Multiple pregnancy, short cervix, part-time worker, steroid use, low educational level and male fetus are risk factors for preterm birth in Japan: a multicenter, prospective study.

AIM: To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin-8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy. METHODS: In a multicenter, prospective, observational study, 1810 Japanese women registering their future delivery were enrolled at 8⁺° to 12⁺6 weeks of gestation. Data on cervical length and delivery were obtained from 1365 pregnant women. Multivariate logistic regression analysis was performed. RESULTS: Short cervical length, steroid use, multiple pregnancy and male fetus were risk factors for preterm birth before 34 weeks of gestation. Multiple pregnancy, low educational level, short cervical length and part-timer were risk factors for preterm birth before 37 weeks of gestation. CONCLUSION: Multiple pregnancy and cervical shortening at 20-24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth.

Management of the occiput posterior presentation: a single institute experience.

AIM: We have examined the risk factors and management processes of the persistent occiput posterior (pOP) position by analyzing medical records from our hospital. MATERIAL AND METHODS: Medical records and delivery notes from January 2007 to December 2009 were reviewed and 103 patients were identified as having the pOP position during active labor. A total of 1054 patients who had occiput anterior (OA) deliveries were used as control. RESULTS: There was no significant difference in population background between the pOP and control groups. Fifty-eight (56%) cases of pOP were identified before the birth of the fetal head whereas 45 were found to be in pOP at the birth. Among these cases identified as pOP before the birth, 30 (52%) patients underwent an attempt to rotate pOP to OA manually. A total of 14 (47%) attempts were successful and delivered OA vaginally. Of 16 cases whose attempts failed, five (31%) had cesarean delivery and 11 had vaginal OP delivery. The overall cesarean rate in this group was 16.7%. Twenty-eight patients who did not have any corrective intervention had a significantly higher rate of cesarean section (60.7%, P<0.001 by χ(2) analysis). The advanced head station and the wider dilatation resulted in a successful manual rotation. CONCLUSIONS: Attempts to correct pOP by manual rotation have better results when the head is in the mid-pelvis. Also, posture change reduces cesarean section rate. The current data suggest attempts to correct pOP to OA reduce cesarean section rate.

Determination of reference intervals of glycated albumin and hemoglobin A1c in healthy pregnant Japanese women and analysis of their time courses and influencing factors during pregnancy.

Glycemic control is an important issue in gestational diabetes mellitus (GDM) and in diabetic pregnant women. We determined the reference intervals of glycated albumin (GA) and hemoglobin A1c (HbA1c) as glycemic control markers in healthy Japanese pregnant women and analyzed their time courses and factors that influence these variables during pregnancy. 676 women were screened for the present study. After the exclusion of non-pregnant and puerperal women, 574 women were studied to determine the reference intervals. HbA1c, GA, casual plasma glucose, urinary glucose, urinary protein, and body mass index (BMI) (non-pregnancy) were measured. HbA1c levels significantly decreased in the second trimester of pregnancy and increased in the third trimester, while GA levels significantly decreased towards the third trimester. Casual plasma glucose levels decreased in the first trimester and subsequently remained constant. The reference intervals of GA and HbA1c in the healthy pregnant women were 11.5-15.7% and 4.5-5.7%, respectively. GA levels were lower (p<0.01) and HbA1c levels were higher (p<0.05) in pregnant women with proteinuria. In the obese group, GA levels were lower (p<0.01) than those of the control group (18.5≤ BMI <25kg/m²), and HbA1c levels were higher (p<0.01) than those of the control group. On the basis of the results of this multicenter study, the reference intervals of GA and HbA1c in healthy Japanese pregnant women were determined. Strict glycemic control is essential to reduce perinatal complications. GA appears to be a useful marker for pregnant women, since it can be measured easily and changes rapidly and markedly.

Primary amenorrhea due to juvenile granulosa-cell tumor of the ovary: a case report.

In general, primary amenorrhea is caused by gonadal dysgenesis, anomalies of internal or external genitalia with or without chromosomal anomalies, and sometimes by hormonal abnormalities that affect the hypothalamus, pituitary, ovaries, adrenals or thyroid, or by chronic or metabolic diseases. We report a rare case of a juvenile granulosa-cell tumor of the ovary that caused primary amenorrhea in a 16-year-old girl. Her hormonal profiles before the operation were characterized by an extremely low level of follicle-stimulating hormone (FSH), a relatively low level of estradiol and a high level of inhibin B. The patient had menarche after the removal of the tumor. Her elevated serum FSH after the operation was the result of a decreased serum level of inhibin that had been produced by the tumor. The present case highlights that a granulosa-cell tumor, known as an inhibin-secreting tumor, should be considered when treating primary amenorrheic girls.

Can digital health technologies exacerbate the health gap? A clustering analysis of mothers' opinions toward digitizing the maternal and child health handbook.

BACKGROUND: The use of mobile health has increased worldwide, but along with its increased utilization comes the risk of the digital divide, inequity in access to information and communications technologies, exerting greater influence on health inequity caused by socioeconomic determinants of health. There is a growing need to investigate whether the digitization of existing health interventions has a risk of worsening the health gap. METHODS: We investigated the attitudes of mothers and pregnant women toward digitization of the Maternal and Child Health Handbook (MCHH), a popular personal health record (PHR) used by almost every pregnant woman or mother in Japan, using a cross-sectional survey. We determined sociodemographic factors associated with favorable opinions toward digitization using a multivariate regression model. We then grouped the participants using partitioning around medoids clustering, a machine-learning approach, to interpret their varying attitudes toward digitization in light of their sociodemographic characteristics as well as their affinity toward the paper MCHH. FINDINGS: Higher income and educational level, older age, and less reliance on the MCHH were significantly associated with favorable opinion toward digitization. Clustering analysis identified four latent clusters. The cluster with the highest socioeconomic status (SES) was the most favorable toward digitization, while two clusters with the lowest SES, one of which relied heavily on the paper MCHH, were less favorable of digitization compared to the high SES cluster. The final cluster was comprised of mothers with the experience of raising multiple children and did not rely heavily on the MCHH. INTERPRETATION: Our study identified a socioeconomic divide in opinions toward digitization of an existing health intervention. A hasty digitization may result in an unbalanced uptake of the digitized health intervention among different social classes.

Incidence and risk factors of early bacterial infections after unrelated cord blood transplantation.

Incidence and characteristics of early bacterial infection within 100 days after unrelated cord blood transplantation (UCBT) were assessed for 664 pediatric and 1208 adult recipients in Japan. Cumulative incidence of early bacterial infection at day 100 post-UCBT was 11% (95% confidence interval [CI], 8%-13%) for children and 21% (CI, 19%-24%) for adults (P < .0001). Early bacterial infection in adults had a significant impact on mortality (hazard ratio [HR] = 2.1, CI, 1.7-2.6; P < .0001), although no significant risk factors were identified. Multivariate analysis identified older age group (6-10, and 11-15 years versus 0-5 years of age) at transplant (HR = 2.0 and 2.7, CI, 1.1-3.5 and 1.4-4.9; P = .020 and .002, respectively) as an independent risk factor of early bacterial infection for children. Early bacterial infection in children did not have a significant impact on mortality when adjusted. Of 315 bacteremia, 74% were caused by Gram-positive microorganisms. Pneumonia occurred in 39 patients including 13 cases of Stenotrophomonas maltophilia pneumonia. Early bacterial infection had a negative effect on survival for adults and the median day of development was 10 days after transplant, suggesting that the prevention of bacterial infection in the very early post-UCBT phase is important.

Comparison of HbA1c and glycated albumin as a control marker for newborn complications in diabetic women in a multicentre study in Japan (Japan glycated albumin study group: study 2).

Background To clarify the relationship between glycated haemoglobin and glycated albumin concentrations during pregnancy with neonatal outcomes, a multicentre study was conducted by the Japanese Society of Diabetes and Pregnancy. Methods A total of 136 patients (type 1: n = 47, type 2: n = 89) who enrolled in the study were diagnosed based on the Japanese Diabetes Society diagnostic criteria for diabetes mellitus. Thresholds for glycated haemoglobin and glycated albumin were set at 5.8% and 15.8%, respectively, as the upper limits of the reference interval in pregnant women. Result Random plasma glucose decreased linearly, and reached the reference interval at 40 weeks. Glycated albumin concentrations also decreased in the same manner. But glycated haemoglobin concentrations were out of the reference interval during the study. The frequency of the neonatal complications did not show significant differences between the glycated haemoglobin ⩾5.8% group and the glycated haemoglobin <5.8% group. On the other hand, the frequency of neonatal complications showed higher tendency of neonatal complications in the incidence of polycythaemia ( P = 0.094) and heavy-for-date ( P = 0.071) in the glycated albumin ⩾15.8% group compared with the glycated albumin <15.8 group. The respiratory disorder in type 1 diabetes was significantly higher than type 2 diabetes. Conclusions For the treatment of pregnant women with diabetes, glycated albumin would be a better marker than glycated haemoglobin. However, glycated albumin is also affected by obesity and albumin, and it is desirable to make a comprehensive judgment with glycated haemoglobin, random plasma glucose and other glycaemic index.

Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia.

In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data have shown that impaired autophagy of extravillous trophoblasts (EVT) may induce poor vascular remodeling in preeclampsia. We have studied the distribution of T cells, NK cells and macrophages in the decidua basalis of 14 normotensive OD pregnancies, 5 preeclamptic OD cases, 16 normotensive pregnancy cases, and 13 preeclamptic cases in natural pregnancy or autologous oocyte IVF-ET (NP/IVF). The populations of decidual CD3(+)T cells, CD8(+)T cells, CD4(+)T cells, Foxp3(+)Treg cells, CD56(+)NK cells, and CD68(+) macrophages in preeclampsia were significantly smaller than those in normal pregnancy in NP/IVF. Those frequencies in normotensive OD pregnancies or preeclamptic cases in OD pregnancies were similar to those in preeclamptic cases in NP/IVF. Impaired vascular remodeling was observed in OD pregnancies, regardless of the presence or absence of preeclampsia. The expression of p62, an impaired autophagy marker in EVT of normotensive or preeclamptic OD pregnancies, was significantly higher than that in normal pregnancies in NP/IVF. Immunological change in the decidua basalis and impairment of autophagy in EVT may induce impairment of spiral artery remodeling in OD pregnancies.

In situ androgen producing enzymes in human prostate cancer.

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5alpha-reductase types 1 and 2, and 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n = 70), and correlated the findings with clinicopathological features of the patients. 17Beta-HSD5 immunoreactivity was detected in 54 cases (77%), 5alpha-reductase type 1 in 51 cases (73%) and 5alpha-reductase type 2 in 39 cases (56%). 5Alpha-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17beta-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgen-producing enzymes, such as 5alpha-reductase type 1 and type 2, and 17beta-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.

Expression of urocortin III/stresscopin in human heart and kidney.

Urocortin III (Ucn III)/stresscopin (SCP) is a novel peptide of the corticotropin-releasing factor (CRF) family and is a specific ligand for the CRF type 2 receptor. We wished to clarify whether Ucn III/SCP is expressed in the human heart and kidney. Immunoreactive Ucn III was detected by RIA in the human heart (0.74-1.15 pmol/g wet weight, mean +/- SEM; n = 4) and kidney (1.21 +/- 0.30 pmol/g wet weight), which were obtained at autopsy. These levels were comparable to the levels in pituitary (2.72 +/- 0.13 pmol/g wet weight; n = 3) and brain tissues ( approximately 1-2 pmol/g wet weight). Furthermore, immunoreactive Ucn III was present in human plasma (51.8 +/- 16.0 pmol/liter; n = 5) and urine (266 +/- 20 pmol/liter; n = 5) obtained from healthy subjects. Reverse-phase HPLC showed a broad peak of immunoreactive Ucn III eluting in the position of synthetic Ucn III in the heart, kidney, and hypothalamus. Material eluting in the position of SCP was also found in the HPLC analysis of these tissue extracts. Immunocytochemistry showed positive staining of Ucn III in the myocardium and the renal tubules, particularly distal tubules. RT-PCR showed expression of Ucn III mRNA in the brain, pituitary, heart, and kidney. The present study has shown expression of Ucn III/SCP in the human heart and kidney as well as brain and pituitary tissues and its presence in plasma and urine. Ucn III/SCP may therefore regulate the cardiac and renal function as a local factor and a circulating hormone.

Orexin-A expression in human peripheral tissues.

Orexin-A is a neuropeptide present in the brain and is known to regulate feeding and sleeping. In this study, we examined the systemic distribution of orexin-A in human tissues. Immunoreactivity for orexin-A was detected in ganglion cells of the thoracic sympathetic trunk, myenteric plexuses and endocrine cells of the gastrointestinal tract, islet cells of the pancreas and syncytiotrophoblasts and decidual cells of the placenta. In the gastrointestinal tract, orexin-A immunoreactivity was detected in the myenteric plexuses from 26 gestational weeks to birth. In double immunostaining in the pancreas, a great majority of insulin-positive cells was simultaneously positive for orexin-A. mRNA expression for prepro-orexin was also detected in the kidney, adrenal gland, pancreas, placenta, stomach, ileum, colon and colorectal epithelial cells. These results suggest the production of orexin-A in various human peripheral tissues and orexin-A may also play important roles in some peripheral organs.

Recombinant activated factor VII (rFVIIa/NovoSeven®) in the management of severe postpartum haemorrhage: initial report of a multicentre case series in Japan.

Only a limited number of case reports documenting the off-label use of recombinant factor VIIa (rFVIIa) in Japanese patients with postpartum haemorrhage (PPH) have been published. Data on Japanese cases with severe PPH in which rFVIIa was administered were collected. Data of obstetric haemorrhage patients treated with rFVIIa between 2005 and 2010 were retrospectively collected throughout Japan. The data included patients' background information, blood product requirements, dose/timing of rFVIIa, and adverse effects. Treating clinicians subjectively assessed the effect of rFVIIa on bleeding at each administration using four categories: "Stopped", "Decreased", "Unchanged", and "Increased". A total of 25 women received rFVIIa for the treatment of obstetric haemorrhage in 18 institutions. After the final administration, bleeding was "stopped" in 16 patients (64%), "decreased" in eight patients (32%), and "unchanged" in one patient (4%). A significant reduction in blood product requirement was observed following the first rFVIIa administration. Hysterectomy was required in two patients (15.4%) after rFVIIa administration. Four asymptomatic thrombotic events were reported in three patients. These results suggest that rFVIIa can be a beneficial therapeutic option that can reduce blood loss and prevent hysterectomy in Japanese patients with massive obstetric bleeding.

Menstrual cycle and menstrual pain problems and related risk factors among Japanese female workers.

Women's employment in Japan has increased substantially in recent decades, however little large scale research has been done on the impact of various types of working conditions on women's health. The aim of this study was to assess the menstrual cycle and menstrual pain problems of female workers and to investigate the factors that relate to them. The questionnaire was distributed to 8,150 women and 2,166 responded (26.6%). An anonymous self-administered questionnaire was used to get information about demographics, menstrual cycle status, the degree of menstrual pain, and employment and environmental factors. Irregular cycle menstruation was experienced in 17.1% of responded workers. We discovered the relationship between irregular menstrual cycles and stress, smell of cigarettes, age and smoking habits. Some degree of menstrual pain was experienced in 77.6% of responded workers. This study showed the relationship between menstrual pain and stress, high temperature and humidity, age, BMI, and number of births. In conclusion, we found that stress is thought to be an important factor related with menstrual cycle irregularities and menstrual pain among Japanese female workers.

Clinical management and outcome of pregnancies complicated by previous abruption.

OBJECTIVES: We studied the clinical management and prognosis of pregnant women with a history of abruption, as well as the associated risk factors. METHODS: We reviewed the cases of 23 patients with a history of abruption and 66 patients with abruption. RESULTS: The recurrence rate of abruption was 4.3%. Intentional care prolonged gestational age in most patients. Although the incidence of abruption was low (0.44%), the consequences could be perinatal death and maternal disseminated vascular coagulation (DIC). CONCLUSION: To prevent abruption recurrence, careful monitoring during hospitalization is important. Both clinical findings and transabdominal echography are useful in diagnosing abruption.

Placental insufficiency in early gestation is associated with hypospadias.

BACKGROUND AND PURPOSE: The association of growth retardation and hypospadias is well established. Fetal testosterone secretion is under the influence of placental human chorionic gonadotropin during first 14 weeks of gestation. We hypothesized that placental insufficiency may disrupt the supply of nutrients and human chorionic gonadotropin to the fetus leading to both growth retardation and hypospadias. To validate this hypothesis, we analyzed extremely low-birth-weight male infants with or without hypospadias for fetal growth parameters. MATERIALS AND METHODS: One hundred four male newborn infants with birth body weight of less than 1500 g admitted to a neonatal intensive care unit over a 4-year period were retrospectively reviewed, recording the presence and type of hypospadias, fetal growth parameters, infant growth parameters at birth, placental weight, placental histopathology, cord information, and maternal morbidity. These data of patients with hypospadias were compared with those of controls. RESULTS: Of the 104 extremely to very low-birth-weight male infants, 16 (15.3%) had hypospadias, and 10 (62.5%) of those had severe proximal hypospadias. Sixty-two controls who did not have hypospadias and whose body weight was less than 1500 g were identified. The incidence of hypospadias in full-term male birth in the hospital was 12 (0.30%) in 3959 births. Birth body weight and their SD for gestational age were lower in patients with hypospadias compared with those for controls (824 +/- 160 vs 1255 +/- 145 g). Placenta-to-fetal ratio (0.323 +/- 0.07 vs 0.229 +/- 0.03) and gestational age were significantly higher in the patients with hypospadias. Histopathologic study of the maternal placenta obtained from the patients with hypospadias revealed pronounced degenerative changes, infarction, and calcification, whereas these abnormalities were rare in controls. CONCLUSIONS: The significant association between the occurrence of hypospadias and early growth retardation with higher placenta-to-fetal ratio and placental abnormalities suggest that placental dysfunction in early gestation may play an important role in the development of hypospadias.

Pulmonary thromboembolism in obstetrics and gynecology increased by 6.5-fold over the past decade in Japan.

BACKGROUND: Although pulmonary thromboembolism (PTE) has been considered relatively uncommon in Japan, its incidence has been on the increase in recent years. METHODS AND RESULTS: To verify the incidence of PTE in Japan, PTE cases of obstetrics and gynecology were investigated among 102 facilities throughout Japan between 1991 and 2000. A total of 254 cases were enrolled, showing a 6.5-fold increase over the past 10 years. PTE occurred in 0.02% of total births; 0.003% after vaginal deliveries and 0.06% after cesarean births (C/S), of which 14.5% resulting in fatality. The mortality rate was 2.5 per 100,000 deliveries. The incidences among gynecological cases were 0.08% of total operations; 0.03% in benign diseases and 0.42% in malignant diseases of which 13.5% resulting in fatality. The mortality rate was 10.8 per 100,000 operations. The risk was 22 times higher in C/S compared with vaginal deliveries, 16 times higher in malignant diseases compared with benign diseases. CONCLUSIONS: As our present survey has shown, PTE has been on the rise in Japan in recent years. C/S and malignant diseases are strong risk factors in obstetrics and gynecology.

Changes in plasma coagulation markers with prophylactic treatment of low molecular weight heparin after cesarean section.

Cesarean section has been identified as a major risk factor for thromboembolism, and additional risk factors place some women at a much higher risk during puerperium. Recently, low molecular weight heparins (LMWHs) have been used for thromboembolism prophylaxis after cesarean section. We investigated the effect of risk factors of thromboembolism on plasma coagulation markers when the LMWH dalteparin was used following cesarean section. Twenty-four women with risk factors other than cesarean section (high-risk group) and 13 without any other risk factors (low-risk group) received dalteparin starting immediately after cesarean section until the patients were mobilized. Sixteen women without any other risk factors served as controls (control group). Activated partial thromboplastin times, thrombin-antithrombin complex, alpha (2)-plasmin inhibitor-plasmin complex, and activated factor X levels were not different between the high-risk and the low-risk groups. However, fibrinogen/fibrin degradation products D-dimer levels were higher in the high-risk group than in the low-risk and control groups on days 3 and 7 after cesarean section. These findings suggest that the D-dimer levels may be elevated by some risk factors and that postoperative D-dimer determinations may be useful in assessing the risk of thromboembolism during LMWH treatment after cesarean section.

Review of the ischemia hypothesis for ocular hypertension other than congenital glaucoma and closed-angle glaucoma.

Experimentally induced ischemia of the endothelial cells surrounding the aqueous drainage sites led to a rise in intraocular pressure (IOP) in monkey and pigeon eyes. Clinical conditions associated with a rise in IOP in human eyes, e.g. peripheral retinal detachments, subluxated lenses, and occlusion of the internal carotid artery, can result in ischemia of the endothelial cells lining Schlemm's canal. These findings led to the hypothesis that ischemia of the endothelial cells of Schlemm's canal induces hypertension in human eyes. Thus, the ischemia hypothesis should be considered in discussions of the etiology of age-related open-angle glaucoma.

Studies on the Purification and Characterization of Human Urinary Plasminogen and Plasmin.

A new method is described for the preparation of highly purified human plasminogen and plasmin with specific activity of 32 CTA units per mg of protein. With this method, the purification of the urinary plasminogen + plasmin antigenic materials from patients with chronic glomerulonephritis, disseminated intravascular coagulation syndrome and severe toxemia of pregnancy was performed, and the resulting highly purified proenzyme and enzyme were analyzed by immunoelectrophoresis, separative agar electrophoresis, gel filtration and SDS-gel electrophoresis.Our findings indicated that urinary plasmin reflects more closely the extent of intraglomerular fibrinolysis, while urinary plasminogen reflects non-selective proteinuria in patients with chronic glomerulonephritis or severe toxemia of pregnancy.