Development of Fast Disintegrating Tablets Containing Loxoprofen Sodium by HYDROFLASH Manufacturing Method.

In order to create and offer superior pharmaceuticals for consumers who wish to be relieved of headache and fever as soon as possible, we established HYDROFLASH manufacturing method that enables us to offer fast disintegration tablets containing loxoprofen sodium (LX), which are difficult to disintegrate. As a result of screening excipients, tablets using mannitol showed the fastest disintegration time, about 2 min. From the result of viscosity measurement, we found that LX produced higher viscosity when dissolved in water. This suggests that tablets containing LX disintegrate slower by inhibiting the penetration of water into the tablet due to the viscosity caused of LX. Therefore, we created a manufacturing method to make it easy for water to penetrate the tablet. It is possible to achieve fastest disintegration in about 30 s for tablets containing LX by granulating in a fluidized-bed with spraying of the dispersion of light anhydrous silicic acid (LASA). LX-containing tablets manufactured by the HYDROFLASH method disintegrated immediately after contact with water. Furthermore, it was observed that LASA was uniformly dotted on the surface of tablets by HYDROFLASH method, compared with other manufacturing methods. We considered that by fluidized-bed granulation with LASA dispersion (HYDROFLASH manufacturing method), water permeates through LASA on the tablet surface regardless of viscosity of LX. Futhermore, LX-containing tablets by the HYDROFLASH method showed that the dissolution rate of LX was nearly 100% at 5 min after starting the test. We considered that the initial dissolution became faster because of the fast disintegration.

Insufficient antenatal identification of fetal growth restriction leading to intrauterine fetal death: a regional population-based study in Japan.

OBJECTIVE: Fetal growth restriction (FGR) is associated with perinatal adverse outcomes including intrauterine fetal death. Antenatally unidentified FGR has a higher risk of intrauterine fetal death than that identified antenatally. We, therefore, investigated the antenatal identification of FGR among intrauterine fetal deaths, and assessed the perinatal factors associated with the identification of FGR. METHODS: This retrospective and population-based study reviewed all stillbirths in Shiga Prefecture, Japan, from 2007 to 2016 with exclusion criteria of multiple births, births at unidentified gestational weeks or < 22 gestational weeks, and lethal disorders. We analyzed cases of FGR, using the Japanese clinical definition: Z-score of estimated fetal weight for gestational age <-1.5 standard deviations (SD). RESULTS: We identified 94 stillbirths with FGR among 429 stillbirths. Thirty-seven cases were antenatally identified during pregnancy management (39%). Dividing cases by a Z-score of -2.5 SD, 51 cases were classified as ≤-2.5 SD. Twenty-eight of the 51 cases (55%) with a Z-score <-2.5 SD were antenatally identified as having FGR, whereas 9 of the 43 cases (21%) with a Z-score ≥-2.5 SD were antenatally identified as having FGR (p = .002). Among cases with a Z-Score <-2.5 SD, 16 of 21 (76%) beyond 28 weeks' gestation and 12 of 30 (40%) before 28weeks' gestation were antenatally identified as having FGR (p = .023). CONCLUSION: Fetal growth restriction leading to intrauterine fetal death in Japan was antenatally identified in less than half of cases. Antenatal identification of FGR was associated with the severity of growth restriction.

Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain monoamine profiles.

Dietary folic acid augmentation during gestation reduces neurodevelopmental disorder risk in offspring; however, it is still unclear if excessive maternal folic acid intake can impair brain function in offspring. We examined if excessive folic acid intake throughout gestation altered the behavior of male offspring under poor nutrition during early gestation (E5.5-E11.5). Dams were divided into four groups: control (CON, 2 mg folic acid/kg of food), excessive folic acid fortification (FF, 10 mg folic acid/kg of food), undernutrition (UN, 40% food reduction from E5.5-E11.5), and excessive folic acid fortification plus undernutrition (UN-FF). Excess maternal folic acid fortification induced hyperactivity in the open-field and lower anxiety-like behavior in the elevated plus maze at 9 weeks of age. These behavioral changes were accompanied by reduced dopamine in the prefrontal cortex (PFC), norepinephrine in the amygdala, and 5-hydroxytryptamine (5-HT) in the dorsal midbrain (DM), PFC, and amygdala where 5-HT neurons project from the DM. Furthermore, canonical discriminant analysis, including dopamine and DOPAC concentrations in the PFC, norepinephrine concentrations in the PFC, amygdala, and pons, and 5-HT and 5-HIAA concentrations in the amygdala and DM, correctly classified 73.5% of the offspring in CON, FF, UN, and UN-FF groups. The first discriminant function mainly classified groups based on nutritional status, whereas the second function mainly classified groups based on folic acid intake. Our study suggests that combined transformations of brain monoamine profiles by maternal undernutrition and excess folic acid intake is involved in the behavioral alteration of offsprings.

Increased Difficulties in Maternal Perception of Decreased Fetal Movement in Cases of Severe Fetal Growth Restriction: A Population-Based Study in Japan.

Fetal growth restriction (FGR) is defined as fetuses who have failed to achieve a normal weight for gestational age. FGR is associated with adverse perinatal outcomes, including stillbirth. Pregnant women often perceive decreased fetal movements before intrauterine fetal death. Previous reports on the association between fetal movements and FGR have mainly targeted livebirths, with few focusing on stillbirths. Studying stillbirths, not livebirths, may help improve perinatal adverse outcomes. This study evaluated the association between FGR leading to stillbirth and maternal perception of decreased fetal movement. This was a population-based study reviewing all stillbirths in Shiga Prefecture, Japan for 10 years. We analyzed 219 stillbirth cases, those with versus without FGR. We then compared maternal visits to healthcare providers due to perception of decreased fetal movement between these two groups. There were 82 stillbirths with FGR, and the remaining 137 stillbirth were without FGR. Women with FGR, compared with those without, were significantly less often to visit the outpatient department due to decreased fetal movement (30%; 25/82 vs. 46%; 63/137: P = 0.034). Pregnant women have more difficulty perceiving decreased fetal movements in cases with severe FGR than in those without FGR. Healthcare providers, including midwives, may need to closely monitor FGR pregnancy in addition to instructing pregnant women to be aware of decreased fetal movement.

Selection of Small Amounts of Glidant Capable of Improving the Tensile Strength of Ibuprofen Tablets.

This study examined the selection of small amounts of excipients capable of improving the compactability of ibuprofen, thereby enabling the miniaturization of ibuprofen tablets. Various glidants in amounts of 1% of the total volume were added to dry surface-modified ibuprofen, and the tensile strengths of the resulting tablets were evaluated. The characteristics of the excipients that affected the tensile strengths of the tablets were then extracted using a tensile strength prediction model. We confirmed that the effective angle of the internal friction of the mixed powder, the coating form of the glidant, the packing fraction of the raw material, and the mixed powder affect the tensile strength of the tablet. A smooth particle layer was formed on the surface of the ibuprofen particles when a glidant with a packing fraction of <0.05 was used. In the sample with a smooth particle layer, the angle of the critical state line increased significantly and the tensile strength improved. We inferred that the smoothness of the particle layer allowed the ibuprofen particles to come into close contact with each other. Consequently, the number of junctions increased, and the frictional force between the particles improved, resulting in tablets with improved tensile strengths. In conclusion, the compactability of ibuprofen was improved by adding 1% glidant with a packing fraction of <0.05. The reduction in excipients will allow the creation of smaller tablets, making them easier to swallow. Therefore, the medication adherence of customers will be improved.

Smoking during Pregnancy Is a Predictor of Poor Perinatal Outcomes in Maternal Anorexia Nervosa: A Case Series and Single-Center Cross-Sectional Study in Japan.

Eating disorders are common psychiatric disorders among women of reproductive age, and the prevalence of eating disorders has been increasing over time in Japan and other countries. The aim of the present study was to assess perinatal outcomes in maternal anorexia nervosa in Japan and to explore methods to improve perinatal outcomes. This study consists of a case series describing 13 single pregnancies of 11 women with a history of anorexia nervosa, and a cross-sectional study comparing 13 cases with 240 healthy controls. In the case group, nine cases conceived while underweight, including three who had fertility treatment. Anorexia symptoms during pregnancy were quite common, and pregnant smokers presented with extremely disturbed eating behaviors. In a cross-sectional study, premature birth and the standard deviations from the mean birth weight and mean head circumference at birth were evaluated as outcome measures. The adjusted odds ratios or the adjusted differences between two means for the above outcomes were estimated by two approaches: multivariate models and matching analysis. Statistical analysis showed that maternal anorexia nervosa was associated with an increased risk of premature birth and symmetric growth restriction mediated by low pre-pregnancy body mass index and poor gestational weight gain which were adjusted as confounders. Smoking during pregnancy was a potential indicator of abnormal eating behavior and could be predictive of poor perinatal outcomes. We therefore conclude that remission of anorexia nervosa before pregnancy could improve perinatal outcomes through both normal nutrition and smoking cessation. Fertility treatment while underweight is not recommended.

Evaluation of the physical properties of dry surface-modified ibuprofen using a powder rheometer (FT4) and analysis of the influence of pharmaceutical additives on improvement of the powder flowability.

In this study, we examined the characteristics of glidant that affect the improvement of the flowability of APIs by using the dry surface modification of ibuprofen. In addition, the screening method of glidant suitable for improving flowability of APIs was examined. As a result of evaluation of mixed powder with surface modification using various inorganic fine particles with different physical properties, it became clear that the packing fraction had the most influence regardless of the component. This was thought to able to coat the surface with small quantities because the smaller the packing fraction, the more it was able to dispersed from the less contacts between the glidant particles. The packing fraction of glidant was correlated with the (SE/CBD)-1 which was calculated value from the results measured with powder rheometer. From this results, when using any excipient as a glidant for dry surface modification, it is now possible to estimate the effect of improving flowability simply by measuring with a powder rheometer. Based on this study, it is possible to select excipients suitable for improving APIs flowability and to estimate the improvement effect, and therefore, it is expected to improve the efficiency of prescription design work.

Chest compression of a pregnant woman by a seatbelt might affect fetal outcome, even in minor to moderate frontal vehicle collisions.

INTRODUCTION: Pregnant women often suffer from negative fetal outcomes, despite wearing a seatbelt correctly. When restrained vehicle passengers are involved in a frontal collision without suffering from any injuries, the forces they experience are particularly concentrated in the chest because of the seatbelt. We analyzed the biomechanics of chest injuries sustained by restrained pregnant drivers and possible effects of these injuries on the fetus. MATERIAL AND METHODS: The Maternal Anthropometric Measurement Apparatus dummy, version 2B, representing a pregnant woman at 30 weeks of gestation, was used. Sled tests were performed for recreating frontal impact situations with vector velocity changes at impact speeds of 13, 26, and 40km/h. Overall kinematics of the dummy were examined using high-speed video imaging. Quantitative dummy responses, such as time course of acceleration of the sled and chest, pressure of the belt, and deflection of the chest (right and left) during impact were also measured. RESULTS: Although collision velocities were different, the distances of forward movement of the dummy were similar (121-129mm) owing to the safety devices. However, maximum deflection of the chest (35.4mm to the left and 15.7mm to the right) was obtained at a 26-km/h collision. Additionally, maximum deflection of 28.7mm to the left and 10.9mm to the right of the chest were obtained at 40km/h. CONCLUSIONS: Because the uterus enlarges and the fundus reaches the lower part of the rib cage during late pregnancy, we consider that the reason for negative fetal outcomes is partly owing to chest compression and subsequent applied forces on the uterus, even in minor to moderate frontal collisions. This knowledge may be useful for forensic scientists who determine the causes and mechanisms of a fetal death or the offenders' responsibilities for both maternal and fetal outcomes when the mother is involved in a frontal vehicle collision.

Fetal movement frequency and the effect of associated perinatal factors: Multicenter study.

BACKGROUND: Decreased fetal movements are associated with adverse perinatal outcomes, including stillbirth. Delayed maternal visits to a health care provider after perceiving decreased fetal movements are frequently observed in stillbirths. Informing pregnant women of the normal range of fetal movement frequency is essential in their earlier visits in order to prevent stillbirth. AIM: To investigate the fetal movement frequency in late pregnancy and the effects of associated perinatal factors. METHODS: This prospective multicenter study was conducted in 20 obstetric facilities in our region of Japan. A total of 2337 pregnant women were asked to record the time it took to perceive 10 fetal movements by the modified 'count to 10' method every day from 34weeks of gestation until delivery. FINDINGS: The 90th percentile of the time for the maternal perception of 10 fetal movements was 18-29min, with a gradually increasing trend toward the end of pregnancy. The numbers of both pregnant women giving birth after 39weeks' gestation and infants with a birth weight exceeding 3000g were significantly higher in mothers who took ≥30min to count 10 fetal movements than in those who took <30min. CONCLUSION: The maternal perception time of fetal movements shows a gradually increasing trend within 30min for 10 fetal movements by the modified 'count to 10' method. Informing pregnant women of the normal range of the fetal movement count time will help improve the maternal recognition of decreased fetal movements, which might prevent fetal death in late pregnancy.

Impact of the recommendation for embryo transfer limitation on multiple pregnancy: A population-based study in Japan.

OBJECTIVE: Limitations on the number of embryos transferred have been recommended worldwide to reduce the number of medically assisted multiple births. Our aim was to evaluate the impact of this recommendation for embryo transfer limitation on perinatal outcomes of multiple births. STUDY DESIGN: A retrospective and population-based study compared all multiple births in Shiga prefecture of Japan in 2014-2015 (2015 group) with those in 2007-2008 (2008 group). The perinatal background and neonatal outcomes of multiple births were compared. RESULTS: The number of multiple pregnancies in the 2015 group (n = 251) was almost the same as in the 2008 group (n = 245). The proportion of multiple pregnancies conceived through assisted reproductive technology significantly decreased to 23% in the 2015 group compared to 31% in the 2008 group. In contrast, the rate of ovulation induction significantly increased to 24% in the 2015 group from 15% in the 2008 group. There was no significant difference in the outcome of multiple-birth infants between the two groups. CONCLUSION: The method of conception in multiple pregnancies markedly shifted from in vitro fertilization to non-in vitro fertilization after the issuance of a recommendation for limits on embryo transfer. It should be necessary for the assessment of the impact of this recommendation to monitor closely multiple pregnancies via non-in vitro fertilization as well as via in vitro fertilization.

Review: Chronic endometritis and its effect on reproduction.

AIM: Chronic endometritis (CE) is a disease of continuous and subtle inflammation characterized by the infiltration of plasma cells in the endometrial stromal area. Although the clinical significance of CE has been thought in clinical practice for a long time because it is either asymptomatic or presents with subtle symptoms, recent studies have shown the potential adverse effects of CE on fertility. In the present review, we focus on the concept, diagnosis, etiology, pathophysiology, diagnosis, impact on reproduction and treatment for it to understand CE. METHODS: The published articles were reviewed. RESULTS: The prevalence of CE has been found to be 2.8-56.8% in infertile women, 14-67.5% in women with recurrent implantation failure (RIF), and 9.3-67.6% in women with recurrent pregnancy loss. Microorganisms are thought to be a main cause of CE, since antibiotic treatment has been reported to be an effective therapy for CE. Common bacteria are frequently detected in the uterine cavity of CE patients by microbial culture. In CE endometrium, the prevalence of immune cells and decidualization has been reported to be modified, and these modifications are thought to adversely affect fertility. The gold standard for the diagnosis of CE is the histological detection of plasma cells in the stromal area of the endometrium in endometrial specimens, although universally accepted criteria for the diagnosis of CE have not been determined. The treatment currently thought to be most effective for the recovery of fertility in CE is administration of oral antibiotics. Patients whose CE has been cured have been reported to have a higher ongoing pregnancy rate, clinical pregnancy rate, and implantation rate compared with patients with persistent CE. CONCLUSION: CE greatly affects implantation and impairs fertility. Antibiotic administration is an effective therapeutic option. Pregnancy rate in in vitro fertilization is improved when CE is cured by antibiotic.

Use of ultrasound shear-wave elastography to evaluate change in cervical stiffness during pregnancy.

AIM: The aim of this study was to evaluate the usefulness of shear-wave elastography (SWE) for measuring change in cervical stiffness during pregnancy, with regions of interest (ROI) designed for easy identification. METHODS: A total of 280 women were enrolled in this study. SWE was performed at a routine prenatal visit. A measurement area was chosen at the anterior part of the cervix, and a circular ROI 5 mm in diameter was set at two points, 5-10 mm (lower point) and 15-20 mm (upper point) from the external cervical os. The generalized estimating equation was used to estimate the correlation between stiffness and gestational age, using generalized linear models. RESULTS: There were significant negative correlations between stiffness and gestational age. The estimated regression equations of the lower and upper points were Y = -0.049X + 3.675 (P < 0.05) and Y = -0.060X + 4.170 (P < 0.05), respectively. The stiffness at the upper point behaved statistically significantly differently to that at the lower point. Softening of the cervix at the upper point was significantly different between single pregnancies and twin pregnancies (P < 0.05), but no marked difference was noted between primiparous and multiparous women. CONCLUSION: Cervical elastography using SWE was useful for measuring change in cervical stiffness during pregnancy, and the upper area of the cervix may be a more relevant assessment point for cervical softening than the lower area.

Excessively delayed maternal reaction after their perception of decreased fetal movements in stillbirths: Population-based study in Japan.

BACKGROUND: Fetal movement is the most common method to evaluate fetal well-being. Furthermore, maternal perception of decreased fetal movements is associated with perinatal demise. Previously, we showed that perception of decreased fetal movements was the most common reason for mothers visiting the outpatient department among those who had stillbirths in our region. Further investigation of stillbirths with decreased fetal movements is essential to find a possible way of preventing stillbirth. AIM: To investigate maternal reaction time after their perceiving decreased fetal movements among stillbirths in our region of Japan. METHODS: This is a population-based study of stillbirths in Shiga Prefecture, Japan conducted from 2007 to 2011. We sent a questionnaire to each obstetrician who had submitted the stillbirth certificate. We reviewed and evaluated the questionnaires returned from the obstetricians. FINDINGS: There were 66 cases (35%) with decreased fetal movements among 188 stillbirths in Shiga during the study period. The number of maternal visits to outpatient department after perception of decreased fetal movements within 24h was only seven (11%) among 64 stillbirths diagnosed at outpatient department. CONCLUSION: We conclude that delayed maternal visit after perceiving decreased fetal movements is frequently observed in stillbirths. Promoting more thorough maternal education on fetal movements, including emphasizing earlier visitation after perceiving decreased fetal movements, may prevent stillbirths.

Fetal Right Ventricular Diverticulum Detected by Prenatal Ultrasound Screening.

Prenatal ultrasound screening has allowed for the detection of in utero cardiac abnormalities. Specifically, distinction is possible between ventricular diverticula and aneurysms, which is important because each condition has a different clinical outcome. We report the case of a 35-year-old, gravida 1, para 1 woman, with no significant past medical history, who underwent routine prenatal ultrasound screening at 32 weeks' gestation. A four-chamber ultrasound of the fetal heart combined with M-mode echocardiography showed abnormal dilatation of the right ventricular chamber measuring 2.2 cm × 1.0 cm but with normal contractility. Delivery was performed at full term by cesarean section, and a right ventricular diverticulum was confirmed by postnatal cardiac computed tomography. The baby developed normally with no cardiac sequelae during followup. This case demonstrates the importance of making a correct diagnosis of ventricular diverticula by prenatal ultrasound when abnormal dilatation of the fetal ventricle is identified during routine screening. Because evaluating the wall contractility by M-mode ultrasound leads to evaluating whether it has the myocardium, we conclude that M-mode echocardiography is effective for the purpose of prenatal cardiac diagnosis and can distinguish between ventricular aneurysms and functioning ventricular diverticula.

Comparative analysis of cesarean section rates using Robson Ten-Group Classification System and Lorenz curve in the main institutions in Japan.

AIM: The aim of this study was to clarify the indication for cesarean section (CS) using the Robson Ten-Group Classification System (RTGCS) and to clarify the center variation using the Lorenz curve in the main institutions in Japan. METHODS: The records of 68 702 deliveries, which were performed in 125 institutions, were extracted from the Japanese perinatal database in 2013 and the cases were classified using the RTGCS, which classifies deliveries into one of 10 groups on the basis of five parameters. The equality of the CS rate of each hospital was evaluated by the Lorenz curve and the Gini coefficient. The standard error (SE) and 95% confidence intervals (95%CI) for the Gini coefficient were determined by the bootstrap method. The institutions were divided into three categories depending on their scale: comprehensive center (CC, Category I), regional center (RC, Category II) and others (Category III). RESULTS: The overall CS rate was 37.3%. The difference between Categories I (42.6%) and II (34.3%) was significant (P = 0.02). The CS rates that were classified as RTGCS group 3 (multiparous, single cephalic, ≥37 weeks, with spontaneous labor) were higher in Category I (4.0%) than in Category II (2.7%, P = 0.01). The Gini coefficient of Category I (0.119 ± 0.015; 95%CI, 0.092-0.152) was significantly lower than that of Category II (0.189 ± 0.013; 95%CI, 0.16-0.217). CONCLUSION: We clarified the indication of CS and center variation. These two types of methods are useful for the evaluation of medical intervention in the perinatal field.

Perinatal Backgrounds and NICU Bed Occupancy of Multiple-Birth Infants in Japan.

Multiple pregnancies (twin, triplet, and higher-order pregnancy) are associated with an increased risk of resultant preterm and low birth weight infants. The increase of multiple pregnancies for several decades in Japan has been an important consideration in bed allocation planning for neonatal intensive care unit (NICU). The guideline of the Japan Society of Obstetrics and Gynecology (JSOG) in 2008 recommended that embryo transfer be limited to one. The epidemiological data of Japanese regional multiple pregnancies before the JSOG recommendation are valuable in assessing the perinatal effects after this recommendation. The aim of this study was to investigate regional backgrounds of multiple pregnancies and neonatal outcomes of multiple births including NICU admission before the JSOG recommendation. This is a retrospective population-based study for 20 months (January, 2007 through August, 2008) in Shiga Prefecture, Japan. Sending questionnaires to institutions treating multiple births in Shiga, we extracted relevant data from the responses of respective obstetricians and neonatologists. There were 245 multiple births including 241 twins and 4 triplets. We found more twin deliveries with higher risks such as monochorionic diamniotic twins or preterm twins less than 34 weeks in hospitals including perinatal centers than in primary obstetrics clinics. More than half of multiple-birth infants (57%) required NICU admission, and nearly 20% of NICU beds in Shiga are occupied with multiple-birth infants. Furthermore, half of multiple-birth infants were conceived with medical assistance. We conclude that multiple pregnancies resulting from medically assisted conception could have a significant impact upon the NICU bed occupancy in Japan.

Possible Prevention of Neonatal Death: A Regional Population-Based Study in Japan.

PURPOSE: The neonatal mortality rate in Japan has currently been at the lowest level in the world. However, it is unclear whether there are still some potentially preventable neonatal deaths. We, therefore, aimed to examine the backgrounds of neonatal death and the possibilities of prevention in a region of Japan. MATERIALS AND METHODS: This is a population-based study of neonatal death in Shiga Prefecture of Japan. RESULTS: The 103 neonatal deaths in our prefecture between 2007 and 2011 were included. After reviewing by a peer-review team, we classified the backgrounds of these neonatal deaths and analyzed end-of-life care approaches associated with prenatal diagnosis. Furthermore, we evaluated the possibilities of preventable neonatal death, suggesting specific recommendations for its prevention. We analyzed 102 (99%) of the neonatal deaths. Congenital malformations and extreme prematurity were the first and the second most common causes of death, respectively. More than half of the congenital abnormalities (59%) including malformations and chromosome abnormality had been diagnosed before births. We had 22 neonates with non-intensive care including eighteen cases with congenital abnormality and four with extreme prematurity. Twenty three cases were judged to have had some possibility of prevention with one having had a strong possibility of prevention. Among specific recommendations of preventable neonatal death, more than half of them were for obstetricians. CONCLUSION: There is room to reduce neonatal deaths in Japan. Prevention of neonatal death requires grater prenatal care by obstetricians before birth rather than improved neonatal care by neonatologists after birth.

RoboJockey: Designing an Entertainment Experience with Robots.

The RoboJockey entertainment system consists of a multitouch tabletop interface for multiuser collaboration. RoboJockey enables a user to choreograph a mobile robot or a humanoid robot by using a simple visual language. With RoboJockey, a user can coordinate the mobile robot's actions with a combination of back, forward, and rotating movements and coordinate the humanoid robot's actions with a combination of arm and leg movements. Every action is automatically performed to background music. RoboJockey was demonstrated to the public during two pilot studies, and the authors observed users' behavior. Here, they report the results of their observations and discuss the RoboJockey entertainment experience.

Recommendations for preventing stillbirth: a regional population-based study in Japan during 2007-2011.

The perinatal mortality rate in Japan has recently been at the lowest level in the world. However, the perinatal mortality rate of Shiga prefecture has been continuously higher than the Japanese average. The reason for this has not yet been explained. The perinatal mortality rate comprises both stillbirths and neonatal deaths. As stillbirths were almost double neonatal deaths, we focused on the stillbirths to determine how they might be prevented. All of the stillbirth certificates in Shiga Prefecture during 2007-2011 were inspected. On the basis of that information, we designed the original questionnaire and sent it to each obstetrician submitting a death certificate to obtain further information associated with the stillbirth. Reviewing retrospectively returned questionnaires by a peer-review team, we evaluated the possibility of preventing stillbirth along with recommendations for prevention. There were 252 stillbirths among 66,682 deliveries in Shiga during this period. We were able to analyze 188 stillbirths (75%). The audit conference judged that 47 cases of them (25%) were determined to have had some possibility of prevention with seven cases (4%) having strong possibility. We identified major causes of preventable stillbirths, including substandard obstetrical management, delayed referral of high-risk women from primary obstetrical clinics to higher perinatal centers, and delayed visits of pregnant women with decreased fetal movements to clinics or hospitals. Based on the results of this study, we conclude that education for pregnant women is required as well as the necessity of improving obstetric care to prevent stillbirths.