Search

IntroductionTheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial.Methods and analysisThis trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication.Ethics and disseminationThis study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications.Trial registrationjRCTs041190065.

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at32 weeks of gestation. This was based on the presence of "dual peaks" (30-31 and 34-35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were "dual peaks" in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at32 and34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R

Background: Amniotic fluid infection with Ureaplasma urealyticum or Mycoplasma hominis can cause chorioamnionitis and preterm birth. The aim of this study was to examine whether vaginal Ureaplasma ...

Background Recent studies have suggested that fetal sex influences maternal glucose and insulin metabolism during pregnancy. We examined whether fetal sex is associated with maternal insulin resistance and the β-cell function during mid-pregnancy. Methods This retrospective study included singleton pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) at 24–34 weeks of gestation due to positive diabetic screening. In addition to plasma glucose (PG), we measured plasma insulin during the OGTT to obtain surrogate indices associated with insulin resistance (IR), including homeostasis assessment model (HOMA) -IR and insulin sensitivity index (IsOGTT), and β-cell function, including insulinogenic index (II), HOMA-β, and area under the curve of insulin response. We compared these indices between women carrying male fetuses to those carrying female fetuses. Results The study population included 617 women (mean age, 32.4 ± 4.9 years) with a mean pre-pregnancy body mass index (BMI) of 22.6±4.5. They underwent the 75g-OGTT at 29.0 ± 2.5 weeks. Two hundred fifty-eight (42%) women were diagnosed with gestational diabetes (GDM). There was no significant difference in maternal age, pre-pregnancy BMI, gestational age at OGTT, PG at OGTT, or the prevalence of GDM between women with a male fetus (n=338) (male group) and those with a female fetus (n=279) (female group). Regarding the indices of IR, IR was significantly higher and insulin sensitivity was lower in the female group than in the male group (HOMA-IR: 7.0 [5-9.6] vs. 6.2 [4.6-8.8], p< 0.05; IsOGTT: 5.86 [4.29-7.83] vs. 6.29 [4.59-8.84], p< 0.01) (median [quartile range]). These differences remained significant after adjustment for maternal age, pre-pregnancy BMI, gestational age and fasting PG at OGTT, and the diagnosis of GDM. In contrast, the β-cell function did not differ between the two groups. Conclusion Maternal IR during mid-pregnancy was significantly higher in women carrying a female fetus than in those with a male fetus. The sex of the fetus may affect maternal insulin sensitivity during mid-pregnancy.

Amniotic fluid infection withThe present retrospective study, which was performed in a perinatal tertiary center, included patients carrying a singleton pregnancy who were referred to the emergency Ob/Gyn unit because of regular preterm uterine contractions and/or short cervical length (20 mm) at 22-33 weeks of gestation, and in whom a vaginalThe median gestational age of the 94 enrolled patients was 29.9 weeks, and 54 (57%) of the patients were vaginalA positive vaginal

A 27-year-old woman with a history of gestational diabetes mellitus (GDM) developed type 1 diabetes mellitus (T1D) in the early postpartum period. Women with a history of GDM are at an increased risk of developing T1D, which is rarer than type 2 diabetes mellitus. A postpartum follow-up 75-g oral glucose tolerance test and the measurement of glutamic acid decarboxylase autoantibodies aided in the early detection of T1D in this patient. Careful attention should be paid to women with a history of GDM who exhibit clinical features suggestive of future development of T1D.

Objective To investigate factors associated with high-risk gestational diabetes (GDM) among patients with GDM. Methods The present retrospective study included women with singleton pregnancies diagnosed with GDM using International Association of Diabetes and Pregnancy Study Group criteria at a single tertiary perinatal care center in Japan between July 1, 2010, and October 31, 2014. High-risk GDM was defined as patients who required at least 20 units of insulin therapy a day, delivering a large-for-gestational age neonate regardless of insulin therapy, or both. Maternal characteristics and diagnostic test results were investigated to identify associations with the high-risk criteria, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results Among 217 patients, 95 (43.8%) were categorized as high risk. After adjusting for confounders, a fasting plasma glucose level at diagnosis of at least 4.66 mmol/L (adjusted OR 2.88, 95% CI 1.51–5.58) and pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 24 (adjusted OR 3.27, 95% CI 1.60–6.90) were independently associated with meeting the high-risk criteria. Conclusion Among Japanese patients with GDM, pre-pregnancy body mass index and fasting plasma glucose levels could be used to identify high-risk patients requiring intensive care during pregnancy. This article is protected by copyright. All rights reserved.

For women with gestational diabetes mellitus (GDM), the evaluation of glucose tolerance (GT) in the early postpartum period is universally recommended. Nevertheless, few studies have evaluated the risk factors for T2DM on the basis of GT data obtained during the early postpartum period. We aimed to identify the risk factors for type 2 diabetes mellitus (T2DM) by evaluating GT in the first 12 weeks postpartum (12wPP) in women with GDM and to categorize the risk using a combination of the principal risk factors. This retrospective multicenter observational study included 399 East Asian women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) within 12wPP, which was repeated annually or biennially and used to identify the postpartum development of T2DM. Forty-three women (10.8%) developed T2DM during a median follow-up period of 789 ± 477 days. The independent risk factors for T2DM were pre-pregnancy obesity (BMI ≥25 kg/m2), early postpartum impairment in glucose tolerance (IGT), and an early postpartum glycated hemoglobin (HbA1c) ≥5.7%. The odds ratios (95% confidence intervals) for T2DM were 3.2 (1.3-7.8) in women with either early postpartum IGT or pre-pregnancy obesity, 9.2 (3.0-28.3) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c

AIMS Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta-2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. METHODS This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (

Aim To investigate the feasibility of a novel method using artificial intelligence (AI), in which the fibrinogen criterion was determined by the quantitative relation between the distributions of fibrin/fibrinogen degradation products (FDPs) and fibrinogen. Methods A dataset of 154 deliveries comprising more than 2000 g of blood lost due to hemorrhage, excluding disseminated intravascular coagulation (DIC), among patients from eight national perinatal centers in Japan from 2011 to 2015 were obtained. The fibrinogen threshold criterion was identified by using the function that best fit the distributions of FDP as determined by AI. FDP production was described by differential equations using a dataset containing fibrinogen levels less than the fibrinogen criterion and solved numerically. Results A fibrinogen level of 237 mg/dL as the threshold criterion was obtained. The FDP threshold criteria were 2.0 and 8.5 mg/dL for no coagulopathy and a failed coagulation system, respectively. Conclusion The fibrinogen threshold criterion for patients with massive hemorrhage excluding DIC at delivery were obtained by selecting the functions that best fit the distributions of FDP data by using AI.

Aim In spite of the recommendation for rescue antenatal corticosteroids (ACS), the optimal time interval between primary and rescue courses has not been clearly demonstrated. The aim of this study was to determine the effects of the interval between a single ACS course and delivery on the incidence of respiratory distress syndrome (RDS). Methods In this retrospective study, we included singleton pregnant women who received a single course of ACS and delivered beyond 48 h after ACS administration between 24 and 33 weeks' gestation. The risk of RDS was compared between patients who delivered within seven days (Group I), 7-14 days (Group II) and beyond 14 days (Group III) after ACS administration. Results We included 83, 14 and 20 patients in Groups I, II and III, respectively. After adjusting for confounders, the ACS delivery interval was significantly associated with RDS in Group II (adjusted odds ratio 12.8, 95% confidence interval 1.31-164.7) and Group III (adjusted odds ratio 64.0, 95% confidence interval 1.32-5808.6). Conclusion A longer ACS delivery interval is associated with a higher risk of RDS. Thus, the use of a rescue course could be expected to reduce the incidence of RDS in patients beyond seven days after ACS administration who remain at risk for preterm delivery within seven days, especially in cases of placenta previa and/or women bearing a male fetus.

Late preterm infants are still high risk for respiratory problems. The aim of this study was to identify risk factors associated with respiratory problems in Japanese late preterm infants.In this retrospective multicenter study, we included singleton late preterm deliveries at 34+(0/7)-36+(6/7) weeks of gestation. We excluded cases with congenital anomalies. We defined neonatal respiratory disorders (NRD) as the combination of the need for mechanical ventilation or the use of nasal continuous positive airway pressure. We examined the perinatal risk factors associated with NRD.We included 683 late preterm infants. We found that 13.7%, 6.8% and 2.6% of the infants with NRD were born at 34, 35 and 36 weeks of gestation, respectively. In a multivariate logistic regression analysis adjusting for confounders, the gestational age (GA) at birth (adjusted odds ratio 0.40 per week [95% confidence interval, 0.25-0.61]), cesarean birth (4.18 [2.11-8.84]), and a low Apgar score (33.3 [9.93-121.3]) were independent risk factors associated with NRD.An earlier GA, cesarean delivery, and a low Apgar score are independent risk factors associated with NRD in singleton late preterm infants. Patients with late preterm deliveries exhibiting these risk factors should be managed in the intensive delivery setting.

Background Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. Methods In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum. Results Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n = 70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n = 18) (46% vs. 78%, p = 0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41 ± 1.02 vs. 2.28 ± 1.05, p = 0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding. Conclusions In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

Summary Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross‐sectional, case‐control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random‐effect meta‐analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12 weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01‐55.86; OR 0.56, 95% CI 0.35‐0.89; OR 0.22, 95% CI 0.13‐0.36; type 2 diabetes mellitus evaluation time 5 y, respectively). Exclusive lactation for more than 6 to 9 weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22‐0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect.

There have been few studies performed to address the association between the degree of physiological increase in maternal insulin resistance during pregnancy and neonatal birthweight in non-diabetic pregnancy. We attempted to determine whether maternal insulin resistance, as measured by homeostasis model assessment-insulin resistance (HOMA-IR), in mid-pregnancy is associated with neonatal birthweight in normal pregnancies. In this retrospective observational study, we measured HOMA-IR in singleton healthy pregnant women who underwent a 75 g oral glucose tolerance test (OGTT) in mid-pregnancy because of a positive diabetes screen. Using multivariate analyses to adjust for maternal parity, pre-gestational obesity, gestational weight gain, plasma glucose levels, and gestational age at delivery, we tested the association between HOMA-IR and birthweight in their offspring. We also tested the association HOMA-IR and a risk of large-for-gestational-age (LGA) infants. In 655 Japanese women, HOMA-IR was positively associated with birthweight after adjusting for these confounders (p

Aim To investigate whether high-intensity breastfeeding (HIB) reduces insulin resistance during early post-partum period in women with gestational diabetes (GDM), independent of post-partum weight change (PWC). Materials and methods In this multicentre prospective study, we included Japanese women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) during early post-partum. We measured plasma insulin during OGTT to obtain a homeostasis model of assessment of insulin resistance (HOMA-IR). We defined the condition in which infants were fed by breastfeeding alone or greater than or equal to 80% of the volume as HIB, and other statuses, including partial and nonbreastfeeding, as non-HIB. We investigated the association between post-partum HOMA-IR and the breastfeeding status after adjusting for confounders including PWC. Results Among 222 women with GDM who underwent the OGTT at 7.9 ± 2.3 weeks post-partum with a PWC of -7.8 ± 3.4 kg, although the rate of abnormal glucose tolerance (prediabetes and diabetes) did not differ between the groups (33% vs 32%), the HOMA-IR in the HIB women (n = 166) was significantly lower than that in the non-HIB women (n = 56) (1.12 ± 0.85 vs 1.72 ± 1.43, P = 0.0002). The effect of the HIB was independently associated with lower HOMA-IR after adjusting for confounders including PMC. However, the subgroup analysis according to their pre-pregnancy obesity states showed that the effect was seen only in the obese subjects (BMI ≥ 25). Conclusions In obese Japanese women with GDM, HIB has a significant effect in reducing insulin resistance during early post-partum, independent of the post-partum weight loss.

Multicentric reticulohistiocytosis (MR) is an uncommon disease characterized by joint and cutaneous manifestations. The diagnosis must be confirmed by histological evidence of typical histiocytes and multinucleated giant cells. Many conditions, including malignancy, have been described in association with MR. We herein report a female case of MR in whom partial improvement was obtained by steroid and low-dose methotrexate treatments. However, ovarian cancer was found and therefore a surgical resection and chemotherapy were performed. These treatments resulted in the complete resolution of the skin and joint symptoms. These findings support the close linkage between MR and malignancy and the efficacy of cytotoxic drugs for the treatment of MR.

Objective: To examine whether maternal meal ingestion affects the fetal circulation in uncomplicated pregnancies. Methods: A simple crossover blinded study was designed for late uncomplicated singleton pregnancies. After overnight fasting, two different maternal meal states were tested. In one state, pregnant women had a standard 600-kcal breakfast at 8 am (phase A). The other state consisted of maintaining fasting (phase B). Both states were assigned to each woman within 3 days in randomized order. Fetal Doppler studies of the umbilical, middle cerebral, and renal arteries and the descending aorta were performed at 7 am (the fasting state) and at 10 am (the fed state or the continuous fasting state). Results: Twenty women underwent the crossover study. Regardless of the maternal meal state, no significant change was observed in the pulsatility index (PI) of either the umbilical artery (n = 20), the middle cerebral artery (n = 19), or the descending aorta (n = 15). However, the PI of the fetal renal artery decreased significantly after maternal meal ingestion (n = 14) (phase A, 2.36 ± 0.16 versus 2.09 ± 0.33; P = .021). There was no such change in the PI after prolonged fasting (phase B, 2.44 ± 0.32 versus 2.39 ± 0.44; P = .75). Conclusion: Fetal renal artery resistance decreased after maternal meal ingestion in normally grown fetuses during late pregnancy. This decrease in the resistance may be associated with increased fetal urine production after maternal meals.

Aims To determine whether treating mild gestational diabetes mellitus (GDM) is associated with improvement of pregnancy outcomes in Japan. Methods In a multi-institutional retrospective study, we examined pregnant women meeting the criteria for mild GDM (i.e., only one abnormal value [OAV] for 75-g OGTT; fasting glucose ≥100 mg/dL, 1-h postprandial glucose ≥180 mg/dL, and 2-h postprandial glucose ≥150 mg/dL), receiving either routine prenatal care (non-treatment group) or dietary intervention alone or dietary intervention with self-monitoring of blood glucose and/or insulin therapy, if necessary (treatment group). Pregnancy outcomes were compared between these groups. Results Data from 893 eligible women were collected from 30 institutions. Participants included 542 untreated and 351 treated women. Although there were no significant differences in baseline clinical characteristics or maternal and perinatal outcomes between these groups, the incidence of large-for-gestational-age (LGA) infants was lower in the treatment group ( P = 0.07). Multiple logistic regression analysis (MLRA) revealed that pre-pregnancy BMI and gestational weight gain were associated with LGA infants, while 75-g OGTT results were unrelated to LGA. When overweight and obese women were the subjects, the number of LGA infants was significantly lower in the intervention than in the control group, and gestational weight gain was significantly lower in the treatment than in the control group. MLRA showed that intervention was significantly related to a lower incidence of LGA infants. Conclusions Our study suggests that maternal BMI impacts fetal growth and that treatment for overweight or obese mothers with OAV is associated with a lower frequency of LGA infants.

To determine whether hyperinsulinemia is related to gestational hypertension.We measured the arterial blood pressure and the level of immunoreactive insulin (IRI) during a 75 g oral glucose tolerance test in a total of 84 pregnant women. Hyperinsulinemia was defined as a fasting IRI levelor = 9 IU/l, while gestational hypertension was defined as arterial blood pressureor = 140/90 mmHg.The incidence of gestational hypertension was higher in the hyperinsulinemic group (n = 29) than in the control group (n = 55) (24.1% vs. 7.3%, respectively P0.05). After controlling for maternal age, parity, pre-pregnancy body mass index and the gestational age at the time of oral glucose tolerance test (OGTT), using a multiple regression model, the relative risk of developing gestational hypertension for a fasting insulin level was 1.19 (95% C.I., 1.03-1.38).Pregnant women with hyperinsulinemia are at increased risk of developing gestational hypertension.

The incidence of macrosomic infants weighing 5,000 g or more is rare. We experienced a case of nondiabetic macrosomia, in which the fetus weighed more than 5,000 g. The newborn was diagnosed as having Simpson-Golabi-Behmel syndrome. We discuss antenatal ultrasonographic findings in the case.

Objectives. We evaluated the efficacy of magnesium sulfate as a second-line tocolysis for 48 hours.Materials and Methods. A multi-institutional, simple 2-arm randomized controlled trial was performed. Forty-five women at 22 to 34 weeks of gestation were eligible, whose ritodrine did not sufficiently inhibit uterine contractions. After excluding 12 women, 33 were randomly assigned to either magnesium alone or combination (ritodrine and magnesium). The treatment was determined as effective if the frequency of uterine contraction was reduced by 30% at 48 hours of the treatment.Results. After magnesium sulfate infusion, 90% prolonged their pregnancy for >48 hours. Combination therapy was effective in 95% (18/19), which was significantly higher than 50% (7/14) for magnesium alone.Conclusion. This randomized trial revealed that combination therapy significantly reduced uterine contractions, suggesting that adjuvant magnesium with ritodrine is recommended, rather than changing into magnesium alone, when uterine contractions are intractable with ritodrine infusion.