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AIM The effect of placenta previa on age-specific placental size has not yet been elucidated. This study aimed to examine the effect of placenta previa on the Japanese standardized z-scores of placental size. METHODS This retrospective cohort study included Japanese participants from Ohta Nishinouchi Hospital with single pregnancies who gave birth during 2013-2019. The participants were categorized into two groups based on the presence or absence of placenta previa. Multiple linear regression analyses were used to identify the association of placenta previa with the z-score of placental size, after adjusting for factors, such as maternal smoking status, maternal age, assisted reproductive technology, myoma uteri, uterine anomaly, maternal hypertension at the time of pregnancy, and body mass index before pregnancy. RESULTS A total of 4071 Japanese women (76 with placenta previa and 3995 without placenta previa) were identified. Placenta previa significantly increased the placental weight z-score (partial regression coefficient: 0.44, 95% confidence interval 0.10-0.70, p

Aims/Introduction To examine adverse outcomes in women with early‐diagnosed gestational diabetes mellitus using data from a large birth cohort study in Japan. Materials and Methods This study analyzed data from singleton pregnancies in the Japan Environment and Children’s Study including births during 2011–2014. Mothers with an HbA1c level ≥6.5% in the first trimester, a history of diabetes mellitus, or steroid use during pregnancy were excluded. The participants were divided into three groups: control (without gestational diabetes mellitus), early‐diagnosed gestational diabetes mellitus (diagnosed before gestational week 24), and late‐diagnosed gestational diabetes mellitus (diagnosed after gestational week 24). Multiple logistic regression analysis was performed to calculate the risk of early‐diagnosed and late‐diagnosed gestational diabetes mellitus for adverse obstetrics outcomes. Results In total, 100,376 eligible participants were included in this study. The number of individuals in control cases, early‐diagnosed gestational diabetes mellitus cases, and late‐diagnosed gestational diabetes mellitus cases was 98,090 (97.7%), 751 (0.7%), and 1,535 (1.5%), respectively. When control cases were used as reference, multiple logistic regression analysis revealed that early‐diagnosed gestational diabetes mellitus increased the risk of hypertensive disorders of pregnancy (adjusted odds ratio: 2.08, 95% confidence interval: 1.51–2.86), early‐onset hypertensive disorders of pregnancy (adjusted odds ratio: 1.91, 95% confidence interval: 1.01–3.65), and late‐onset hypertensive disorders of pregnancy (adjusted odds ratio: 1.92, 95% confidence interval: 1.29–2.86). Conclusion Early‐diagnosed gestational diabetes mellitus is associated with serious obstetric complications. Our findings indicate the necessity of further investigations to validate the benefit of early screening for gestational diabetes mellitus in pregnant women., Occurrence of gestational diabetes mellitus by gestational week.

AIM Age at menarche is used as a risk indicator of gestational diabetes mellitus, preterm birth, and fetal growth. However, little is known regarding the age impact on obstetric outcomes among nulliparous women. This study investigated whether menarche age was correlated with obstetric outcomes among nulliparous women. METHODS We analyzed the data obtained for 37 645 singleton pregnancies between 2011 and 2014 in the Japan Environment and Children's Study. Age at menarche was categorized into the ≤9-, 10-, 11-, 12-, 13-, 14-, and ≥15-year-old groups (n = 363, 3155, 8390, 11 164, 6713, 5446, and 2414, respectively). We calculated the relative risk for cases of preterm birth

No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses.Impact statementWhat is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors.What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses.What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.

Background Polycystic ovary syndrome (PCOS) causes anovulation and is associated with a reduced clinical pregnancy rate. Metformin, which is widely used for treating PCOS, can lead to successful pregnancy by restoring the ovulation cycle and possibly improving endometrial abnormality during the implantation period. However, the mechanism by which metformin improves endometrial abnormality remains unknown. Women with PCOS have an aberrant expression of steroid hormone receptors and homeobox A10 (HOXA10), which is essential for embryo implantation in the endometrium. Methods In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro. Expression of AR and HOXA10 was evaluated by immunohistochemistry, fluorescent immunocytochemistry, and western blot analysis. Results AR expression was localized in both epithelial and stromal cells; however, HOXA10 expression was limited to only stromal cells in this study. In women with PCOS, 3 months after metformin treatment, the expression of AR was reduced in epithelial and stromal cells in comparison to their levels before treatment. In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment. Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro. Conclusions Our results suggest that metformin may have a direct effect on the abnormal endometrial environment of androgen excess in women with PCOS. Trial registration The study was approved by the Ethical Committee of Fukushima Medical University (approval no. 504, approval date. July 6, 2006), and written informed consent was obtained from all patients. https://www.fmu.ac.jp/univ/sangaku/rinri.html

High serum immunoglobulin E (IgE) levels are associated with cardiovascular events. We aimed to evaluate the association between total IgE levels during the first trimester of pregnancy and pregnancy-induced hypertension (PIH) development in a large Japanese cohort. We analysed data pertaining to singleton primipara pregnancies recorded in the Japan Environment and Children’s Study involving births from 2011 to 2014. Serum IgE levels were determined using the immunonephelometric technique. High serum IgE was defined as level ≥ 170 IU/ml. Hypertensive disorders in pregnancy (HDP) were categorized into early onset (Eo) PIH (developed

Background Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis. Methods In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0–3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2. Result Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9–20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7–21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3–101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5–134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7–7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2–7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4–30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia. Conclusion Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.

Background : The relationship between postpartum depression symptoms (PPDS) and gestational weight gain is controversial. We aimed to examine the risk of gestational weight gain for PPDS at 1 month postpartum based on the pre-pregnancy body mass index (BMI). Methods : A prospective cohort study recruited 80 927 Japanese women 2011-2014. They categorized according to their pre-pregnancy BMI into group 1 ( Results : Among participants in group 3, insufficient gestational weight gain was a risk factor for PPDS (adjusted odds ratio: 1.24, 95% confidence interval: 1.14–1.36). This result was not modified by intermediate factors. Limitations : The criteria of appropriate gestational weight gain were determined from the adverse pregnancy outcomes not validated for PPDS. Other confounding factors for PPDS like psychotic disorders were not examined. Conclusions : For women with a pre-pregnancy BMI between 20.0 and

Objectives Determining the appropriate preconception care to reduce the occurrence of hypertensive disorders of pregnancy (HDP) remains a challenge in modern obstetrics. We aimed to examine the association between pre-pregnancy sodium (Na) intake and the development of HDP in normotensive women. Study Design From the Japan Environment and Children’s study (JECS) database, we identified 85,152 normotensive Japanese women who were recruited to the JECS between January 2011 and March 2014. Participants were categorized into five groups according to pre-pregnancy Na intake quintiles (Q1 and Q5 were the lowest and highest Na intake groups, respectively). Main outcome measures Multiple logistic regressions were performed to identify the effect of pre-pregnancy Na intake on HDP, early-onset ( Results Using Q3 (the middle Na intake group) as the reference, multiple logistic regression showed that both the lowest (Q1) and highest (Q5) Na intake groups had an increased risk of HDP with SGA [adjusted odds ratio (aOR): 1.50, 95% confidence interval (CI): 1.02–2.21 and aOR: 1.52, 95% CI: 1.03–2.24, respectively]. Conclusions Both lower and higher Na intake before pregnancy increases the risk of HDP with SGA in normotensive Japanese women. This finding may indicate new recommendations for Na intake before pregnancy to prevent HDP.

A high maternal body mass index (BMI) is associated with increased risks of asphyxia-related neonatal morbidity. We evaluated the association between maternal pre-pregnancy BMI and foetal acidosis while accounting for the mode of delivery. Participants from the Japan Environment and Children’s Study with singleton pregnancies after 22 weeks of gestation who gave birth during 2011–2014 were included. The participants (n = 71,799) were categorised into five groups according to the pre-pregnancy BMI: G1 (BMI 2), G2 (18.5 to 2), G3 (20.0 to 2), G4 (23.0 to 2), and G5 (≥ 25.0 kg/m2). Foetal acidosis was defined as umbilical artery pH (UmA-pH) 2 significantly increased the likelihood of foetal acidosis in newborns delivered vaginally. We found no association between pre-pregnancy BMI and foetal acidosis in newborns delivered via caesarean section. Counselling for body weight control before pregnancy and adequate management and selection of the mode of delivery in pregnant women with a high BMI who are in labour may be essential to avoid foetal acidosis.

Transdermal nitric oxide donor may be a relatively safe treatment strategy for fetal growth restriction and oligohydramnios due to placental insufficiency.

Cesarean scar pregnancy (CSP) is a rare complication involving the implantation of the gestational sac in a cesarean delivery scar. The authors report a case of unexpected placenta accreta spectrum (PAS) caused by late diagnosed CSP, necessitating emergent hysterectomy. A 28-year-old Japanese woman with two previous cesarean deliveries presented to our hospital at 11 weeks of gestation with abnormal transvaginal ultrasound findings obtained at another hospital;however, transabdominal ultrasound revealed that the fetus was already present in the uterine cavity at this time. At 28 weeks, there was no evidence of placenta previa. The woman developed preeclampsia at 29 weeks, and a cesarean section was conducted. Intraoperative findings confirmed PAS, and hysterectomy was conducted immediately.

ObjectivesTo evaluate the association between the urinary 8-hydroxy-2′-deoxyguanosine (U8-OHdG) levels and the incidence of small-for-gestational age (SGA) infants and to assess the utility of U8-OHdG as a biomarker to predict the incidence of SGA infants.DesignProspective cohort study.SettingThe Japan Environment and Children’s Study.ParticipantsData of participants enrolled in the Japan Environment and Children’s Study, a nationwide birth cohort study, between 2011 and 2014 were analysed; 104 062 fetal records were analysed. Data of women with singleton pregnancies ≥22 weeks of gestation were analysed.Primary and secondary outcome measuresU8-OHdG levels were assessed using liquid chromatography-tandem mass spectrometry. Participants were categorised into the following three groups according to the quartile of the distribution of U8-OHdG: low U8-OHdG (2.95 ng/mgCre) groups. Additionally, participants in the 90th percentile for U8-OHdG levels were analysed. Odds ratios (ORs) for SGA infants (ResultsData of 80 212 participants were analysed. The adjusted ORs for SGA infants (ConclusionsElevated U8-OHdG levels were associated with an increased incidence of SGA infants. However, this parameter would not be a useful screening tool for predicting SGA infants owing to its low sensitivity and specificity.

AIM The effect of gestational weight gain on placental weight has not been elucidated. We aimed to examine the effect of body weight gain during pregnancy on the Japanese standardized z-score of placental weight, based on the pre-pregnancy body mass index. METHODS This retrospective cohort study included Japanese women with singleton pregnancies who gave birth during 2013-2019 at Ohta Nishinouchi Hospital. Participants (n = 3610) were categorized by their pre-pregnancy body mass index: G1 (

This is the fourth reported case of central diabetes insipidus with oligohydramnios. Central diabetes insipidus does not adversely affect pregnancy; it can present with oligohydramnios, which can be improved by treating central diabetes insipidus.

Background: This study aimed to evaluate differences in maternal characteristics and obstetric and childhood outcomes between term births according to the use of tocolytic treatment. Methods: This study analyzed the data of the participants enrolled in the Japan Environment and Children’s Study between 2011 and 2014. Data of 63,409 women with singleton births after 37 weeks of gestation were analyzed. We compared maternal characteristics, obstetric outcomes, and childhood outcomes between term births with tocolytic treatment and those without tocolytic treatment. Multiple logistic regression was used to calculate adjusted odds ratios for childhood outcomes with significant between-group differences in the univariable analysis for term births with tocolytic agents, with term births without tocolytic agents as the reference group. Results: In term births with tocolytic agents, participants had significantly younger age, leaner body mass index, higher oxidative stress during pregnancy, shorter pregnancy period, lighter neonatal birth weight, lower incidence of gestational diabetes mellitus, higher incidence of preterm premature rupture of membrane, higher rates of cesarean section, lower incidence of meconium-stained amniotic fluid during pregnancy, and higher incidence of childhood allergic disorders. The incidence of childhood developmental disorders showed no significant between-group differences. The adjusted odds ratio for childhood allergic disorders in term births with tocolytic agents was 1.09 (95% confidence interval, 1.04-1.14). Conclusions: This study found no significant association between tocolytic treatment and the incidence of childhood developmental disorders in children with term births. However, tocolytic treatment showed an association with a slightly increased incidence of childhood allergic disorders.

Background Placenta accreta spectrum (PAS) is a life-threating complication in the field of obstetrics. Sometimes we face with unexpected PAS cases which is potentially higher maternal mortality and morbidity compared with expected cases. The present study was conducted to examine the prevalence of PAS and to elucidate its risk factors using a large Japanese birth cohort study. Methods We reviewed the results of a nationwide prospective birth cohort study in Japan, and identified 90,554 participants treated from 2011 to 2014 in 15 regional centers. Multiple regression models were created to identify the risk factors for PAS. These data were obtained from self-reported questionnaires or patient medical records. Results This analysis consisted of 202 cases of PAS (18 with placenta previa and 184 without placenta previa) and 90,352 cases without PAS. The multiple logistic regression analysis showed that placenta previa (adjusted odds ratio [aOR]: 12.86, 95% confidence interval [CI] 7.70–21.45, P P P = 0.013), more than two previous cesarean sections (aOR: 2.51, 95% CI 1.35–4.67, P = 0.004), and uterine anomalies (aOR: 3.97, 95% CI 1.24–12.68, P = 0.020) increased the risk of PAS. Conclusion In general population, placenta previa, assisted reproductive technology-related pregnancy, smoking during pregnancy, repeated cesarean sections, and uterine anomalies were risk factors for PAS in the Japanese population.

AIM The presence of amniotic fluid sludge has been identified as a risk factor for preterm birth. We sought to validate the clinical characteristics of amniotic fluid sludge in Japanese pregnant women with preterm labor and intact membranes. METHODS This was a retrospective study of 54 patients. The presence of amniotic fluid sludge was confirmed using transvaginal ultrasonography data during pregnancy. The following data were collected: gestational age, the presence of histologic chorioamnionitis, time from the diagnosis of threatened premature labor to delivery, oncofetal fibronectin (onfFN) levels, C-reactive protein peak value levels, cervical length at the time of onset of threatened premature labor and types of neonatal complications. RESULTS Significant differences (P = 0.03) were observed in the age at delivery in relation to the presence of amniotic sludge: delivery occurred at 28.3 ± 4.5 weeks and 31.7 ± 4.3 weeks in sludge positive patients and sludge-negative patients, respectively. Presence of sludge in patients diagnosed with histological chorioamnionitis at

Postpartum hemorrhage within 24 hours after delivery remains the leading cause of maternal mortality worldwide. Puerperal genital hematoma (PGHA) is a rare complication of postpartum hemorrhage, and PGHA can be life-threatening if hemostasis is not properly achieved. However, a reliable management algorithm for PGHA based on the clinical findings has not been developed. The objectives were to evaluate the management strategies for PGHA and identify the clinical findings that help select the treatment for PGHA. The medical records of women who were treated for PGHA in our department were reviewed, and data regarding the clinical findings and the treatment strategy for PGHA were analyzed. Thirty-four women who underwent treatment for PGHA were identified and divided into three groups according to the final procedure that achieved hemostasis: conservative management (CM) (n = 9), surgical management (SURG) (n = 15), and arterial embolization management (AEM) (n = 10). Regarding the clinical findings on initial evaluation, the shock index was significantly higher in the AEM group than in the CM or SURG group; and initial platelet count and fibrinogen level were significantly lower in the AEM group than in the CM group. There was no significant difference in any computed tomography (CT) finding among the three groups. In conclusion, this study clearly shows the difference in clinical findings among treatment strategies for PGHA. We suggest that the clinical findings of shock index, platelet count, and fibrinogen level together with CT findings are helpful and valuable for selecting the treatment strategy for PGHA.

INTRODUCTION This study evaluated the risk of preterm birth, low birthweight and small-for-gestational-age neonates born to mothers with adenomyosis during pregnancy. MATERIAL AND METHODS We used the results of a Japanese nationwide prospective birth cohort study, identifying 93 668 singleton deliveries from 2011 to 2014. We identified 314 pregnancies with adenomyosis using self-reported questionnaires. Multiple logistic regression analyses were conducted to examine whether adenomyosis was associated with adverse pregnancy outcome. Maternal age, smoking status, method of conception, history of parity, fibroids, endometriosis and body mass index before pregnancy were analyzed as confounding factors. RESULTS Multiple logistic regression analysis showed that pregnancy with adenomyosis was a risk factor for preterm birth at less than 37 weeks (adjusted odds ratio [aOR: 2.49, 95% confidence interval [CI] 1.89-3.41), preterm birth at less than 34 weeks (aOR 1.91, 95% CI 1.02-3.55), low birthweight

The phenotype of an unbalanced translocation is characterized by the dosage effects of the affected genes in the translocated chromosome. We present the case of a fetus with a paternally derived unbalanced 46,XY,der(10)t(6;10)(p22;q26.1) translocation, detected following growth retardation and cardiac malformation. In trisomy 6p and 10q26 monosomy, external surface malformations, including characteristic facial abnormalities, and neurological or higher effects have been reported. Developmental delay and hypotonia are reported in ≤ 80% of cases of 10q monosomy. Herein, low birth weight, cephalic abnormalities including microcephaly, low-set ears and a high arched palate, ambiguous genitalia including scrotal hypoplasia and cryptorchidism, and congenital heart defects, including ventricular septal defect and pulmonary atresia, were observed. Neurological impact was not evaluated due to neonatal death. The mortality rate and frequency of low birth weight in such translocations has been seldom reported. In this case, severe cardiac malformation and low birth weight may have caused early neonatal death. Whilst Trisomy 6 is associated with low birth weight and perinatal death, few studies have reported these outcomes in 10q26 deletion syndrome. Our findings therefore contribute to the evidence base regarding unbalanced translocations and may improve the clinical management of such patients.

AIM There is strong evidence that weekly intramuscular (IM) injections of 250 mg of 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduce the risk of recurrent preterm birth (PTB); however, whether a lower dose of 17-OHPC could reduce the risk of recurrent PTB remains unclear. This study aimed to assess whether 125 mg of 17-OHPC reduces recurrent PTB among women with a prior singleton spontaneous PTB and cervical length >25 mm. METHODS This retrospective cohort study at a tertiary-care medical center in Japan included women with a prior singleton spontaneous PTB between 20 and 36 weeks' gestation and cervical length >25 mm, between 2008 and 2018. Primary outcomes were PTB

Selenium (Se) acts as a cofactor of antioxidant enzymes. Preconception care may reduce the risk of gestational diabetes mellitus (GDM). We examined the association between preconception Se intake and the risk of GDM in Japanese women. Using the Japan Environment and Children’s Study database, we identified 92,764 Japanese women recruited between January 2011 and March 2014. Participants were categorized into five groups according to preconception Se intake quintiles (Q1 and Q5 were the lowest and highest Se intake groups, respectively). GDM was categorized as early-onset (Eo-GDM) or late-onset (Lo-GDM) diagnosed before or after 24 weeks, respectively. Multiple logistic regressions were performed to identify the effect of preconception Se intake on GDM, Eo-GDM, and Lo-GDM. Using Q3 (the middle Se intake group) as the reference, a multiple logistic regression analysis showed that the highest (Q5) Se intake group demonstrated increased risks of GDM (adjusted odds ratio (aOR): 1.15, 95% confidence interval (CI): 1.01–1.30) and the lowest (Q1) Se intake group had increased risks of Lo-GDM (aOR: 1.19, 95% CI: 1.01–1.41). Thus, both high and low preconception Se intakes increase risks of glucose intolerance during pregnancy. This finding may indicate new recommendations for preconception Se intake to prevent GDM.

Background The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. Methods This study retrospectively analyzed data from the Japan Environment and Children's Study, a nationwide prospective birth cohort study, conducted between 2011 and 2014. Data of women with singleton live births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, including smoking environment and childhood viral infections, a logistic regression model was used to calculate odds ratios for "wheezing ever," diagnosis of asthma in the last 12 months, and "asthma ever" in women with MRA, with women who did not receive MRA as the reference. Additionally, participants were stratified by term births, and odds ratios for outcomes were calculated using a logistic regression model. Results A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing was 1.17 (95% confidence interval, 1.12-1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. Conclusion MRA was associated with a slightly increased incidence of childhood wheezing up to three years, irrespective of term or preterm birth status. It is important that perinatal physicians consider the potential effects of MRA on the offspring's childhood health.

Maternal diabetes insipidus does not usually adversely affect the course of pregnancy. We present a rare case of central diabetes insipidus diagnosed at 31 weeks of gestation with fetal oligohydramnios successfully treated with intranasal desmopressin. To date, only three cases of diabetes insipidus with oligohydramnios have been reported.

Objective Placental abruption is a significant obstetric complication that affects both maternal and neonatal mortality and morbidity. The present study examined the effect of maternal age on the incidence of placental abruption. Methods We used data of singleton pregnancies from the Japan Environment and Children’s Study, which was a prospective birth cohort study conducted between January 2011 and March 2014 across 15 regional centers in Japan. A multiple regression model was used to identify whether maternal age ( Results A total of 94,410 Japanese women (93,994 without placental abruption and 416 with placental abruption) were recruited. Herein, 764, 8421, 25915, 33517, and 25793 women were aged Conclusions In the Japanese general population, besides advanced maternal age, teenage pregnancy was associated with placental abruption. Recently, the mean maternal age has been changing in Japan. Therefore, it is important for obstetric care providers to provide proper counseling to young women based on up-to-date evidence.

High serum immunoglobulin E (IgE) levels are associated with cardiovascular events. We aimed to evaluate the association between total IgE levels during the first trimester of pregnancy and hypertensive disorders of pregnancy (HDP) development in a large Japanese cohort. We analysed data pertaining to singleton primipara pregnancies recorded in the Japan Environment and Children’s Study involving births in 2011–2014. First trimester’s serum IgE levels were determined using the immunonephelometric technique. High serum IgE was defined as IgE levels ≥170 IU/ml. A multiple logistic regression model was used to estimate the risk of high serum IgE levels on HDP, comprising early-onset and late-onset hypertension. A total of 32,518 participants were enrolled. The prevalence of total, early-onset, and late-onset HDP was 3.2%, 0.6%, and 2.3%, respectively. Patients with high serum IgE levels had an increased risk of late-onset hypertension (adjusted odds ratio [aOR]: 1.19, 95% confidence interval: 1.01–1.40). No correlation was found with either HDP (total) or early-onset hypertension (aOR: 1.15 and 0.85, 95% confidence interval: 0.99–1.32 and 0.60–1.21, respectively). High serum IgE levels during the first trimester are associated with late-onset hypertension. Our results could influence and shape further research regarding the pathogenesis of late-onset hypertension.

Inappropriate gestational weight gain (GWG), either above or below the recommended values, has been associated with an increased risk of adverse obstetric outcomes. To evaluate the risks of GWG for foetal acidosis according to pre-pregnancy body mass index (BMI) and mode of delivery, we analysed women with singleton pregnancies between 2011 and 2014 in the Japan Environment and Children’s Study. Participants (n = 71,799) were categorised according to pre-pregnancy BMI. GWG was categorised into insufficient, appropriate, or excessive. Foetal acidosis was defined as umbilical artery pH (UmA-pH) 2 especially in those with vaginal deliveries. Conversely, excessive GWG was not significantly associated with increased foetal acidosis in obese women and in women whose pre-pregnancy BMI was ≥ 25.0 kg/m2.

We aimed to examine the impact of a daily pro-inflammatory diet during pregnancy on intrapartum fetal acidemia using a large birth cohort study in Japan. We used data on singleton pregnancies in the Japan Environment and Children’s Study (JECS) involving births from 2011 to 2014 through vaginal delivery to calculate the maternal dietary inflammatory index (DII). Participants were categorized according to DII quintiles. A multiple logistic regression model was used to estimate the risk of a pro-inflammatory diet on fetal umbilical artery pH. In total, 56,490 participants were eligible for this study. Multiple regression analysis showed that nulliparous women who had undergone vaginal delivery and were consuming a pro-inflammatory diet had an increased risk of pH &lt, 7.10 (adjusted odds ratio [aOR]: 1.64, 95% confidence interval [CI]: 1.12–2.39). Among these women, the risk of pH &lt, 7.10 was not affected by the duration of labor (aOR: 1.64, 95% CI: 1.11–2.42). In conclusion, following a pro-inflammatory diet during pregnancy is a risk factor for fetal acidosis among nulliparous women undergoing vaginal delivery. A high DII diet during pregnancy may modify the intrapartum fetal heart rate pattern via intrauterine inflammation.

Introduction Pyoderma gangrenosum and myelodysplastic syndrome in pregnant women are both very rare, but can coexist. Here, we present a case of pyoderma gangrenosum in a cesarean section wound in a woman with myelodysplastic syndrome. Case A 34-year-old woman presented with thrombocytopenia and macrocytic anemia during pregnancy. The pregnancy was uneventful until 36 weeks of gestation, when premature rupture of membranes occurred and a cesarean section was performed for breech presentation. She presented four days later with redness and blisters at the wound site. Surgical site infection was diagnosed but did not improve with antibiotics, and multiple wound cultures were negative. Skin biopsy indicated pyoderma gangrenosum, and the redness and blisters responded to oral prednisolone. Post-partum bone marrow aspiration showed myelodysplastic syndrome. As the patient demonstrated no symptoms such as abnormal bleeding, no additional treatment was started, and she went on to receive regular follow-up for myelodysplastic disorder. Discussion This case shows the need for further assessment of hematological disorders diagnosed in pregnancy in women with pyoderma gangrenosum post-partum., Highlights • Pyoderma gangrenosum and myelodysplastic syndrome in pregnant women are both very rare conditions. • Myelodysplastic syndrome is the most frequent hematological disorder associated with pyoderma gangrenosum. • We report the case of a woman diagnosed pyoderma gangrenosum with myelodysplastic syndrome. • This case shows the need for bone marrow biopsy in women with hematological abnormalities and pyoderma gangrenosum.

Hypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial. Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis. This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children’s Study. The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching. Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples. Welch’s t-test was used to analyse metabolite peak areas in the two groups. A total of 166 charged metabolites were identified. The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls. Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP. Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.

To evaluate the association between disease activity, serological activity, and adverse pregnancy outcomes (APOs) in women with systemic lupus erythematosus (SLE) and determine the cut-off values of complements to predict APOs in live birth cases. This retrospective chart review included pregnant women with SLE who had singleton live births after 22 weeks between 2006 and 2020. First trimester maternal disease activity was assessed for SLE onset during pregnancy, antiphospholipid syndrome, SLE pregnancy disease activity index (SLEPDAI), disease flare-ups, lupus nephritis, pancytopenia, and daily prednisolone dosage. Serological activity was assessed for autoantibodies and complements. APOs included preterm birth (PTB), low birth weight infants, small-for-gestational age infants, preterm premature rupture of membranes, and preeclampsia (PE). Chi-square and Fisher’s exact tests were used to compare categorical variables; a receiver-operating characteristic analysis was performed to calculate the cut-off values of complements to predict APOs. Fifty-two participants met the inclusion criteria. The incidence of PTB and PE was associated with a high SLEPDAI (p

Introduction Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder. No definitive clinical signs of antenatal PWS have been identified. Case A healthy, nulliparous, 29-year-old woman demonstrated polyhydramnios at 27 weeks of gestation. Cardiotocography (CTG) showed an absence of foetal heart rate (FHR) acceleration and moderate FHR variability. Daily CTG demonstrated an absence of FHR acceleration. A male newborn was delivered by caesarean section, weighing 2492 g, which is appropriate for gestational age; the Apgar scores at 1 and 5 min were 6 and 6, respectively, and the umbilical artery pH was 7.295. The newborn exhibited marked hypotonia, lack of sucking, and cryptorchidism. FISH analysis performed due to severe hypotonia showed 46, XY. Ish del (15) (q11. 2q 11.2), which led to the diagnosis of PWS. Discussion Polyhydramnios and abnormal FHR patterns may be associated with feeding difficulty and hypotonia. These signs may be an indication for antenatal molecular genetic testing to diagnose PWS., Highlights • Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder. • Polyhydramnios and abnormal foetal heart rate patterns may be associated with feeding difficulty and hypotonia. • These signs may be an indication for antenatal molecular genetic testing to diagnose Prader-Willi syndrome.

Objective: To evaluate the incidence of adverse pregnancy outcomes (APOs) in women with uterine myomas and clarify the effect of uterine myomas on pregnancy outcomes. Design: Prospective cohort study Setting: The Japan Environment and Children’s Study (between 2011–2014) Population: Women (86,370) with singleton births after 22 weeks of gestation. Methods: Using logistic regression, the adjusted odds ratios (aORs) for APOs were calculated considering women without uterine myomas as the reference. Additionally, we used logistic regression to evaluate the effect of intrauterine infection (II) on the incidence of preterm births (PTB) and preterm premature rupture of membranes (pPROM). Main Outcome Measures: PTB (before 37 and 34 weeks), pPROM, II, and gestational hypertension (GH). Results: In women with uterine myomas, the aORs for PTB before 37 and 34 weeks, pPROM, II, and GH were 1.37 (95% confidence interval [CI], 1.22–1.54), 1.61 (95% CI, 1.27–2.05), 1.65 (95% CI, 1.33–2.04), 1.05 (95% CI, 0.75–1.46), and 1.20 (95% CI, 1.05–1.38), respectively. In women with both uterine myomas and intrauterine infection, the aORs for PTB before 37 weeks and pPROM were not significantly increased. Conclusions: Intra-pregnancy uterine myomas were associated with an increased risk of APOs. II in women with uterine myomas was not associated with PTB or pPROM. These data suggest a potential mechanical disadvantage in pregnant women with uterine myomas. Funding: Ministry of the Environment, Japan Key words: uterine myoma, preterm birth, preterm premature rupture of membrane, intrauterine infection

Functional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical re-organization after FEST and weather it can improve upper-limb motor function after traumatic brain injury (TBI). Therefore, our study examined cortical and motor changes in a single male participant with chronic TBI suffering from mild motor impairment during 3-months of FEST and at 3-months follow-up. FEST was applied to enable upper-limb grasping and reaching movements during each session, which was performed for 45-60 min, 3 days per week, over 12-weeks. Short-term assessments were examined before and after each session, while long-term assessments were performed at baseline, after 6- and 12-weeks of FEST, and during follow-up 6- and 12-weeks after completing FEST. Short-term assessments carried out using transcranial magnetic stimulation (TMS) showed reduced cortical silent period (CSP), which is related to cortical and/or subcortical inhibition. At the same time, no changes in motor evoked potentials (MEP) were observed, suggesting corticospinal excitability was unaffected. Long-term assessments indicate increased MEP corticospinal excitability after 12-weeks of FEST, which remained during both follow-ups, while no changes in CSP were observed. Similarly, long-term assessments using TMS mapping showed larger hand MEP area in the primary motor cortex (M1) after 12-weeks of FEST as well as during both follow-ups. Corroborating TMS results, fMRI imaging data showed M1, as well as sensory, premotor, parietal area, and supplementary motor area activations increased after 12-weeks of FEST and during both follow-ups. While clinical scores did not change considerably, writing test performance indicates mild improvements after FEST. Our results suggest that FEST can effectively increase cortical activations, while writing tests confirmed functional improvements in fine motor function even after chronic TBI. These results demonstrated long-term recovery mechanisms of FEST, which include cortical re-organization or neuroplasticity to improve motors function after neurological injury.

The daily diet plays a role in systematic inflammation and may be one of the causes of preterm birth. We aimed to examine the effect of a daily proinflammatory diet before pregnancy on gestational age and birthweight using a large birth cohort in Japan. We used data of singleton pregnancies in the Japan Environment and Children's Study involving live birth from 2011 to 2014 to calculate the dietary inflammatory index. We used individual meals with 30 food parameters from a semiquantitative food frequency questionnaire, which assessed diet intake before pregnancy. Participants were categorized according to the quartile of dietary inflammatory index. A multiple logistic regression model was used to estimate the risk of a proinflammatory diet on preterm birth (PTB) before 37 or 34 weeks and low birthweight (LBW) less than 2,500 or 1,500 g, accounting for maternal age, body mass index before pregnancy, smoking status, education, and household income. After applying our inclusion criteria, 89,329 participants were eligible for the present study. Multiple regression analysis showed that the proinflammatory diet had an increased risk of PTB

Systemic lupus erythematosus, simply known as lupus, is associated with adverse obstetric outcomes. This study evaluated the incidence of preterm births (before 37 and 34 weeks), low birthweight infants (

A 35-year-old female patient with chronic myeloid leukemia (CML) wanted to have a child. She had been treated with imatinib and had achieved major molecular remission, after which imatinib was intentionally discontinued, and interferon-α treatment was initiated. After three failed cycles of artificial insemination with her husband’s semen, the patient underwent treatment with assisted reproductive technology. After two cycles of in vitro fertilization, two embryos (8-cell stage and blastocyst) were cryopreserved. The patient again had elevated major BCR-ABL mRNA levels; thus, infertility treatment was discontinued. After 18 months of dasatinib treatment, major molecular remission was again observed, and the patient underwent vitrified–warmed embryo transfer with a single blastocyst. After that, she became pregnant. Discontinuation of tyrosine kinase inhibitors combined with the timely initiation of infertility treatments, including assisted reproductive technology, might thus be useful for treating women with CML who wish to become pregnant.

This study was designed to determine the effects of a food thickener and deglutition aid jelly for oral administration, jelly wafer, on the pharmacokinetics of levofloxacin orally disintegrating tablets. With an increase in immersion time, the disintegration time of levofloxacin orally disintegrating tablets immersed in food thickener was prolonged, whereas that of the tablets immersed in jelly wafer was shortened. The dissolution behavior of non-immersed levofloxacin orally disintegrating tablets was not similar to that of tablets immersed in food thickener, but was similar to that of tablets immersed in jelly wafer. The time to reach the maximum systemic levofloxacin concentration was the same for non-immersed orally disintegrating tablets and tablets immersed in food thickener and jelly wafer. Moreover, there was no significant difference in the maximum concentration after administration between non-immersed orally disintegrating tablets and tablets immersed in food thickener or jelly wafer. These findings suggest that drugs with a high bioavailability, such as levofloxacin, enter the systemic circulation even when administered with a food thickener or jelly wafer., Food Technology; Pharmaceutical Chemistry; Pharmacokinetics; jelly-wafer; Levofloxacin; food thickener; orally-disintegrating tablet.

Ankle dorsiflexion force control is essential for performing daily living activities. However, the involvement of the corticospinal pathway during different ankle dorsiflexion tasks is not well understood. The objective of this study was to compare the corticospinal excitability during: (1) unilateral and bilateral; and (2) ballistic and tonic ankle dorsiflexion force control. Fifteen healthy young adults (age: 25.2 ± 2.8 years) participated in this study. Participants performed unilateral and bilateral isometric ankle dorsiflexion force-control tasks, which required matching a visual target (10% of maximal effort) as quickly and precisely as possible during ballistic and tonic contractions. Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex to elicit motor-evoked potentials (MEPs) from the right tibialis anterior during: (i) pre-contraction phase; (ii) ascending contraction phase; (iii) plateau phase (tonic tasks only); and (iv) resting phase (control). Peak-to-peak MEP amplitude was computed to compare the corticospinal excitability during each experimental condition. MEP amplitudes significantly increased during unilateral contraction compared to bilateral contraction in the pre-contraction phase. There were no significant differences in the MEP amplitudes between the ballistic tasks and tonic tasks in any parts of the contraction phase. Although different strategies are required during ballistic and tonic contractions, the extent of corticospinal involvement appears to be similar. This could be because both tasks enhance the preparation for precise force control. Furthermore, our results suggest that unilateral muscle contractions may largely facilitate the central nervous system during movement preparation for unilateral force control compared to bilateral muscle contractions.

Introduction Pyoderma gangrenosum (PG) in pregnant women is rare and resembles surgical site infection (SSI). Here we present two cases of PG after caesarean section. Case 1 A 29-year-old woman, who had a history of recurrent wound dehiscence after surgery, exhibited wound ulceration and exudate 6 days after caesarean section. Antibiotics were ineffective and multiple wound cultures were negative. Skin biopsy indicated PG and oral steroid administration resulted in wound improvement. Case 2 A 27-year-old woman, who had a history of PG, exhibited wound ulceration and exudate 5 days after caesarean section. The lesion developed despite antibiotic administration, and multiple wound cultures were negative. Skin biopsy indicated PG and the wound improved after oral steroid administration. Discussion Definitive diagnosis of PG is essential because its treatment differs from that of SSI. PG after caesarean section can be misdiagnosed as SSI, even when there is a history of wound dehiscence or PG., Highlights • Pyoderma gangrenosum is rare in pregnancy and resembles surgical site infection. • Treatment of pyoderma gangrenosum differs from that of surgical site infection. • Pyoderma gangrenosum after caesarean section can be misdiagnosed as surgical site infection.

We investigated whether bilateral lower-limb control and leg dominance affect force control ability in 15 healthy young adults (9 males and 6 females, age =26.8 ± 4.1 years). Participants performed isometric ankle dorsiflexion force control tasks, matching a visual target (10% of maximal effort) as quickly and precisely as possible in ballistic and tonic tasks. Performance was evaluated using force error, force steadiness, amount of muscle activity of the tibialis anterior, and response time characteristics. Results showed no significant effects of leg dominance during both ballistic and tonic tasks, while bilateral condition resulted in significantly larger error, less force steadiness, compared to unilateral condition, and only during the tonic task. Consequently, bilateral control, specifically in tasks utilizing feedback control (i.e., tonic task) might affect force control ability, possibly because of the interhemispheric inhibition to meet bilateral task complexity and integrate afferent bilateral sensory information from both right and left legs.

Inappropriate gestational weight gain (GWG), either above or below the recommended values, has been associated with an increased risk of adverse obstetric outcomes. To evaluate the risks of GWG for foetal acidosis according to pre-pregnancy body mass index (BMI) and mode of delivery, we analysed women with singleton pregnancies between 2011 and 2014 in the Japan Environment and Children's Study. Participants (n = 71,799) were categorised according to pre-pregnancy BMI. GWG was categorised into insufficient, appropriate, or excessive. Foetal acidosis was defined as umbilical artery pH (UmA-pH) 7.20 or 7.10. Multiple logistic regressions were performed for each BMI category to identify the risks of GWG for foetal acidosis, accounting for the mode of delivery. Excessive GWG was significantly associated with increased foetal acidosis in overweight women and in women whose pre-pregnancy BMI was 23.0-25.0 kg/m

This study aimed to clarify the association between uterine myomas and preterm birth (PTB), preterm premature rupture of membranes (pPROM), and intrauterine infection (II). The study was based on data from the Japan Environment and Children’s Study, a nationwide birth-cohort study. Data of 86,370 women with singleton births after 22 weeks of gestation (with uterine myomas, n = 5354) were retrospectively analyzed. Using logistic regression, adjusted odds ratios (aORs) for PTB, pPROM, and II were calculated considering women without uterine myomas as the reference. Additionally, the effects of II on the incidence of PTB and pPROM were evaluated. In women with uterine myomas, the aORs for PTB before 37 and 34 weeks, pPROM, and II were 1.37 (95% confidence interval, 1.22–1.54), 1.61 (1.27–2.05), 1.65 (1.33–2.04), and 1.05 (0.75–1.46), respectively. The aORs for PTB and pPROM in women with II and uterine myomas were not significantly increased. Uterine myomas during pregnancy were associated with an increased incidence of PTB and pPROM. However, II in women with uterine myomas was not associated with an increased incidence of PTB or pPROM. These findings suggest a potential risk of occult PTB in pregnant women with uterine myomas.

Molecular dynamics (MD) simulation is an important tool to understand the physical and chemical properties of cement hydrates at the atomic level. MD with the machine learning potential (MLP) is considered a promising approach for accurate prediction of material properties. However, the applications of machine learning MD for multicomponent systems with a liquid–solid interface have been limited so far. In this work, we used artificial neural networks (ANNs) to construct MLPs for tobermorite minerals. Two MLPs were produced by optimization using different objective functions: one MLP was optimized for both the forces and energies of density functional theory (DFT) results (MLP-FE), and the other MLP was fitted to only the energies (MLP-E). Accuracy assessments of the MLPs were performed for lattice parameters, elastic constants, and bulk, shear moduli, and vibrational density of states. The results of the assessments showed that the accuracy of the potentials largely depended on the objective functions used in the training of the ANNs, i.e., MLP-FE was comparable to the potential energy surface (PES) of DFT, although MLP-E failed to reproduce the several physical quantities given by DFT. To evaluate the applicability of MLP-FE to extended systems beyond the limits of DFT calculations, a large scale MD simulation of a nanoporous tobermorite model was demonstrated using MLP-FE. The transport and distribution properties of atoms in the liquid part of the porous model were investigated. Slow diffusion of water confined in a nanopore was detected, and the results were consistent with experimental data and previous works using classical force fields. The results obtained in this study suggested that MD with MLP is a practical method for large scale molecular simulations of cement hydrates with DFT accuracy.

OBJECTIVE To validate the utility of fetal fibronectin (fFN) and cervical length (CL) in predicting preterm delivery among symptomatic nulliparous women. METHODS A retrospective cohort study of nulliparous women who presented with uterine contractions, abdominal pain, or cervical change at 21-34 gestational weeks at Fukushima Medical University Hospital, Japan, between 2008 and 2017. fFN (categorized as 200 ng/dL) and CL (≥15 mm or