Language：English   Publisher：Pediatrics and Neonatology  

Background: To evaluate the efficacy and safety of gastric lavage (GL) in neonates with coffee-ground hematemesis due to swallowing maternal blood by postnatal day 1. Methods: This multicenter, randomized controlled trial included term neonates presenting coffee-ground hematemesis by postnatal day 1. Patients were randomly assigned to GL or non-GL groups. The primary outcome was the rate of feeding intolerance (FI) within 24 h. Secondary outcomes included onset of FI, residual gastric volume, vomiting episodes, weight changes, and bilirubin levels. Adverse events were monitored. Results: Eighty neonates were analyzed (40 per group). FI occurred in 15.0 % of the GL group and 27.5 % of the non-GL group (p = 0.17). However, in the subgroup of neonates exclusively fed with formula, FI was significantly lower in the GL group than in the non-GL group (16.0 % vs. 47.4 %, p = 0.02). GL significantly reduced residual gastric volume but showed no significant differences in other secondary outcomes. No adverse events related to GL were observed. Post hoc analysis indicated that a larger sample size would be needed to detect statistical significance; and subgroup findings suggested potential benefit in selected populations. Conclusions: GL did not significantly reduce the incidence of FI in neonates with coffee-ground hematemesis and thus it cannot be considered superior based on current results. However, it was well tolerated, and the study may have been underpowered. Exploratory analyses suggested potential benefits, particularly among formula-fed neonates, warranting further investigation.

DOI： 10.1016/j.pedneo.2025.05.014

Open Access

Scopus

PubMed

Language：English   Publisher：Pediatric Research  

Background: An association between total hydrocortisone (HC) dosage in infants with extremely low birth weight (ELBW) and subsequent neurodevelopmental outcomes up to school age remains unclear. Method: We conducted a retrospective longitudinal cohort study across eight centers in Japan, including ELBW infants born between 2015 and 2017. We investigated the association between total HC dosage administered up to 36 weeks postmenstrual age and neurodevelopmental outcomes to school age. Results: Linear mixed model analysis showed a significant association between higher HC dosage and lower developmental and intelligence quotient (DQ/IQ) scores. This trend persisted at 6 years of age, suggesting a sustained effect of HC on cognitive outcomes. For every 10 mg increase in HC dosage, IQ scores decreased by 2.82 points (95% CI: −3.89 to −1.06, p = 0.001). The interaction term between HC dosage and time was not statistically significant (0.10, 95% CI: −0.18 to 0.37, p = 0.481), suggesting the association of HC dosage on DQ/IQ did not vary substantially throughout the study period. Conclusions: We found a relationship between total neonatal HC dosage in ELBW infants and DQ/IQ scores over time that persisted at school age. Clinicians should be aware of this potential dose-dependent effect on neurodevelopmental outcomes. Impact: As neonatal dexamethasone administration is known to affect neurodevelopment outcomes, hydrocortisone (HC) is considered an alternative to dexamethasone as a glucocorticoid treatment. In infants with extremely low birth weight (ELBW), a relationship has been noted between total HC dosage and neurodevelopment in early childhood. We confirmed the association between total HC dosage in infants with ELBW and poor developmental and intelligence quotients to school age. Although HC is commonly used in the management of ELBW infants, clinicians should be aware of its potential dose-dependent effects on neurodevelopmental outcomes.

DOI： 10.1038/s41390-025-04426-x

Open Access

Web of Science

Scopus

PubMed

Language：English   Publisher：Pediatrics International  

DOI： 10.1111/ped.70122

Open Access

Web of Science

Scopus

PubMed

Language：English  

DOI： 10.1093/stcltm/szae071

Open Access

PubMed

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

Introduction: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. Methods: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. Results: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.65, 95% CI: −3.73, −1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.66, 95% CI: −3.89, −1.42). Conclusion: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

DOI： 10.1159/000534934

Open Access

Web of Science

Scopus

PubMed

Language：English   Publisher：Scientific Reports  

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

Open Access

Web of Science

Scopus

PubMed

Language：English   Publisher：Pediatrics International  

DOI： 10.1111/ped.15698

Web of Science

Scopus

PubMed

Language：English   Publisher：Frontiers in Pediatrics  

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 < 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 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 < 0.01, p < 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

Open Access

Web of Science

Scopus

PubMed

Language：English  

DOI： 10.3389/fncel.2020.00212

Open Access

Language：English  

DOI： 10.1136/bmjopen-2021-057073

Open Access

DOI： 10.1089/scd.2019.0221

Web of Science

PubMed

DOI： 10.3389/fneur.2018.00987

Open Access

Web of Science

PubMed

DOI： 10.3389/fneur.2018.00757

Open Access

Web of Science

PubMed

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.11251/ojjscn.45.21

Open Access

Authorship：Lead author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

Authorship：Lead author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

Authorship：Lead author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

Event date： 2017.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：埼玉   Country：Japan  

Event date： 2017.6

Language：English   Presentation type：Oral presentation (general)  

Venue：Boston, USA   Country：United States