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The objective of this study was to determine how many pregnant Japanese women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) experience perinatal mortality in the presence of fetal anomalies.Our investigation included data from 205 secondary/tertiary obstetric facilities located widely in Japan. The Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan was used for comparison.Of 237 941 women giving birth at 205 hospitals, 1796 (0.8%) and 13 037 (5.5%) had DM and GDM, respectively. The perinatal mortality rates (per 1000 births) were 10.6 (19/1796) for women with DM, 5.2 (68/13037) for women with GDM, and 3.7 (7612/2039504) for the general Japanese population. Detailed information was available for 63 (72%) of the 87 perinatal deaths occurring in women with diabetes including DM and GDM; fetal anomalies were associated with 40% (25/63) of perinatal deaths, exceeding 16% (1211/7612) in the general Japanese population (P0.0001). The leading four fetal anomalies associated with perinatal mortality in women with diabetes were fetal trisomy (6 cases: 1 of trisomy-13 and 5 of trisomy-18), non-immune hydrops fetalis (5 cases), cardiac deformities (3 cases) and holoprosencephaly (2 cases).Perinatal mortality was more likely to occur in women with glucose intolerance. In the Japanese infants that succumbed to perinatal mortality, fetal anomaly was more prevalent in those born to women with a glucose intolerance than in those born to the general population.

We created a new reference standard focusing on the hemispheric anteroposterior cerebellar diameter (APCD) in addition to the transverse cerebellar diameter (TCD) and discussed whether or not the cerebellar measurement was useful for the detection of trisomy 18 (T18).In 150 normal fetuses between 14 and 36 weeks of gestational age (GA), the TCD and APCD were prospectively measured. In 26 cases with T18, the value was compared with the control.At22 weeks of gestation, the TCD reference standard was calculated as follows: TCD = (1.027 × GA) - 0.674 (R(2) = 0.97, P 0.001). The reference standard of the APCD was calculated as follows: APCD = (0.682 × GA) - 3.925 (R(2) = 0.73, P 0.001). In eight cases with T18, the TCD was below the 5th percentile value in 7/8 (88%) cases and the APCD was below the 5th percentile value in 8/8 (100%) cases. At22 weeks of gestation, the reference standard of the TCD was calculated as follows: TCD = (1.603 × GA) - 13.216 (R(2) = 0.92, P 0.001). The reference standard of the APCD was calculated as follows: APCD = (0.859 × GA) - 7.30 (R(2) = 0.84, P 0.001). In 18 cases with T18, the TCD was below the 5th percentile value in 14/18 (78%) cases and the APCD was below the 5th percentile value in 18/18 (100%) cases.APCD reference standard, divided by the gestational age of more or less than 22 weeks, might be useful to diagnose T18.

Autonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL).Heart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale.The K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL ≥4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups.The physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL.

Fontan operation is performed to provide palliation for patients with many forms of highly complex congenital heart disease that cannot support a biventricular circulation. Increasing numbers of women who have undergone these connections in childhood are now reaching their childbearing years, and some are becoming pregnant. The low flow and fixed cardiac output of a Fontan circulation poses a number of problems during pregnancy. Here, we report two cases of pregnancy and delivery with Fontan circulation. Case 1, who underwent Fontan procedure for congenital pulmonary atresia with intact vertical septum at age 7, delivered a male infant weighing 1073 g by cesarean section at 28(6/7) weeks due to massive genital bleeding. Case 2 underwent Fontan procedure for double inlet left ventricle and delivered by vacuum extraction a male infant weighing 2142 g, while monitoring central venous pressure at 37(5/7) weeks. The former had ascites and dose of diuretic had to be added at early pregnancy, and the latter had no adverse cardiac and obstetric events. These cases suggest that patients after adequate Fontan palliation could complete pregnancy without long-term cardiac sequelae, but might be complicated with cardiac or obstetrical events. Intensive care should be required with specialists, including a neonatologist, anesthesiologist and cardiologist. We have added a literature review of pregnancy with Fontan circulation, referring to previous reports.

Male-to-female (MTF) transsexuals are treated with estrogen with and without progestin through a variety of routes. The aim of this study is to evaluate the arterial stiffness in MTF transsexuals undergoing hormonal treatment.We evaluated the arterial stiffness in 156 MTF transsexuals (22 untreated and 129 treated with estrogen only or plus progestin) using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor.MTF transsexuals treated with parenteral estrogen were significantly older than untreated MTF transsexuals. Hematocrit, uric acid and activated partial thromboplastin time in treated MTF transsexuals were significantly lower than in untreated MTF transsexuals. The level of high-density lipoprotein cholesterol in MTF transsexuals treated with oral estrogen was significantly higher than in untreated MTF transsexuals or those treated with parenteral estrogen with and without progestin. The systolic blood pressure in MTF transsexuals treated with estrogen only is significantly lower than that in untreated MTF transsexuals. The brachial-ankle pulse wave velocity was significantly decreased in MTF transsexuals treated with estrogen compared to that in untreated MTF transsexuals or in those treated with estrogen plus progestin. The carotid augmentation index in MTF transsexuals treated with oral estrogen was significantly lower than that in MTF transsexuals treated with parenteral estrogen or oral estrogen plus progestin.Estrogen treatment is likely to have some beneficial effects on lipid metabolism and vascular function in MTF transsexuals; however, progestin administered with estrogen may have adverse effects on arterial stiffness.

The aim of this study was to investigate the cellular effects of intermittent high glucose on the human BeWo placental choriocarcinoma cell line, used as a model of the effects of glucose fluctuation in diabetic pregnancies.BeWo cells were subjected to three different glucose conditions for 48 h: 7 mmol/L (control), 42 mmol/L (high glucose), or 7 and 42 mmol/L glucose (intermittent, alternated every 6 h). Cell viability was assessed using cell counts, a cell proliferation assay, and a cell viability assay. Apoptosis was also studied using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and by immunocytochemistry of fractin, the N-terminal fragment of actin, which can distinguish apoptotic from necrotic cells. Furthermore, the expression of the well-known survival factors of trophoblast cells, heparin-binding epidermal growth factor-like growth factor and leptin, was evaluated by real-time polymerase chain reaction and Western blot analyses.Intermittent high-glucose conditions significantly decreased cell viability and enhanced apoptosis compared with control or continuous high-glucose conditions. Furthermore, the expression of heparin-binding epidermal growth factor-like growth factor, but not that of leptin, was significantly increased under intermittent high-glucose conditions compared to its expression under either control or continuous high-glucose conditions.These data indicate that intermittent high glucose is more deleterious to BeWo cells than continuous high-glucose conditions. Although further in vitro and in vivo study is necessary, excess fluctuation of glucose levels in the placental circulation might be involved in the impairment of placental development leading to the placental dysfunction.

Although risk factors for cardiovascular disease, such as obesity, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS), impairment of vascular function is still controversial. We evaluated the vascular function in young women with PCOS.We evaluated arterial stiffness in 54 women with PCOS and 24 healthy control women using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor for the left common carotid artery and studied the correlations of various factors.There was no significant difference in age or body mass index between the controls and the women with PCOS. These women with PCOS had a significantly higher serum testosterone and C-reactive protein levels and showed insulin resistance and dyslipidemia. The mean blood pressure in women with PCOS was within the normal range, but still significantly higher than those in the controls. Women with PCOS had a significantly higher brachial-ankle pulse wave velocity (baPWV) than that for the controls (P0.02), whereas there was no significant difference in the carotid augmentation index between the two groups. Stepwise multiple regression analysis revealed that blood pressure influences the baPWV in women with PCOS. Arterial stiffness evaluated using the baPWV in mildly-hypertensive women (systolic blood pressure ≥120 mmHg or diastolic blood pressure ≥90 mmHg) with PCOS was significantly higher than that in the controls or normotensive women with PCOS.Early changes in vascular function were detected in mildly-hypertensive women with PCOS. Lifestyle interventions to prevent hypertension, such as diet and exercise, should be the first-line of treatment in women with PCOS.

Aim: Recent progress in adiposcience has revealed several important adipose-tissue-originated factors, so-called adipokines. Retinol-binding protein 4 (RBP4), a protein expressed and secreted by adipocytes, has been identified as a novel regulator of insulin resistance. Physiological insulin resistance occurs during the pregnancy of mammals to accommodate fetal growth, and it has been suggested that insulin resistance and hyperinsulinemia might also be associated with pregnancy-induced hypertension (PIH). In order to shed light on the role of RBP4 during pregnancy, we attempted to assess RBP4 levels during pregnancy. Fetal growth could be affected by aberrant regulation of RBP4 levels in fetal circulation per se, so we examined the RBP4 levels in cord blood samples of growth restricted cases. Methods: Circulating RBP4 levels were examined in non-pregnant and pregnant healthy women using Western blotting. Also, RBP4 levels in normal pregnancy and PIH were quantitated using Dot-blot analysis. RBP4 levels in cord blood samples also were evaluated in selected cases. Results: RBP4 levels tended to decrease after early gestation with no obvious difference between mid- to late-gestation. RBP4 levels were increased in pregnant women with PIH compared with normal pregnancies (P

Hypercalcemia is one of the important paraneoplastic syndromes, mostly occurring in patients with advanced cancer. Clear cell carcinoma is known to be one of the most common histological subtypes of ovarian tumor associated with hypercalcemia. We present a case of ovarian clear cell carcinoma with hypercalcemia caused by elevated serum parathyroid hormone-related protein (PTHrP). PTHrP mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemical analysis in the primary and metastasis lesions. Serum calcium and PTHrP levels returned to normal after antihypercalcemic treatment and a radical operation, but they elevated along with the recurrence. Because tumor markers such as carcinoembryonic antigen, carbohydrate antigen (CA)125 and CA19-9 were unstable owing to the patient's liver cirrhosis and were not reliable data for management, serum calcium and PTHrP levels are shown to have been a potential indicator of the recurrence in this case.