Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

Association Between Interpregnancy Interval and Risk of Preterm Birth and Its Modification by Folate Intake: The Japan Environment and Children's Study.

BACKGROUND: Both short and long interpregnancy intervals (IPIs) have been associated with risk of preterm birth, but the evidence is limited in Asians. It is also uncertain whether the association is modified by dietary folate intake or folic acid supplementation during pregnancy. Thus, we examined associations between IPI and risk of preterm birth and effect modification of those associations by dietary intake of folate and supplementation with folic acid on the basis of a nationwide birth cohort study. METHODS: Among 103,062 pregnancies registered in the Japan Environment and Children's Study, 55,203 singleton live-birth pregnancies were included in the analysis. We calculated IPI using birth date, gestational age at birth of offspring, and birth data of the latest offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) of the risk of preterm birth were estimated according to IPI categories. RESULTS: Both <6-month and ≥120-month IPIs were associated with an increased risk of preterm birth, compared with an 18-23-month IPI. The multivariable ORs were 1.63 (95% CI, 1.30-2.04) for <6-month and 1.41 (95% CI, 1.11-1.79) for ≥120-month IPIs. These associations were confined to women with inadequate intake of dietary folate and folic acid supplementation during pregnancy. Multivariable ORs were 1.76 (95% CI, 1.35-2.29) for <6-month IPI and 1.65 (95% CI, 1.24-2.19) for ≥120-month IPI. CONCLUSION: Both <6-month and ≥120-month IPIs were associated with an increased risk of preterm birth. These higher risks were confined to women with inadequate intake of dietary folate and folic acid supplementation during pregnancy.

Neonatal outcomes of congenital diaphragmatic hernia in full term versus early term deliveries: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to review the optimal timing of delivery at term for neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). We reviewed the literature up to December 19, 2022 using MEDLINE and the Cochrane Library databases. The inclusion criteria were original articles, comparative studies of CDH neonates delivered at an early term (37-38 weeks of gestation) and at full term (39 weeks of gestation or later), and comparative studies investigating outcomes of CDH neonates. Six studies met the inclusion criteria, including 985 neonates delivered at an early term and 629 delivered at full term. The cumulative rate of survival to discharge showed no significant difference between CDH neonates delivered at an early term (395/515; 76.7%) or at full term (345/467; 73.9%) (risk ratio [RR] 1.01; 95% confidence interval [CI], 0.89-1.16; p = 0.85). Furthermore, the number of neonates requiring oxygen therapy at discharge was not significantly different between CDH neonates delivered at an early term (32/370; 8.6%) and at full term (14/154; 9.1%) (RR, 0.99; 95% CI, 0.36-2.70; p = 0.99). Therefore, the optimal timing of delivery at term for neonates with CDH remains unclear.

Outcome of Inducing Labor in Pregnancies with Suspected Fetal Growth Restriction: Oxytocin Discontinuation during the Active Phase of Labor versus Conventional Management.

OBJECTIVE: Although fetal growth restriction (FGR) is associated with an increased risk of cesarean delivery during induced labor, there is limited evidence to guide labor management. This study aimed to investigate the prognosis of induced labor in pregnancies with suspected FGR and whether oxytocin discontinuation during the active phase of labor affects maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study investigated singleton pregnancies with vertex presentation and indications for labor induction owing to FGR after 34.0 weeks of gestation at Osaka University Hospital. From January 2010 to December 2013, women were conventionally managed, and oxytocin was continued until delivery unless there was an indication for discontinuation (conventional management group). From January 2013 to December 2020, oxytocin was routinely discontinued, or the dose was reduced at the beginning of the active phase of labor (oxytocin discontinuation group). RESULTS: A total of 161 women (conventional management group, n = 74; oxytocin discontinuation group, n = 87) were included. After the active phase of induced labor, the total incidence of cesarean delivery was very low (3.1%), and the duration was short (173 ± 145 minutes). Oxytocin discontinuation was associated with lower cesarean delivery (1.1 vs. 5.4%; p = 0.12) and uterine tachysystole (9.8 vs. 23.0%; p = 0.08) rates and longer duration of the second stage of labor (mean: 56.5 ± 90 vs. 34.2 ± 45 minutes; p = 0.08) than conventional management; however, the difference was not significant. The other maternal and neonatal outcomes, including postpartum hemorrhage, did not also significantly differ between them. CONCLUSION: After the active phase of induced labor for suspected FGR, the risk of cesarean delivery is low, and the high incidence of uterine tachysystole and rapid labor progression should be considered cautiously. Oxytocin can be safely discontinued during the active phase of labor in women undergoing labor induction for FGR without an increased risk of cesarean delivery or other unfavorable outcomes. KEY POINTS: · The cesarean delivery rate was low after the active phase.. · The labor progress after the active phase was rapid.. · Oxytocin can be safely discontinued during the active phase..

Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children's Study.

BACKGROUND: Intervention studies have shown that isoflavone treatment improved glucose metabolism, indicating that soy intake may have a potential role in diabetes prevention. OBJECTIVES: We aimed to investigate the prospective association of soy isoflavone and soy food intakes with incidence of gestational diabetes mellitus (GDM) in a birth cohort study. METHODS: We recruited 97,454 pregnant women (median gestational age 12 weeks) between January 2011 and March 2014. Dietary intakes during the 12 months preceding study enrollment were assessed by a semi-quantitative food frequency questionnaire. The relative risks of GDM associated with soy isoflavone and soy food intakes were obtained by Poisson regression. Demographic information, histories of diseases, socioeconomic status, lifestyles, and dietary habits, obtained by a self-administrated questionnaire, were used for covariate adjustments. RESULTS: We identified 1904 cases of GDM (2.2%) among 84,948 women. Compared with those in the lowest quintile of soy isoflavone intake, women in the highest quintile were found to have experienced a significantly lower risk of GDM (multivariate relative risk = 0.82; 95% confidence interval: 0.70, 0.95; P for trend = 0.05). Similar results were observed for genistein and daidzein. Regarding soy foods, intakes of miso soup and natto were inversely associated with GDM incidence (both P for trend ≤ 0.01), whereas the association for tofu intake appeared to be nonlinear (P for trend = 0.74). CONCLUSIONS: Higher intakes of miso soup and natto before and during early pregnancy, compared with lower intakes, may be associated with a lower incidence of GDM.

The RPOC long axis is a simple indicator for predicting the need of invasive strategies for secondary postpartum hemorrhage in either post-abortion or post-partum women: a retrospective case control study.

BACKGROUND: The retained products of conception (RPOC) and related conditions (RPOC-ARC) are the main cause of secondary postpartum hemorrhage (sPPH), but there is no clear consensus for their management. The purpose of this study was to characterize those RPOC-ARC that require invasive treatment and those that could be managed more conservatively. METHODS: We retrospectively analyzed 96 cases of RPOC-ARC that occurred after miscarriage, abortion, or delivery at a gestational age between 12 and 42 completed weeks, that were managed within our institution from May 2015 to August 2020. We reviewed the associations between the occurrence of sPPH requiring invasive treatment with clinical factors such as the maternal background and the characteristics of the lesions. RESULTS: The range of gestational age at delivery in our study was 12-21 weeks in 61 cases, 22-36 in 5, and 37 or later in 30. Among them, nine cases required invasive procedures for treatment. The onset of sPPH was within one month of delivery in all but two cases, with a median of 24 days (range 9-47). We found significant differences between requirements for invasive versus non-invasive strategies according to gestational age at delivery, assisted reproductive technology (ART) pregnancy, amount of blood loss at delivery, and the long axis of the RPOC-ARC lesion (p = 0.028, p = 0.009, p = 0.004, and p = 0.002, respectively). Multivariate analysis showed that only the long axis of the lesion showed a significant difference (p = 0.029). The Receiver Operating Characteristic (ROC) curve for predicting the need for invasive strategies using the long axis of the lesion showed that with a cutoff of 4.4 cm, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was 87.5, 90.0, 43.8, and 98.7%, respectively. CONCLUSION: The long axis of the RPOC-ARC is a simple indicator for predicting which sPPH will require invasive procedures, which use is rare in cases with lesions less than 4.4 cm or those occurring after the first postpartum month. Conservative management should be considered in such cases.

Chocolate consumption and risk of gestational diabetes mellitus: the Japan Environment and Children's Study.

The association of chocolate consumption with risk of gestational diabetes has not been examined. We aimed to investigate the prospective association between chocolate consumption and risk of gestational diabetes in a large birth cohort in Japan. A total of 97 454 pregnant women with a median gestational age of 12 weeks were recruited from January 2011 to March 2014. Data on demographic information, disease history, socio-economic status, lifestyle and dietary habits were obtained at the study enrolment. Dietary intake during the past 12 months before study enrolment was assessed through a semi-quantitative FFQ. The logistic regression was used to obtain the OR of gestational diabetes in relation to chocolate consumption. Among 84 948 women eligible for the analysis, 1904 cases of gestational diabetes (2·2 %) were identified during the period of pregnancy. After controlling for potential confounding factors including age, smoking status, drinking status, education level, occupation, pre-pregnant BMI, depression, previous history of macrosomia babies, parity, physical activity and dietary factors, women in the highest quartile of chocolate consumption, compared with those in the lowest quartile, had a significantly lower risk of developing gestational diabetes (OR 0·78, 95 % CI 0·67, 0·90; P for trend = 0·002). Stratified analyses suggested that the association was not significantly modified by pre-pregnancy BMI, age, parity, smoking status or drinking status. The present prospective cohort study provided evidence that chocolate consumption was associated with a significant lower risk of gestational diabetes in Japanese women.

Single versus multiple cervical dilation by osmotic dilator before induction of labor for second-trimester abortion.

AIM: In this study, we aimed to investigate whether there was a significant prognostic difference between single and multiple cervical dilations when inducing second-trimester abortion. METHODS: We conducted a retrospective review of 238 pregnant women who underwent termination of pregnancy at 12-21 weeks of gestation at Osaka University Hospital in Osaka, Japan, between January 2010 and May 2018. Termination of pregnancy was performed by vaginal administration of 1 mg gemeprost every 3 h for up to five doses per day after uterine cervical dilation using lamicel. RESULTS: The women were categorized into two groups: 191 women had a delivery time of <24 h, whereas 47 had delivery times >24 h. Contrasting the groups, there were significant differences with regard to numbers of primiparas (88 [46.1%] and 32 [68.1%], respectively) and lamicel exchanges ± SD (1.9 ± 0.67 for <24 h and 2.4 ± 0.87 for >24 h, respectively). Additionally, we compared the prognosis of primiparas that received just a single lamicel with that of primiparas that had ≥2 exchanged, but no significant differences were noted in the number of patients with a delivery time of >24 h and the number of used gemeprost. CONCLUSION: Primipara is a risk factor for delayed delivery time of induced abortion. However, increasing the number of exchanged lamicel did not significantly reduce the delivery time; therefore, it should be performed as minimally as possible.

Association between gestational weight gain and risk of overweight at 3 years old: The Japan Environment and Children's Study.

BACKGROUND: It is unclear if gestational weight gain (GWG) increases the risk of children with overweight. OBJECTIVES: We examined the association between GWG and the risk of overweight in 3-year-old children in the Japanese nationwide birth cohort study. METHODS: Among 64 336 singleton births, we calculated the risk ratios (RRs) and 95% confidence intervals (95% CIs) of the association between GWG categories and children with overweight, following an adjustment of the confounding variables. RESULTS: GWG was positively associated with the risk of overweight among 3-year-old children. The multivariable RR (95% CI) was 1.21 (1.17-1.25) per 5 kg increase of the GWG. The multivariable RR (95% CI) for excessive GWG was 1.20 (1.12-1.28) and 1.27 (1.16-1.39) based on the modified Japanese and IOM criteria, respectively, compared to adequate GWG. The multivariable RR (95% CI) of overweight with children for inadequate versus adequate GWG was 0.83 (0.78-0.88) and 0.84 (0.79-0.89) based on the modified Japanese and IOM criteria, respectively. CONCLUSIONS: GWG was positively associated with a high risk of overweight at 3 years of age. The risk of offspring overweight was 20%-27% higher and 16%-17% lower with excessive GWG and inadequate GWG, respectively, compared to adequate GWG, based on the aforementioned criteria.

Association between perceived happiness levels and peripheral circulating pro-inflammatory cytokine levels in middle-aged adults in Japan.

OBJECTIVES: The idea that perceived happiness may be associated with health and well-being is a recent topic of focus. However, the neurobiological mechanisms underlying the positive effects of happiness on psychological and physiological wellness remain obscure. In this study, we attempted to clarify the association between systemic inflammation and happiness. METHODS: We recruited 160 healthy volunteers for experiment 1 and compared peripheral inflammatory markers, namely the concentrations of pro-inflammatory cytokines in the serum, between perceived high-happiness and low-happiness groups. Subsequently, we recruited 7 romantic couples for experiment 2 and investigated changes in peripheral pro-inflammatory cytokine levels after the evocation of happiness, which was induced by warm physical contact with the partner. RESULTS: We found that circulating levels of interferon-γ (IFN-γ), which can affect brain functions and induce depressive symptoms, were lower in the high-happiness group than in the low-happiness group. A negative correlation between the levels of perceived happiness and IFN-γ concentrations was also observed. Furthermore, we also found that experimentally induced happiness could reduce peripheral IFN-γ levels. CONCLUSIONS: These results revealed an association between the perception of happiness and systemic inflammation. Increased happiness may suppress the peripheral circulation of pro-inflammatory cytokines.

Psychological and physiological responses to odor-evoked autobiographic memory.

OBJECTIVE: The "Proust phenomenon" occurs when a certain smell evokes a specific memory. Recent studies have demonstrated that odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli because of the direct neural communication between the olfactory system and the amygdala. The amygdala is known to regulate various physiological activities including the endocrine and immune systems; therefore, odor-evoked autobiographic memory may trigger various psychological and physiological responses; however, the responses elicited by this memory remains obscure. In this study, we aimed to investigate the psychological and physiological responses accompanying odor-evoked autobiographic memory. METHODS: We recruited healthy male and female volunteers and investigated changes in their mood states and autonomic nervous, endocrine, and immune activities when autobiographic memory was evoked in the participants by asking them to smell an odor(s) that was nostalgic to them. RESULTS: The autobiographic memories associated with positive emotion resulted in increased positive mood states, such as comfort and happiness, and decreased negative mood states, such as anxiety. Furthermore, heart rate was decreased, skin-conductance level was increased, and peripheral interleukin-2 level was decreased after smelling the nostalgic odor. These psychological and physiological responses were significantly correlated. CONCLUSIONS: The present study suggests that odor-evoked autobiographic memory along with a positive feeling induce various physiological responses, including the autonomic nervous and immune activities. To the best of our knowledge, the present study is the first to observe an interaction between odor-evoked autobiographic memories and immune function.

Hypertensive Disorders of Pregnancy in Relation to Coffee and Tea Consumption: The Japan Environment and Children's Study.

BACKGROUND: The association between coffee/tea intake and hypertensive disorders of pregnancy (HDP) remains unclear. This study aimed to investigate the association of caffeine, coffee, and tea intake during pregnancy with the risk of HDP. METHODS: We assessed this association in 85,533 singleton pregnant women with live births in the Japan Environment and Children's Study, a prospective cohort in Japan that included women from early pregnancy onward. Caffeinated and decaffeinated coffee and tea (green, oolong, and black) consumption during pregnancy was assessed using a validated food frequency questionnaire conducted at mid-pregnancy, and caffeine intake was calculated based on coffee and tea consumption. Multivariable logistic regression was used to assess the association with the risk of HDP. RESULTS: HDP developed in 2222 women (2.6%). Caffeine intake was weakly associated with increased risk of HDP; the multivariable odds ratio of HDP for the highest versus the lowest quartile was 1.26 (95% confidence interval: 1.11, 1.43). Coffee drinkers of two or more cups per day showed a decreased risk compared with non-drinkers (multivariable odds ratio 0.79; 0.62, 0.99) even after adjustment for total caffeine intake. Tea consumption was not associated with the risk of HDP. CONCLUSIONS: Our study suggests that higher caffeine intake may increase HDP risk, while coffee drinkers had a lower risk. Further high-quality studies are needed to replicate these findings, and to elucidate if other substances in coffee may be protective against HDP.

Diagnosis, Management, and Therapy of Fetal Ovarian Cysts Detected by Prenatal Ultrasonography: A Report of 36 Cases and Literature Review.

BACKGROUND: Fetal ovarian cysts are the most frequently diagnosed intra-abdominal cysts; however, the evidence for perinatal management remains controversial. METHODS: We retrospectively reviewed cases of fetal ovarian cysts diagnosed by prenatal ultrasonography at our institution between January 2010 and January 2020. The following were investigated: gestational age at diagnosis, cyst size, appearance, prenatal ultrasound findings, and postnatal outcomes. Prior to 2018, expectant management was applied in all cases; after 2018, in utero aspiration (IUA) of simple cysts ≥40 mm was performed. RESULTS: We diagnosed 29 and seven simple and complex cysts, respectively. Fourteen patients had simple cysts with a maximum diameter <40 mm, and two of them progressed to complex cysts during follow-up; however, when the diameter was limited to <35 mm, no cases showed progression to complex cyst. Fifteen of the simple cysts were ≥40 mm; three progressed to complex cysts, and two of them were confirmed to be ovarian necrosis. In four patients who underwent IUA, the ovaries could be preserved. CONCLUSIONS: IUA is a promising therapy for preserving ovaries with simple cysts ≥40 mm in diameter; however, the indications for fetal surgery and the appropriate timing of intervention require further study.

Complement activation by an angiogenic imbalance leads to systemic vascular endothelial dysfunction: A new proposal for the pathophysiology of preeclampsia.

The underlying mechanism of preeclampsia by which an angiogenic imbalance results in systemic vascular endothelial dysfunction remains unclear. Complement activation directly induces endothelial dysfunction and is known to be involved in preeclampsia; nevertheless, the association between complement activation and angiogenic imbalance has not been established. This study aimed to evaluate whether angiogenic imbalance affects the expression and secretion of inhibitory complement factor H (CFH) in endothelial cells, resulting in complement activation and systemic vascular endothelial dysfunction. Viability of human umbilical vein endothelial cells (HUVECs) was assessed upon CFH knockdown by targeted-siRNA, and were incubated with complement factors. HUVECs were also treated with placental growth factor (PlGF) and/or soluble fms-like tyrosine kinase 1 (sFlt1), and CFH expression and secretion were measured. These cells were evaluated by cell viability assay and cell surface complement activation was quantified by immunocytochemical assessment of C5b-9 deposition. HUVECs transfected with CFH-siRNA had significantly lower viability than that of control cells. Moreover, the expression and secretion of CFH were significantly increased upon PlGF treatment compared with PlGF + sFlt1 combo. HUVECs treated with PlGF had less C5b-9 deposition and higher viability than HUVECs treated with PlGF + sFlt1. In summary, CFH was found to be essential for endothelial cell survival by inhibiting complement activation. An angiogenic imbalance, including decreased PlGF and increased sFlt1, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction.

Optimal timing of delivery for pregnancies with prenatally diagnosed congenital diaphragmatic hernia: a propensity-score analysis using the inverse probability of treatment weighting.

OBJECTIVE: To evaluate the optimal timing of neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). METHODS: Data from a retrospective cohort study conducted by the Japanese CDH Study Group between 2011 and 2018 were divided into two groups according to delivery timing: 36-37 and 38-41 weeks of gestation (wg). Death before 90 days as the primary outcome and the duration of hospitalization, oxygen therapy and tube feeding at discharge as the secondary outcomes were analyzed with generalized linear model applying inverse probability of treatment weighting method. We also performed layered analysis according to stomach position. RESULT: Among 493 neonates with prenatally diagnosed, isolated and left CDH, 237 were born at 38-41wg. The duration of hospitalization was significantly shorter in those born at 38-41wg, especially among those with stomach malposition, and the other outcomes showed no difference. CONCLUSIONS: Delivery at 38-41wg could be beneficial for those with high grade stomach position.

Sonographic findings after induced medical abortion at 12-21 weeks of gestation: Retrospective cohort study.

OBJECTIVE: To evaluate sonographic findings and clinical outcomes after induced medical abortions. STUDY DESIGN: We reviewed records of women who had induced medical abortions at 12-21 weeks of gestation at the Osaka University Hospital between January 2010 and May 2018. Clinicians evaluated each patient using two-dimensional grayscale transvaginal ultrasonography approximately 1 day, 1 week and 1 month after abortion as a routine care in our hospital. Clinicians employed color Doppler imaging if they detected hyperechoic mass within the endometrial cavity. We evaluated the endometrial vascularity as follows: grade 1, minimal flow; grade 2, moderate flow; and grade 3, highly vascular. We evaluated the incidence of vascularity and assessed the clinical course according to the quantity of vascularity. Clinicians did not provide intervention based on ultrasound findings alone. RESULTS: Of 319 patients, 75 (24%) had vascularity at one or more evaluations, including 1% (3/319), 12% (38/319) and 15% (48/319) at 1 day, 1 week and 1 month after abortion, respectively. Of these, 44 had grade 1, 16 had grade 2, and 15 had grade 3. Fifty-four women (72%) with a vascularity had no symptoms. All sonographically-identified vascularity resolved spontaneously regardless of symptoms and quantity of vascularity within 150 days (mean interval 68.6 ± 32.2 days). No patients required transfusion or invasive procedures. CONCLUSIONS: Vascular endometrial findings were prevalent after induced medical abortions; however, most were asymptomatic, appeared an average of approximately 3 weeks after abortion, and all resolved spontaneously. IMPLICATIONS: Although hypervascularity can be found routinely on ultrasonography after induced medical abortions, this finding commonly resolves spontaneously regardless of symptoms and its quantity. Thus, hemodynamically stable patients, even those with sonographic hypervascularity, can be managed expectantly.

Conservative management for adherent placenta after live birth in angular or interstitial pregnancies: A new entity "angular placenta attachment".

OBJECTIVE: Angular and interstitial pregnancies have been reported with live births and are often complicated by adherent placentas. Most cases had been treated with hysterectomy or corneal resection. CASE REPORT: We successfully treated four patients with conservative management (including one reported previously). Case 1 had a vaginal delivery, but the placenta remained attached. We maintained the patient under observation and delivered the placenta on postpartum day 9. Case 2 underwent a C-section. Uterine artery embolization controlled the hemorrhage without placenta removal. The placenta had disappeared by postpartum day 136. Case 3 underwent a C-section. The right uterine angle, where the placenta was attached, was bulging. We manually removed the placenta. CONCLUSION: We propose a new entity in angular or interstitial pregnancies called "angular placenta attachment" that could be diagnosed during C-sections or after vaginal delivery without placental separation. Expectant management may be considered for adherent placentas in these cases.

Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library.

INTRODUCTION: Preeclampsia therapy has not been established, except for the termination of pregnancy. The aim of this study was to identify a potential therapeutic agent from traditional Japanese medicine (Kampo) using the drug repositioning method. MATERIALS AND METHODS: We screened a library of 74 Kampo to identify potential drugs for the treatment of preeclampsia. We investigated the angiogenic effects of these drugs using human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were performed to measure the levels of placental growth factor (PlGF) in conditioned media treated with 100 µg/mL of each drug. We assessed whether the screened drugs affected cell viability. We performed tube formation assays to evaluate the angiogenic effects of PlGF-inducing drugs. PlGF was measured after administering 10, 50, 100, and 200 µg/mL of the candidate drug in the dose correlation experiment, and at 1, 2, 3, 6, 12, and 24 h in the time course experiment. We also performed tube formation assays with the candidate drug and 100 ng/mL of soluble fms-like tyrosine kinase 1 (sFlt1). PlGF production by the candidate drug was measured in trophoblastic cells (BeWo and HTR-8/SVneo). The Mann-Whitney U test or one-way analyses of variance followed by the Newman-Keuls post-hoc test were performed. P-values < 0.05 were considered significant. RESULTS: Of the 7 drugs that induced PlGF, Tokishakuyakusan (TS), Shoseiryuto, and Shofusan did not reduce cell viability. TS significantly facilitated tube formation (P = 0.017). TS administration increased PlGF expression in a dose- and time-dependent manner. TS significantly improved tube formation, which was inhibited by sFlt1 (P = 0.033). TS also increased PlGF production in BeWo (P = 0.001) but not HTR-8/SVneo cells (P = 0.33). CONCLUSIONS: By using the drug repositioning method in the in vitro screening of the Kampo library, we identified that TS may have a therapeutic potential for preeclampsia. Its newly found mechanisms involve the increase in PlGF production, and improvement of the antiangiogenic state.

Self-Reported Eating Speed and Incidence of Gestational Diabetes Mellitus: the Japan Environment and Children's Study.

There is little evidence linking eating speed to gestational diabetes mellitus (GDM) incidence. We therefore aimed to evaluate the prospective association of eating speed with GDM incidence. Overall, 97,454 pregnant women were recruited between January 2011 and March 2014. Singleton pregnant women who did not have GDM, heart disease, stroke, cancer, type 1 diabetes, and/or type 2 diabetes at the time of study enrollment were eligible. Each woman was asked about her eating speed at that time via a questionnaire. Odds ratios of GDM in relation to eating speed were obtained using logistic regression. Among the 84,811 women eligible for analysis, 1902 cases of GDM were identified in medical records. Compared with women who reported slow eating speed, the age-adjusted odds ratios (95% confidence interval) of GDM for women who reported medium, relatively fast, or very fast eating speed were 1.03 (0.90, 1.18), 1.07 (0.94, 1.23), and 1.28 (1.05, 1.58), respectively. Adjustment for demographic, lifestyle-related, and dietary factors including dietary fat, dietary fiber, and energy intakes yielded similar results. The association was attenuated and no longer significant after further adjustment for pre-pregnancy body mass index. The mediation analysis showed that being overweight accounted for 64% of the excess risk of GDM associated with eating speed. In conclusion, women who reported very fast eating speed, compared with those reporting slow eating speed, were associated with an increased incidence of GDM, which may be largely mediated by increased body fat.

Efficacy of Prophylactic Antibiotics in Bakri Intrauterine Balloon Placement: A Single-Center Retrospective Analysis and Literature Review.

Objective Bakri intrauterine balloon (BIUB) placement is an effective treatment for postpartum hemorrhage (PPH). This study aims to evaluate the risk of infection during BIUB placement. Study Design Data for all deliveries ( n = 2,144) at our institution between January 2014 and March 2018 were retrospectively reviewed. Patients diagnosed with PPH ( n = 758) were included in our analysis, further divided into BIUB ( n = 80) and non-BIUB groups ( n = 678), and subdivided into vaginal delivery (VD), elective cesarean delivery (CD), and emergency CD groups. Postpartum endometritis rate was compared in each group. A single dose of prophylactic antibiotics was administered for BIUB placement in the VD group. In the CD groups, antibiotics were administered preoperatively once, and no additional antibiotics for BIUB placement were administered. To obtain an antibiotics administration protocol to be applied during BIUB placement, we electronically searched the PubMed and Scopus databases. Results No significant differences were observed in endometritis rates between BIUB and non-BIUB groups of all groups. In the literature review, of 27 suitable publications identified, multiple doses of antibiotics were administered in 17 (62.9%) studies and none investigated the efficacy of a protocol for antibiotic. Conclusion Our protocol might be effective and sufficient in preventing postpartum BIUB placement-related endometritis.