2026/07/31 更新

写真a

フマ カズヤ
夫馬 和也
FUMA Kazuya
所属
医学部附属病院 産科婦人科 病院助教
職名
病院助教

学位 1

  1. 博士(医学) ( 2024年3月   名古屋大学 ) 

 

論文 28

  1. Longitudinal BMI Trajectory in Reproductive-Age Women at Risk of Prediabetes: Implications for Preventive Screening.

    Tano S, Fuma K, Matsuo S, Katsuki S, Inamura T, Fujito S, Kajiyama H, Ushida T

    American journal of preventive medicine     頁: 108525   2026年7月

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    記述言語:英語  

    DOI: 10.1016/j.amepre.2026.108525

    PubMed

  2. Blood pressure trajectories during pregnancy, labor, and postpartum period: a multicenter study in Japan Open Access

    Ushida, T; Shimaya, T; Inamura, T; Katsuki, S; Tano, S; Matsuo, S; Fuma, K; Yoshida, S; Yamashita, M; Kajiyama, H

    HYPERTENSION RESEARCH     2026年6月

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    記述言語:英語   出版者・発行元:Hypertension Research  

    In this study, we characterized the physiological blood pressure (BP) trajectories from an estimated pre-pregnancy period through pregnancy, labor, and postpartum among low-risk, normotensive women. This retrospective multicenter observational study was conducted at 12 primary obstetric care facilities in Japan and included 14,240 low-risk, normotensive women with term singleton deliveries between 2011 and 2018. Longitudinal outpatient BP trajectories during pregnancy and the postpartum period were modeled using linear mixed-effects models with restricted cubic splines. The pre-pregnancy BP was approximated using 1:1 matching with non-pregnant women undergoing routine health checkups. Changes in intrapartum BP were evaluated in women who underwent vaginal delivery (n = 11,836). The outpatient BP followed a classic gestational pattern, with a nadir at approximately 25 weeks of gestation, followed by a gradual increase toward term. The estimated pre-pregnancy BP was lower than the outpatient BP measured during early pregnancy. During the first stage of labor, systolic and diastolic BPs increased by up to 15.7 mmHg and 13.4 mmHg, respectively, compared with the final outpatient measurements, returning to near-outpatient levels within 2 h after delivery. During the postpartum period, the BP increased, peaked at days 5–7, and then gradually declined by approximately 5 weeks, converging toward non-pregnant levels. Low-risk normotensive women demonstrated elevated BP in early pregnancy relative to the estimated non-pregnant baseline during labor and in the first postpartum week. These data provide physiological reference patterns that may aid the interpretation of intrapartum and postpartum hypertension. (Figure presented.)

    DOI: 10.1038/s41440-026-02708-3

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  3. Facility-Level Factors Associating Antenatal Corticosteroid Administration Rates and Subsequent Term Birth Rates: A Nationwide Cross-Sectional Observational Study Using the 2020-2022 Perinatal Registry Database in Japan Open Access

    Fuma, K; Ushida, T; Imaizumi, T; Tano, S; Matsuo, S; Katsuki, S; Imai, K; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   52 巻 ( 3 ) 頁: e70237   2026年3月

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    記述言語:英語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: The antenatal corticosteroid (ACS) administration rate in Japan is low. To achieve both high coverage and low overtreatment of ACS, understanding of facility-level factors is important. This study aimed to identify facility-level factors associated with ACS coverage and overtreatment and simulate the potential consequences of increased ACS use. Methods: This observational study used data from the 2020 to 2022 Perinatal Registry Database maintained by the Japan Society of Obstetrics and Gynecology. Primary outcomes were: (1) ACS administration rate among preterm births before 34 weeks (ACS/34w rate) and (2) proportion of term births among ACS recipients (term/ACS proportion). Multivariable regression analyses examined associations with facility-level factors including perinatal care level, location, delivery volume, and prevalence of maternal conditions. A simulation estimated the impact of increasing ACS/34w rate to 80% in facilities with lower baseline rates. Results: In the facility-level analysis of 244 facilities (376 717 records), the mean ACS/34w rate was 63.4%, and term/ACS proportion was 12.0%. The proportion of threatened preterm labor (coefficient: 4.4 [95% confidence interval: 2.1–6.7]), deliveries < 34 weeks (3.0 [0.1–5.8]), and cesarean section rate (−2.4 [−4.5 to −0.2]) were significantly associated with ACS/34w rate. ACS/34w rate (2.0 [0.8–3.3]), annual delivery volume (2.1 [0.6–3.5]), and cesarean section rate (1.5 [0.2–2.7]) were positively associated with term/ACS proportion, while perinatal care level was inversely associated (−3.5 [−6.3 to −0.6]). Simulation estimated 2311 additional ACS recipients and 465 term births per year. Conclusions: Facility-level factors influence ACS coverage and overtreatment. These findings may inform strategies for optimizing ACS use.

    DOI: 10.1111/jog.70237

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  4. Gestational Age-Dependent Effects of Antenatal Magnesium Sulfate on Fetal S100B Levels: An Observational Study Using Cord Serum Open Access

    Shimaya, T; Fuma, K; Tano, S; Matsuo, S; Ushida, T; Imai, K; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   52 巻 ( 2 ) 頁: e70208   2026年2月

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    記述言語:英語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: Magnesium sulfate (MgSO<inf>4</inf>) is widely used for fetal neuroprotection in preterm births before 32 weeks of gestation, yet it remains unclear whether its effect depends on gestational age. S100 calcium-binding protein B (S100B), a protein secreted by astrocytes, is recognized as a biomarker of neural distress. This study aimed to investigate the relationship between antenatal MgSO<inf>4</inf> administration and umbilical cord serum S100B levels, with a focus on gestational age. Methods: This retrospective study included women who delivered between 22<sup>+0</sup> and 33<sup>+6</sup> weeks of gestation at a tertiary center. Patients with hypertensive disorders of pregnancy, category 1 cesarean sections, multiple pregnancies, major congenital anomalies, or insufficient MgSO<inf>4</inf> administration were excluded. Cord blood samples were analyzed for S100B levels using ELISA. Multiple linear regression and restricted cubic spline modeling were performed to assess the association between MgSO<inf>4</inf> and S100B levels across different gestational ages. Results: Among 69 eligible patients, MgSO<inf>4</inf> administration was significantly associated with higher cord serum S100B levels who delivered at ≥ 30 weeks of gestation (adjusted estimate 0.39, 95% confidence interval 0.17–0.62), but not in those who delivered at < 30 weeks (−0.12, −0.43 to 0.19) in multiple linear regression adjusted for birth weight and antenatal corticosteroids. This association remained consistent across multiple sensitivity analyses. S100B levels exhibited a gestational age-dependent increase in response to MgSO<inf>4</inf>, peaking at approximately 32 weeks in restricted cubic spline modeling. Conclusions: Antenatal MgSO<inf>4</inf> administration beyond 30 weeks of gestation at delivery is associated with increased fetal S100B levels, suggesting a potential gestational age-specific response.

    DOI: 10.1111/jog.70208

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  5. Synergistic use of 1,5-AG and HbA1c for early prediction of gestational diabetes: capturing BMI-dependent glycemic phenotypes Open Access

    Tano, S; Inamura, T; Fuma, K; Matsuo, S; Imai, K; Katsuki, S; Kishigami, Y; Oguchi, H; Kotani, T; Ushida, T; Kajiyama, H

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS   313 巻 ( 1 ) 頁: 4   2026年1月

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    記述言語:英語   出版者・発行元:Archives of Gynecology and Obstetrics  

    Purpose: Recognizing metabolic heterogeneity in gestational diabetes mellitus (GDM) and body mass index (BMI)-linked phenotypes, we evaluated whether combining hemoglobin A1c (HbA1c, reflecting fasting glycaemia) and 1,5-anhydroglucitol (1,5-AG, reflecting post-load glucose excursions) improves early prediction and whether performance differs by BMI. Methods: In this multicenter retrospective study, pregnant women who had 1,5-AG and HbA1c measured before 20 weeks of gestation at two tertiary centers in Japan were included. Spearman’s correlation was used to assess associations between glycemic markers and glucose levels. Predictive performance for GDM was evaluated using ROC analysis, and stratified analyses were conducted by pre-pregnancy BMI. Results: Among 191 participants, 45 (24.1%) developed GDM: 35.1 ± 4.9 years, pre-pregnancy BMI 22.9 ± 4.3 kg/m<sup>2</sup>, and sampling at 14.3 [IQR 14.0–14.7] weeks. HbA1c correlated with fasting glucose (r = 0.35) while 1,5-AG correlated inversely with 2-h glucose (r = − 0.39). They themselves were not significantly correlated (r = − 0.13). As single predictors, performance depended on BMI: in ≥ 25.0 kg/m<sup>2</sup>, HbA1c outperformed 1,5-AG (AUC 0.776 vs 0.618); in BMI < 25.0 kg/m<sup>2</sup>, 1,5-AG outperformed HbA1c (AUC 0.704 vs 0.640). In both BMI strata, the dual-marker model was superior (AUC 0.833 and 0.803, respectively) and provided more balanced sensitivity, accuracy, and F1. Pre-pregnancy BMI correlated positively with fasting plasma glucose (r = 0.47) but not with 1-h or 2-h glucose (r = 0.20 and r = 0.16, respectively), supporting BMI-related metabolic variation. Conclusion: Combining 1,5-AG and HbA1c enhances early prediction of GDM by capturing complementary glycemic abnormalities linked to BMI-specific metabolic phenotypes.

    DOI: 10.1007/s00404-025-08281-3

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  6. Maternal Renal Function During Pregnancy and the Early Postpartum Period in Normotensive and Hypertensive Pregnancies Open Access

    Ushida, T; Katsuki, S; Fuma, K; Tano, S; Matsuo, S; Yoshida, S; Yamashita, M; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   51 巻 ( 12 ) 頁: e70172   2025年12月

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    記述言語:英語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: We aimed to assess renal function trends during pregnancy and the early postpartum period and establish trimester-specific reference ranges for maternal renal function parameters in Japan, including comparisons with pregnancies complicated by hypertensive disorders of pregnancy (HDP) and preeclampsia. Methods: This multicenter retrospective study used data collected from 12 primary maternity care units in Japan between 2011 and 2018. Serum creatinine and blood urea nitrogen (BUN) levels were analyzed from early pregnancy to postpartum Day 7 in 17 460 women with uncomplicated term pregnancies (37<sup>0/7</sup>–41<sup>6/7</sup> weeks of gestation) and 1460 women with HDP. Additionally, 17 460 non-pregnant women matched for age, body weight, and height were included in the study. Results: Serum creatinine and BUN levels were lower in women with uncomplicated pregnancies than in non-pregnant women and reached their lowest levels in the second trimester. The 97.5th percentile serum creatinine value was 0.52 mg/dL in the second trimester, compared with 0.82 mg/dL in non-pregnant women. The median serum creatinine levels in uncomplicated pregnancies were approximately 30% lower than those in non-pregnant women. Serum creatinine levels began to normalize during the postpartum period but did not return to baseline non-pregnant status by Day 7. In women with HDP and preeclampsia, serum creatinine levels increased in the late third trimester and peaked on postpartum Day 1; in 7.0% of women with preeclampsia, they exceeded 1.0 mg/dL. Conclusion: We determined reference ranges for maternal renal markers in a Japanese cohort study. Maternal renal function shows dynamic alterations from the non-pregnant state through pregnancy to the postpartum period.

    DOI: 10.1111/jog.70172

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  7. Predicting gestational diabetes before conception for personalized interpregnancy weight management Open Access

    Tano, S; Kotani, T; Inamura, T; Fuma, K; Matsuo, S; Yoshihara, M; Imai, K; Nomoto, M; Moriyama, Y; Yoshida, S; Yamashita, M; Kishigami, Y; Oguchi, H; Ushida, T; Kajiyama, H

    SCIENTIFIC REPORTS   15 巻 ( 1 ) 頁: 45510   2025年11月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    The growing recognition of the importance of interpregnancy care to reduce gestational diabetes mellitus (GDM) risk underscores the importance of effective preventive strategies. However, developing effective systems is still challenging. We aimed to bridge this gap by developing a weight management specific prediction model. This study retrospectively analyzed the data of women who underwent two childbirths across 15 medical facilities, including both primary and tertiary facilities. A derivation cohort was constructed using data from 2009 to 2019 (n = 1,640). Data between 2020 and 2024 was used to construct a separate temporal-validation cohort (n = 293). Using the data from another tertiary center between 2017 and 2023, the geographical-validation cohort was constructed (n = 339). A prediction model for GDM development in the second pregnancy was developed by applying logistic regression analysis using 5 key clinical information. GDM in the second pregnancy occurred in 9.5% (156 of 1,640, derivation), 16.7% (49 of 293, temporal-validation), and 7.7% (26 of 339, geographical-validation). The prediction model demonstrated consistent discrimination across cohorts, with c-statistics of 0.75, 0.80, and 0.79, respectively. Precision–recall analyses, accounting for the low prevalence of GDM, further confirmed performance well above the baseline (0.095 in the derivation cohort), with AUC-PRs of 0.43, 0.47, and 0.41 for the three cohorts. Calibration showed alignment with slopes of 1.04, 0.87, and 0.59 for each cohort. This simple and accurate model supports personalized weight management goals, offering a practical tool to reduce GDM risk in future pregnancies through inter-pregnancy weight management.

    DOI: 10.1038/s41598-025-30028-y

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  8. Estimated fetal weight or gestational age: which is crucial for fetal cardiac evaluation? Open Access

    Tano, S; Inamura, T; Kato, M; Ito, M; Takeda, T; Kinoshita, F; Fuma, K; Matsuo, S; Ushida, T; Imai, K; Kajiyama, H; Kotani, T; Kishigami, Y; Oguchi, H

    PEDIATRIC RESEARCH     2025年11月

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    記述言語:英語   出版者・発行元:Pediatric Research  

    Background: Fetal cardiac output is typically assessed using gestational age (GA) or estimated fetal weight (EFW), but the optimal reference remains unclear due to limited validation. Methods: We retrospectively analyzed prospectively collected data from singleton fetuses at 27 + 2 to 29 + 6 weeks of gestation. Subjects included those with small for gestational age (SGA; EFW <10th percentile), large for gestational age (LGA; EFW > 90th percentile), and appropriate for gestational age (AGA), all without structural abnormalities. Associations between fetal cardiac output and both GA and EFW were evaluated using generalized additive models. Results: Among 443 fetuses with EFWs ranging from 873 to 1631 g, GA showed no significant association with any cardiac parameter (p ≥ 0.282). In contrast, EFW demonstrated significant and largely linear associations with all parameters (p < 0.001, F ≥ 16.7), consistent across GA and EFW ranges. Cardiac parameter distributions by EFW were similar across AGA, SGA, and LGA groups. Conclusion: EFW showed stronger and more consistent correlations with fetal cardiac parameters than GA, supporting its use as a more reliable reference for fetal cardiac evaluation across different growth statuses. Impact: Fetal cardiac output is typically assessed using reference ranges based on either gestational age (GA) or estimated fetal weight (EFW), both derived from appropriate for gestational age (AGA) fetuses. We showed that EFW is superior to GA for fetal cardiac evaluation. Including non-AGA fetuses confirmed they can be assessed similarly to AGA fetuses. The new EFW-based reference ranges offer a uniform standard, enabling more definitive assessments across varied fetal growth.

    DOI: 10.1038/s41390-025-04584-y

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  9. Risk factors of adverse pregnancy outcomes in patients with immunoglobulin A nephropathy Open Access

    Asano, Y; Imaizumi, T; Fuma, K; Watanabe, Y; Tanaka, A; Furuhashi, K; Maruyama, S

    SCIENTIFIC REPORTS   15 巻 ( 1 ) 頁: 40427   2025年11月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Pregnancy and childbirth are major concerns for women with immunoglobulin A nephropathy (IgAN), because it peaks in their child-bearing age. To provide evidence for optimal pre-conception care, we investigated whether the disease control status, assessed by blood pressure and/or urine protein level, is associated with adverse pregnancy outcomes. This case–control study used data from 924,238 patients with chronic kidney disease obtained from a hospital claims database. We included 297 pregnancies with IgAN and collected data on antihypertensive medications and glucocorticoid therapy within six months before conception as the exposures. The outcomes were hypertensive disorders of pregnancy (HDP) that required intravenous nicardipine and preterm delivery. We estimated the adjusted odds ratios (aORs) using multivariable logistic regression. The prescriptions of antihypertensive medications other than renin–angiotensin–aldosterone system inhibitors (RASi) were significantly associated with both severe HDP requiring intravenous nicardipine (aOR: 5.01, 95% confidence interval [CI]: 1.43–17.5) and preterm delivery (aOR: 6.45, 95% CI: 1.81–23.0), compared with those of only RASi. No significant associations were observed between glucocorticoid therapy and outcomes. Regarding pre-conception care, our findings suggest that pre-conception antihypertensive medication use, as a surrogate marker for underlying hypertension, may help identify women with IgAN at higher risk of adverse pregnancy outcomes.

    DOI: 10.1038/s41598-025-21529-x

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  10. Recognizing an Incarcerated Gravid Uterus When the Cervical Canal Is Absent on Transvaginal Ultrasound.

    Okawa A, Tano S, Inoue M, Inamura T, Katsuki S, Fuma K, Matsuo S, Ushida T, Imai K, Kotani T, Kajiyama H

    Cureus   17 巻 ( 11 ) 頁: e97996   2025年11月

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    記述言語:英語  

    DOI: 10.7759/cureus.97996

    PubMed

  11. Ultrasound-guided insertion of controlled-release dinoprostone vaginal delivery system (PROPESS)

    Imai, K; Tano, S; Fuma, K; Matsuo, S; Ushida, T; Kajiyama, H; Kotani, T

    JOURNAL OF MEDICAL ULTRASONICS   52 巻 ( 4 ) 頁: 443 - 444   2025年10月

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    記述言語:英語   出版者・発行元:Journal of Medical Ultrasonics Singapore  

    DOI: 10.1007/s10396-025-01552-1

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  12. Quantitative assessment of placental alpha macroglobulin-1 for predicting impending preterm delivery in asymptomatic women with a short cervix Open Access

    Nozaki, Y; Imai, K; Miki, R; Tano, S; Fuma, K; Matsuo, S; Ushida, T; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   51 巻 ( 9 ) 頁: e70071   2025年9月

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    記述言語:英語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aims: Preterm delivery (PTD) is a leading cause of neonatal morbidity and mortality. Accurate prediction is crucial for optimizing clinical outcomes, particularly in women with a short cervix. Although fetal fibronectin (FFN) is widely used to predict PTD, placental alpha-microglobulin-1 (PAMG-1) has gained attention for its potential to improve predictive accuracy. This study aimed to evaluate the utility of quantitative PAMG-1 assessment for predicting impending PTD in asymptomatic women with a short cervix (≤25 mm) between 24 and 34 weeks of gestation. Methods: This observational cohort study analyzed 212 cervicovaginal fluid samples from 77 patients (132 from 49 singleton and 80 from 28 twin pregnancies). PAMG-1 and FFN levels were measured, and multivariate logistic regression was performed to evaluate their association with PTD risk. Results: In singleton pregnancies, positive PAMG-1 was independently associated with impending PTD, with odds ratios of 7.84 (95% confidence interval [CI], 2.02–30.50; p = 0.003) and 7.34 (95% CI, 2.75–19.60; p < 0.001) for PTD within 1 and 2 weeks, respectively. Quantitative PAMG-1 showed a dose-dependent relationship, with PTD risks increasing from 4.3% (<1000 pg/mL) to 50.0% (≥3000 pg/mL) within 1 week and from 10.0% to 90.0% for PTD within 2 weeks. In twin pregnancies, both PAMG-1 and FFN showed limited predictive utility. Conclusions: This study highlights the potential of PAMG-1 quantification as a valuable tool for refining PTD risk stratification, particularly in singleton pregnancies. While further prospective multicenter validation is needed, these findings provide new clinical insights for improving PTD management.

    DOI: 10.1111/jog.70071

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  13. Antenatal corticosteroid treatment for women with hypertensive disorders of pregnancy: A population-based study in Japan Open Access

    Ushida, T; Fuma, K; Katsuki, S; Tano, S; Matsuo, S; Imai, K; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   51 巻 ( 7 ) 頁: e16364   2025年7月

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    記述言語:英語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: This study aimed to evaluate the current antenatal corticosteroid (ACS) treatment practices for hypertensive disorders of pregnancy (HDP) in Japan, by evaluating annual trends and identifying clinical disparities and factors influencing non-administration of ACS. Methods: This retrospective population-based study was conducted using the Japanese Perinatal Research Network Database from 2013 to 2022. We analyzed ACS administration rates over time, across facility types, and the timing of delivery. Factors influencing non-administration were identified using univariate and multivariate logistic regression analyses. Results: ACS administration rates among patients with HDP nearly doubled over the past decade, reaching 64.0% in 2022. Approximately 70% of patients with HDP who received ACS delivered before 34 weeks of gestation; however, only 30% achieved the optimal administration-to-birth interval of 48 h to 7 days. ACS administration rates in patients with HDP differed by facility type: 67.8% (1641/2419) in general perinatal medical centers, 60.5% (1107/1830) in regional perinatal medical centers, and 39.7% (23/58) in non-perinatal medical centers. Factors contributing to non-administration included smoking during pregnancy, eclampsia, placental abruption, HELLP syndrome, regional perinatal medical centers, non-perinatal medical centers, and gestational hypertension. Conversely, conditions such as fetal growth restriction, threatened preterm labor, and preterm premature rupture of membranes were associated with higher rates of ACS administration. Conclusions: Although ACS administration rates in patients with HDP have improved over time, challenges remain in achieving optimal administration timing and addressing facility-based disparities. To improve administration rates, clinicians should increase awareness of ACS treatment and proactively manage HDP-related emergencies.

    DOI: 10.1111/jog.16364

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  14. Knowledge and counseling practices of obstetric care providers for women with hypertensive disorders of pregnancy in Japan

    Ushida, T; Kato, A; Katsuki, S; Tano, S; Matsuo, S; Fuma, K; Imai, K; Kajiyama, H; Kotani, T

    Hypertension Research in Pregnancy   13 巻 ( 2 ) 頁: 29 - 38   2025年5月

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    記述言語:英語   出版者・発行元:日本妊娠高血圧学会  

    DOI: 10.14390/jsshp.hrp2024-015

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  15. Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy Open Access

    Tano, S; Kotani, T; Inamura, T; Kinoshita, F; Fuma, K; Matsuo, S; Yoshihara, M; Imai, K; Yoshida, S; Yamashita, M; Kishigami, Y; Oguchi, H; Kajiyama, H; Ushida, T

    SCIENTIFIC REPORTS   15 巻 ( 1 ) 頁: 18123   2025年5月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    To evaluate the role of high glucose variability (High-GV) in early pregnancy as a potential mediating factor between pre-pregnancy overweight/obesity and late-onset HDP (LoHDP), where effective preventive strategies remain limited. This multicenter retrospective study analyzed data from 802 pregnancies across 14 facilities. Pregnancies with a 75 g-OGTT performed by 20 weeks of gestation were included. Structural equation modeling (SEM) was used to evaluate direct and indirect effects of body mass index (BMI), High-GV, and covariates (e.g., age, ART, primiparity) on LoHDP. Overweight/obese women had significantly higher rates of High-GV (26.1 vs. 16.4%, p = 0.001) and LoHDP (17.6 vs. 7.9%, p < 0.001) compared to non-overweight/obese women. SEM revealed that BMI influenced LoHDP through both direct and indirect pathways. BMI had a direct effect on LoHDP (β = 0.20, p < 0.01), and an indirect effect mediated by High-GV, with BMI significantly associated with High-GV (β = 0.15, p < 0.01), and High-GV positively associated with LoHDP (β = 0.12, p < 0.01). In Non-GDM pregnancies, High-GV showed an even stronger association with LoHDP (β = 0.25, p < 0.001). This study identifies High-GV as a key mediator linking pre-pregnancy overweight/obesity to LoHDP. These findings suggest that targeting glucose variability in early pregnancy could mitigate LoHDP risk, particularly in overweight/obese women, regardless of GDM status. Future preventive strategies should integrate multifaceted approaches addressing maternal BMI and glucose regulation to improve maternal and neonatal outcomes.

    DOI: 10.1038/s41598-025-02965-1

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  16. Butyrate-producing bacteria in pregnancy maintenance: mitigating dysbiosis-induced preterm birth Open Access

    Uchida, A; Imai, K; Miki, R; Hamaguchi, T; Nishiwaki, H; Ito, M; Ueyama, J; Hattori, S; Tano, S; Fuma, K; Matsuo, S; Ushida, T; Ohno, K; Kajiyama, H; Kotani, T

    JOURNAL OF TRANSLATIONAL MEDICINE   23 巻 ( 1 ) 頁: 533   2025年5月

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    記述言語:英語   出版者・発行元:Journal of Translational Medicine  

    Background: Preterm birth (PTB) is a major contributor to neonatal morbidity, mortality, and long-term health complications. Despite advances in perinatal care, PTB rates remain high, and its multifactorial etiology is not fully understood. Increasing evidence suggests that maternal gut microbiota plays a critical role in pregnancy maintenance, potentially through modulation of immune responses. However, the underlying causal mechanisms remain unclear. We hypothesized that dysbiosis disrupts immune tolerance and promotes PTB, and that butyrate (short-chain fatty acid produced by specific gut bacteria) may counteract this effect by enhancing regulatory T cell (Treg)-mediated immune regulation. Methods: We established a dysbiosis-induced PTB mouse model using vancomycin treatment combined with subclinical immune activation via anti-CD3ε antibody. Pregnant mice were fed either a standard or butyrate-enriched diet. Outcomes included gestational length, PTB incidence, live pup rates, and Treg cell levels assessed by flow cytometry. Parallelly, 16S rRNA gene sequencing was performed on fecal samples from 32 pregnant women to compare gut microbial composition between spontaneous PTB and term birth groups. Multivariate logistic regression and correlation analyses were conducted to assess associations with gestational outcomes. Results: Vancomycin-induced dysbiosis in mice significantly reduced Treg cell populations and increased PTB rates (43.3% in dysbiosis vs. 0% in controls; p < 0.05), while butyrate supplementation reduced PTB incidence (p = 0.03), prolonged gestation (p = 0.01), and restored Treg counts (p < 0.001). In human samples, significant reductions in Lachnospiraceae and Ruminococcaceae, representative butyrate-producing bacteria, were seen in PTB cases. Their combined abundance was independently associated with sPTB risk (p = 0.019) and positively correlated with gestational age (r = 0.59, p < 0.001). Conclusions: Our findings demonstrate that maternal dysbiosis increases PTB risk via impaired immune tolerance, and that butyrate supplementation effectively reverses this effect in vivo. Human data support the translational relevance of butyrate-producing microbiota in pregnancy maintenance. These results highlight butyrate as a promising target for dietary interventions aimed at reducing PTB incidence by restoring immune homeostasis. Trial registration Not applicable.

    DOI: 10.1186/s12967-025-06534-y

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  17. Effect of chorioamnionitis on postnatal growth in very preterm infants: a population-based study in Japan Open Access

    Ushida, T; Nosaka, R; Nakatochi, M; Kobayashi, Y; Tano, S; Fuma, K; Matsuo, S; Imai, K; Sato, Y; Hayakawa, M; Kajiyama, H; Kotani, T

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS   311 巻 ( 5 ) 頁: 1321 - 1330   2025年5月

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    記述言語:英語   出版者・発行元:Archives of Gynecology and Obstetrics  

    Purpose: There is growing evidence that preterm infants born to mothers with chorioamnionitis (CAM) have increased risk of various neonatal morbidities and long-term neurological disorders; however, the effect of CAM on postnatal growth remains insufficiently investigated. This study evaluated the effect of histological CAM on postnatal growth trajectories in very preterm infants using a nationwide neonatal database in Japan. Method: A multicenter retrospective study was conducted using clinical data of 4220 preterm neonates who weighed ≤ 1500 g and were born at < 32 weeks of gestation between 2003–2017 (CAM group: n = 2110; non-CAM group: n = 2110). Z-scores for height and weight were evaluated at birth and 3 years of age. Univariable and multivariable analyses were conducted to evaluate the effect of histological CAM on ΔZ-scores of height and weight during the first three years with a stratification by infant sex and the stage of histological CAM. Results: Multivariable analyses showed that histological CAM was associated with accelerated postnatal increase (ΔZ-score) in weight (β coefficient [95% confidence interval]; 0.10 [0.00 to 0.20]), but not in height among females (0.06 [− 0.04 to 0.15]) and not in height and weight among males (0.04 [− 0.04 to 0.12] and 0.02 [− 0.07 to 0.11], respectively). An interaction analysis demonstrated no significant difference in the effect of histological CAM on the ΔZ-scores of height and weight during the first three years between male and female infants (height, p = 0.81; weight p = 0.25). Conclusions: Intrauterine exposure to maternal CAM contributes to accelerated postnatal weight gain in female preterm infants during the first three years.

    DOI: 10.1007/s00404-024-07757-y

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  18. Dietary supplements and prevention of preeclampsia Open Access

    Ushida, T; Tano, S; Matsuo, S; Fuma, K; Imai, K; Kajiyama, H; Kotani, T

    HYPERTENSION RESEARCH   48 巻 ( 4 ) 頁: 1444 - 1457   2025年4月

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    記述言語:英語   出版者・発行元:Hypertension Research  

    Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE. In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE. Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan. According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions. We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE. (Figure presented.)

    DOI: 10.1038/s41440-025-02144-9

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  19. Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders Open Access

    Fuma, K; Iitani, Y; Imai, K; Ushida, T; Tano, S; Yoshida, K; Yokoi, A; Miki, R; Kidokoro, H; Sato, Y; Hara, Y; Ogi, T; Nomaki, K; Tsuda, M; Komine, O; Yamanaka, K; Kajiyama, H; Kotani, T

    COMMUNICATIONS BIOLOGY   8 巻 ( 1 ) 頁: 75   2025年1月

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    記述言語:英語   出版者・発行元:Communications Biology  

    Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c<sup>+</sup> microglia, key contributors to myelination through IGF-1 production, in this pathology. In the mouse model, the CD11c<sup>+</sup> microglial population was significantly lower in the MIA group than in the control group on postnatal day 3 (PN3d). Furthermore, myelination-related protein levels significantly decreased in the MIA group at PN8d. In humans, preterm infants with HCA exhibited higher IL-6 and IL-17A cord-serum levels and lower IGF-1 levels than those without HCA, followed by a higher incidence of delayed myelination on magnetic resonance imaging at the term-equivalent age. In silico analysis revealed that the transient induction of CD11c<sup>+</sup> microglia during early development occurred similarly in mice and humans. Notably, a lack of high CD11c<sup>+</sup> microglial population has been observed in children with neurodevelopmental disorders. This study reports impaired induction of CD11c<sup>+</sup> microglia during postnatal development in a mouse model of MIA associated with delayed myelination. Our findings may inform strategies for improving outcomes in infants with HCA. (Figure presented.)

    DOI: 10.1038/s42003-025-07511-3

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  20. Effect of Cytokine Concentrations on Long-term Neurological Outcomes in Fetal Pleural Effusion Managed with Thoracoamniotic Shunt

    Imai, K; Tano, S; Fuma, K; Matsuo, S; Ushida, T; Kajiyama, H; Kotani, T

    JMA JOURNAL   8 巻 ( 1 ) 頁: 288 - 292   2025年1月

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  21. Effect of Cytokine Concentrations on Long-term Neurological Outcomes in Fetal Pleural Effusion Managed with Thoracoamniotic Shunt.

    Imai K, Tano S, Fuma K, Matsuo S, Ushida T, Kajiyama H, Kotani T

    JMA journal   8 巻 ( 1 ) 頁: 288 - 292   2025年1月

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    記述言語:英語  

    DOI: 10.31662/jmaj.2024-0227

    PubMed

  22. Effect of Cytokine Concentrations on Long-term Neurological Outcomes in Fetal Pleural Effusion Managed with Thoracoamniotic Shunt

    Imai Kenji, Tano Sho, Fuma Kazuya, Matsuo Seiko, Ushida Takafumi, Kajiyama Hiroaki, Kotani Tomomi

    JMA Journal   8 巻 ( 1 ) 頁: 288 - 292   2025年1月

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    記述言語:英語   出版者・発行元:Japan Medical Association / The Japanese Associaiton of Medical Sciences  

    DOI: 10.31662/jmaj.2024-0227

    CiNii Research

  23. Effect of Cytokine Concentrations on Long-term Neurological Outcomes in Fetal Pleural Effusion Managed with Thoracoamniotic Shunt

    Imai, K; Tano, S; Fuma, K; Matsuo, S; Ushida, T; Kajiyama, H; Kotani, T

    JMA JOURNAL     2024年12月

  24. Patient awareness of long-term cardiovascular and metabolic disease risks after hypertensive disorders of pregnancy in Japan Open Access

    Ushida, T; Tano, S; Matsuo, S; Fuma, K; Imai, K; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   51 巻 ( 1 ) 頁: e16183   2024年12月

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    記述言語:英語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: Given the increasing recognition of the importance of postpartum follow-up care for women with a history of hypertensive disorders of pregnancy (HDP) to mitigate their future risk of cardiovascular and metabolic diseases, here we aimed to evaluate the current status of postpartum follow-up care in Japan and explore the challenges to its implementation. Methods: A web-based survey was conducted using a smartphone application among postpartum women between March and May 2024 to assess their knowledge of HDP-related future risk and postpartum follow-up care. Results: A total of 880 valid responses were obtained, 73 (8.3%) of which were from women with a history of HDP. Of them, 56.2% were aware of the heightened risk of cardiovascular disease and even fewer knew about the risks of metabolic syndrome (37.0%) and the preventive use of low-dose aspirin (12.3%); in fact, 31.5% reported receiving no information about their risk or preventive measures from healthcare providers. Furthermore, 43.8% did not consult specialists or attend regular checkups after their 1-month checkup. Among women with a history of HDP, those who received information and guidance were more likely to implement behavioral changes than those who did not. Conclusions: Patient awareness level of HDP-related risk was low and the information provided by their healthcare professionals was insufficient, indicating that postpartum follow-up care in Japan is not satisfactory. This study highlights the need for improved educational strategies and systematic follow-up protocols to ensure that women are adequately informed and supported in managing their long-term health risks.

    DOI: 10.1111/jog.16183

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  25. Impact of antenatal corticosteroids on subcortical volumes in preterm infants at term-equivalent age: A retrospective observational study Open Access

    Fuma, K; Ushida, T; Kawaguchi, M; Nosaka, R; Kidokoro, H; Tano, S; Imai, K; Sato, Y; Hayakawa, M; Kajiyama, H; Kotani, T

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY   302 巻   頁: 7 - 14   2024年11月

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    記述言語:英語   出版者・発行元:European Journal of Obstetrics and Gynecology and Reproductive Biology  

    Objective: Antenatal corticosteroids (ACS) is a well-established treatment for women at risk of preterm birth that improves neonatal outcomes. However, several concerns have been raised regarding the potential long-term adverse effects of ACS on the offspring's developing brain. Here we investigated the association between ACS and subcortical segmental volumes in preterm infants at term-equivalent age. Study design: This retrospective observational study was conducted using the clinical data of preterm singleton infants born between 22<sup>0/7</sup> and 33<sup>6/7</sup> gestational weeks at Nagoya University Hospital in 2014–2020. Subcortical volumes of the bilateral thalami, caudate nuclei, putamens, pallidums, hippocampi, amygdalae, and nuclei accumbens were evaluated using an automated segmentation tool, Infant FreeSurfer, and compared between neonates exposed to a single course of ACS (n = 46) and those who were not (n = 13) by multiple linear regression analysis (covariates: postmenstrual age at magnetic resonance imaging, infant sex, and gestational age at birth). We compared each subcortical volume stratified by gestational age at birth (<28 vs. ≥28 gestational weeks). Results: Multivariate analyses revealed significantly smaller volumes in the bilateral amygdalae (left, p < 0.03; right, p < 0.03) and caudate nuclei (left, p < 0.03; right, p = 0.04) in neonates with ACS. Significantly smaller volumes in these regions were observed only in neonates born at 28 weeks of gestation or later. Conclusions: ACS was associated with smaller volumes of the bilateral amygdalae and caudate nuclei at term-equivalent age. This association was observed exclusively in infants born at 28 weeks of gestation or later.

    DOI: 10.1016/j.ejogrb.2024.08.034

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  26. Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan Open Access

    Fuma, K; Kotani, T; Tsuda, H; Oshiro, M; Tano, S; Ushida, T; Imai, K; Sato, Y; Kajiyama, H

    BMC PREGNANCY AND CHILDBIRTH   24 巻 ( 1 ) 頁: 607   2024年9月

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    記述言語:英語   出版者・発行元:BMC Pregnancy and Childbirth  

    Background: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. Methods: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1–7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. Results: The ACS 1–7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1–7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. Conclusions: An ACS-to-delivery interval of 1–7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

    DOI: 10.1186/s12884-024-06790-8

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  27. 特集 これでマスター! 最新 産婦人科ホルモン療法 第2章 各論 C 周産期 4 胎児肺成熟の促進

    夫馬 和也, 小谷 友美

    産科と婦人科   91 巻 ( 13 ) 頁: 299 - 305   2024年3月

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    出版者・発行元:診断と治療社  

    DOI: 10.34433/og.0000000672

    CiNii Research

  28. Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles Open Access

    Iitani, Y; Miki, R; Imai, K; Fuma, K; Ushida, T; Tano, S; Yoshida, K; Yokoi, A; Kajiyama, H; Kotani, T

    PEDIATRIC RESEARCH   95 巻 ( 1 ) 頁: 167 - 173   2024年1月

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    記述言語:英語   出版者・発行元:Pediatric Research  

    Background: Increased maternal interleukin (IL)-17A and activated microglia are pivotal factors contributing to the pathological phenotypes of maternal immune activation (MIA), developing neurodevelopmental disorders in offspring. This study aimed to determine whether IL-17A affects the microglial microRNA (miRNA) profiles. Methods: The miRNA expression profiles of primary cultured microglia stimulated with recombinant IL-17A were examined comprehensively using miRNA sequencing and validated through qRT-PCR. The expressions of miRNAs target genes identified using bioinformatics, were investigated in microglia transfected with mimic miRNA. The target gene’s expression was also examined in the fetal brains of the MIA mouse model induced by maternal lipopolysaccharide (LPS) administration. Results: Primary cultured microglia expressed the IL-17A receptor and increased proinflammatory cytokines and nitric oxide synthase 2 upon treatment with IL-17A. Among the three miRNAs with |log<inf>2</inf>FC | >1, only mmu-miR-206-3p expression was significantly up-regulated by IL-17A. Transfection with the mmu-miR-206-3p mimic resulted in a significant decrease in the expression of Hdac4 and Igf1, target genes of mmu-miR-206-3p. Hdac4 expression also significantly decreased in the LPS-induced MIA model. Conclusions: IL-17A affected microglial miRNA profiles with upregulated mmu-miR-206-3p. These findings suggest that targeting the IL-17A/mmu-miR-206-3p pathway may be a new strategy for predicting MIA-related neurodevelopmental deficits and providing preventive interventions. Impact: Despite the growing evidence of interleukin (IL)-17A and microglia in the pathology of maternal immune activation (MIA), the downstream of IL-17A in microglia is not fully known.IL-17A altered microRNA profiles and upregulated the mmu-miR-206-3p expression in microglia. The mmu-miR-206-3p reduced autism spectrum disorder (ASD) related gene expressions, Hdac4 and Igf1.The Hdac4 expression was also reduced in the brain of MIA offspring.The hsa-miR-206 sequence is consistent with that of mmu-miR-206-3p.This study may provide clues to pathological mechanisms leading to predictions and interventions for ASD children born to mothers with IL-17A-related disorders.

    DOI: 10.1038/s41390-023-02825-6

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▼全件表示

科研費 2

  1. 出生前ステロイドの至適使用戦略と胎児への長期的副作用の予防についての研究

    研究課題/研究課題番号:26K19983  2026年4月 - 2029年3月

    科学研究費助成事業  若手研究

    夫馬 和也

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    担当区分:研究代表者 

    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    出生前ステロイドは、早産前1週間以内の投与が望ましいが、早産時期を正確に予測する方法が確立していないことが課題であり、結果的に早すぎる投与や不必要な投与に繋がっている。また、高用量のステロイドによる胎児脳への「プログラミング作用」により、児に長期的影響を及ぼす懸念もあるため、影響を最小限にするための工夫が必要である。そこで本研究は、出生前ステロイドの投与を最適化するために、①日本のステロイド投与現状の理解、②投与すべき患者選択に役立つ検査の開発、③児に与える影響の理解、④動物実験による児への悪影響の軽減、の4つを目的とした。本研究から得られる知見により、早産児の予後向上につながると期待される。

  2. 出生前ステロイドの胎児脳プログラミング作用を軽減するための、新規治療薬の開発

    研究課題/研究課題番号:24K23509  2024年7月 - 2026年3月

    科学研究費助成事業  研究活動スタート支援

    夫馬 和也

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    担当区分:研究代表者 

    配分額:2730000円 ( 直接経費:2100000円 、 間接経費:630000円 )

    出生前ステロイドは早産児の生存率を向上させる重要な治療だが、胎児脳への「プログラミング作用」により、児の長期神経発達を悪化させる懸念がある。本研究では「デプログラミング作用」を持つと報告されているメラトニンを、出生前ステロイドマウスモデルに投与することで、胎仔脳への副作用を軽減できるかどうかを検討する。具体的には、視床下部―下垂体―副腎系への効果を評価する。
    本研究から得られる知見により、早産児の神経発達を向上させるための新たな治療戦略が明らかとなる可能性がある。また、現在明らかになっていない出生前ステロイドによる胎児脳へのプログラミング作用の機序の一端が明らかになる可能性がある。
    生後4週齢のマウスにストレスを与え、ストレス反応を評価する方法として、げっ歯類では一般的に行われている20分間の拘束ストレスを採用し、ストレス前(0分値)、ストレス後(20分値および60分値)にマウス尾静脈から採血を行った。C57BL/6Jは体格が小さく採血量が不足したため、ICRをもちいた。すると、ストレス前と後では有意にマウス血清コルチコステロン濃度が上昇することが複数回のテストで確認され、ストレス反応を評価する系として妥当であることが確認された。生後4週齢のマウスはヒトの発達では幼児~学童期に相当するため、この時期のストレス反応を評価することは神経発達症の病態解明の上で極めて重要であると考えられる。
    次に、出生前ステロイドに暴露させた妊娠マウスの仔の4週齢において、ストレス反応がコントロールに比べ変化があるかどうかを検討した。様々な濃度・妊娠日齢・タイミングでベタメタゾンを皮下投与したが、ヒト臨床用量(体重換算)の投与量では、4週齢のストレス反応には有意な変化を与えなかった。先行研究ではラットやより大型の動物では出生前ステロイドにより仔のストレス反応に変化がみられたとする報告があるものの、ICRマウスで評価した報告はこれまでなく、マウスでは反応が乏しい可能性が示唆された。そこで投与量を臨床用量の4~10倍に増量したところ、拘束ストレス後の血清コルチコステロイド濃度が高い傾向を示したため、今後は高用量での投与モデルでの研究を継続する予定である。出生前ステロイド投与があった児となかった児で、新生児期・学童期のストレス反応が異なることは、ヒトでも複数報告があり、マウスで再現が得られれば、ヒトとマウスの共通の表現型として、トランスレーショナルリサーチの可能性が開ける。
    出生前ステロイドが仔のストレス反応に与える影響を、マウスで再現するモデル作成に難渋している。ステロイドの投与量を増量することで、再現の傾向が見られており、引き続き実験を重ねる予定である。
    これまで、数時間かけて各群の複数のマウスに拘束ストレス・採血の実験系を実施していたが、コルチコステロンの日内変動はマウスでも知られていることから、実験時間を同じくする工夫が必要であるとわかり、今後の課題となっている。