Updated on 2024/11/18

写真a

 
TANO Sho
 
Organization
Nagoya University Hospital Obstetrics and Gynecology Assistant Professor
Graduate School
Graduate School of Medicine
Title
Assistant Professor

Degree 1

  1. M.D., PhD. ( 2022.9   Nagoya University ) 

Research Areas 1

  1. Life Science / Obstetrics and gynecology

Committee Memberships 3

  1. 日本超音波医学会中部地方会   運営委員  

    2024.9   

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    Committee type:Academic society

  2. 日本周産期・新生児医学会   評議員  

    2024.7 - 2026.7   

  3. 日本胎盤学会   評議員  

    2023.4 - 2026.3   

Awards 7

  1. Best Scientific Paper of the Year

    2022.6   Japan Society of Obstetrics and Gynecology  

  2. 第48回日本女性栄養・代謝学会学術集会 優秀演題賞

    2024.8   日本女性栄養・代謝学会  

  3. 2024年度臨床研究Award

    2024.6   日本周産期・新生児医学会  

  4. 日本超音波医学会第97回学術集会 奨励賞

    2024.6   日本超音波医学会  

  5. 第39回日本糖尿病・妊娠学会年次学術集会 若手奨励賞

    2023.11   日本糖尿病・妊娠学会  

  6. 令和4年度名古屋大学医師会 研究奨励賞

    2022.11   名古屋大学医師会  

  7. 第42回日本妊娠高血圧学会学術集会 学術奨励賞

    2022.10   日本妊娠高血圧学会  

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Papers 40

  1. Assisted reproductive technology and prolonged third stage of labour: a multicentre study in Japan

    Kato A., Ushida T., Matsuo S., Tano S., Imai K., Yoshida S., Yamashita M., Kajiyama H., Kotani T.

    Reproductive BioMedicine Online   Vol. 49 ( 6 )   2024.12

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    Research question: What are the risk factors for a prolonged third stage of labour, closely related to postpartum haemorrhage, and what is the effect of assisted reproductive technology (ART) on the third stage of labour? Design: Clinical data of women who delivered vaginally at term at 12 primary maternity hospitals in Japan (2010–2018) (n = 25,336) were obtained; 1148 (4.5%) conceived through ART and 2246 (8.9%) through non-ART treatments. The risk of a prolonged third stage of labour (defined as ≥20 min) was evaluated by univariable and multivariable regression analyses. Adjusted odds ratios (aOR) of a prolonged third stage of labour were evaluated, stratified by the type of ART, with natural conception as a reference. Results: Multivariable analysis showed that pregnancy achieved through ART (aOR 4.38, 95% CI 3.12 to 6.15), history of spontaneous miscarriage (OR 1.40, 95% CI 1.06 to 1.84) and prolonged labour (OR 1.52, 95% CI 1.09 to 2.12) were identified as independent risk factors. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC–FET) and blastocyst-stage embryo transfer were significantly associated with a prolonged third stage of labour (aOR 4.07, 95% CI 2.75 to 6.04, aOR 4.11, 95% CI 2.58 to 6.57 and aOR 2.13, 95% CI 1.15 to 3.95, respectively). No significant difference was observed in the duration of third stage of labour between natural conception and non-ART treatment (P = 0.61). Conclusion: Pregnancy achieved through ART, particularly FET, HRC–FET and blastocyst-stage embryo transfer, was a significant risk factor for a prolonged third stage of labour.

    DOI: 10.1016/j.rbmo.2024.104382

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

    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   Vol. 302   page: 7 - 14   2024.11

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    Language:English   Publisher: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 220/7 and 336/7 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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  3. Aging affects regrowth of stealthperitoneal dissemination of advanced ovarian cancer: a multicenter retrospective cohort study

    Fujimoto, H; Yoshihara, M; Ricciardelli, C; Tano, S; Iyoshi, S; Miyamoto, E; Mogi, K; Hayashi, M; Hayakawa, S; Nomura, S; Kitami, K; Uno, K; Yoshikawa, N; Emoto, R; Matsui, S; Kajiyama, H

    SCIENTIFIC REPORTS   Vol. 14 ( 1 ) page: 23537   2024.10

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    Ovarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology.

    DOI: 10.1038/s41598-024-66419-w

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

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

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS     2024.10

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    Publisher: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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  5. Elevated levels of apolipoprotein A4 in umbilical cord serum from the maternal major depressive disorder

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

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH     2024.9

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    Publisher:Journal of Obstetrics and Gynaecology Research  

    Aim: Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD). Methods: Liquid chromatography–tandem mass spectrometry (LC–MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme-linked immunosorbent assay. Results: The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum. Conclusions: The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring.

    DOI: 10.1111/jog.16096

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  6. Possible Efficacy of Vaginal Progesterone on Asymptomatic Women with a Short Cervix after 24 Weeks of Gestation: A Historical Cohort Study in Japan

    Otsuka, N; Imai, K; Tano, S; Matsuo, S; Ushida, T; Nomoto, M; Iitani, Y; Ishi, M; Kawai, Y; Furui, T; Kajiyama, H; Kotani, T

    JMA JOURNAL     2024.9

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

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

    BMC PREGNANCY AND CHILDBIRTH   Vol. 24 ( 1 )   2024.9

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    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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  8. TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta

    Miki R., Matsuo S., Ushida T., Tano S., Imai K., Nawa A., Kajiyama H., Kotani T.

    Molecular and Cellular Endocrinology   Vol. 591   page: 112277   2024.9

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    Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.

    DOI: 10.1016/j.mce.2024.112277

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  9. PATHOPHYSIOLOGY OF INCREASED VASCULAR PERMEABILITY MEDIATED BY PLACENTA-DERIVED EXTRACELLULAR VESICLES IN PREECLAMPSIA.

    Matsuo, S; Yokoi, A; Ushida, T; Yoshida, K; Kitagawa, M; Inami, E; Tano, S; Imai, K; Kajiyama, H; Kotani, T

    PLACENTA   Vol. 154   page: 226 - 226   2024.9

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  10. Identifying the high-benefit population for weight management-based cardiovascular disease prevention in Japan

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

    Preventive Medicine Reports   Vol. 43   2024.7

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    Background: Cardiovascular-disease (CVD) is the leading cause of death, and the association between obesity and CVD is particularly significant among women. Given the evidence highlighting the significance of weight-gain velosity, we aimed to elucidate its influence on cardio-ankle vascular index (CAVI), a reliable surrogate marker of CVD, and identify the high-benefit population where this influence is most pronounced. Methods: This multicenter retrospective study used electronic data from annual health checkups for workers in Japan. Individuals who voluntarily measured CAVI in 2019 were included, and weight-gain velosity was defined as the mean BMI gain from 2015 to 2019. Our primary outcome was the relationship between weight-gain velosity and CAVI. Results: Among 459 individuals, 53 had CAVI ≥ 9. Random forest analysis revealed that age was the most important factor, followed by lipid metabolism, weight-gain velosity, and glucose metabolism, with sex being the least important. Non-linear regression analysis of the effect of age on CAVI ≥ 9 showed the effect was pronounced after age 60, and the trend was greater in women. Among individuals aged 60 or younger, the aOR of weight-gain velosity for CAVI ≥ 9 was significantly positive (aOR 11.95, 95 %CI 1.13–126.27), while it was not significant for those older than 60. The relationship between weight-gain velosity and CAVI provides a new perspective on CVD risk factors. The effects of age, especially after 60, and weight-gain velosity in early- to middle-adulthood on arterial stiffness are emphasized. Conclusions: These findings underscore the importance of weight management under age 60, especially in women.

    DOI: 10.1016/j.pmedr.2024.102782

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  11. Amniotic fluid-derived small extracellular vesicles for predicting postnatal severe outcome of congenital diaphragmatic hernia.

    Matsuo S, Yokoi A, Yoshida K, Kitagawa M, Asano-Inami E, Miura M, Yasui T, Tano S, Ushida T, Imai K, Kajiyama H, Kotani T

    Journal of extracellular biology   Vol. 3 ( 6 ) page: e160   2024.6

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    DOI: 10.1002/jex2.160

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  12. Postpartum and interpregnancy care of women with a history of hypertensive disorders of pregnancy

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

    HYPERTENSION RESEARCH   Vol. 47 ( 6 ) page: 1457 - 1469   2024.3

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    Hypertensive disorders of pregnancy (HDP) are common complications associated with maternal and neonatal morbidity and mortality worldwide. Insights gained from long-term cohort studies have revealed that women with a history of HDP are predisposed to recurrent HDP in subsequent pregnancies and face heightened risks for cardiovascular and metabolic diseases later in life. Pregnancy is a unique condition that overloads maternal cardiac and metabolic functions, and is recognized as a “maternal stress test” for future cardiovascular and metabolic diseases. Pregnancy and postpartum period provide a valuable opportunity for identifying women with underlying and unrecognized cardiovascular and metabolic risk factors. Establishing an effective postpartum healthcare program for women who have experienced HDP is crucial in reducing the future risk of health complications. Postpartum care consists of supportive care for both mothers and children, including not only the assessment of physical and psychological well-being but also long-term postpartum preventive health management. Interpregnancy care is a continuum from postpartum care and includes supportive care to prepare for future pregnancies. Various initiatives across nations have been initiated to establish follow-up programs for women with a history of HDP; however, sufficient evidence of the impact of such programs is not available. Substantial challenges persist in establishing an efficient postpartum follow-up program, including educational strategies, selection of effective lifestyle interventions, and collaboration among various healthcare providers. This review outlines the postpartum and interpregnancy care of women who have experienced HDP as well as the current status and challenges of related healthcare initiatives in Japan. (Figure presented.)

    DOI: 10.1038/s41440-024-01641-7

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  13. Predicting preterm birth within 2 weeks in asymptomatic women with a short cervix: Combined effects of cervicovaginal fluid cytokine levels and fetal fibronectin test

    Ohori, Y; Imai, K; Tano, S; Owaki, T; Miki, R; Nozaki, Y; Ushida, T; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH     2024.1

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    Language:English   Publisher:Journal of Obstetrics and Gynaecology Research  

    Aims: To predict preterm birth (PTB) accurately, we conducted a comprehensive cytokine assay using cervicovaginal fluid (CVF) and evaluated the additive effects of cytokine levels on the fetal fibronectin (fFN) test. Methods: A total of 645 CVF samples were collected from 256 asymptomatic pregnant women between 24 and 35 weeks gestation, exhibiting short cervix. After selection based on specific criteria, 17 cytokines in 105 CVF samples were simultaneously measured using multiplex assay. Multivariate logistic regression analysis was performed to evaluate the association between cytokine levels and impending PTB, which is defined as PTB within 2 weeks after CVF collection. Moreover, receiver operating characteristic (ROC) analysis was performed in women with positive fFN results, which was validated using another set of 65 CVF samples. Results: In positive fFN women, the CCL2 level was significantly higher in the impending PTB group than the other group (p < 0.01) and a predictor of impending PTB (adjusted odds ratio 1.020, 95% confidence interval [95% CI] 1.003–1.038, p = 0.020). The cutoff value of CCL2 was 64.8 pg/mL (are under the curve 0.726, p = 0.004, 95% CI 0.593–0.859, sensitivity 45.2%, specificity 91.7%). Additionally, the reliable classification performance of proposed ROC model could be validated. However, measuring cytokine levels could not help in predicting impending PTB in women with negative fFN or normal labor onset in healthy-term women. Conclusion: Comprehensive analysis of CVF cytokines revealed that the CCL2 level significantly improves the prediction of impending PTB in asymptomatic fFN-positive women with a short cervix, which may contribute to better clinical management.

    DOI: 10.1111/jog.15889

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  14. Risk factors for non-previa placenta accreta spectrum in pregnancies conceived through frozen embryo transfer during a hormone replacement cycle in Japan

    Matsuo, S; Kotani, T; Tano, S; Ushida, T; Imai, K; Nakamura, T; Osuka, S; Goto, M; Osawa, M; Asada, Y; Kajiyama, H

    REPRODUCTIVE MEDICINE AND BIOLOGY   Vol. 23 ( 1 ) page: e12592   2024.1

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    Purpose: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies. Methods: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer—HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)—were collected. Univariable logistic regression analyses were conducted. Results: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98–21.02]), endometrial thickness <8.0 mm (6.11 [1.06–35.12]), resolved low-lying placenta (5.73 [2.13–15.41]), multiparity (2.90 [1.26–6.69]), polycystic ovarian syndrome (2.62 [1.02–6.71]), and subchorionic hematoma (2.49 [1.03–6.04]). Conclusions: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

    DOI: 10.1002/rmb2.12592

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  15. Practical weight management to minimize pregnancy complications and promote women’s health: the possibility of interpregnancy care

    Kotani T., Tano S., Ushida T., Imai K., Kajiyama H.

    Nagoya Journal of Medical Science   Vol. 86 ( 2 ) page: 160 - 168   2024

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    Publisher:Nagoya Journal of Medical Science  

    Pregnancy is an excellent opportunity to provide medical interventions to women. It is also a stress test used to predict health. Numerous studies have demonstrated that the pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are critical factors for pregnancy complications such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), large or small gestational age infants, and spontaneous preterm birth (sPTB). These complications are associated with an increased risk of cardiovascular disease (CVD), which is a leading cause of mortality in women. In addition, complications adversely affect the short- and long-term prognoses of children. Optimal GWG to reduce complications is recommended based on pre-pregnancy BMI; however, racial differences should also be noted. The values in the Japanese guidelines are lower than those in the American Institute of Medicine guidelines. The Asian BMI thresholds for CVD risk are also lower than those in Europe. Therefore, weight management should be based on racial/genetic background. Interpregnancy weight gain or loss has also been reported to be associated with the risk of pregnancy complications; however, few studies have been conducted in Asian populations. Our previous reports suggested that avoiding an excess of 0.6 kg/m2/year of annual BMI gain may reduce the risk of HDP or GDM, and insufficient gain of < 0.25 kg/m2/year may increase sPTB recurrence. Annual BMI is useful for practical weight control during interpregnancy. Based on these findings, effective approaches should be established to improve the health of women and their offspring.

    DOI: 10.18999/nagjms.86.2.160

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  16. Sex-specific differences in head circumference of term singletons after assisted reproductive technology: a multicentre study in Japan

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

    REPRODUCTIVE BIOMEDICINE ONLINE   Vol. 47 ( 6 ) page: 103331   2023.12

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    Research question: Does fertility treatment, specifically assisted reproductive technology (ART), affect head circumference in term singletons? Design: A total of 32,651 women who delivered at term at 12 maternity hospitals in Japan between 2010 and 2018 were included in the analysis; of these, 1941 (5.9%) and 2984 (9.1%) women conceived through ART and non-ART fertility treatments (timed intercourse, ovulation induction or artificial insemination), respectively. The study evaluated the adjusted odds ratios of head circumference ≥90th percentile stratified by infant sex and type of ART procedure after adjusting for covariates, with natural conception as the reference group. Results: ART significantly increased the risk of head circumference ≥90th percentile (adjusted odds ratio 1.56 [95% confidence interval 1.25–1.96]), whereas non-ART fertility treatment did not increase the risk (1.14 [0.92–1.42]). This increased risk of head circumference ≥90th percentile was observed exclusively in male neonates (1.73 [1.33–2.26]) and not in female neonates (1.18 [0.76–1.85]) in the ART group. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with head circumference ≥90th percentile (1.60 [1.26–2.02], 1.70 [1.30–2.22] and 1.72 [1.33–2.24], respectively). Conclusions: The use of ART, particularly FET, HRC-FET or blastocyst-stage embryo transfer, was linked with a heightened risk of head circumference ≥90th percentile compared with non-ART fertility treatment or natural conception. The increased risk was observed only in male neonates.

    DOI: 10.1016/j.rbmo.2023.103331

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  17. Long-term effects of gestational weight gain on mortality

    Kotani, T; Tano, S

    LANCET   Vol. 402 ( 10415 ) page: 1809 - 1811   2023.11

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    DOI: 10.1016/S0140-6736(23)01837-8

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  18. 9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins

    Mogi, K; Koya, Y; Yoshihara, M; Sugiyama, M; Miki, R; Miyamoto, E; Fujimoto, H; Kitami, K; Iyoshi, S; Tano, S; Uno, K; Tamauchi, S; Yokoi, A; Shimizu, Y; Ikeda, Y; Yoshikawa, N; Niimi, K; Yamakita, Y; Tomita, H; Shibata, K; Nawa, A; Tomoda, Y; Kajiyama, H

    SCIENTIFIC REPORTS   Vol. 13 ( 1 ) page: 19208   2023.11

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    Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25–50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

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  19. The prognostic impact of limited-staging surgery in patients with stage ia epithelial ovarian cancer: a multi-center study with a propensity score-adjusted analysis

    Miyamoto, E; Suzuki, H; Yoshihara, M; Iyoshi, S; Mogi, K; Uno, K; Fujimoto, H; Kitami, K; Tano, S; Kajiyama, H

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 33 ( SUPPL_4 ) page: A196 - A196   2023.11

  20. Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles

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

    PEDIATRIC RESEARCH   Vol. 95 ( 1 ) page: 167 - 173   2023.9

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    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 |log2FC | >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.

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  21. The balance between fetal oxytocin and placental leucine aminopeptidase (P-LAP) controls human uterine contraction around labor onset

    Yoshihara, M; Mizutani, S; Matsumoto, K; Kato, Y; Masuo, Y; Harumasa, A; Iyoshi, S; Tano, S; Mizutani, H; Kotani, T; Mizutani, E; Shibata, K; Kajiyama, H

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY-X   Vol. 19   page: 100210   2023.9

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    A fetal pituitary hormone, oxytocin which causes uterine contractions, increases throughout gestation, and its increase reaches 10-fold from week 32 afterward. Oxytocin is, on the other hand, degraded by placental leucine aminopeptidase (P-LAP) which exists in both terminal villi and maternal blood. Maternal blood P-LAP increases with advancing gestation under the control of non-genomic effects of progesterone, which is also produced from the placenta. Progesterone is converted to estrogen by CYP17A1 localized in the fetal adrenal gland and placenta at term. The higher oxytocin concentrations in the fetus than in the mother demonstrate not only fetal oxytocin production but also its degradation and/or inhibition of leakage from fetus to mother by P-LAP. Until labor onset, the pregnant uterus is quiescent possibly due to the balance between increasing fetal oxytocin and P-LAP under control of progesterone. A close correlation exists between the feto-placental and maternal units in the placental circulation, although the blood in the two circulations does not necessarily mix. Fetal maturation results in progesterone withdrawal via the CYP17A1 activation accompanied with fetal oxytocin increase. Contribution of fetal oxytocin to labor onset has been acknowledged through the recognition that the effect of fetal oxytocin in the maternal blood is strictly regulated by its degradation by P-LAP under the control of non-genomic effects of progesterone. In all senses, the fetus necessarily takes the initiative in labor onset.

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  22. Comparison of the efficacy between controlled-release dinoprostone delivery system (PROPESS) and Cook's double balloon catheter plus oxytocin: A retrospective single-center study in Japan

    Imai, K; Nozaki, Y; Ushida, T; Tano, S; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 49 ( 9 ) page: 2317 - 2323   2023.9

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    Aims: To compare the efficacy of the controlled-release dinoprostone delivery system (PROPESS) and Cook's double balloon catheter (DBC) plus oxytocin as induction treatment. Methods: A total of 197 term pregnant women with unfavorable cervix were admitted for scheduled induction and enrolled retrospectively (PROPESS, 113; Cook's DBC plus oxytocin, 84). The main birth outcomes were cervical ripening at the treatment-end and 24 h after the treatment-start, and rate of vaginal birth. Logistic regression and propensity score matching analyses were performed to evaluate the association between the outcomes and clinical characteristics including which treatment was selected. Results: The choice of PROPESS was associated with the success of cervical ripening at 24 h after (adjusted odds ratio (OR) 2.17, 95% confidence interval (CI) 1.11–4.26, p = 0.024) and increased the rate of vaginal birth (adjusted OR 2.03, 95% CI 1.04–3.98, p = 0.039). Similar trends in the association between PROPESS and birth outcomes were maintained after adjusting for propensity scores (p = 0.072 and p = 0.163, respectively). However, some of the women with gestational age of early 39 weeks and low Bishop scores could achieve cervical ripening at 24 h after using Cook's DBC plus oxytocin, and none by PROPESS. Conclusion: Our findings suggest the possibility of slight advantages of PROPESS for scheduled induction of labor. In women with early term and extremely low Bishop scores, Cook's DBC plus oxytocin may be a superior or alternative treatment to PROPESS. Therefore, the optimal choice of induction treatment should be managed on an individual basis.

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  23. The prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer: a multi-center study with a propensity score-adjusted analysis

    Miyamoto, E; Suzuki, H; Yoshihara, M; Mogi, K; Iyoshi, S; Uno, K; Fujimoto, H; Kitami, K; Tano, S; Emoto, R; Matsui, S; Kajiyama, H

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   Vol. 53 ( 8 ) page: 698 - 703   2023.7

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    Objective: Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. Methods: We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. Results: In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. Conclusions: The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.

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

    Nakamura, N; Ushida, T; Onoda, A; Ueda, K; Miura, R; Suzuki, T; Katsuki, S; Mizutani, H; Yoshida, K; Tano, S; Iitani, Y; Imai, K; Hayakawa, M; Kajiyama, H; Sato, Y; Kotani, T

    FRONTIERS IN PEDIATRICS   Vol. 11   page: 1168173   2023.7

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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 < 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.

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  25. Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study

    Tano, S; Kotani, T; Ushida, T; Yoshihara, M; Imai, K; Nakamura, N; Iitani, Y; Moriyama, Y; Emoto, R; Kato, S; Yoshida, S; Yamashita, M; Kishigami, Y; Oguchi, H; Matsui, S; Kajiyama, H

    DIABETOLOGY & METABOLIC SYNDROME   Vol. 15 ( 1 ) page: 123   2023.6

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    Background: Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies. Methods: This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG. Results: Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02–1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38–0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11–1.73), respectively. Conclusions: A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.

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  26. Clinical significances of Bishop score and vaginal bleeding to controlled-release dinoprostone delivery system (PROPESS) efficacy for cervical ripening: A retrospective single-center study in Japan

    Imai, K; Aoki, C; Tano, S; Iitani, Y; Nakamura, N; Ushida, T; Kajiyama, H; Kotani, T

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 49 ( 4 ) page: 1154 - 1160   2023.4

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    Aims: To evaluate the effect of vaginal bleeding on the efficacy of controlled-release dinoprostone delivery system (PROPESS) for cervical ripening and the factors affecting the PROPESS efficacy in a Japanese clinical setting. Methods: A total of 100 term pregnant women in whom PROPESS was used due to an unfavorable cervix (Bishop score ≤ 6) were enrolled. We retrospectively investigated which factors, including vaginal bleeding, were associated with the success of cervical ripening using logistic regression analysis. Moreover, the effect of vaginal bleeding on vaginal acidity was examined in 24 selected cases (control, 11; rupture of membrane, 4; and vaginal bleeding, 8). Results: A 25 women successfully ripened the cervix (effective group), and 75 were unsuccessful (noneffective group). Bishop score at insertion (adjusted odds ratio: 1.87; 95% confidence interval: 1.23–2.86; p = 0.004), and vaginal bleeding at PROPESS insertion (adjusted odds ratio 6.63; 95% confidence interval 1.21–36.36; p = 0.029) affected cervical ripening success. The cases with vaginal bleeding showed a significantly higher vaginal pH than the control cases (median value: 6.75 and 5.0, respectively). We identified no obvious adverse outcomes, such as tachysystole, fetal heart rate abnormality, or low Apgar/pH, associated with vaginal bleeding at insertion. Conclusions: Our findings suggest that the PROPESS efficacy depends on Bishop score at insertion and that vaginal bleeding at PROPESS insertion might have a significantly positive effect on cervical ripening in term pregnant women.

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  27. Trend changes in age-related body mass index gain after coronavirus disease 2019 pandemic in Japan: a multicenter retrospective cohort study

    Tano, S; Kotani, T; Ushida, T; Iitani, Y; Imai, K; Kinoshita, F; Kajiyama, H

    REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY   Vol. 21 ( 1 ) page: 7   2023.1

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    Background: Accumulating studies suggest that strict lockdown with enforcement including segregation to control the coronavirus disease 2019 (COVID-19) pandemic is associated with excess weight gain, but the such lockdown was not practiced in Japan. We aimed to compare the age-related weight gain before and after the COVID-19 pandemic in Japan where achieved epidemic control based on individual voluntary action. Methods: This multicenter retrospective cohort study used electronic data from annual health checkups for workers from January 2015 to December 2021 at four facilities belonging to the Central Clinic Group, Aichi, Japan. We defined pre-pandemic and post-pandemic periods as January 2015–December 2019 and January 2020–December 2021, respectively. Participants were grouped by sex, age, and body mass index (BMI) stratus as of 2015, and the pre-pandemic and post-pandemic age-related BMI changes in overall individuals and each specific group were compared using a paired t-test. Results: The total number of eligible participants was 19,290. During the pre-pandemic period, the mean BMI increased linearly in every group. The mean age-related BMI changes in females’ pre-pandemic and post-pandemic periods were + 0.11 and + 0.02 kg/m2/year, respectively. This significant decrease was also shown in males, + 0.11 in the pre-pandemic and − 0.02 kg/m2/year in the post-pandemic periods. The reduction was consistently observed in all age strata. Furthermore, a significant reduction was also observed in the normal-weight females of reproductive ages aged 15–44 years. Conclusions: This is the first report showing that age-related weight gain was reduced after the COVID-19 pandemic in Japan, which could affect the reproductive age of females.

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  28. Predictive performance of Shock Index for postpartum hemorrhage during cesarean delivery

    Mizutani H., Ushida T., Ozeki K., Tano S., Iitani Y., Imai K., Nishiwaki K., Kajiyama H., Kotani T.

    International Journal of Obstetric Anesthesia     page: 103957   2023

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    Background: The Shock Index (SI), defined as heart rate divided by systolic blood pressure, is reportedly an early surrogate indicator for postpartum hemorrhage (PPH). However, most previous studies have used clinical data of women who delivered vaginally. Therefore, we aimed to evaluate the SI pattern during cesarean delivery and determine its usefulness in detecting PPH. Methods: This was a single-center retrospective study using the clinical data of women (n = 331) who underwent cesarean delivery under spinal anesthesia at term between 2018 and 2021. We assessed the SI pattern stratified by total blood loss and evaluated the predictive performance of each vital sign in detecting PPH (total blood loss ≥1000 mL) based on the area under the receiver operating characteristic curve (AUROC). Results: At 10–15 min after delivery, the mean SI peaked between 0.84 and 0.90 and then decreased to a level between 0.72 and 0.77, which was similar to that upon entering the operating room. Among 331 women, 91 (27.5%) were diagnosed with PPH. There was no correlation between SI and total blood loss (rs = 0.02). The SI had low ability to detect PPH (AUROC 0.54, 95% confidence interval 0.47 to 0.61), which was similar to other vital signs (AUROCs 0.53–0.56). Conclusion: We determined the pattern of SI during cesarean delivery. We found no correlation between SI and total blood loss. Unlike in vaginal delivery, the prognostic accuracy of SI for PPH detection in cesarean delivery was low.

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  29. A case of non-immune hydrops fetalis with maternal mirror syndrome diagnosed by trio-based exome sequencing: An autopsy case report and literature review

    Tano, S; Kotani, T; Yoshihara, M; Nakamura, N; Matsuo, S; Ushida, T; Imai, K; Ito, M; Oka, Y; Sato, E; Hayashi, S; Ogi, T; Kajiyama, H

    MOLECULAR GENETICS AND METABOLISM REPORTS   Vol. 33   page: 100925   2022.12

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    Non-immune hydrops fetalis (NIHF) indicates the risk for stillbirth. Although the causes vary and most NIHFs have no identifiable cause, recent advances in exome sequencing have increased diagnostic rates. We report a case of NIHF that developed into a giant cystic hygroma complicated by maternal mirror syndrome. Trio-based exome sequencing showed a de novo heterozygous missense variant in the RIT1 (NM_006912: c.246 T > G [p.F82L]). The RIT1 variants are known causative variants of Noonan syndrome (NS; OMIM #163950). The location of the RIT1 variants in the previously reported NS cases with NIHF or/and maternal mirror syndrome was mainly in the switch II region, including the present case. While a further accumulation of cases is needed, exome sequencing, which can identify the variant type in detail, might help predict the phenotype and severity of NIHF.

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  30. Optimal annual body mass index change for preventing spontaneous preterm birth in a subsequent pregnancy

    Tano, S; Kotani, T; Ushida, T; Yoshihara, M; Imai, K; Nakano-Kobayashi, T; Moriyama, Y; Iitani, Y; Kinoshita, F; Yoshida, S; Yamashita, M; Kishigami, Y; Oguchi, H; Kajiyama, H

    SCIENTIFIC REPORTS   Vol. 12 ( 1 ) page: 17502   2022.10

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    Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Although PTB is known to recur, interpregnancy preventive strategies for PTB have not been established to date. Annual BMI change can serve as a specific target value for preventing obstetric complications during interpregnancy care/counseling. This value can also account for age-related weight gain (0.2 kg/m2/year). In a multicenter retrospective study, we investigated the optimal annual BMI change for preventing PTB recurrence using the data of individuals who had two singleton births from 2009 to 2019. The association between annual BMI change and spontaneous PTB (sPTB) was analyzed by separating cases of medically indicated PTB (mPTB) from those of sPTB. Previous history of sPTB was strongly associated with sPTB in the subsequent pregnancy (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 6.5–24.8). Increase in annual BMI was negatively associated with sPTB (aOR, 0.6; 95% CI 0.5–0.9). The sPTB recurrence rate was significantly lower in patients with an annual BMI change of ≥ 0.25 kg/m2/year than in those with an annual BMI change of < 0.25 kg/m2/year (7.7% vs. 35.0%, p = 0.011). Our findings suggest that age-related annual BMI gain between pregnancies may help prevent sPTB recurrence.

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  31. 5p deletion with congenital diaphragmatic hernia: a case report

    Kotani, T; Ushida, T; Nakamura, N; Imai, K; Iitani, Y; Tano, S; Iwagaki, S; Takahashi, Y; Ito, M; Hayakawa, M; Kajiyama, H

    JOURNAL OF MEDICAL CASE REPORTS   Vol. 16 ( 1 ) page: 390   2022.10

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    Background: 5p deletion syndrome is known as cri-du-chat syndrome, but there are no reports on congenital diaphragmatic hernia complications associated with it. Case presentation: A 28-year-old primigravida Japanese woman was referred for 5 mm of nuchal translucency. Fetal growth restriction was found at 20 weeks, and a left-sided congenital diaphragmatic hernia was diagnosed at 24 weeks. The karyotype of the fetus was diagnosed as 46, XX, del(5)(p14) and referred to our hospital. At 36 + 6 weeks, a 1524 g female infant was delivered after premature membrane rupture, with Apgar scores of 4 and 6 at 1 and 5 minutes, respectively. The baby was intubated immediately with sedation and muscle relaxation, after birth for initial treatment for congenital diaphragmatic hernia. The peripheral blood karyotype was consistent with the prenatal result. The infant was discharged alive, without any respiratory support, after the defect of the diaphragm was repaired. Conclusion: The results of this study may be helpful for antenatal genetic counseling.

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  32. Who are the long-term survivors of recurrent ovarian carcinoma?: a retrospective analysis of a multicenter study

    Yoshihara, M; Mogi, K; Kitami, K; Uno, K; Iyoshi, S; Tano, S; Fujimoto, H; Miyamoto, E; Yoshikawa, N; Emoto, R; Matsui, S; Kajiyama, H

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 27 ( 10 ) page: 1660 - 1668   2022.10

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    Background: The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. Methods: We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. Results: We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026–3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546–5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. Conclusion: RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.

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  33. DEVELOPING OF A NOVEL THERAPEUTIC AGENT FOR FGR THROUGH DRUG REPOSITIONING

    Tano, S; Kotani, T; Ushida, T; Nakamura, N; Iitani, Y; Yoshihara, M; Imai, K; Kajiyama, H

    PLACENTA   Vol. 128   page: 124 - 124   2022.10

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  34. Proton beam therapy for the isolated recurrence of endometrial cancer in para-aortic lymph nodes: a case report

    Uno, K; Yoshihara, M; Tano, S; Takeda, T; Kishigami, Y; Oguchi, H

    BMC WOMENS HEALTH   Vol. 22 ( 1 ) page: 375   2022.9

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    Background: Proton beam therapy penetrates tumor tissues with a highly concentrated dose. It is useful when normal structures are too proximate to the treatment target and, thus, may be damaged by surgery or conventional photon beam therapy. However, proton beam therapy has only been used to treat recurrent endometrial cancer in a few cases; therefore, its effectiveness remains unclear. Case presentation: We herein report a case of the isolated recurrence of endometrial cancer in the para-aortic lymph nodes in a 59-year-old postmenopausal woman that was completely eradicated by proton beam therapy. The patient was diagnosed with stage IIIC2 endometrial cancer and treated with 6 courses of doxorubicin (45 mg/m2) and cisplatin (50 mg/m2) in adjuvant chemotherapy. Fifteen months after the initial therapy, the isolated recurrence of endometrial cancer was detected in the para-aortic lymph nodes. The site of recurrence was just under the left renal artery. Due to the potential risks associated with left kidney resection due to the limited surgical space between the tumor and left renal artery, proton beam therapy was administered instead of surgery or conventional photon beam therapy. Following proton beam therapy, the complete resolution of the recurrent lesion was confirmed. No serious complications occurred during or after treatment. There have been no signs of recurrence more than 7 years after treatment. Conclusions: Proton beam therapy is a potentially effective modality for the treatment of recurrent endometrial cancer where the tumor site limits surgical interventions and the use of conventional photon beam therapy.

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  35. Obesity contributes to the stealth peritoneal dissemination of ovarian cancer: a multi-institutional retrospective cohort study

    Iyoshi, S; Sumi, A; Yoshihara, M; Kitami, K; Mogi, K; Uno, K; Fujimoto, H; Miyamoto, E; Tano, S; Yoshikawa, N; Emoto, R; Matsui, S; Kajiyama, H

    OBESITY   Vol. 30 ( 8 ) page: 1599 - 1607   2022.8

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    Objective: The clinical significance of a higher BMI on the prognosis of ovarian cancer remains controversial; therefore, a more detailed analysis is demanded. This study investigated the impact of BMI on peritoneum-specific recurrence to clarify the involvement of adipose tissue in the proliferation of cancer cells at sites of peritoneal dissemination. Methods: Among 4,730 patients with malignant ovarian tumors, 280 diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIC epithelial ovarian cancer and who underwent complete resection in the primary surgery were included in the present study. Results: There were 42, 201, and 37 women in the low, normal, and high BMI groups, respectively. Peritoneum-specific recurrence-free survival and overall survival were both significantly shorter in patients with a high BMI than in those with a normal BMI (p = 0.028 and 0.018, respectively). No significant differences were observed in the distribution of sites of recurrence between these two groups. A multivariate analysis identified obesity as an independent prognostic factor in addition to pT3 tumor staging and positive ascites cytology. Conclusions: Patients with a high BMI had a significantly worse prognosis than those with a normal BMI, and peritoneal adipose tissue may have contributed to this difference.

    DOI: 10.1002/oby.23497

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  36. Crosstalk between foetal vasoactive peptide hormones and placental aminopeptidases regulates placental blood flow: Its significance in preeclampsia

    Yoshihara, M; Mizutani, S; Matsumoto, K; Kato, Y; Masuo, Y; Tano, S; Mizutani, H; Kotani, T; Mizutani, E; Shibata, K; Kajiyama, H

    PLACENTA   Vol. 121   page: 32 - 39   2022.4

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    In pregnancy, placental circulation occurs through two independent circulation systems: foetoplacental and uterine (spiral artery)-placental lake. Crosstalk between the foetal peptide hormones, angiotensin II (A-II) and vasopressin (AVP), and their degrading placental aminopeptidases (APs), aminopeptidase A for A-II and placental leucine aminopeptidase for both AVP and oxytocin, primarily regulate placental circulation. On the other hand, placental circulation represents an arteriovenous shunt. In normal pregnancy, the blood pressure decreases, despite increased cardiac output and plasma volume, probably due to the arteriovenous shunt in the growing placenta. Actually, the foetal vasoactive hormones in the foetoplacental circulation are much higher than those in the maternal circulation throughout pregnancy. In normal pregnancy, AP activity derived from the placenta in maternal blood increases with gestation and placental growth. Foetal hypoxia increases the secretion of foetal both AVP and A-II. Although there is an increase in both AP activities in the maternal blood in normal pregnancy, their activities increase more than those in normal pregnancy during mild preeclampsia. However, both AP activities decline significantly compared than those in severe preeclampsia. This suggests that AP prevents leakage of increased foetal vasoactive hormones into the maternal blood in mild preeclampsia, and its protective role breaks down in severe preeclampsia, leading to a massive leak of the hormones into maternal circulation and consequent marked contraction of both the maternal vessels and the uterus. Consequently, AP activity in both placenta and maternal blood acts as the foeto-maternal barrier for foetal vasoactive hormones and thus contributes to the onset of preeclampsia.

    DOI: 10.1016/j.placenta.2022.02.016

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  37. Annual Body Mass Index Gain and Risk of Gestational Diabetes Mellitus in a Subsequent Pregnancy

    Tano, S; Kotani, T; Ushida, T; Yoshihara, M; Imai, K; Nakano-Kobayashi, T; Moriyama, Y; Iitani, Y; Kinoshita, F; Yoshida, S; Yamashita, M; Kishigami, Y; Oguchi, H; Kajiyama, H

    FRONTIERS IN ENDOCRINOLOGY   Vol. 13   page: 815390   2022.3

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    Language:English   Publisher:Frontiers in Endocrinology  

    Introduction: Weight change during the interpregnancy is related to gestational diabetes mellitus (GDM) in the subsequent pregnancy. In interpregnancy care/counseling, the timeframe for goal setting is important, while the timing of the next conception is unpredictable and preventing age-related body weight gain is difficult. This study aimed to investigate the association between annual weight gain during the interpregnancy, which provide clearer timeframe, and GDM in subsequent pregnancies. Methods: This multicenter retrospective study was conducted by collecting data on two pregnancies of the same women in 2009–2019. The association between annual BMI gain and GDM during the subsequent pregnancy was examined. Results: This study included 1,640 pregnant women. A history of GDM [adjusted odds ratio (aOR), 26.22; 95% confidence interval (CI), 14.93–46.07] and annual BMI gain (aOR, 1.48; 95% CI, 1.22–1.81) were related to GDM during the subsequent pregnancy. In the women with a pre-pregnant BMI of <25.0 kg/m2 and without GDM during the index pregnancy, an annual BMI gain of ≥0.6 kg/m2/year during the interpregnancy were associated with GDM in subsequent pregnancies; however, in the other subgroups, it was not associated with GDM in subsequent pregnancies. Conclusions: For women with a pre-pregnant BMI of <25.0 kg/m2 and without GDM during the index pregnancy, maintaining an annual BMI gain of <0.6 kg/m2/year may prevent GDM during the subsequent pregnancy.

    DOI: 10.3389/fendo.2022.815390

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  38. Factors associated with response to compression-based physical therapy for secondary lower limb lymphedema after gynecologic cancer treatment: a multicenter retrospective study

    Yoshihara, M; Kitamura, K; Tsuru, S; Shimono, R; Sakuda, H; Mayama, M; Tano, S; Uno, K; Ukai, MO; Kishigami, Y; Oguchi, H; Hirota, A

    BMC CANCER   Vol. 22 ( 1 ) page: 25   2022.1

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    Background: Lower limb lymphedema (LLL) is one of the most refractory and debilitating complications related to gynecological cancer treatment. We investigated factors associated with response to compression-based physical therapy (CPT) for secondary LLL after gynecologic cancer treatment. Methods: We performed a multicenter retrospective study using the records of seven medical institutions from 2002 and 2014. Patients who developed LLL after gynecological cancer treatment were included. Limb volumes were calculated from the lengths of the limb circumferences at four points. All participants underwent compression-based physical therapy for LLL. Factors, including MLD, indicative of circumference reductions in LLL were determined. Results: In total, 1,034 LLL met the required criteria of for the study. A multivariate linear regression analysis identified age; body mass index (BMI); endometrial cancer; radiotherapy; and initial limb circumference as significant independent prognostic factors related to improvement in LLL. In analysis of covariance for improvement in LLL adjusted by the initial limb circumference and stratified by BMI and radiotherapy, patients with BMI 28 kg/m2 or higher and receiving radiation rarely responded to CPT. Conclusions: Improvements in the lower limb circumference correlated with clinical histories and physical characteristics, which may be used as independent prognostic factors for successful CPT for LLL after gynecological cancer treatment.

    DOI: 10.1186/s12885-021-09163-y

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  39. Annual body mass index gain and risk of hypertensive disorders of pregnancy in a subsequent pregnancy Reviewed

    Sho Tano, Tomomi Kotani, Takafumi Ushida, Masato Yoshihara, Kenji Imai, Tomoko Nakano-Kobayashi, Yoshinori Moriyama, Yukako Iitani, Fumie Kinoshita, Shigeru Yoshida, Mamoru Yamashita, Yasuyuki Kishigami, Hidenori Oguchi, Hiroaki Kajiyama

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 22519   2021.11

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

    DOI: 10.1038/s41598-021-01976-y

  40. Relationship between vaginal group B streptococcus colonization in the early stage of pregnancy and preterm birth: a retrospective cohort study Reviewed

    Tano, S., Ueno, T., Mayama, M., Yamada, T., Takeda, T., Uno, K., Yoshihara, M., Ukai, M., Suzuki, T., Kishigami, Y., & Oguchi, H

    BMC Pregnancy Childbirth   Vol. 21 ( 1 ) page: 141 - 141   2021.2

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

    DOI: 10.1186/s12884-021-03624-9

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Books 2

  1. 増刊号 産婦人科医のための緊急対応サバイバルブック Ⅲ. 産科編 ❷周産期救急疾患への初期対応 常位胎盤早期剝離

    田野 翔, 小谷 友美( Role: Joint author)

    臨床婦人科産科  2024.4 

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    Book type:General book, introductory book for general audience

  2. 特集 産婦人科における素朴な疑問と解説(2)産科編 Rh式血液型不適合妊娠よりずっと頻度が高いABO式血液型不適合妊娠でトラブルが少ないのはなぜ? 

    ( Role: Contributor)

    産科と婦人科  2022.11 

Presentations 2

  1. 周産期医療と妊娠糖尿病リスク管理を通じた女性の生涯ヘルスケア向上へのアプローチ Invited

    第40回 日本糖尿病・妊娠学会 年次学術集会  2024.11.23  日本糖尿病・妊娠学会

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    Event date: 2024.11

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  2. 妊娠初期の血糖変動と妊娠高血圧症候群 -周産期領域における血糖変動の臨床的意義とバイオマーカーー

    田野 翔

    日本周産期・新生児医学会 第42回周産期学シンポジウム  2024.1.27  日本周産期・新生児医学会

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    Presentation type:Symposium, workshop panel (public)  

KAKENHI (Grants-in-Aid for Scientific Research) 1

  1. 多角的アプローチに基づく女性の心血管疾患リスク軽減に向けた疾病予防モデルの構築

    Grant number:23K19800  2023.8 - 2025.3

    科学研究費助成事業  研究活動スタート支援

    田野 翔

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    Authorship:Principal investigator 

    Grant amount:\2730000 ( Direct Cost: \2100000 、 Indirect Cost:\630000 )

    女性の心血管疾患(CVD)リスク軽減に妊娠高血圧症候群(HDP)発症予防は極めて重要であり、HDPとCVDの共通のリスクに肥満がある。体重管理が発症予防に重要であるが、体重管理の方法についてはエビデンスがなかった。本研究の目的は、周産期データと健診データのビッグデータを連結し、得られた詳細なデータについて機械学習を用いて解析し、我々の先行研究で新たに提唱した体重変化量に基づく体重管理によってハイリスク女性の数を減らすポピュレーションアプローチに、中間因子である血糖変動に着目したハイリスクアプローチを組み合わせた多角的な疾病予防モデルを構築し、最終的に女性の生涯を通じた健康支援を行うことである。