岡 一路

  (株)メディカ出版, Sep. 2019, with NEO, (2019秋季増刊) (2019秋季増刊), 111 - 115, Japanese


• 【新生児医療67の臨床手技とケア タイミング、流れ&コツ、評価まで見える】(第3章)新生児ケアの手技 (6節)検査、治療時のケア 黄疸計の使い方と光線療法

  阿部 真也, 森本 紗代, 藤岡 一路

  (株)メディカ出版, Sep. 2019, with NEO, (2019秋季増刊) (2019秋季増刊), 254 - 260, Japanese


• 出生後初回の採血で著明な高K血症を呈した尿路奇形を伴わない続発性偽性低アルドステロン症の1新生児例

  市川 裕太, 藤岡 一路, 芦名 満理子, 阿部 真也, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠

  (株)日本小児医事出版社, Aug. 2019, 小児科臨床, 72(8) (8), 1030 - 1034, Japanese


• UGT1A1遺伝子G71Rヘテロ接合変異を有し,完全母乳栄養中に遷延性高ビリルビン血症を呈した一絨毛膜二羊膜双胎の早産児例

  大山正平, 八木佑加子, 山名啓司, 藤岡一路, 飯島一誠, 岡橋彩, 中村肇, 森岡一朗, 森岡一朗

  (株)日本小児医事出版社, Mar. 2019, 小児科臨床, 72(3) (3), 319 - 323, Japanese


• 軽度の片側性水腎症に合併した続発性偽性低アルドステロン症の1新生児例

  西田浩輔, 藤岡一路, 芦名満理子, 阿部真也, 福嶋祥代, 生田寿彦, 大山正平, 飯島一誠

  (株)日本小児医事出版社, Mar. 2019, 小児科臨床, 72(3) (3), 337 - 341, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 生体侵襲とショックの基礎病態学、今 Cecal Slurry法を用いた早産児マウス敗血症モデルの利点と課題

  藤岡 一路

  (一社)日本Shock学会, Feb. 2019, Shock: 日本Shock学会雑誌, 33(2) (2), 28 - 33, Japanese


• 極低出生体重児と自閉スペクトラム症児の3歳時の発達特徴の比較

  万代ツルエ, 前山花織, 岩谷壮太, 藤岡一路, 北山真次, 飯島一誠, 森岡一朗, 森岡一朗

  (一社)日本新生児成育医学会, Feb. 2019, 日本新生児成育医学会雑誌, 31(1) (1), 90 - 96, Japanese


• 胎児期に臍帯嚢胞を指摘された尿膜管遺残の1例

  金谷真吾, 福嶋祥代, 阿部真也, 芦名満理子, 大山正平, 生田寿彦, 藤岡一路, 宮内玄徳, 中谷太一, 會田洋輔, 大片祐一, 尾藤祐子, 飯島一誠

  2019, 日本小児科学会雑誌, 123(3) (3)


• Cecal Slurry法を用いて作成した新生児腹膜炎性敗血症モデルマウスに対するインスリン療法の保護効果の検討

  宮内玄徳, 藤岡一路, 大片祐一, 尾藤祐子, 會田洋輔, 冨岡雄一郎, 中谷太一, 橘木由美子, 中井優美子

  2019, 日本小児外科学会雑誌, 55(3) (3)


• 輪状膵に伴う先天性多発十二指腸閉鎖症の術後に閉塞性黄疸を来したDown症候群の1例

  芦名満理子, 大山正平, 生田寿彦, 福嶋祥代, 大久保沙紀, 山名啓司, 藤岡一路, 宮内玄徳, 大片祐一, 尾藤祐子, 飯島一誠, 森岡一朗

  2019, 日本小児科学会雑誌, 123(3) (3)


• 胃泡拡大が診断契機となった胎児期に発症した小腸軸捻転症の1例

  福嶋祥代, 芦名満理子, 大山正平, 生田寿彦, 大久保沙紀, 山名啓司, 藤岡一路, 宮内玄徳, 大片祐一, 尾藤祐子, 飯島一誠, 森岡一朗

  2019, 日本小児科学会雑誌, 123(3) (3)


• 生後急速に進行する腹部膨満の原因として壁内神経節細胞の未熟生が考えられた早産児の1例

  福嶋祥代, 阿部真也, 芦名満理子, 大山正平, 生田寿彦, 藤岡一路, 宮内玄徳, 會田洋輔, 大片祐一, 尾藤祐子, 飯島一誠

  2019, 日本小児科学会雑誌, 123(3) (3)


• 症候性先天性サイトメガロウイルス感染症に対する胎児治療と新生児治療

  谷村憲司, 内田明子, 森實真由美, 西田浩輔, 藤岡一路, 森岡一朗, 峰松俊夫, 山田秀人

  (一社)日本周産期・新生児医学会, Jan. 2019, 日本周産期・新生児医学会雑誌, 54(別冊) (別冊), 26 - 27, Japanese


• NICU最前線 家族への説明に使える!新生児の検査・検査値まるわかり基本マスター 6)聴覚検査(ABR,OAEなど)

  西田浩輔, 藤岡一路

  10 Nov. 2018, Neonatal Care, 31(11) (11), 1061‐1066, Japanese


• 後方視的研究の手法 裏技!仮説なしデータ蓄積から始まる研究デザイン

  藤岡 一路

  (公社)日本新生児成育医学会, Oct. 2018, 日本新生児成育医学会雑誌, 30(3) (3), 592 - 592, Japanese


• Risk factors associated with poor outcome in growth‐restricted fetuses born at less than 30 weeks of gestation

  内山美穂子, 谷村憲司, 白國あかり, 森實真由美, 出口雅士, 藤岡一路, 森岡一朗, 山田秀人

  「産婦人科の進歩」編集室, Aug. 2018, 産婦人科の進歩, 70(3) (3), 270 - 277, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 生体侵襲とショックの基礎病態学、今 Cecal Slurry法を用いた早産児マウス敗血症モデルの利点と課題

  藤岡 一路

  (一社)日本Shock学会, Jun. 2018, Shock: 日本Shock学会雑誌, 33(1) (1), 32 - 32, Japanese


• ヘムオキシゲナーゼ‐1制御を介した早産児敗血症の新規治療法の開発

  藤岡一路, 西田浩輔, 飯島一誠

  Apr. 2018, 母子健康協会小児医学助成研究報告書, 29th, 7‐9, Japanese


• 新生児分野で臨床応用が期待される基礎研究 Cecal slurry法を用いた早産児マウス敗血症モデルの作成と臨床応用

  藤岡 一路

  (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 195 - 195, Japanese


• 重症small for gestational age児における尿道下裂合併症例とその出生時臨床像の検討

  芦名満理子, 藤岡一路, 福嶋祥代, 生田寿彦, 大山正平, 大久保沙紀, 山名啓司, 飯島一誠, 森岡一朗

  (株)日本小児医事出版社, Feb. 2018, 小児科臨床, 71(2) (2), 180 - 184, Japanese

  Link to Kobe Univ. Repository (Kernel)


• Efficacy of antiviral treatment on abnormal auditory brainstem responses in congenital cytomegalovirus-infected infants

  Ichiro Morioka, Shohei Ohyama, Sachiyo Fukushima, Kosuke Nishida, Keiji Yamana, Kazumichi Fujioka, Kazumoto Iijima, Mayumi Morizane, Kenji Tanimura, Masashi Deguchi, Hideto Yamada

  Nov. 2017, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 124, 80 - 81, English

  Summary international conference


• Neurological outcomes at 18 months of age and neonatal risk factors for severe sequelae in congenitally cytomegalovirus-infected infants treated by antiviral treatment early in life

  Ichiro Morioka, Sachiyo Fukushima, Shohei Ohyama, Kosuke Nishida, Keiji Yamana, Kazumichi Fujioka, Kazumoto Iijima, Mayumi Morizane, Kenji Tanimura, Masashi Deguchi, Hideto Yamada

  Nov. 2017, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 124, 80 - 80, English

  Summary international conference


• 早産児敗血症においてヘムオキシゲナーゼ‐1が果たす役割の解明

  藤岡一路

  (一社)神緑会, Aug. 2017, 神緑会学術誌, 33, 61 - 64, Japanese


• SGA児の長期予後 SGA児の胎盤における胎盤形成遺伝子Retrotransposon-like1(Rtl1)メチル化異常の検討

  藤岡 一路, 前山 花織, 西田 浩輔, 大山 正平, 福嶋 祥代, 山名 啓司, 黒川 大輔, 岩谷 壮太, 西村 範行, 飯島 一誠, 森岡 一朗

  (一社)日本周産期・新生児医学会, Jun. 2017, 日本周産期・新生児医学会雑誌, 53(2) (2), 476 - 476, Japanese


• INDUCTION OF HEME OXYGENASE-1 IS PROTECTIVE AGAINST SEPSIS IN A PRETERM MOUSE MODEL

  Kazumichi Fujioka, Flora Kalish, Hui Zhao, Ronald J. Wong, David K. Stevenson

  Jun. 2017, SHOCK, 47(6) (6), 32 - 32, English

  Summary international conference


• 早産低出生体重児と高ビリルビン血症 早産児の総ビリルビン・アンバウンドビリルビンを用いた光線療法・交換輸血治療基準の評価

  森岡 一朗, 香田 翼, 岩谷 壮太, 黒川 大輔, 山名 啓司, 西田 浩輔, 大山 正平, 藤岡 一路, 飯島 一誠, 中村 肇

  (一社)日本周産期・新生児医学会, Jun. 2017, 日本周産期・新生児医学会雑誌, 53(2) (2), 474 - 474, Japanese


• 早産児マウス敗血症モデルの作成

  藤岡一路

  (一社)日本Shock学会, Apr. 2017, Shock, 31(2) (2), 17 - 21, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 経管栄養間隔の変更が極低出生体重児の経腸栄養確立に及ぼす影響の検討

  FUJIOKA KAZUMICHI, MIZOBUCHI MASAMI, WADA KEIKO, IWATANI SOTA, SAKAI HITOMI, YOSHIMOTO SEIJI, NAKAO HIDETO

  (一社)日本新生児成育医学会, Feb. 2015, 日本未熟児新生児学会雑誌, 27(1) (1), 114 - 119, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 日本人Small-for-gestational age児における血管内皮増殖因子遺伝子多型の関与の検討

  藤岡 一路

  (公社)日本新生児成育医学会, Oct. 2014, 日本未熟児新生児学会雑誌, 26(3) (3), 484 - 484, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 一絨毛膜二羊膜性双胎における出生時血清NT-pro BNP濃度と生後早期心不全との関連性に関する研究

  藤岡 一路, 坂井 仁美, 芳本 誠司, 中尾 秀人

  (一社)神緑会, Aug. 2014, 神緑会学術誌, 30, 55 - 57, Japanese


• 輸入不活化ポリオワクチン初回免疫後のポリオウイルス中和抗体価に関する検討

  藤岡一路, 藤岡一路, 飯島一誠

  (一社)日本渡航医学会, May 2014, 日本渡航医学会誌, 7(1) (1), 10 - 12, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 第3次周産期医療センターで対応したドバイからの帰国超早産児の1例

  藤岡一路, 上村和也, 梶笑美子, 和田佳子, 坂井仁美, 溝渕雅巳, 芳本誠司, 中尾秀人

  (一社)日本渡航医学会, May 2014, 日本渡航医学会誌, 7(1) (1), 40 - 42, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 人工呼吸管理を要する超早産児における気管内吸引液分析の有用性

  溝渕雅巳, 岩谷壮太, 田中聡, 藤岡一路, 和田佳子, 坂井仁美, 芳本誠司, 中尾秀人

  近畿新生児研究会, Mar. 2014, 近畿新生児研究会会誌, (22) (22), 12 - 16, Japanese


• 神経管閉鎖障害を合併した脊椎肋骨異形成症の2例

  和田佳子, 坂井仁美, 芳本誠司, 田中聡, 藤岡一路, 岩谷壮太, 溝渕雅巳, 中尾秀人

  近畿新生児研究会, Mar. 2014, 近畿新生児研究会会誌, (22) (22), 29 - 32, Japanese


• 日本人Small-for-gestational age児におけるレニン・アンジオテンシン系遺伝子多型の関与の検討

  藤岡 一路, 森岡 一朗, 長坂 美和子, 香田 翼, 松尾 希世美, 横田 知之, 柴田 暁男, 山田 秀人, 飯島 一誠

  (一社)日本新生児成育医学会, Feb. 2014, 日本未熟児新生児学会雑誌, 26(1) (1), 153 - 159, Japanese

  Link to Kobe Univ. Repository (Kernel)


• Successful Treatment with Vincristine of a Preterm Infant with Intractable Huge Infantile Hepatic Hemangioma Involving Kasabach-Merritt Syndrome

  TANAKA SATOSHI, IWATANI SOTA, SOFUE TOSHIKI, FUJIOKA KAZUMICHI, WADA KEIKO, SAKAI HITOMI, MIZOBUCHI MASAMI, YOSHIMOTO SEIJI, NAKAO HIDETO

  (公社)日本小児科学会, Jan. 2014, 日本小児科学会雑誌, 118(1) (1), 52 - 56, Japanese


• 新生児編 II.X線診断 A.単純X線診断 27 胸部X線診断―縦隔腫瘍,CCAM,肺分画症

  藤岡一路, 芳本誠司

  (株)東京医学社, Dec. 2013, 周産期医学, 43(増刊) (増刊), 483 - 486, Japanese


• A postnatally diagnosed case of congenital rubella syndrome, complicated with Transposition of the great arteries

  FUJIOKA KAZUMICHI, KAJI EMIKO, IWATANI SOTA, WADA KEIKO, SAKAI HITOMI, MIZOBUCHI MASAMI, YOSHIMOTO SEIJI, NAKAO HIDETO

  (一社)日本周産期・新生児医学会, Dec. 2013, 日本周産期・新生児医学会雑誌, 49(4) (4), 1286 - 1290, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 予防接種Q&A 日本脳炎―追加接種:流行地への渡航 174.東南アジアの日本脳炎流行地へ出かけるときは,成人でも追加接種を受けたほうがよいですか

  藤岡一路

  (株)東京医学社, Nov. 2013, 小児内科, 45(増刊) (増刊), 454 - 455, Japanese


• Early detection of ventilator‐associated pneumonia using analyses of tracheal aspirate fluid in extremely low birth weight infant: a case report

  溝渕雅巳, 田中聡, 藤岡一路, 岩谷壮太, 和田佳子, 坂井仁美, 芳本誠司, 中尾秀人

  (一社)日本周産期・新生児医学会, Sep. 2013, 日本周産期・新生児医学会雑誌, 49(3) (3), 1078 - 1082, Japanese


• 一絨毛膜二羊膜双胎と二絨毛膜二羊膜双胎の一児発育不全(selective IUGR)における出生時NT-proBNP値の比較

  藤岡 一路, 田中 聡, 岩谷 壮太, 和田 佳子, 坂井 仁美, 溝渕 雅巳, 芳本 誠司, 中尾 秀人

  日本周産期・新生児医学会, Jun. 2013, 日本周産期・新生児医学会雑誌, 49, 715 - 715, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 2012年度に当院で経験した先天性風疹症候群の2例

  藤岡 一路, 坂井 仁美, 田中 聡, 岩谷 壮太, 和田 佳子, 溝渕 雅巳, 芳本 誠司, 中尾 秀人

  日本周産期・新生児医学会, Jun. 2013, 日本周産期・新生児医学会雑誌, 49, 737 - 737, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 日本人small-for-gestational age児における血管内皮増殖因子遺伝子多型の関与の検討

  藤岡 一路, 森岡 一朗, 長坂 美和子, 香田 翼, 松尾 希世美, 横田 知之, 森川 悟, 三輪 明弘, 柴田 暁男, 山田 秀人, 飯島 一誠

  (一社)日本新生児成育医学会, Jun. 2013, 日本未熟児新生児学会雑誌, 25(2) (2), 231 - 236, Japanese

  Link to Kobe Univ. Repository (Kernel)


• Imported Inactivated Polio Vaccine Use in Kobe City

  FUJIOKA KAZUMICHI, FUJIOKA KAZUMICHI, IIJIMA KAZUMOTO

  (公社)日本小児科学会, Apr. 2013, 日本小児科学会雑誌, 117(4) (4), 766 - 772, Japanese


• 特徴的な皮膚所見から早期診断し早期治療を行えた電撃性紫斑病の1例

  鴨井 良明, 香田 翼, 松尾 希世美, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 森岡 一朗, 横山 直樹, 飯島 一誠

  (公社)日本小児科学会, Jan. 2013, 日本小児科学会雑誌, 117(1) (1), 138 - 138, Japanese


• 長期予後からみた出生前診断症例における周産期管理の再評価 長期予後からみた出生前診断と治療 母体及び胎盤・臍帯要因で極低出生体重児として出生した重度胎児発育不全児の3歳時の精神運動発達

  森岡 一朗, 万代 ツルエ, 香田 翼, 松尾 希世美, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 園山 綾子, 谷村 憲司, 北山 真次, 横山 直樹, 飯島 一誠, 山田 秀人

  (一社)日本周産期・新生児医学会, Sep. 2012, 周産期学シンポジウム, (30) (30), 53 - 59, Japanese


• いつでも遭遇しうる!輸入感染症・性感染症への対策UP DATE 3 トラベルワクチンの考え方と接種状況

  藤岡一路, 藤岡一路

  (株)メディカ出版, Aug. 2012, Infect Control, 21(8) (8), 840 - 843, Japanese


• 在胎週数相当の-2SD未満のSmall‐for‐Gestational‐Age児の臨床像:単一施設の入院症例における検討

  藤岡一路, 藤岡一路, 森岡一朗, 三輪明弘, 横田知之, 香田翼, 松尾希世美, 森川悟, 森川悟, 柴田暁男, 横山直樹, 山田秀人

  (一社)神緑会, Aug. 2012, 神緑会学術誌, 28, 73 - 77, Japanese


• 新生児慢性肺疾患とVEGF遺伝子多型の関連

  藤岡 一路, 森岡 一朗, 香田 翼, 松尾 希世美, 横田 知之, 森川 悟, 三輪 明弘, 柴田 暁男, 横山 直樹, 飯島 一誠, 山田 秀人

  日本周産期・新生児医学会, 20 Jun. 2012, 日本周産期・新生児医学会雑誌, 48(2) (2), 359 - 359, Japanese


• ウリナスタチンとオクトレオチドの投与が胎児水腫における全身浮腫、乳糜胸の改善に効果的であった一例

  横田 知之, 香田 翼, 松尾 希世美, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 森岡 一朗, 横山 直樹, 飯島 一誠

  (一社)日本周産期・新生児医学会, Jun. 2012, 日本周産期・新生児医学会雑誌, 48(2) (2), 452 - 452, Japanese


• キングスカレッジ・プログラム留学報告書

  FUJIOKA KAZUMICHI

  日本未熟児新生児学会, Jun. 2012, 日本未熟児新生児学会雑誌 = Journal of Japan Society for Premature and Newborn Medicine, 24(2) (2), 327 - 334, Japanese

  Others

  Link to Kobe Univ. Repository (Kernel)


• 一般小児科外来診療におけるトラベルメディスンの意義

  藤岡一路

  (一社)日本渡航医学会, May 2012, 日本渡航医学会誌, 5(1) (1), 40 - 44, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 母体に基礎疾患のない成熟児に発症した早発型ビタミンK欠乏性出血症の5例

  松尾 希世美, 森岡 一朗, 香田 翼, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 横山 直樹, 飯島 一誠

  (公社)日本小児科学会, Feb. 2012, 日本小児科学会雑誌, 116(2) (2), 344 - 344, Japanese


• 生後早期の腹部手術後に生じる低アルブミン血症は高アンバウンドビリルビン血症を引き起こす

  森岡一朗, 森岡一朗, 三輪明弘, 横田知之, 香田翼, 松尾希世美, 藤岡一路, 藤岡一路, 柴田暁男, 大片祐一, 久松千恵子, 横山直樹, 横山直樹, 山田秀人, 飯島一誠

  2012, 日本周産期・新生児医学会雑誌, 48(2) (2)


• 留学体験記 英国滞在で気づいたこと

  藤岡 一路

  日本未熟児新生児学会, 2012, 日本未熟児新生児学会雑誌 = Journal of Japan Society for Premature and Newborn Medicine, 24(3) (3), 461 - 461, Japanese


• バルガンシクロビル内服治療により聴性脳幹反応異常が改善した先天性サイトメガロウィルス感染症の2例

  松尾 希世美, 森岡 一朗, 香田 翼, 山本 暢之, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 早川 晶, 横山 直樹, 松尾 雅文

  (公社)日本小児科学会, Dec. 2011, 日本小児科学会雑誌, 115(12) (12), 1937 - 1937, Japanese


• 在宅医療へ移行できた周産期型低ホスファターゼ症の1例

  森岡 一朗, 香田 翼, 松尾 希世美, 横田 知之, 藤岡 一路, 森川 悟, 粟野 宏之, 三輪 明弘, 柴田 暁男, 横山 直樹

  (公社)日本小児科学会, Dec. 2011, 日本小児科学会雑誌, 115(12) (12), 1942 - 1942, Japanese


• 長期予後からみた出生前診断と治療 母体及び胎盤臍帯要因で極低出生体重児として出生した重度胎児発育不全児の3歳時の精神運動発達

  森岡 一朗, 万代 ツルエ, 香田 翼, 松尾 希世美, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 園山 綾子, 谷村 憲司, 北山 真次, 横山 直樹, 飯島 一誠, 山田 秀人

  (一社)日本周産期・新生児医学会, Dec. 2011, 日本周産期・新生児医学会雑誌, 47(別冊) (別冊), 16 - 16, Japanese


• 米国移民ビザ申請者の予防接種 : 輸入ワクチンを利用しての留学渡航ワクチン外来の実際

  山本 厚太, 阿部 泰尚, 藤岡 一路

  日本医事新報社, Nov. 2011, 日本医事新報, (4570) (4570), 86 - 92, Japanese

  Introduction commerce magazine


• 先天性サイトメガロウイルス感染症における脳室拡大と聴性脳幹反応異常の関連

  松尾 希世美, 森岡 一朗, 香田 翼, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 横山 直樹, 山田 秀人

  (一社)日本新生児成育医学会, Oct. 2011, 日本未熟児新生児学会雑誌, 23(3) (3), 564 - 564, Japanese


• 院外出生児に対する先制的接触感染予防策がメチシリン耐性黄色ブドウ球菌(MRSA)の院内感染を減少させる

  森岡 一朗, 香田 翼, 松尾 希世美, 横田 知之, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 横山 直樹, 山田 秀人

  (一社)日本新生児成育医学会, Oct. 2011, 日本未熟児新生児学会雑誌, 23(3) (3), 726 - 726, Japanese


• An assessment of transplacental transmission of the novel influenza A (H1N1) 2009 virus

  AMANO Mariko, MORIOKA Ichiro, MORIZANE Mayumi, MORIMOTO Noriyuki, FUJIOKA Kazumichi, SIBATA Akio, YOKOYAMA Naoki, ARAKAWA Soichi, MAKINO Akiko, SINYA Kyoko, MATSUO Masafumi, YAMADA Hideto

  (一社)日本周産期・新生児医学会, May 2011, 日本周産期・新生児医学会雑誌, 47(1) (1), 50 - 53, Japanese


• 神戸海星病院小児科外来のトラベルワクチン接種状況

  藤岡 一路

  (一社)日本渡航医学会, Apr. 2011, 日本渡航医学会誌, 4(1) (1), 5 - 9, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 神戸海星病院小児科外来における外国人医療

  藤岡 一路

  (一社)日本渡航医学会, Apr. 2011, 日本渡航医学会誌, 4(1) (1), 1 - 4, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 集学的治療により救命しえたPotter sequenceの1例

  忍頂寺 毅史, 藤岡 一路, 橋村 裕也, 貝藤 裕史, 森岡 一朗, 野津 寛大, 横山 直樹, 飯島 一誠, 松尾 雅文

  日本小児腎不全学会, Aug. 2010, 日本小児腎不全学会雑誌, 30(0) (0), 178 - 180, Japanese


• Clinical Study of Apnea Attacks on Very Low Birth Weight Infants : Second : Report : Effect of Severe Apnea Attacks on Growth and Neurodevelopmental Outcome at 3 and 6 years of corrected age

  藤岡 一路, 石田 明人, 村瀬 真紀, 橋本 総子, 山内 淳, 豊嶋 大作, 湊川 誠

  日本未熟児新生児学会, 15 Jun. 2010, 日本未熟児新生児学会雑誌 = Journal of Japan Society for Premature and Newborn Medicine, 22(2) (2), 51 - 60, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 早産児無呼吸発作と神経学的予後に関する検討(第二報) 重症無呼吸発作が3歳時・6歳時における身体発育・精神運動発達に与える影響の検討

  藤岡 一路, 石田 明人, 村瀬 真紀, 橋本 総子, 山内 淳, 豊嶋 大作, 湊川 誠

  (一社)日本新生児成育医学会, Jun. 2010, 日本未熟児新生児学会雑誌, 22(2) (2), 229 - 238, Japanese


• 早産児無呼吸発作と神経学的予後に関する検討(第一報) 長期予後検討のための早産児無呼吸発作の実態把握

  藤岡 一路, 石田 明人, 村瀬 真紀, 橋本 総子, 山内 淳, 豊嶋 大作, 湊川 誠, 伊東 利幸

  (一社)日本新生児成育医学会, Feb. 2010, 日本未熟児新生児学会雑誌, 22(1) (1), 89 - 96, Japanese


• A Newborn Case of Hemophagocytic Lymphohistiocytosis with Idiopathic Pulmonary Hemosiderosis

  FUJIOKA Kazumichi, MORIOKA Ichiro, MIWA Akihiro, SAITO Atsuro, HASHIMOTO Fusako, MORIKAWA Satoru, SHIBATA Akio, YOKOYAMA Naoki, MATSUO Masafumi

  日本未熟児新生児学会, Feb. 2010, 日本未熟児新生児学会雑誌, 22(1) (1), 97 - 103, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 日齢14に発症した新生児甲状腺機能亢進症の1例

  長坂 美和子, 藤岡 一路, 森川 悟, 三輪 明弘, 柴田 暁男, 森岡 一朗, 横山 直樹, 松尾 雅文

  (公社)日本小児科学会, Dec. 2009, 日本小児科学会雑誌, 113(12) (12), 1895 - 1895, Japanese


• A first newborn delivered from a pregnant woman with novel influenza A (2009 pandemic H1N1) virus infection while being symptomatic in Japan : A newborn case with a use of oseltamivir

  MORIOKA Ichiro, MORIZANE Mayumi, YAMAZAKI Mineo, HASHIMOTO Fusako, SAITO Atsuro, FUJIOKA Kazumichi, MORIKAWA Satoru, MIWA Akihiro, SHIBATA Akio, YOKOYAMA Naoki, ARAKAWA Soichi, YAMADA Hideto, MATSUO Masafumi

  (一社)日本周産期・新生児医学会, Dec. 2009, 日本周産期・新生児医学会雑誌, 45(4) (4), 1514 - 1517, Japanese


• 感染対策 新生児感染症に対する超高速PCR装置を用いた迅速診断法の開発(第1報)

  森川 悟, 森岡 一朗, 榎本 真宏, 藤岡 一路, 三輪 明弘, 柴田 暁男, 横山 直樹, 西尾 久英, 松尾 雅文

  (一社)日本周産期・新生児医学会, Dec. 2009, 日本周産期・新生児医学会雑誌, 45(4) (4), 1176 - 1178, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 新生児内分泌 RAA系ホルモンの動態からみた一絨毛膜性双胎管理における体重差の意義

  藤岡 一路, 森岡 一朗, 森川 悟, 三輪 明弘, 榎本 真宏, 柴田 暁男, 横山 直樹, 松尾 雅文

  (一社)日本周産期・新生児医学会, Dec. 2009, 日本周産期・新生児医学会雑誌, 45(4) (4), 1271 - 1273, Japanese


• A case of severe hydrops fetalis with chylothorax, a nodular lesion in the liver, and unilateral multicystic kidney

  FUJIOKA Kazumichi, MORIOKA Ichiro, MORIKAWA Satoru, MIWA Akihiro, ENOMOTO Masahiro, SHIBATA Akio, SUZUKI Kaho, MATSUOKA Syozo, KONDO Takeshi, YOKOYAMA Naoki, MATSUO Masafumi

  日本周産期・新生児医学会, Aug. 2009, 日本周産期・新生児医学会雑誌, 45(3) (3), 888 - 894, Japanese


• 同種免疫性血小板減少症の1例

  藤岡一路, 村瀬真紀, 伊藤利幸, 湊川誠, 中岡総子, 山内淳, 豊嶋大作, 西山敦史, 神岡一郎, 住永亮, 石田明人

  (株)日本小児医事出版社, Jul. 2009, 小児科臨床, 62(7) (7), 1661 - 1665, Japanese

  Link to Kobe Univ. Repository (Kernel)


• Lessons from 6 suspected cases of congenital toxoplasmosis

  藤岡 一路, 村瀬 真紀, 伊東 利幸, 湊川 誠, 中岡 総子, 山内 淳, 豊嶋 大作, 西山 敦史, 神岡 一郎, 住永 亮, 石田 明人

  日本小児医事出版社, May 2009, Japanese journal of pediatrics, 62(5) (5), 937 - 942, Japanese


• 新型インフルエンザが地域で散発的に発生した場合のNICU医療者としての対応

  原田明佳, 北島順子, 佐藤歩, 添野愛基, 野矢三樹, 宮島悠子, 山本和歌子

  (一社)日本新生児成育医学会, Feb. 2009, 日本未熟児新生児学会雑誌, 21(1) (1), 142 - 145, Japanese

  Introduction other


• 無分葉型全前脳胞症の1例

  藤岡 一路, 中岡 総子, 山内 淳, 豊嶋 大作, 西山 敦史, 湊川 誠, 神岡 一郎, 伊東 利幸, 住永 亮, 村瀬 真紀, 石田 明人, 潤井 誠司郎

  加古川市民病院, Jan. 2008, 加古川市民病院誌, (8) (8), 1 - 4, Japanese

  Link to Kobe Univ. Repository (Kernel)


• 胎内腸重積による腸閉鎖にて穿孔性腹膜炎および短腸症候群を来たした一例

  豊嶋 大作, 樋上 敦紀, 牟禮 岳男, 湊川 誠, 伊東 利幸, 村瀬 真紀, 藤岡 一路, 伴 紘文, 金澤 育子, 福岡 一郎, 住永 亮, 石田 明人, 佐々木 康成, 久野 克也

  加古川市民病院, Jan. 2008, 加古川市民病院誌, (8) (8), 5 - 7, Japanese


• 当院で経験した結節性硬化症4例についての報告

  樋上 敦紀, 石田 明人, 住永 亮, 村瀬 真紀, 伊東 利幸, 湊川 誠, 神岡 一郎, 牟禮 岳男, 金澤 育子, 伴 紘文, 豊嶋 大作, 藤岡 一路

  加古川市民病院, Jan. 2007, 加古川市民病院誌, (7) (7), 1 - 3, Japanese


• 【周産期医学必修知識】新生児 血中ナトリウム異常症

  藤岡 一路, 中尾 秀人

  (株)東京医学社, Dec. 2006, 周産期医学, 36(増刊) (増刊), 659 - 660, Japanese


• 感染症 こう門蝿症の1例

  藤岡一路, 柴田暁男, えびら ひとみ, 津本尚美, 山岡利佳, 若槻真吾, 中村豊, 村上龍助

  (株)日本小児医事出版社, Nov. 2005, 小児科臨床, 58(11) (11), 2286 - 2288, Japanese

• 労力を無駄にしないための 臨床研究テーマの選び方: 論文執筆マニュアルを開く前に読みたい没ネタ回避術 (Cブックス)

  藤岡 一路

  Single work, メディカ出版, Aug. 2021, ISBN: 4840475784


• 産科婦人科疾患最新の治療2013-2015

  南江堂, May 2013, ISBN: 4524268960

  


• 子どもたちのための病院医療のポケットブック―限られた医療資源による一般的な病気の管理のためのガイドライン

  日本小児医事出版社, May 2010, ISBN: 4889242007

  

• 新規の長期間作用型抗RSウイルスモノクローナル抗体製剤 「ベイフォータス」への期待

  藤岡一路

  RSV Expert meeting in Hyogo, Jun. 2024

  [Invited]

  Public discourse


• 糞便懸濁液投与法を用いた早産児マウス敗血症モデルの確立と応用

  藤岡 一路

  第28回日本エンドトキシン・自然免疫研究会, Dec. 2023

  [Invited]

  Invited oral presentation


• 症候性先天性サイトメガロウイルス感染症に対するバルガンシクロビル治験の解説

  藤岡一路

  神戸市小児科医会・学術講演会2023, Jul. 2023

  [Invited]

  Invited oral presentation


• 私の小規模な失敗 〜労力を無駄にしないための臨床研究テーマの選び方〜

  藤岡 一路

  日本医療薬学会 第3回臨床研究セミナー「観察研究を始めてみよう」, Apr. 2023, Japanese

  [Invited]

  Public discourse


• 新生児研究と人材育成

  藤岡一路

  福島県NICU情報交換会, Mar. 2023

  [Invited]

  Invited oral presentation


• シンポジウム4 「打ち破れ、中小NICUだからこそできる研究プロダクト！」 Niche な目の付け所をどのように導き出すか

  藤岡一路

  第66回日本新生児成育医学会・学術集会, Nov. 2022, Japanese, (公社)日本新生児成育医学会, Domestic conference

  [Invited]

  Nominated symposium


• 「ショックに関する新しい側⾯からの臨床研究」⼀絨⽑膜性双胎における⽣後早期循環不全の内分泌学的検討

  藤岡 一路

  第36回日本Shock学会学術集会, May 2022

  [Invited]

  Nominated symposium


• 「ショックに関する基礎的研究の最先端」糞便懸濁液投与モデル（Cecal Slurry model）におけるヒトリコンビナントトロ ンボモジュリンの敗⾎症保護効果の検討

  藤岡 一路

  第36回日本Shock学会学術集会, May 2022

  [Invited]

  Nominated symposium


• 私の小規模な臨床研究

  藤岡 一路

  あいち新生児フォーラム, May 2022

  [Invited]

  Public discourse


• 電解質異常から発見する小児遺伝性腎疾患 新生児高カリウム血症の原因としての偽性低アルドステロン症Ⅰ型

  藤岡一路, 野津寛大

  第125回日本小児科学会学術集会, Apr. 2022

  [Invited]

  Nominated symposium


• 神戸から見た日本の新生児医療 〜出版・臨床・研究から見えてきたもの〜

  藤岡 一路

  令和3年度香川県新生児医療症例検討会, Feb. 2022

  [Invited]

  Public discourse


• 糞便懸濁液投与（Cecal Slurry）法により作製した非外科的敗血症モデルマウ スを用いた新生児敗血症の新規治療法開発

  藤岡 一路

  第21回新生児科指導医教育セミナー, Jan. 2022

  [Invited]

  Public discourse


• 少人数制講義 「統計」

  藤岡一路

  日本新生児成育医学会 第24回教育セミナー, Nov. 2021

  [Invited]

  Public discourse


• 新生児偽性低アルドステロン症

  藤岡 一路

  第65回日本新生児成育医学会・学術集会, May 2021, Japanese, (公社)日本新生児成育医学会

  [Invited]

  Invited oral presentation


• 一絨毛膜性双胎の新生児循環について

  藤岡 一路

  第10回神戸産婦人科臨床フォーラム, Jan. 2020

  [Invited]

  Public discourse


• 「エンドトキシン研究：ベンチサイドからのメッセージ」 糞便懸濁液投与（Cecal Slurry, CS）法を用いた早産児マウス敗血症モデルの作成と臨床課題への応用

  藤岡 一路

  第25回エンドトキシン・自然免疫研究会, Nov. 2019

  [Invited]

  Nominated symposium


• 後方視的研究を英文論文として採択させるために

  藤岡 一路

  第64回日本新生児成育医学会・学術集会, Nov. 2019, Japanese, (公社)日本新生児成育医学会

  [Invited]

  Public discourse


• 「研修医・専攻医が行う後方視的研究の実際」（仮説無きデータ蓄積から何かを生み出す工夫）

  藤岡 一路

  第二回近畿小児内分泌塾, Oct. 2019

  [Invited]

  Public discourse


• 新生児敗血症モデルマウスに対するTrained Immunity誘導の保護効果

  藤岡 一路, 芦名満理子, 宮内玄徳, 菅秀太郎, 阿部真也, 大山正平, 西田浩輔

  第26回外科侵襲とサイトカイン研究会, Jul. 2019

  Public symposium


• 研修医・専攻医が行う後方視的研究の実際

  藤岡 一路

  第2回 兵庫新生児セミナー, Jun. 2019

  [Invited]

  Public discourse


• 後方視的研究の手法 裏技!仮説なしデータ蓄積から始まる研究デザイン

  藤岡 一路

  第63回日本新生児成育医学会・学術集会, Nov. 2018, Japanese, (公社)日本新生児成育医学会

  [Invited]

  Public discourse


• 小児の感染症について〜新規抗インフルエンザウイルス剤も踏まえて〜

  藤岡 一路

  しおのぎKidsフォーラム, Nov. 2018

  [Invited]

  Public discourse


• NICU臨床の片手間で行う基礎研究・・・それってやる意味あるんですか！？

  藤岡 一路

  第1回 兵庫新生児セミナー, Aug. 2018

  [Invited]


• 生体侵襲とショックの基礎病態学、今 Cecal Slurry法を用いた早産児マウス敗血症モデルの利点と課題

  藤岡 一路

  第33回日本Shock学会総会, Jun. 2018, Japanese, (一社)日本Shock学会

  Public symposium


• 日常のNICUケアを再考する~経管栄養/サーファクタント投与/MD双胎管理~

  藤岡 一路

  第７回周産期セミナー ワンランク上のNICUケア, May 2018

  [Invited]

  Public discourse


• 小児の感染症について

  藤岡 一路

  平成30年度 第1回『兵庫地区薬剤師会研修会』, May 2018

  [Invited]


• 新生児分野で臨床応用が期待される基礎研究 Cecal slurry法を用いた早産児マウス敗血症モデルの作成と臨床応用

  藤岡 一路

  第121回日本小児科学会学術集会, Apr. 2018, Japanese, (公社)日本小児科学会

  [Invited]

  Nominated symposium


• 小児患者を扱う際のコツとポイント

  藤岡 一路

  兵庫県放射線技師会 第12回臨床学術講演会, Mar. 2018

  [Invited]


• 正期産児の退院時診察のポイントと１か月検診までの注意点

  藤岡 一路

  神戸市産婦人科医会講演会, Nov. 2017

  [Invited]

  Public discourse


• SGA児の長期予後 SGA児の胎盤における胎盤形成遺伝子Retrotransposon-like1(Rtl1)メチル化異常の検討

  藤岡 一路, 前山 花織, 西田 浩輔, 大山 正平, 福嶋 祥代, 山名 啓司, 黒川 大輔, 岩谷 壮太, 西村 範行, 飯島 一誠, 森岡 一朗

  第53回日本周産期・新生児医学会学術集会, Jul. 2017, Japanese, (一社)日本周産期・新生児医学会

  Public symposium


• 新生児疾患におけるHeme Oxygenase-1（HO-1）の役割

  藤岡 一路

  第8回新生児科指導医教育セミナー, May 2017

  [Invited]

  Public discourse


• 日本人Small-for-gestational age児における血管内皮増殖因子遺伝子多型の関与の検討

  藤岡 一路

  第59回日本未熟児新生児学会・学術集会, Nov. 2014, Japanese, (公社)日本新生児成育医学会

  [Invited]

  Invited oral presentation


• 産科早期退院の課題 新生児黄疸管理について考える 米国の現状

  藤岡 一路, 森岡 一朗

  第50回日本周産期・新生児医学会学術集会, Jul. 2014, Japanese, (一社)日本周産期・新生児医学会

  [Invited]

  Nominated symposium


• 佐多フェローシップキングスカレッジプログラム留学体験記 英国滞在で気づいたこと

  藤岡 一路

  第57回日本未熟児新生児学会・学術集会,, 2012

  [Invited]

  Invited oral presentation


• 新生児内分泌 RAA系ホルモンの動態からみた一絨毛膜性双胎管理における体重差の意義

  藤岡 一路, 森川 悟, 三輪 明弘, 榎本 真宏, 柴田 暁男, 森岡 一朗, 横山 直樹, 松尾 雅文

  第45回日本周産期・新生児医学会学術集会, Jul. 2009, Japanese, (一社)日本周産期・新生児医学会

  Public symposium

• JAPAN SOCIETY OF OBSTETRICS AND GYNECOLOGY


• JAPAN SOCIETY FOR NEONATAL HEALTH AND DEVELOPMENT


• THE JAPANESE SOCIETY FOR PEDIATRIC INFECTIOUS DISEASES


• The Japan Shock Society

• Pathogenesis of neonatal pseudohypoaldosteronism using urinary sediment cells of the patient and nenatal mouse kidneys

  藤岡 一路

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2023 - 31 Mar. 2026


• Extended exposure of preterm infants to maternal voice to improve neuro-developmental outcomes

  岩田 欧介, 岡村 尚昌, 國吉 康夫, 永田 雅子, 藤岡 一路, 日下 隆, 有光 威志, 荒木 由布子

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), Nagoya City University, 01 Apr. 2020 - 31 Mar. 2025

  本研究は，母親の歌や語り掛け・読み聞かせを編集加工・最適化し，生後早期から早産児に聞かせることによって，遠隔期の言語・認知機能が改善するかを，短期脳科学ツールと長期言語認知発達評価から詳細に検討するプロジェクトである．多施設での症例集積を予定していたが，Covid19パンデミックによる制約から，当面研究代表施設である名古屋市立大学病院NICUによる単施設研究として実施し，研究分担者では，得られたデータの解析・二次利用や，施設独自の関連研究を実施するよう軌道修正している．代表施設では，2020年度に倫理審査・機器整備を完了し，2021年度にパイロット研究による観察系の動作確認を行い，母親の語り掛けや読み聞かせを録音・加工するアルゴリズムが確立されている．Covid19パンデミックによる長引く面会停止により，症例のリクルートメントが中断しているが，2022年度は面会制限が緩和される見通しであり，状況の改善を待って症例リクルートメントを開始したい． 代表施設では，近赤外線分光法を用いたベッドサイドでの脳組織構造変化の評価法を確立する研究，生後1か月の健常児における環境と睡眠周期の関係を明らかにする研究，NICU入院時における自閉症スペクトラム障害発生状況の詳細評価に関する研究を関連研究として実施し，本研究で使用するポリグラフ・近赤外線スペクトロスコピーおよびアクチグラフのバリデーションを行うことができた（それぞれ国際査読誌に公表）．東京大学・静岡大学・香川大学・久留米大学チームは，本研究再開後に得られる検体アッセイおよびデータ解析法を確立している．神戸大学・慶応義塾大学チームは，新生児脳波を用いて遠隔期の高次脳機能を予測するプロジェクトを軌道に乗せ，成果を上げている．


• 疾患特異的iPS細胞を用いた先天性中枢性低換気症候群における低CO2感受性の分子機構

  日本医療研究開発機構(AMED), 再生医療実現拠点ネットワークプログラム, May 2021 - Mar. 2024, Principal investigator


• The Protective Role of Trained Immunity against Lethal Sepsis in Neonatal Mice

  藤岡 一路

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2020 - 31 Mar. 2023

  近年、少量のLPS等に暴露させ自然免疫系を活性化させ、感染防御効果を誘導するTrained Immunity(TI)の概念が注目されている。本研究の目的は、非致死量の糞便懸濁液（Cecal slurry, CS）を予め投与してTIを誘導した新生仔マウスに致死的敗血症を誘導して、TIの保護効果を検討することである。 本年度は、日齢3に0.5mg/g CS（非致死量, PTx群）または生食(Veh群)を前投与し、72時間後（7日齢）にCS 1.5mg/g(LD83)を投与し、敗血症誘導3, 6時間後の肝臓免疫関連遺伝子発現・炎症性脂質メディエーター発現を検討した。 肝臓PCRアレイ結果については、PTx群をVeh群と比較した場合は、敗血症誘導6時間後にPTx群において免疫関連遺伝子5種（Cd14, C5aR1, IL-1r1, Mx1, Irf7）の有意な発現抑制を認めた（fold change>4.0, p<0.05）。 敗血症誘導後の肝臓脂質メディエーター動態は、PTx群においてVeh群と比較し、敗血症誘導3時間後にアラキドン酸（AA）由来LM（15deoxy-d12,14 PGJ2）が有意に減少しており、敗血症誘導6時間後にエイコサペンタエン酸（EPA）由来LM4種（12-HEPE, 15-HEPE, 18-HEPE, EPA）、ドコサヘキサエン酸（DHA）由来LM5種（4-HDHA, 7-HDHA, 14-HDHA, 17-HDHA, DHA）、AA由来LM4種（5-HETE, 12-HETE, 15-HETE, AA）が有意に低下していた。 以上の結果より、軽微な先行感染は敗血症誘導6時間後の肝臓免疫関連遺伝子および炎症性脂質メディエーター発現を抑制することが明らかとなった。現時点では、本モデルにおけるTIの保護効果は、異常な全身性炎症反応の制御を介したものと考えている。


• Evaluation of pharmaceutical HO-1 induction and mesenchymal stem cell combination therapy in meconium peritonitis mouse model

  FUJIOKA KAZUMICHI

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists, Grant-in-Aid for Early-Career Scientists, Kobe University, 01 Apr. 2018 - 31 Mar. 2020

  Background: Meconium peritonitis is caused by leakage of meconium into the fetal peritoneal cavity due to intestinal perforation. Objective: To generate a neonatal mouse model of meconium peritonitis via IP administration of human meconium suspension or “slurry” (MS) by applying the CS methodology. Methods: Fresh meconium was suspended in PBS to 500 mg/mL. 200 μL of MS (meconium) or PBS (control) was administered IP to 4d-old wild-type FVB mice pups. Body weight and survivals was monitored. Results: Administration of MS resulted in significant decreases in weight gain and survival (0.8±7.5% (n=26), and 58.8% (n=34), respectively) compared with PBS controls (18.6±4.8% (n=10) and 100% (n=10), respectively). Conclusions: IP administration of MS resulted in significant mortality and weight loss to 4d-old newborn pups, and affects blood gasses and electrolytes. Therefore, we conclude that this MS model can be used to study the pathophysiology and treatment of meconium peritonitis.


• 新生児ビタミンK欠乏症性出血症の新規診断法の検討

  渡邊 優子, 藤岡 一路, 芦名 満理子

  日本学術振興会, 科学研究費助成事業 奨励研究, 奨励研究, 神戸大学, 2019 - 2019

  出血傾向のない日齢0～30日の新生児339人の残余血清計858件を、MU-Ⅲ抗体を用いたPIVKA-Ⅱ測定試薬(CLEIA法)で測定し、各日齢での血清PIVKA-Ⅱ濃度の中央値および95パーセントタイル値の経時的な基準曲線を導き出した。ビタミンK製剤の投与方法の違いにより、在胎週数37週未満の早産児と37週以上の正産期児で測定値を分けて比較したところ、各群において、ビタミンK製剤の影響のない日齢0日と比べ、ビタミンK製剤2回投与後の日齢5日では、PIVKA-Ⅱ濃度は有意に低下した。日齢5～30日の間にPIVKA-Ⅱ濃度は上昇しなかった。


• The role of Heme Oxygenase-1 in neonatal sepsis using preterm mouse model

  FUJIOKA KAZUMICHI

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up, Grant-in-Aid for Research Activity Start-up, Kobe University, 26 Aug. 2016 - 31 Mar. 2018

  To induce sepsis, the cecal slurry (CS) model was applied to 4d-old mouse pups. In brief, adult cecums were harvested, and their contents were diluted with PBS-glycerol for CS stock preparations. HO-1 heterozygote (Het, HO-1+/-) and wild-type (WT) mice were administered CS IP at a dose of 2.0-mg/g (LD40 for WT mice, Fujioka et al, Shock 47:242, 2017), and then monitored for survival. To study the protective role of HO-1 induction, 30-micro mol heme/kg was given to 3d-old pups of both genotypes 24h prior to sepsis induction. Treatment with 2.0-mg CS/g caused a significantly higher mortality in Het (85.0%) than WT (40.9%, p<0.01) pups. Most importantly, induction of HO-1 by heme significantly reduced mortality in both WT (6.3%) and Het (23.5%) pups. In addition, expression profiles measured using PCR arrays showed significant increases in cytokines in both genotypes 6h post-sepsis induction. This increase was generally attenuated in pups of both genotypes pre-treated with heme.


• 胎便性腹膜炎モデルマウスに対する薬物的ヘムオキシゲナーゼ-1誘導/間葉系幹細胞投与併用療法の開発

  藤岡 一路

  公益財団法人 川野小児医学奨学財団, 川野正登記念研究助成金若手枠, 2018, Principal investigator

  Competitive research funding


• モデルマウス及び患者検体を用いた胎便性腹膜炎の病態解明と新規治療法の開発 副題：胎便性腹膜炎モデルマウスに対する薬物的ヘムオキシゲナーゼ‐1誘導/間葉系幹細胞投与併用療法の開発

  藤岡 一路

  公益財団法人 小児医学研究振興財団, 研究助成金, 2017, Principal investigator

  Competitive research funding


• A study regarding aberrant methylation of Retrotransposon-like 1 gene in human placentas of intrauterine growth restriction

  FUJIOKA Kazumichi

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 2011 - 2012

  A purpose of this study was to clarify the aberrant methylation of Retrotransposon-like 1 gene (Rtl1) in human placenta of intrauterine growth retardation (IUGR). We could not find different methylation pattern of Rtl1in human placentas of IUGR and healthy newborns. However, we detected the VEGFand RASpolymorphisms that are associated with IUGR.


• The relationship between N-terminal prohormone brain natriuretic peptide levels at birth and postnatal cardiac dysfunction in monochorionic diamniotic twins

  Kazumichi Fujioka

  The Kobe Shinryokukai Association, 研究助成金, 2012, Principal investigator

  Competitive research funding


• A study regarding the expressions of Sirt-1 gene in the patient with intrauterine growth restriction

  Kazumichi Fujioka

  The Morinaga Hoshi-kai Foundation in Japan, 研究奨励金, 2010 - 2011, Principal investigator

  Competitive research funding


• Novel genes of placenta in intrauterine growth restriction

  Kazumichi Fujioka

  Kobe University, The Support Program for Improving Graduate School Education, 2009 - 2011, Principal investigator

  Competitive research funding


• A study regarding gene expressions of Retrotransposon-like 1 in human placentas of intrauterine growth restriction

  MORIOKA Ichiro, FUJIOKA Kazumichi

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 2009 - 2010

  A purpose of this study was to find abnormal expressions of Retrotransposon-like 1 gene (Rtl1) in human placentas of intrauterine growth restriction (IUGR). We found for the first time that different expressions of Rtl1 were observed in human placentas of IUGR and healthy newborns.

• Frontiers Topic Editor

  Frontiers Topic Editor

  Frontiers in Pediatrics

  Feb. 2022 - Present

  Peer review etc


• Editorial Board member

  Editorial Board member

  PeerJ - Life and Environment

  Jul. 2021 - Present


• Academic Editor

  Academic Editor

  PLOS ONE

  Sep. 2020 - Present


• Associate Editor

  Associate Editor

  BMC Pediatrics

  May 2020 - Present


• Editor (Pediatrics and neonatology Section)

  Editor (Pediatrics and neonatology Section)

  Open Medicine

  Apr. 2020 - Present


• Guest Editor

  Guest Editor

  International Journal of Environmental Research and Public Health

  Nov. 2020 - Dec. 2021

  Peer review etc


• Review Editor

  Review Editor

  Frontiers in Pediatrics

  Oct. 2019