Research activity information

• Oct. 2023 The 22nd Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS 2023), Outstanding Congress Awards, Viral Load Change during Antiviral Therapy Is Not Useful for the Prediction of Hearing Dysfunction in Symptomatic Congenital Cytomegalovirus Infection

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

• Prepregnancy obesity is an independent risk factor for neonatal vitamin K deficiency at birth.

  Yu Masuda, Mariko Ashina, Yukihito Imagawa, Keisuke Shirai, Yuki Nakata, Takumi Kido, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka

  BACKGROUND: Neonatal vitamin K deficiency (VKD) is a known risk factor for vitamin K deficiency bleeding (VKDB), a potentially life-threatening condition. However, maternal risk factors for VKD at birth remain poorly understood. OBJECTIVE: This study aimed to identify maternal factors associated with neonatal VKD at birth, with a focus on prepregnancy obesity. METHODS: We conducted a retrospective matched case-control study of neonates admitted to our hospital between 2018 and 2023. VKD was defined as serum protein induced by vitamin K absence-II (PIVKA-II) levels ≥1000 mAU/mL on day 0 of life before vitamin K administration. For each VKD case, two gestational age- and sex-matched controls were selected. Maternal background characteristics were compared, and multivariate logistic regression was performed to identify independent risk factors for neonatal VKD. RESULTS: Among 64 neonates with VKD and 128 controls, maternal prepregnancy obesity (body mass index ≥25) was significantly more common in the VKD group. Multivariate analysis identified prepregnancy obesity as an independent risk factor for neonatal VKD (odds ratio 3.97, P < 0.001). Additionally, maternal prepregnancy BMI was positively correlated with neonatal PIVKA-II levels at birth (r = 0.285, P < 0.0001). CONCLUSIONS: Maternal prepregnancy obesity is independently associated with an increased risk of VKD in neonates at birth. These findings suggest that targeted evaluation and vitamin K management strategies are warranted in pregnancies complicated by maternal obesity.

  Feb. 2026, Nutrition (Burbank, Los Angeles County, Calif.), 142, 112954 - 112954, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Changes in Neutrophil Count During Valganciclovir Therapy for Symptomatic Congenital Cytomegalovirus Infection.

  Aoi Kawamura, Shinya Abe, Keisuke Shirai, Yu Masuda, Yukihito Imagawa, Yuki Nakata, Takumi Kido, Mariko Ashina, Hisayuki Matsumoto, Kenji Tanimura, Yasumasa Kakei, Takumi Imai, Kandai Nozu, Kazumichi Fujioka

  Background/Objectives: Neutropenia is a common adverse effect of oral valganciclovir (VGCV) treatment in infants with congenital cytomegalovirus infection (CCMVI), with an estimated prevalence of 20%. However, its clinical course and associated factors, including the influence of VGCV dosage, remain inadequately characterized. Methods: We conducted a single-center retrospective cohort study of infants treated with VGCV for symptomatic congenital CMV infection (CCMVI) at the Kobe University Hospital between 1 April 2009 and 31 March 2017. Detailed descriptive analyses of neutropenia were performed, and factors associated with its onset were explored using univariable logistic regression analyses. Results: A total of 31 patients were included, and neutropenia occurred in 35% of them during the 6-week treatment period. Its occurrence was observed throughout the treatment course, with no substantial difference in incidence between the 16 mg/kg/day and 32 mg/kg/day dosing groups. Neutropenia was more likely to occur in infants with shorter gestational age. Conclusions: Neutropenia occurred in 35% of patients during 6 weeks of VGCV treatment, irrespective of dosage, and was more common in those with shorter gestational age.

  Jul. 2025, Biomedicines, 13(7) (7), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 新生児が呈した代謝性アルカローシスより母親のトラセミド自己内服が疑われた一例

  橋本 真梨, 北廣 優実, 尊田 有香子, 八木 美樹, 糸原 光太郎, 城戸 拓海, 藤岡 一路, 今福 仁美, 大村 友博, 矢野 育子

  (一社)日本TDM学会, Jul. 2025, TDM研究, 42(2) (2), 194 - 194, Japanese


• Clinical and Biochemical Characteristics of Pseudohypoaldosteronism Type 1 with and Without Genetic Mutations: A Literature Review.

  Yuki Nakata, China Nagano, Yukihito Imagawa, Keisuke Shirai, Yu Masuda, Takumi Kido, Mariko Ashina, Kandai Nozu, Kazumichi Fujioka

  Background/Objectives: Pseudohypoaldosteronism type 1 (PHA-1) is a rare disorder characterized by aldosterone resistance, leading to hyponatremia, hyperkalemia, and elevated renin and aldosterone levels in neonates and infants. While genetic mutations in NR3C2 (mineralocorticoid receptor, MR) and SCNN1A/B/G (epithelial sodium channel, ENaC) are established causes of primary PHA-1, cases without detectable mutations have also been reported. This study aimed to compare the clinical characteristics of genetically confirmed PHA-1 cases-with or without mutations-and to assess genotype-phenotype correlations. Methods: A literature review was conducted using the Medline database, covering studies published from 1966 to October 2023. Included cases were diagnosed with PHA-1 and had undergone genetic testing for NR3C2 and SCNN1A/B/G. Clinical and biochemical data were compared across three groups: MR, ENaC, and non-mutation. Additional subgroup analysis based on mutation type (truncating vs. non-truncating) was also performed. Results: A total of 164 patients from 64 studies met the inclusion criteria. The ENaC group showed significantly higher serum potassium levels than the MR and non-mutation groups. Serum aldosterone levels were significantly higher in the MR group compared to the non-mutation group. A genotype-phenotype correlation was evident in the ENaC group, with truncating variants associated with more severe hyperkalemia. No such correlation was observed in the MR group. Conclusions: This review highlights distinct clinical features of PHA-1 according to genetic status. Aldosterone levels may aid in guiding decisions regarding genetic testing. Furthermore, variant type in ENaC-related PHA-1 may predict biochemical severity and should be considered in clinical management strategies.

  Jun. 2025, Journal of clinical medicine, 14(13) (13), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 当院で経験した無症候性先天性サイトメガロウイルス感染症児における発達遅滞の検討

  城戸 拓海, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2025, 日本周産期・新生児医学会雑誌, 61(Suppl.1) (Suppl.1), P299 - P299, Japanese


• 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)


• A neonatal mouse model of meconium peritonitis generated using human meconium slurry.

  Mariko Ashina, Takumi Kido, Keisuke Shirai, Yu Masuda, Yukihito Imagawa, Yuki Nakata, Kandai Nozu, Kazumichi Fujioka

  BACKGROUND: Meconium peritonitis is a noninfectious chemical peritonitis that occurs following fetal intestinal perforation and leakage of meconium into the abdominal cavity. Because of the lack of appropriate animal models, its pathophysiology has not yet been elucidated. We aimed to create a neonatal mouse model of meconium peritonitis using human meconium slurry (MS). METHODS: A stock MS solution prepared from fresh meconium obtained from healthy term infants was administered intraperitoneally to 4-d-old newborn mice. An MS LD40 was then administered, and changes in body weight, hematology, serum biochemistry, and immunomodulatory gene expression were determined. The MS was subjected to antibiotic treatment and heat inactivation to validate the content. Finally, comparisons with nonsurgical neonatal sepsis mouse models were performed. RESULTS: Dose-dependent mortality rates were observed, with an LD40 of 200 µL/body weight established. Substantial hematological and hepatorenal abnormalities and increased inflammatory gene expression were observed. Although antibiotic treatment was ineffective, the survival rate was improved by enzymatic inactivation of MS. Importantly, the systemic responses to MS were distinct from those observed in neonatal sepsis model mice. CONCLUSION: The MS model closely reflects the pathology of human neonatal meconium peritonitis and maybe useful in research elucidating the pathophysiology of this condition. IMPACT: In this study, we generated a neonatal mouse model of meconium peritonitis through intraperitoneal administration of human meconium slurry. We clarified that the pathogenic agent in meconium slurry is mainly a digestive enzyme, and that the systemic responses elicited by meconium slurry were distinct from those in a neonatal sepsis mouse model. As our mouse model is simple and highly reproducible, it is useful for elucidating the pathophysiology of meconium peritonitis.

  Apr. 2025, Pediatric research, 97(5) (5), 1742 - 1749, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 乳児血管腫に対して,早期にプロプラノロール内服療法を行った超早産児の1例

  鳥井 大輝, 中田 有紀, 今川 幸人, 増田 祐, 白井 佳祐, 城戸 拓海, 芦名 満理子, 野津 寛大, 藤岡 一路

  兵庫県小児科医会, 2025, 兵庫県小児科医会報, (83) (83), 35 - 40, Japanese


• 妊娠後期の短期間のルイボスティー摂取による動脈管早期収縮が疑われた1例

  渡邊 侑奈, 城戸 拓海, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 野津 寛大, 藤岡 一路

  兵庫県小児科医会, 2025, 兵庫県小児科医会報, (83) (83), 41 - 47, Japanese


• 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.

  Nov. 2024, The Pediatric infectious disease journal, 43(11) (11), e390-e396, English, International magazine

  Scientific journal


• 当院で経験した無症候性先天性サイトメガロウイルス感染症児における遅発性難聴の検討

  城戸 拓海, 鳥井 大輝, 渡邊 侑奈, 藤本 将史, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 藤岡 一路

  (公社)日本新生児成育医学会, Oct. 2024, 日本新生児成育医学会雑誌, 36(3) (3), 562 - 562, Japanese


• 羊水中8-OHdG値測定と新生児呼吸障害の予測

  城戸 拓海, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 藤岡 一路

  (一社)日本周産期・新生児医学会, Jun. 2024, 日本周産期・新生児医学会雑誌, 60(Suppl.1) (Suppl.1), P276 - P276, Japanese


• 【要点が分かる&ケアに生かせる 新生児スタッフが知っておきたいガイドライン7選】先天性サイトメガロウイルス感染症ガイドライン

  城戸 拓海, 藤岡 一路

  (株)メディカ出版, Apr. 2024, with NEO, 37(2) (2), 163 - 166, Japanese


• 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


• 生直後から右肺上葉の無気肺を認め遷延した新生児の一例

  高原 結子, 城戸 拓海, 酒井 善紀, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 野津 寛大, 藤岡 一路

  兵庫県小児科医会, 2024, 兵庫県小児科医会報, (81) (81), 41 - 46, Japanese


• 長期間の呼吸循環管理を要した特発性動脈管早期閉鎖症の一例

  高橋 愛音, 城戸 拓海, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 野津 寛大, 藤岡 一路

  兵庫県小児科医会, 2024, 兵庫県小児科医会報, (82) (82), 19 - 24, 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

  松浦 春香, 仲宗根 瑠花, 福田 拓弥, 垂井 智前, 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

  兵庫県小児科医会, 2024, 兵庫県小児科医会報, (82) (82), 31 - 37, Japanese


• 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

  Scientific journal


• 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


• 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

  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


• Impact after the Change from Voluntary to Universal Oral Rotavirus Vaccination on Consecutive Emergency Department Visits for Acute Gastroenteritis among Children in Kobe City, Japan (2016-2022).

  Hiroshi Yamaguchi, Kandai Nozu, Hiroaki Hanafusa, Yoshinori Nambu, Takumi Kido, Atsushi Kondo, Akihiro Tamura, Hiroyuki Awano, Ichiro Morioka, Hiroaki Nagase, Akihito Ishida

  Rotavirus (RV) is the leading cause of acute gastroenteritis (AGE), particularly in infants. In 2006, the high efficacy of oral RV vaccines (RVVs, RotarixTM and RotaTeqTM) was demonstrated. Voluntary RVV started in Japan in 2011, and in October 2020 were launched as universal oral RVVs in Japan. However, the impact of changes from voluntary to universal RVVs has not been studied in a primary emergency medical center in Japan. We investigated changes in the number of pediatric patients with AGE after introducing universal RVVs in our center. A clinical database of consecutive patients aged <16 who presented to Kobe Children’s Primary Emergency Medical Center between 1 April 2016 and 30 June 2022 was reviewed. After implementing universal RVVs, fewer children presented with RV-associated AGE (the reduction of proportion of the patients in 2022 was −61.7% (all ages), −57.9% (<1 years), −67.8% (1−<3 years), and −61.4% (3−<5 years) compared to 2019). A similar decrease in those of age who were not covered by the universal RVV was observed. There was a significant decline in the number of patients with AGE during the RV season who presented to the emergency department after implementing universal RVVs.

  Oct. 2022, Vaccines, 10(11) (11), English, International magazine

  Scientific journal


• 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


• 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


• 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


• 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


• 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


• 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


• 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


• 受容的対応が奏功した標準的治療に拒否的な重症アトピー性皮膚炎患者の1例

  増田 知佳, 橋本 総子, 北角 英晶, 本郷 裕斗, 城戸 拓海, 藤村 順也, 松本 和徳, 金川 温子, 平田 量子, 中尻 智史, 沖田 空, 阪田 美穂, 親里 嘉展, 西山 敦史, 米谷 昌彦

  兵庫県小児科医会, 2020, 兵庫県小児科医会報, (73) (73), 12 - 18, Japanese


• 一般市中病院小児科におけるドクターカー運用

  城戸 拓海, 西山 敦史, 藤村 順也, 松本 和徳, 金川 温子, 中尻 智史, 平田 量子, 石森 真吾, 橋本 総子, 沖田 空, 阪田 美穂, 親里 嘉展, 中田 一弥, 切田 学, 米谷 昌彦

  兵庫県小児科医会, 2020, 兵庫県小児科医会報, (73) (73), 26 - 31, Japanese


• 熱中症を契機に診断された結晶誘発性関節炎の1例

  城戸 拓海, 切田 学

  (一社)日本集中治療医学会, Jan. 2016, 日本集中治療医学会雑誌, 23(Suppl.) (Suppl.), 703 - 703, Japanese

• 患者由来iPS細胞を用いた先天性中枢性低換気症候群の病態メカニズムの解析

  城戸拓海, 城戸拓海, 小柳三千代, 藤岡一路, 青井貴之

  2023, 日本再生医療学会総会(Web), 22nd


• 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, 小柳三千代, 藤岡一路, 荒田晶子, 青井貴之

  2022, 日本再生医療学会総会(Web), 21st


• 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

  過去10年間の精神疾患合併妊婦の出生児184名を対象に、自宅退院困難に関連する要因について検討を行った。その結果、乳児院入所或いは特別養子縁組の転帰となった自宅退院困難群は6名(3.3%)であった。自宅困難群では[シングルマザー][配偶者の精神疾患罹患][妊娠中の保護入院]が有意に多く、自宅困難と最も関連していたのは[シングルマザー][妊娠中の医療保護入院]であった。以上より、[シングルマザー][妊娠中の医療保護入院]の条件を有する精神疾患合併妊婦には積極的なサポートが必要と考えられた。

  (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

• 【要点が分かる&ケアに生かせる 新生児スタッフが知っておきたいガイドライン7選】先天性サイトメガロウイルス感染症ガイドライン

  城戸 拓海, 藤岡 一路

  (株)メディカ出版, Apr. 2024, Japanese, ISBN: 9784840482578

• 当院で経験した無症候性先天性サイトメガロウイルス感染症児における発達遅滞の検討

  城戸 拓海, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 藤岡 一路

  日本周産期・新生児医学会雑誌, Jun. 2025, Japanese, (一社)日本周産期・新生児医学会


• 当院で経験した無症候性先天性サイトメガロウイルス感染症児における遅発性難聴の検討

  城戸 拓海, 鳥井 大輝, 渡邊 侑奈, 藤本 将史, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 藤岡 一路

  日本新生児成育医学会雑誌, Oct. 2024, Japanese, (公社)日本新生児成育医学会


• 羊水中8-OHdG値測定と新生児呼吸障害の予測

  城戸 拓海, 今川 幸人, 白井 佳祐, 増田 祐, 中田 有紀, 芦名 満理子, 藤岡 一路

  日本周産期・新生児医学会雑誌, Jun. 2024, Japanese, (一社)日本周産期・新生児医学会


• Establishment of PHOX2B-GFP reporter iPS cell lines derived from healthy individuals and congenital central hypoventilation syndrome patients.

  Takumi Kido, Yukito Imagawa, Michiyo Koyanagi, Takashi Aoi, Kazumichi Fujioka

  The 22nd Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS 2023), Oct. 2023, English

  Poster presentation


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

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

  The 22nd Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS 2023), Oct. 2023, English

  Oral presentation


• 患者由来iPS細胞を用いた先天性中枢性低換気症候群の病態メカニズムの解析

  城戸拓海, 城戸拓海, 小柳三千代, 藤岡一路, 青井貴之

  日本再生医療学会総会(Web), 2023


• 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

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


• 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

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


• 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

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


• 超早期発症炎症性腸疾患の1新生児例

  城戸 拓海, 本郷 裕斗, 西田 浩輔, 大西 徳子, 小寺 孝幸, 森川 悟, 佐藤 有美, 森沢 猛, 米谷 昌彦

  日本小児科学会雑誌, Mar. 2019, Japanese, (公社)日本小児科学会


• High flow nasal cannulaと口腔・食道内持続吸引が有効であった食道閉鎖症の1例

  城戸 拓海, 小寺 孝幸, 本郷 裕斗, 西田 浩輔, 大西 徳子, 森川 悟, 岩出 珠幾, 佐藤 有美, 森沢 猛, 安福 正男, 久野 克也, 米谷 昌彦

  日本小児科学会雑誌, Mar. 2019, Japanese, (公社)日本小児科学会


• 一般市中病院における小児患者に対するドクターカー運用の現状と課題

  城戸 拓海, 藤村 順也, 前田 晶子, 増田 知佳, 本郷 裕斗, 松本 和徳, 金川 温子, 中尻 智史, 平田 量子, 橋本 総子, 沖田 空, 阪田 美穂, 親里 嘉展, 西山 敦史, 米谷 昌彦

  日本小児科学会雑誌, Feb. 2019, Japanese, (公社)日本小児科学会


• 超早期発症型炎症性腸疾患の1新生児例

  城戸 拓海, 森沢 猛, 松本 朋子, 吉田 阿寿美, 増田 祥行, 小寺 孝幸, 山名 啓司, 森川 悟, 佐藤 有美, 米谷 昌彦

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


• 在宅医療へ向けて経口Prostaglandin E1製剤によりLipo-PGE1持続静注から離脱できた肺動脈閉鎖兼心室中隔欠損症合併13トリソミーの1例

  城戸 拓海, 本郷 裕斗, 西田 浩輔, 大西 徳子, 小寺 孝幸, 森川 悟, 佐藤 有美, 森沢 猛, 米谷 昌彦

  日本新生児成育医学会雑誌, Oct. 2017, Japanese, (公社)日本新生児成育医学会