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

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.

DOI： 10.1016/j.eurox.2023.100210

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

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.

DOI： 10.1111/jog.15734

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記述言語：英語   出版者・発行元：Japanese Journal of Clinical Oncology  

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.

DOI： 10.1093/jjco/hyad039

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記述言語：英語   出版者・発行元：Frontiers in Pediatrics  

Introduction: To investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid. Methods: Pregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15–20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring. Results: Offspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p < 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p < 0.01, p < 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease. Conclusion: The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.

DOI： 10.3389/fped.2023.1168173

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記述言語：英語   出版者・発行元：Diabetology and Metabolic Syndrome  

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.

DOI： 10.1186/s13098-023-01103-z

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

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.

DOI： 10.1111/jog.15575

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記述言語：英語   出版者・発行元：Reproductive Biology and Endocrinology  

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.

DOI： 10.1186/s12958-023-01061-1

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記述言語：英語   出版者・発行元：International Journal of Obstetric Anesthesia  

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.

DOI： 10.1016/j.ijoa.2023.103957

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記述言語：英語   出版者・発行元：Molecular Genetics and Metabolism Reports  

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.

DOI： 10.1016/j.ymgmr.2022.100925

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

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.

DOI： 10.1038/s41598-022-22495-4

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記述言語：英語   出版者・発行元：Journal of Medical Case Reports  

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.

DOI： 10.1186/s13256-022-03579-1

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記述言語：英語   出版者・発行元：International Journal of Clinical Oncology  

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.

DOI： 10.1007/s10147-022-02214-9

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記述言語：英語   出版者・発行元：BMC Women's Health  

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.

DOI： 10.1186/s12905-022-01961-1

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記述言語：英語   出版者・発行元：Obesity  

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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記述言語：英語   出版者・発行元：Placenta  

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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記述言語：英語   出版者・発行元：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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記述言語：英語   出版者・発行元：BMC Cancer  

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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