Search

The 2017 clinical guidelines for obstetrical practice by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists were revised and published as the 2020 edition (in Japanese). The aim of these guidelines is to present appropriate standard obstetric diagnosis and management procedures that have reached consensus among Japanese obstetricians. The 2020 guidelines include 113 clinical questions and an appendix, followed by answers (CQA; originally 112 in the 2017 edition), a discussion, list of references, and some tables and figures presenting common problems and questions encountered in obstetrical practice. Each answer comes with a recommendation level of A, B, or C and has been prepared based principally on evidence or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 113 CQAs and the appendix are presented here to promote a better understanding of the current standard care practices for pregnant and lactating women in Japan.

This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self-monitoring fetal heart rate (FHR) in low-risk singleton pregnant women.This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self-monitoring FHR using the mobile CTG device.A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10 min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4-100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self-monitoring using the iCTG.The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.

Prenatal diagnoses of mitochondrial diseases caused by defects in nuclear DNA (nDNA) or mitochondrial DNA have been reported in several countries except for Japan. The present study aimed to clarify the status of prenatal genetic diagnosis of mitochondrial diseases caused by nDNA defects in Japan. A comprehensive genomic analysis was performed to diagnose more than 400 patients, of which, 13 families (16 cases) had requested prenatal diagnoses. Eight cases diagnosed with wild type homozygous or heterozygous variants same as either of the heterozygous parents continued the pregnancy and delivered healthy babies. Another eight cases were diagnosed with homozygous, compound heterozygous, or hemizygous variants same as the proband. Of these, seven families chose to terminate the pregnancy, while one decided to continue the pregnancy. Neonatal- or infantile-onset mitochondrial diseases show severe phenotypes and lead to lethality. Therefore, such diseases could be candidates for prenatal diagnosis with careful genetic counseling, and prenatal testing could be a viable option for families.

Background This study aimed to determine the factors associated with an unfavorable clinical course (emergency surgery and/or prolonged hospitalization) in patients requiring hospitalization owing to pelvic inflammatory disease (PID). Methods A retrospective study was performed on 117 patients diagnosed with PID who were admitted to our hospital between January 2014 and December 2018. Multivariate regression analysis was conducted to determine the factors associated with emergency surgical intervention, and prolonged hospitalization in a subgroup of successful expectant management (n = 93). Results The average age (mean ± standard deviation) of the patients was 41.2 ± 12.5 years; 16 (13.7%) were postmenopausal; 81 patients (69.2%) complicated with a tubo-ovarian abscess (TOA) of which 59 (72.9%) had an ovarian endometrioma; and 19 patients (16.2%) had a history of various intrauterine manipulations. Emergency surgery was performed in 24 patients (20.5%), and patients with TOA underwent emergency surgery more often than did patients without TOA (25.9% vs. 8.3%, p = 0.03), and TOA was associated with longer length of hospital stay (17.1 days vs. 8.0 days, p = 0.01). Smoking, postmenopausal status, past medical history of PID, and high C-reactive protein (CRP) level at admission were significantly associated with emergency surgery. In patients with successful expectant management, obesity (body mass index ≥ 30) and high WBC and CRP level at admission were significantly associated with prolonged hospitalization. Conclusions Of the patients requiring hospitalization owing to PID, TOA was associated with both emergency surgery and prolonged hospital stay. Patients with increased inflammatory markers and obesity should be considered to be at a high risk for unfavorable clinical course in the management of PID.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Aim We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. Methods Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. Results Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

Abdominal wall hypoplasia is a widely known clinical finding of genetic disorders such as the prune belly syndrome. On the other hand, there are few cases of abdominal wall muscle hypoplasia associated with fetal ascites due to fetal hydrops caused by fetal anemia have been reported. We report a case of fetal chylous ascites without anemia, resulting in abdominal wall muscle hypoplasia and flabby skin. At 17 weeks of gestation, fetal ascites was first detected and deteriorated without anemia. At 28, 33 and 36 weeks of gestation, paracentesis was performed three times because of cardiovascular impairment, confirming chylous ascites. After birth, the baby exhibited a flabby skin and lateral abdominal wall hypoplasia, resulting in difficulties in maintaining a sitting posture at 10 months of age. The genetic test using the TruSight One Sequencing Panels found no genetic variants. This case suggests that abdominal wall hypoplasia could be associated with fetal ascites without anemia.

We report a case of Group A streptococcal infection-induced toxic shock syndrome (GAS-TSS) with severe acute respiratory distress syndrome (ARDS), successfully treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO). A 31-year-old woman was transferred due to high fever, continuous uterine contractions and fetal bradycardia at 31 weeks of gestation. She was in a shock status on arrival, and as fetal heart beat disappeared, we canceled the cesarean section and took priority in maternal rescue. At 21 h after the admission, pulseless ventricular tachycardia occurred, and V-A ECMO was introduced after defibrillation, which dramatically improved her respiratory and circulatory conditions. On the 3rd day, GAS was isolated from blood culture. The patient was freed from V-A ECMO on the 5th day and was discharged on the 25th day without permanent impairment. V-A ECMO should be considered as an effective therapeutic option against ARDS and circulation failure in GAS-TSS during pregnancy.

Aims/Introduction The aim of the present study was to examine the associations of pregestational body mass index (BMI) and gestational weight change with birthweight for gestational age in Japanese mothers with gestational diabetes mellitus (GDM). Materials and Methods We retrospectively examined the clinical and laboratory characteristics of 101 mothers with GDM (pregestational BMI 24.7 ± 5.8 kg/m2; maternal age at delivery 34.7 ± 5.1 years; gestational age 38.5 ± 1.4 weeks) at a single center from January 2011 to December 2016. Results Gestational weight changes were 6.22 ± 5.39 kg, and infant birthweights were 2,987.3 ± 393.6 g. Multivariable analysis showed that, in all mothers, pregestational BMI and gestational weight change were positively associated with infant birthweight (P

Prenatal diagnoses of mitochondrial diseases caused by defects in nuclear DNA (nDNA) or mitochondrial DNA have been reported in several countries except for Japan. The present study aimed to clarify the status of prenatal genetic diagnosis of mitochondrial diseases caused by nDNA defects in Japan. A comprehensive genomic analysis was performed to diagnose more than 400 patients, of which, 13 families (16 cases) had requested prenatal diagnoses. Eight cases diagnosed with wild type homozygous or heterozygous variants same as either of the heterozygous parents continued the pregnancy and delivered healthy babies. Another eight cases were diagnosed with homozygous, compound heterozygous, or hemizygous variants same as the proband. Of these, seven families chose to terminate the pregnancy, while one decided to continue the pregnancy. Neonatal- or infantile-onset mitochondrial diseases show severe phenotypes and lead to lethality. Therefore, such diseases could be candidates for prenatal diagnosis with careful genetic counseling, and prenatal testing could be a viable option for families.

Coronavirus disease 2019 (COVID‐19) has spread worldwide within a short period, and there is still no sign of an end to the pandemic. Management of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected pregnant women at the time of delivery presents a unique challenge. To fulfill the goal of providing adequate management of such women and their infants, and to decrease the risk of exposure of the healthcare providers, tentative guidelines are needed until more evidence is collected. Practical preventative action is required that takes into account the following infection routes: (i) aerosol transmission from mothers to healthcare providers, (ii) horizontal transmission to healthcare providers from infants infected by their mothers, and (iii) horizontal transmission from mothers to infants. To develop standard operating procedures, briefings/training simulations should be carried out, taking into account the latest information. Briefings should be carefully conducted to clarify the role and procedures. Healthcare providers should wear personal protective equipment. If it is physically possible, neonatal resuscitation should be performed in a separate area next to the delivery room. If a separate area is not available, the infant warmer should be placed at least 2 m away from the delivery table, or partitioned off in the same room. A minimum number of skilled personnel should participate in resuscitation using the latest neonatal resuscitation algorithms.

To examine the effects of strict glycemic control on the birthweight of infants born to Japanese patients with early- or mid-to-late-detected gestational diabetes mellitus (ed- or md-GDM).We retrospectively examined the characteristics of 101 patients with GDM who underwent guideline-based glycemic control. A 75-g oral glucose tolerance test was conducted to diagnose GDM at gestational weeks 11-15 (ed-GDM subgroup) and 24-28 (md-GDM subgroup).Infant birthweight was significantly lower in the ed-GDM subgroup (n = 25) than in the md-GDM subgroup (n = 76) (2688.3 ± 470.4 g vs. 3052.4 ± 383.1 g, p 0.05), and the proportion of low-birthweight infants (2500 g) was significantly higher in the ed-GDM subgroup than in the md-GDM subgroup (32.0% vs. 5.3%, p 0.005). Fasting plasma glucose (FPG) levels during early treatment and before delivery were significantly lower in the ed-GDM subgroup than in the md-GDM subgroup (76.1 ± 10.4 mg/dL vs. 85.5 ± 9.6 mg/dL, p 0.001; 80.5 ± 10.4 mg/dL vs. 90.4 ± 10.3 mg/dL, p 0.0001).Patients with ed-GDM showed significantly lower FPG levels during treatment compared to those with md-GDM, presumably indicating an association with the delivery of low-birthweight infants.

Introduction Recent studies have shown that the endometrium possesses unique microbiomes, including Lactobacillus. However, the roles of these microbes are currently unknown, especially in placentation and the early stage of pregnancy. Methods The immortalized human first-trimester trophoblast cell line HTR-8/SVneo was cultured in the presence or absence of Lactobacillus crispatus. Invasive and migrative activities were directly evaluated using an optical microscope and a time-lapse imaging system. Protein levels of the invasion-related protein matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 were evaluated using ELISA. Results Matrigel invasion of HTR-8/SVneo cells was significantly increased by L. crispatus, though migration was not affected. The culture supernatant of L. crispatus also promoted invasion. Additionally, levels of the active forms of MMP-1 and MMP-2 in the cell culture medium were upregulated by L. crispatus treatment, but that of MMP-9 was not changed. Discussion L. crispatus promotes trophoblast invasion with an increase in MMP-1 and MMP-2 activation. Our results might explain why Lactobacillus dominance in the endometrium seems beneficial for implantation. Nevertheless, further research is required to determine whether the promotion of trophoblast invasion by L. cripatus is favorable for successful placentation at the early stage of pregnancy.

Background: Prenatal diagnoses of mitochondrial diseases caused by defects in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) have been reported in several countries except for Japan. The present study aimed to clarify the status of prenatal genetic diagnosis of mitochondrial diseases caused by nDNA defects in Japan. A comprehensive genomic analysis was performed to diagnose more than 400 patients, of which, 13 families (18 cases) had requested prenatal diagnoses. Results: Eight cases diagnosed with wild homozygous or heterozygous variants same as either of the heterozygous parents continued the pregnancy and delivered healthy babies. Another eight cases were diagnosed with homozygous, compound heterozygous, or hemizygous variants same as the proband. Of these, seven families chose to terminate the pregnancy, while one decided to continue the pregnancy.Conclusions: Neonatal- or infantile-onset mitochondrial diseases show severe phenotypes and lead to lethality. Therefore, such diseases could be candidates for prenatal diagnosis with careful genetic counseling, and prenatal testing could be a viable option for families.

The use of home-based image sensors for biological and environmental monitoring provides novel insight into health and development but it is difficult to evaluate people during their normal activities in their home. Therefore, we developed a low-cost infrared (IR) technology-based motion, location, temperature and thermal environment detection system that can be used non-invasively for long-term studies in the home environment. We tested this technology along with the associated analysis algorithm to visualize the effects of parental care and thermal environment on developmental state change in a non-human primate model, the common marmoset (Callithrix jacchus). To validate this system, we first compared it to a manual analysis technique and we then assessed the development of circadian rhythms in common marmosets from postnatal day 15&ndash, 45. The semi-automatically tracked biological indices of locomotion velocity (BV) and body surface temperature (BT) and the potential psychological index of place preference toward the door (BD), showed age-dependent shifts in circadian phase patterns. Although environmental variables appeared to affect circadian rhythm development, principal component analysis and signal superimposing imaging methods revealed a novel phasic pattern of BD-BT correlation day/night switching in animals older than postnatal day 38 (approximately equivalent to one year of age in humans). The origin of this switch was related to earlier development of body temperature (BT) rhythms and alteration of psychological behavior rhythms (BD) around earlier feeding times. We propose that this cost-effective, inclusive sensing and analytic technique has value for understanding developmental care conditions for which continual home non-invasive monitoring would be beneficial and further suggest the potential to adapt this technique for use in humans.

Objective Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). Study design A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. Results Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. Conclusion These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

Objectives: To establish the reference values for PAPP-A and total hCG between 11 and 13 weeks of gestation for the use of risk assessment of fetal aneuploidy in Japanese pregnant women.Methods: A ...

AIM To assess the preventive effect on preterm birth of intravaginal ulinastatin (urinary trypsin inhibitor; UTI) administration during the mid-trimester in women with singleton pregnancy and both cervical shortening and lower genital infections. METHODS Pregnant women with a short cervical length

The data collected by nation-wide study of noninvasive prenatal genetic testing (NIPT) for trisomy 21 from 21,610 pregnant women with advanced maternal age in Japan were reported. Among 188 NIPT-positive cases, 180 cases were true positive. The incidence of aneuploidy according to maternal age was estimated using a state-space model. Although, the frequency of trisomy increased exponentially with maternal age as previously reported, the maternal age-specific risk for trisomy 21 that was based on the clinical performance of NIPT was lower than the predicted risk in previous Western cohorts based on the data from invasive prenatal testing (Bayesian two-sided tail-area probability P = 0.0156). The empirical positive predictive value (PPV) of NIPT is likely to turn out higher than that of the theoretical PPV calculated from the sensitivity/specificity of the test and the incidence of trisomy 21 from this study.

Background Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Methods Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O2, 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. Results HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle treatment group. To determine the involvement of microglia in the process of neuronal loss by HI insult, we further examined the influence of hypoxia on rat primary cultured microglia by the quantitative real-time polymerase chain reaction. Hypoxia did not cause the upregulation of interleukin-1beta (IL-1β) mRNA expression, but decreased the microglial intrinsic nitric oxide synthase (iNOS)/arginase1 mRNA expression ratio. NE treatment further decreased the microglial iNOS/arginase1 mRNA expression ratio. In contrast, no significant neuroprotective effect was observed at P14 when atomoxetine was administered at 3 h after HI insult. Conclusions These findings suggested that the enhancement of intrinsic neurotransmitter NE signaling by a selective NE reuptake inhibitor, atomoxetine, reduced the perinatal HI insult brain injury. In addition, atomoxetine treatment was associated with changes of TUNEL, pCREB, and BDNF expression levels, and microglial numbers, morphology, and responses.

Aim Antenatal maternal administration of magnesium sulfate (MgSO4 ) reduces cerebral palsy in preterm infants. However, it remains controversial as to whether it also reduces occurrence of white matter damage, or periventricular leukomalacia. We assessed the effect of MgSO4 against white matter damage induced by hypoxic-ischemic insult using a neonatal rat model and culture of premyelinating oligodendrocytes (pre-OL). Methods Rat pups at postnatal day (P) 6 were administered either MgSO4 or vehicle intraperitoneally before hypoxic-ischemic insult (unilateral ligation of the carotid artery followed by 6% oxygen for 1 h). The population of oligodendrocyte (OL) markers and CD-68-positive microglia at P11, and TdT-mediated biotin-16-dUTP nick-end labeling (TUNEL)-positive cells at P8 were evaluated in pericallosal white matter. Primary cultures of mouse pre-OL were subjected to oxygen glucose deprivation condition, and the lactate dehydrogenase release from culture cells was evaluated to assess cell viability. Results Pretreatment with MgSO4 attenuated the loss of OL markers, such as myelin basic protein and Olig2, in ipsilateral pericallosal white matter and decreased the number of CD-68-positive microglia and TUNEL-positive cells in vivo. Pretreatment with MgSO4 also inhibited lactate dehydrogenase release from pre-OL induced by oxygen glucose deprivation in vitro. Conclusion Pretreatment with MgSO4 attenuates white matter damage by preventing cell death of pre-OL.

Aim The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. Methods Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. Results From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. Conclusion Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Background: Some women with negative results on non-invasive prenatal genetic testing (NIPT) may have ambivalent feelings later. This study aimed to investigate the factors generating ambivalent feel-ings among women who gave birth after having received negative results on NIPT. Methods: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted for those 1562 women who responded to the open-ended question. The con-tents of these qualitative data were analyzed using the N-Vivo software package. Results: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or abortion, assuming the possibility that they were positive. Conclusions: Three major interrelated factors affected the feeling of ambivalence in women. High-lighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.

Background This study aimed to investigate the factors affecting ambivalent feelings among women who gave birth after having received negative results on non-invasive prenatal genetic testing (NIPT). Methods A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted for those 1562 women who responded to the open-ended question. The contents of these qualitative data were analyzed using the N-Vivo software package. Results Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or abortion, assuming the possibility that they were positive. Conclusions Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during the genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.

Objective To investigate the rates of termination of pregnancy (TOP) for fetal chromosomal abnormalities and factors related to such parental decision in Japan. Methods A multicenter retrospective cohort study of chromosomal abnormalities diagnosed before 22 weeks of gestation between April 2008 and March 2015. The pregnancy outcomes and parental decisions were investigated. Results Among 931 fetuses with chromosome abnormalities, the total TOP rate was 75.1% (699/931). TOP rates were 89.3% (585/655) in autosomal aneuploidies and 40.8% (51/125) in sex chromosome aneuploidies. Trisomy 21 showed the highest TOP rate (93.8% [390/416]) followed by trisomy 18 (84.5% [163/193]) and trisomy 13 (71.9% [23/32)]. Indications for karyotyping were related to a parental decision for TOP (p

The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P

Aim This is the first report of a randomized trial of cerclage on pure cervical shortening without vaginosis or cervicitis. The objective of our multicenter randomized controlled trial was to assess the benefits of ultrasound-indicated cervical cerclage in the mid-trimester to prevent preterm birth in women who have no signs of infection or inflammation of the lower genital tract. Material and Methods Women with a short cervical length < 25 mm between 16 and 26 weeks of gestation were randomly assigned to receive a Shirodkar cerclage, McDonald cerclage, or bedrest (no cerclage). Before being randomly assigned to one of the three groups, all women were screened for infection/inflammation of the lower genital tract; those with positive results were excluded from the study. The ratio of preterm delivery as a primary end-point was evaluated in the groups. Results A total of 106 singleton patients with a short cervical length were assessed for study eligibility; 106 patients were randomized to the three treatment options. Ultimately, 98 patients (in the Shirodkar [n = 34], McDonald [n = 34] and bedrest [n = 30] groups) were analyzed. No differences in preterm delivery or perinatal outcomes were found between the three groups. Significantly fewer patients in the Shirodkar group required hospitalization for treatment of threatened preterm labor when compared to patients in the bedrest group. Conclusion For women with a short cervical length < 25 mm between 16 and 26 weeks of gestation, Shirodkar cerclage might be considered to reduce the occurrence of threatened preterm labor.

OBJECTIVE To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (

To assess the preventive effect on preterm birth of intravaginal ulinastatin (urinary trypsin inhibitor; UTI) administration during the mid-trimester in women with singleton pregnancy and both cervical shortening and lower genital infections.Pregnant women with a short cervical length 25 mm between 16 and 26 weeks of gestation and who had been diagnosed with a lower genital infection were randomly assigned for intravaginal UTI administration or placebo. All of the women were screened for infection or inflammation of the lower genital tract, and women with negative results were excluded.Of the 92 patients with a short cervical length who were assessed for eligibility for this study, 86 singleton patients were enrolled. All patients were randomized to one of two treatment groups: patients administered UTI (n = 35) and placebo (n = 35). There were no differences between the two groups in the incidence of preterm delivery before 28, 30, 32, 34 and 37 weeks of gestation and in perinatal outcomes.For women diagnosed with a short cervical length 25 mm) between 16 and 26 weeks of gestation and lower genital infection, who were at risk of preterm birth, administration of transvaginal UTI with vaginal irrigation showed no apparent benefit. Future research on the efficacy of UTI should evaluate modified modes of UTI application.

The expression of numerous microRNAs (miRNAs) in the trophoblasts changes under low oxygen conditions. However, little is known regarding the regulation of the trophoblast invasion by miRNAs under low oxygen conditions. The aim of this study was to identify those miRNAs and their target genes associated with the trophoblast invasion under low oxygen conditions. Culturing the extravillous trophoblast (EVT) cell line, HTR-8/SVneo, at 2% oxygen as compared to 20% oxygen suppressed trophoblast invasion that correlated with increased expression of microRNA-135b (miR-135b) and decreased expression of the its predicted target gene CXCL12. Overexpression of miR-135b suppressed CXCL12 mRNA expression and invasion of HTR-8/SVneo cells. Adding a neutralizing antibody against CXCL12 to the culture medium suppressed HTR-8/SVneo cell invasion. Reporter assays showed that the 3'UTR sequence of CXCL12 was directly targeted by miR-135b. Our results suggest that miR-135b and CXCL12 play important roles in modulating the EVT invasion under low oxygen conditions.

Aim To evaluate whether the presence of amniotic components in the maternal uterine vasculature could be a specific pathological indicator for amniotic fluid embolism (AFE). Methods Medical records of patients treated between January 2006 and March 2013 were retrospectively examined to identify patients who underwent post-partum hysterectomy or autopsy due to maternal death. Three subjects with AFE with disseminated intravascular coagulation (DIC)-type post-partum hemorrhage (PPH), and 13 non-AFE subjects were included in analysis. Histochemical staining using hematoxylin–eosin (HE) and alcian blue, and immunohistochemical staining for sialyl-Tn were conducted to detect amniotic components in the maternal uterine vasculature. Results Alcian blue was positive for amniotic components in the uterine vasculature of all subjects with AFE and of several subjects without AFE. Similarly, HE and sialyl-Tn were negative in some AFE subjects and positive in some non-AFE subjects. Conclusions The presence of maternal intravascular fetal material is not a specific indicator for AFE with DIC-type PPH. Therefore, the presence of fetal components in the uterine vasculature is unlikely to be a definitive indicator for AFE.

Objective The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). Study design This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. Results A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. Conclusion A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.

Antenatal maternal administration of magnesium sulfate (MgSORat pups at postnatal day (P) 6 were administered either MgSOPretreatment with MgSOPretreatment with MgSO