Papers - SATO, Yoshiaki

Next-generation sequencing-based detection of Ureaplasma in the gastric fluid of neonates with respiratory distress and chorioamnionitis. Reviewed International journal

Toshihiko Okumura, Kazuhiro Horiba, Nobuyuki Tetsuka, Yoshiaki Sato, Yuichiro Sugiyama, Kazunori Haruta, Makoto Yamaguchi, Takako Suzuki, Yuka Torii, Jun-Ichi Kawada, Tomoo Ogi, Masahiro Hayakawa, Yoshinori Ito

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   Vol. 36 ( 1 ) page： 2207113 - 2207113   2023.12

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BACKGROUND: Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. OBJECTIVE: The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. METHODS: Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. RESULTS: Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. CONCLUSION: Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.

DOI： 10.1080/14767058.2023.2207113

PubMed

Antenatal corticosteroids and outcomes of small for gestational age infants born at 24-31 gestational weeks: a population-based propensity score matching analysis. Reviewed International journal

Takafumi Ushida, Masahiro Nakatochi, Yumiko Kobayashi, Noriyuki Nakamura, Kazuya Fuma, Yukako Iitani, Kenji Imai, Yoshiaki Sato, Masahiro Hayakawa, Hiroaki Kajiyama, Tomomi Kotani

Archives of gynecology and obstetrics   Vol. 308 ( 5 ) page： 1463 - 1471   2023.11

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PURPOSE: To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24-31 gestational weeks compared with non-SGA infants. METHODS: A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500 g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. RESULTS: In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50-0.88] and 0.62 [0.50-0.78], respectively), respiratory distress syndrome (0.77 [0.69-0.87] and 0.63 [0.58-0.68], respectively), and composite adverse outcomes (0.73 [0.58-0.91] and 0.57 [0.50-0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. CONCLUSIONS: ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants.

DOI： 10.1007/s00404-022-06834-4

PubMed

Various Organ Damages in Rats with Fetal Growth Restriction and Their Slight Attenuation by Bifidobacterium breve Supplementation. Reviewed

Tsuji M, Tanaka N, Koike H, Sato Y, Shimoyama Y, Itoh A

Life (Basel, Switzerland)   Vol. 13 ( 10 )   2023.10

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DOI： 10.3390/life13102005

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Systemic administration of clinical-grade multilineage-differentiating stress-enduring cells ameliorates hypoxic-ischemic brain injury in neonatal rats. Reviewed International journal

Kazuto Ueda, Yoshiaki Sato, Shinobu Shimizu, Toshihiko Suzuki, Atsuto Onoda, Ryosuke Miura, Shoji Go, Haruka Mimatsu, Yuma Kitase, Yuta Yamashita, Keiichi Irie, Masahiro Tsuji, Kenichi Mishima, Masaaki Mizuno, Yoshiyuki Takahashi, Mari Dezawa, Masahiro Hayakawa

Scientific reports   Vol. 13 ( 1 ) page： 14958 - 14958   2023.9

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Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic-ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.

DOI： 10.1038/s41598-023-41026-3

PubMed

Vascular perforation of umbilical venous catheter and awaiting it to be shallow. Reviewed

Taniguchi A, Hayakawa M, Sato Y

Nagoya journal of medical science   Vol. 85 ( 3 ) page： 635 - 638   2023.8

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DOI： 10.18999/nagjms.85.3.635

PubMed

Dedifferentiated fat cells administration ameliorates abnormal expressions of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis Reviewed

Haruka Mimatsu, Atsuto Onoda, Tomohiko Kazama, Koji Nishijima, Yoshie Shimoyama, Shoji Go, Kazuto Ueda, Yoshiyuki Takahashi, Taro Matsumoto, Masahiro Hayakawa, Yoshiaki Sato

Scientific Reports   Vol. 13 ( 1 ) page： 8266   2023.5

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Abstract

Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C–C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation.

DOI： 10.1038/s41598-023-34156-1

PubMed

Other Link： https://www.nature.com/articles/s41598-023-34156-1

Antenatal corticosteroids-to-delivery interval associates cord blood S100B levels. Reviewed International journal

Kazuya Fuma, Tomomi Kotani, Takafumi Ushida, Kenji Imai, Yukako Iitani, Noriyuki Nakamura, Rika Miki, Satoru Katsuki, Fumie Kinoshita, Yoshiaki Sato, Masahiro Hayakawa, Hiroaki Kajiyama

The journal of obstetrics and gynaecology research   Vol. 49 ( 4 ) page： 1129 - 1136   2023.4

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AIM: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS-to-delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS-to-delivery interval on cord blood S100 calcium-binding protein B (S100B) levels as a biomarker of brain damage. METHODS: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS-to-delivery interval, retrospectively: non-ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. RESULTS: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non-ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). CONCLUSIONS: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms.

DOI： 10.1111/jog.15582

PubMed

Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight. Reviewed

Tsuji M, Mukai T, Sato Y, Azuma Y, Yamamoto S, Cayetanot F, Bodineau L, Onoda A, Nagamura-Inoue T, Coq JO

Scientific reports   Vol. 13 ( 1 ) page： 3841   2023.3

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DOI： 10.1038/s41598-023-30817-3

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Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats. Reviewed International journal

Mahboba Jabary, Atsuto Onoda, Yuma Kitase, Kazuto Ueda, Haruka Mimatsu, Shoji Go, Ryosuke Miura, Masahiro Tsuji, Yoshiyuki Takahashi, Masahiro Hayakawa, Yoshiaki Sato

Scientific reports   Vol. 13 ( 1 ) page： 2732 - 2732   2023.2

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Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance; however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats.

DOI： 10.1038/s41598-023-28584-2

PubMed

Refractory pneumothorax due to tracheal laceration in extremely preterm infant. Reviewed

Maeda T, Suzuki T, Mizutani K, Hasegawa H, Sato Y

Pediatrics international : official journal of the Japan Pediatric Society   Vol. 65 ( 1 ) page： e15698   2023.1

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DOI： 10.1111/ped.15698

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Case report: High-dose epoprostenol therapy in pediatric patients with pulmonary hypertension and developmental lung disease Reviewed

Yoshie Fukasawa, Hidenori Yamamoto, Miharu Ito, Akiko Saito, Kiyotaka Go, Yoshihito Morimoto, Kazushi Yasuda, Yoshiaki Sato, Masahiro Hayakawa, Taichi Kato

Frontiers in Pediatrics   Vol. 11   page： 1116434   2023

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Pulmonary hypertension (PH) with developmental lung disease is a life-threatening disease and accounts for 10%–12% of pediatric PH patients. Administration of specific pulmonary vasodilators to pediatric PH patients has brought about improvement of their long-term prognosis. Intravenous epoprostenol therapy is a gold standard therapy for severe idiopathic pulmonary arterial hypertension (IPAH), but there are few reports demonstrating the efficacy of epoprostenol for pediatric PH patients with developmental lung disease, especially when treating with high doses of epoprostenol. Two cases of pediatric PH patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and congenital diaphragmatic hernia (CDH) with bronchopulmonary dysplasia (BPD), respectively, treated with epoprostenol above 100 ng/kg/min are presented. In these two cases, severe PH was improved significantly by an aggressive increase of the epoprostenol infusion rate with administration of oral pulmonary vasodilators and appropriate respiratory management, without any significant adverse effects. High-dose epoprostenol therapy may be one of the therapeutic options in pediatric PH patients with developmental lung disease.

DOI： 10.3389/fped.2023.1116434

PubMed

Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model Reviewed

Noriyuki Nakamura, Takafumi Ushida, Atsuto Onoda, Kazuto Ueda, Ryosuke Miura, Toshihiko Suzuki, Satoru Katsuki, Hidesuke Mizutani, Kosuke Yoshida, Sho Tano, Yukako Iitani, Kenji Imai, Masahiro Hayakawa, Hiroaki Kajiyama, Yoshiaki Sato, Tomomi Kotani

Frontiers in Pediatrics   Vol. 11   page： 1168173   2023

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Introduction

To investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid.

Methods

Pregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15–20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring.

Results

Offspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p &amp;lt; 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p &amp;lt; 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p &amp;lt; 0.01, p &amp;lt; 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease.

Conclusion

The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.

DOI： 10.3389/fped.2023.1168173

PubMed

末梢挿入式中心静脈カテーテル(PICC)長期留置後の抜去困難症例　PICC抜去困難症の対応手順の作成 Reviewed

橋本佑樹、村松友佳子、伊藤美春、齊藤明子、佐藤義朗、早川昌弘

日本新生児成育医学会雑誌   Vol. 35 ( 1 ) page： 91－94   2023

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

Shoko Ozeki, Jun-ichi Kawada, Daiki Yamashita, Chika Yasufuku, Takuya Akano, Masahiro Kato, Konomi Suzuki, Chihiro Tano, Kazuki Matsumoto, Shu-hei Mizutani, Ayumi Mori, Nobuhiro Nishio, Hiroyuki Kidokoro, Yoshihiro Yasui, Yoshiyuki Takahashi, Yoshiaki Sato, Anna Shiraki, Kazuto Ueda, Shotaro Ando, Noriko Nagai, Tsutomu Aoshima, Michio Suzuki, Tetsuo Kubota, Motomasa Suzuki, Satoru Doi, Daichi Fukumi, Yuichiro Sugiyama, Masafumi Morishita, Naoko Nishimura, Mizuki Takagi, Hirokazu Kurahashi, Yohei Takeuchi, Kenji Kuraishi, Osamu Shinohara, Takashi Kawabe, Nobuhiro Watanabe, Shinji Hasegawa, Taichiro Muto, Shinji Kido, Shinya Hara, Shin Hoshino

Open Forum Infectious Diseases   Vol. 9 ( 11 ) page： ofac562   2022.11

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Abstract

Background

Mitigation measures implemented during the coronavirus disease 2019 (COVID-19) pandemic remarkably reduced the incidence of infectious diseases among children. However, a re-emergence of respiratory syncytial virus (RSV) infection was observed in 2021 in Japan. We compared the clinical characteristics of hospitalized patients with RSV infection before and during COVID-19.

Methods

We retrospectively enrolled children aged &amp;lt;6 years who were hospitalized with RSV infection in 18 hospitals and compared their clinical characteristics before (January 2019 to April 2020, 1675 patients) and during COVID-19 (September 2020 to December 2021, 1297 patients).

Results

The mean age of patients with RSV infection was significantly higher during COVID-19 than before (17.4 vs 13.7 months, P &amp;lt; .001). Compared with before COVID-19, a 2.6-fold increase in RSV cases in the 2–5 years age group was observed from sentinel surveillance during COVID-19, whereas a 1.2-fold increase was noted in the same age group among hospitalized patients. On average for all patients, consolidation shadows obtained on radiography were less frequently observed (26.1 vs 29.6%, P = .04), and reduced respiratory assistance (42.2% vs 48.7%, P &amp;lt; .001) and hospitalization stay (5.7 vs 6.0 days, P &amp;lt; .001) was required in patients with RSV infection during COVID-19.

Conclusions

Coronavirus disease 2019 and social activity restriction caused epidemiological changes in pediatric RSV infections, and a majority of patients with RSV infection aged ≥2 years did not develop severe symptoms requiring hospitalization. The RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons.

DOI： 10.1093/ofid/ofac562

PubMed

Other Link： https://academic.oup.com/ofid/article-pdf/9/11/ofac562/47043659/ofac562.pdf

Impact of hypertensive disorders of pregnancy on respiratory outcomes in extremely and very preterm infants: A population-based study in Japan. Reviewed International journal

Takafumi Ushida, Noriyuki Nakamura, Masahiro Nakatochi, Yumiko Kobayashi, Yoshiaki Sato, Yukako Iitani, Kenji Imai, Tomoko Nakano-Kobayashi, Masahiro Hayakawa, Hiroaki Kajiyama, Tomomi Kotani

Pregnancy hypertension   Vol. 29   page： 54 - 60   2022.8

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OBJECTIVES: We aimed to evaluate the impact of hypertensive disorders of pregnancy (HDP) on short- and medium-term respiratory outcomes in extremely and very preterm infants using the Neonatal Research Network of Japan database. STUDY DESIGN: This was a population-based retrospective study of preterm infants weighing ≤ 1500 g born between 22 and 31 weeks of gestation between 2003 and 2017. After 1:1 stratification matching by four factors (maternal age, gestational age, parity, and year of delivery), a total of 5137 infants in each group (HDP and non-HDP groups) were selected. MAIN OUTCOME MEASURES: The association between HDP and various respiratory outcomes was evaluated using univariate and multivariate logistic regression analyses. RESULTS: In the multivariate analyses, HDP was associated with higher odds for respiratory distress syndrome (RDS) (odds ratio 1.83, 95% confidence interval [1.65-2.03]), but reduced odds of persistent pulmonary hypertension of the newborn (PPHN) (0.34 [0.26-0.46]) and inhaled nitric oxide use (0.43 [0.33-0.55]). Although HDP was associated with an increased risk of chronic lung disease (CLD) in the univariate analysis, this association was not significant after adjustment for covariates (0.94 [0.83-1.07]). No significant association was found between HDP and home oxygen therapy (HOT) and medium-term oxygen use. CONCLUSION: The impact of maternal HDP largely differed depending on respiratory disorders and respiratory support. HDP was associated with higher odds of RDS but reduced odds of PPHN. The risks for CLD, HOT, and medium-term respiratory outcomes in the HDP group were comparable to those in the non-HDP group.

DOI： 10.1016/j.preghy.2022.06.003

PubMed

Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial. Reviewed International journal

Nao Matsuyama, Shinobu Shimizu, Kazuto Ueda, Toshihiko Suzuki, Sakiko Suzuki, Ryosuke Miura, Akemi Katayama, Masahiko Ando, Masaaki Mizuno, Akihiro Hirakawa, Masahiro Hayakawa, Yoshiaki Sato

BMJ open   Vol. 12 ( 4 ) page： e057073   2022.4

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INTRODUCTION: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in newborns with HIE. This is the first clinical trial of CL2020 cells in neonates. METHODS AND ANALYSIS: This is a single-centre, open-label, dose-escalation study enrolling up to 12 patients. Neonates with HIE who receive a course of therapeutic hypothermia therapy, which cools to a body temperature of 33°C-34°C for 72 hours, will be included in this study. A single intravenous injection of CL2020 cells will be administered between 5 and 14 days of age. Subjects in the low-dose and high-dose cohorts will receive 1.5 and 15 million cells per dose, respectively. The primary outcome is the occurrence of any adverse events within 12 weeks after administration. The main secondary outcome is the Bayley Scales of Infant and Toddler Development Third Edition score and the developmental quotient per the Kyoto Scale of Psychological Development 2001 at 78 weeks. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The Nagoya University Hospital Institutional Review Board (No. 312005) approved this study on 13 November 2019. The results of this study will be published in peer-reviewed journal and reported in international conferences. TRIAL REGISTRATION NUMBERS: NCT04261335, jRCT2043190112.

DOI： 10.1136/bmjopen-2021-057073

PubMed

Relationship between Neonatal MRI Findings and Emotional/Behavioral Evaluation in Early Childhood for Extremely Low-Birth-Weight Infants. Reviewed International journal

Akinobu Taniguchi, Masahiro Hayakawa, Erina Kataoka, Naozumi Fujishiro, Yoshiaki Sato

Journal of clinical medicine   Vol. 11 ( 3 )   2022.1

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The aim of this study is to investigate whether it is possible to detect future behavioral and emotional problems in extremely low-birth-weight infants by evaluating the neonatal head magnetic resonance imaging (MRI) using a scoring system. This study included 62 extremely low-birth-weight infants born between April 2015 and March 2017 and those who had undergone MRI at 36 to 42 weeks of gestation. These subjects were administered with the Strength and Difficulties Questionnaire (SDQ) at age 4-5, and the patients who responded to the questionnaire were included in the study. A positive correlation was observed between the Global Brain Abnormality Score and Total Difficulties Score of the SDQ (r = 0.26, p = 0.038). However, no significant difference was observed between the median Global Brain Abnormality Score of the normal and borderline-range group and the Total Difficulties Score of the clinical-range group (p = 0.51). This study demonstrated the relationship between the MRI findings in the newborn period and the emotional and behavioral problems in early childhood, but it is not clinically useful as a predictive marker.

DOI： 10.3390/jcm11030772

PubMed

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

Satoru Katsuki, Takafumi Ushida, Hiroyuki Kidokoro, Noriyuki Nakamura, Yukako Iitani, Kazuya Fuma, Kenji Imai, Tomoko Nakano-Kobayashi, Yoshiaki Sato, Masahiro Hayakawa, Jun Natsume, Hiroaki Kajiyama, Tomomi Kotani

Early human development   Vol. 163   page： 105479 - 105479   2021.12

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

DOI： 10.1016/j.earlhumdev.2021.105479

PubMed

Trajectory of the incidence of brushes on preterm electroencephalogram and its association with neurodevelopment in extremely low birth weight infants. Reviewed International journal

Takashi Maeda, Hiroyuki Kidokoro, Takashi Tachibana, Anna Shiraki, Hiroyuki Yamamoto, Tomohiko Nakata, Tatsuya Fukasawa, Tetsuo Kubota, Yoshiaki Sato, Toru Kato, Jun Natsume, Akihisa Okumura, Masahiro Hayakawa

Brain & development   Vol. 43 ( 10 ) page： 979 - 987   2021.11

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BACKGROUND: Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. METHODS: We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of <85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging. RESULTS: The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient. CONCLUSION: The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.

DOI： 10.1016/j.braindev.2021.07.003

PubMed

Impact of maternal hypertensive disorders of pregnancy on brain volumes at term-equivalent age in preterm infants: A voxel-based morphometry study. Reviewed International journal

Takafumi Ushida, Hiroyuki Kidokoro, Noriyuki Nakamura, Satoru Katsuki, Kenji Imai, Tomoko Nakano-Kobayashi, Yoshinori Moriyama, Yoshiaki Sato, Masahiro Hayakawa, Jun Natsume, Hiroaki Kajiyama, Tomomi Kotani

Pregnancy hypertension   Vol. 25   page： 143 - 149   2021.8

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OBJECTIVES: Infants born to mothers with hypertensive disorders of pregnancy (HDP) reportedly have negative behavioral and neurodevelopmental outcomes. However, the effects of maternal HDP on infant brain growth have not been fully evaluated. We aimed to evaluate brain volumes and brain injury in preterm infants born to mothers with HDP using magnetic resonance (MR) imaging at term-equivalent age. STUDY DESIGN: In this cohort study, MR imaging was performed for 94 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018. Twenty infants were born to mothers with HDP and 74 to mothers without HDP. MAIN OUTCOME MEASURES: Total brain volumes and regional volumetric alterations were assessed by voxel-based morphometry, and brain injury was evaluated using the Kidokoro global brain abnormality score. Developmental quotient was assessed at a corrected age of 1.5 years in 59 infants (HDP, n = 11; non-HDP, n = 48). RESULTS: No significant differences were observed in the gray and white matter volumes of the two groups (HDP: 175 ± 24 mL, 137 ± 13 mL, respectively; non-HDP: 172 ± 24 mL, 142 ± 13 mL, respectively). Additionally, no regional volumetric alterations were observed between the two groups after covariate adjustment (gestational age and infant sex). The total Kidokoro score and developmental quotient were similar in both groups. CONCLUSIONS: No significant differences in the global and regional brain volumes were observed. Further research is needed to confirm our findings at different time points of MR imaging and in different populations.

DOI： 10.1016/j.preghy.2021.06.003

PubMed