Heparinoid enhances the efficacy of a bactericidal agent by preventing Cutibacterium acnes biofilm formation via quorum sensing inhibition.

Cutibacterium acnes is an opportunistic pathogen in acne vulgaris. C. acnes produces autoinducer-2 (AI-2）, a signaling molecule used for communication known as quorum sensing (QS）. In C. acnes, QS reportedly upregulates biofilm formation leading to resistance against bactericidal agents. In this study, we analyzed how heparinoid affected QS and biofilm formation of the opportunistic pathogen C. acnes. We also verified whether heparinoid would suppress biofilm formation and enhance the efficacy of the bactericidal agent 4-isopropyl-3-methylphenol (IPMP) against C. acnes biofilms. We ran an AI-2 bioassay using Vibrio harveyi ATCC BBA-1121. Heparinoid exhibited inhibitory activity against AI-2 at concentrations of 0.003-0.005%, suggesting an AI-2 analog-derived or C. acnes culture supernatant-derived inhibition of the AI-2 activity. To evaluate how heparinoid suppresses biofilm formation in C. acnes, we completed a biofilm assay in 96-well plates. We also evaluated the bactericidal activity of IPMP against the C. acnes biofilm prepared with or without heparinoid. Heparinoid inhibited C. acnes biofilm formation and IPMP bactericidal efficacy increased upon heparinoid-mediated suppression of biofilm formation. In this study, we clarified that heparinoid inhibits the AI-2-mediated QS of C. acnes, thereby suppressing biofilm formation and increasing IPMP bactericidal efficacy, potentially suppressing acne vulgaris.

Does maternal oxygen administration during non-reassuring fetal status affect the umbilical artery gas measures and neonatal outcomes?

PURPOSE: To clarify whether maternal oxygen administration during vaginal delivery improves umbilical artery (UA) gas measurements and neonatal outcomes. METHODS: Singleton pregnancies requiring operative vaginal delivery or emergency cesarean section (CS) due to non-reassuring fetal status (NRFS) during vaginal delivery at our hospital from 2018 to 2021 were retrospectively investigated. Intrapartum fetal wellbeing was evaluated based on the 5-tier fetal heart rate (FHR) pattern which is a delivery management method widely used in Japan. Operative vaginal deliveries or emergency CS was performed under integrated judgment in NRFS. Patients were divided into the oxygen group to whom oxygen (10 L/min) was supplied by a facemask and the room air group. The UA gas measurements and neonatal outcomes were compared. The oxygen administration was classified by conditions before and after the coronavirus disease 2019 pandemic. As a secondary evaluation, stratification of FHR pattern levels and factors associated with UA pH < 7.15 were examined. RESULTS: A total of 250 patients required obstetric surgical delivery due to NRFS, including 140 (56%) and 110 (44%) in the oxygen and room air groups, respectively. No differences in maternal background factors were found between both groups, except for maternal age. UA gas measurements and neonatal outcomes also showed no significant differences. No significant factors were extracted in the multivariate analysis for UA pH < 7.15. CONCLUSIONS: Trans-maternal oxygen administration for intrapartum NRFS did not affect neonatal cord blood gasses or neonatal outcomes. Thus, routine oxygen administration for intrapartum NRFS may not always be necessary.

Perinatal outcomes of cases with umbilical hypocoiled cord: a study at a single perinatal center.

OBJECTIVES: To evaluate the perinatal outcomes of hypocoiled cord. METHODS: This retrospective study was carried out in the Department of Obstetrics and Gynecology at Showa University Hospital between 2011 and 2017. Umbilical cord index (UCI) was calculated by dividing the total number of coils by the total length of umbilical cord. All umbilical cords were measured and calculated coiling index by obstetrician after delivery. Perinatal outcomes like non-reassuring fetal status (NRFS), emergency cesarean sections, and other perinatal complications were compared. RESULTS: From January 2011 to December 2017, a total of 4047 fetuses were born at our hospital after 28 weeks' gestation. After excluding 100 fetuses of hypercoiled cord, a total of 3947 fetuses were included in this study, of which 71 fetuses were hypocoiled cord and 3876 fetuses were normal coiled cord. There were no association between maternal background and both UCI group. NRFS during labor was significantly associated with hypocoiled cord compared with normal cord (p = .02). Additionally, the rates of emergency cesarean section were raised in cases of hypocoiled cord (p = .02). CONCLUSION: In this study, it was found that hypocoiled cord is related to NRFS and emergency cesarean section. In addition, hypocoiled cord was not associated with any maternal factors. However, in previous studies, no opinion has been reported on the timing of diagnosis of hypocoiled cord during pregnancy. It is difficult to evaluate hypocoiled cord correctly in third trimester. It is a task to find the hypocoiled cord correctly before birth.

Ultrasonographic study of umbilical cord twist direction during second trimester.

OBJECTIVE: To explore/study/evaluate the relationships among umbilical twist direction, the degree of umbilical twist and differences of umbilical arterial diameters (UAD). METHODS: All obstetric patients presenting for prenatal care of singleton fetuses between 18 and 25 weeks gestation to a single provider (MN) from 2015 to 2018 had detailed umbilical cord Doppler measurements. Data including the cord twist direction, degree of twist and number of twists per cord segment length, and the diameters of each UA (UAD) and the umbilical vein (UVD) were extracted from the records. UAs were described as right or left depending on their position at the fetal cord insertion. Three groups were identified: Group A: right UAD > left UAD and Group B: left UAD > right UAD Group C: equal UAD. The coiling index was calculated as the inverse of the length of cord required for one complete 360 degrees wrap of the UA around the cord. According to the difference of UADs, the variables of right and left UADs, the coiling index, and frequencies of umbilical twist direction were analyzed using non-parametric methods. RESULTS: 485 singleton fetuses and umbilical cords were examined. The value of the antenatal coiling index in cases with left UAD greater than right was 0.43 ± 0.16, which was significantly higher than 0.38 ± 0.16 with right UAD greater than left (p = .001). There were significant differences between the two groups in the values of right and left UAD, value of right minus left UAD, absolute value between right and left UAD, antenatal coiling index, antenatal coiling index due to umbilical twist direction and frequencies of cord twist direction. CONCLUSION: The direction of umbilical twist may be in part dependent on differences in diameters of the umbilical arteries, in addition to other fetal characteristics such as fetal movement, or handedness of fetus or mother, fetal hemodynamic forces and structure of muscles of umbilical vessels.

Prenatal Identification of Confined Placental Mosaicism in Pregnant Women with Fetal Growth Restriction.

We examined the influence of confined placental mosaicism (CPM) as a cause of fetal growth restriction (FGR), and whether CPM can be screened using cell-free DNA (cfDNA) analysis of the maternal plasma. We analyzed cfDNA in the maternal plasma of 40 FGR cases with an estimated fetal weight of less than - 2.0 SD using massively parallel sequencing to detect chromosomal aberrations. Fetal and placental genotyping was performed to confirm CPM cases. cfDNA analyses of maternal plasma detected suspected CPM cases with chromosomal aneuploidy or copy number variations in 5 of 40 cases (12.5%). For 4 cases in which the entire placenta consisted of cells with chromosomal abnormalities, fetal growth was severely restricted. CPM can be screened by cfDNA analysis in maternal plasma, accounting for approximately 10% of the causes of moderate or severe FGR, and the higher the proportion of abnormal karyotype cells in the placenta, the more severe the placental dysfunction and FGR.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

AIM: This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. METHODS: We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. RESULTS: Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. CONCLUSION: Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

Accuracy of the FMF Bayes theorem-based model for predicting preeclampsia at 11-13 weeks of gestation in a Japanese population.

This study aimed to investigate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) Bayes theorem-based model for the prediction of preeclampsia (PE) at 11-13 weeks of gestation in the Japanese population. In this prospective cohort study, we invited 2655 Japanese women with singleton pregnancies at 11-13 weeks of gestation to participate, of whom 1036 women provided written consent. Finally, we included 913 women for whom all measurements and perinatal outcomes were available. Data on maternal characteristics and medical history were recorded. Mean arterial pressure (MAP), uterine artery pulsatility index, and maternal serum placental growth factor (PlGF) were measured. The patients delivered their babies at Showa University Hospital between June 2017 and December 2019. Participants were classified into high- and low-risk groups according to the FMF Bayes theorem-based model. Frequencies of PE were compared between groups. The screening performance of the model was validated using the area under receiver operating characteristic (AUROC) curve. A total of 26 patients (2.8%) developed PE, including 11 patients (1.2%) with preterm PE (delivery at <37 weeks). The frequency of preterm PE was significantly higher in the high-risk group than in the low-risk group (3.8% vs. 0.2%, p < 0.05). This population model achieved a 91% detection rate for the prediction of preterm PE at a screen-positive rate of 10% by a combination of maternal characteristics, MAP, and PlGF. The AUROC curve for the prediction of preterm PE was 0.962 (0.927-0.981). In conclusion, the prediction of preterm PE using the FMF Bayes theorem-based model is feasible in the Japanese population.

First-trimester measurements of the three-dimensional ultrasound placental volume and uterine artery Doppler in early- and late-onset fetal growth restriction.

Objectives: To clarify whether early-onset fetal growth restriction (EO-FGR) could be distinguished from late-onset (LO)-FGR using ultrasonographic evaluations of the uterine artery (UtA) Doppler indices and the three-dimensional (3D) ultrasound placental volume (PV) in the first trimester.Methods: Subjects with 1362 singleton pregnancies who underwent an ultrasound scan at 11-13 weeks were enrolled prospectively. The UtA Doppler and PV indices in cases with EO-FGR (<32 weeks at diagnosis) and LO-FGR (≥32 weeks at diagnosis) later in pregnancy were compared with the control group.Results: Twenty-eight EO-FGR, 73 LO-FGR, and 1261 control groups were analyzed. The crown-rump length (CRL) and PV were smaller in both EO and LO-FGR groups than in the control group. The UtA resistance index (RI) Z-score was significantly higher in the EO-FGR group than in the control group (0.723 versus 0.086, p < .001), but did not differ between LO-FGR and the control group. The area under the receiver operating characteristics curve for the prediction of EO-FGR by combining the uterine artery resistance index (UtA-RI) and CRL was 0.760 (95% CI: 0.654-0.865). The detection rate for EO-FGR was 45.8%, with a 10% false-positive rate.Conclusions: Both EO- and LO-FGR are associated with a small CRL in the first trimester. High UtA-RI is associated with EO-FGR, while a small maternal height and PV are associated with LO-FGR.

Impact of first trimester determination of abnormal cord insertion on twin-to-twin transfusion syndrome and other adverse outcomes in monochorionic diamniotic twins: A retrospective cohort study.

OBJECTIVE: To assess the influence of abnormal cord insertion (CI) detected by first trimester ultrasonography on the development of twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twins. METHOD: In this retrospective cohort study, consecutive patients with MCDA twins who underwent fetal ultrasound screening in the first trimester between January 2011 and January 2017 were enrolled. The CI sites were evaluated between 11 + 0 and 13 + 6 weeks' gestation. All twin pairs were assigned to the abnormal CI group (twin pair with velamentous cord insertion (VCI) and/or marginal cord insertion (MCI) in one or both twins) or the normal CI group (twin pair with both normal CI). The relationships of adverse outcomes in two groups were analyzed. RESULTS: A total of 109 MCDA twin pairs were examined; 15 cases were classified into the abnormal CI group and 94 cases into the normal CI group. The incidence of TTTS was significantly higher in the abnormal than in the normal CI group (26.7% vs 7.45%, P = .04). In patients who developed TTTS, all donors had VCI. CONCLUSION: Ultrasound evaluation of abnormal CI at 11 + 0 to 13 + 6 weeks' gestation in MCDA twins is valuable in the assessment of the risk for TTTS.

Differences in perinatal outcomes according to forming period of single umbilical cord in singleton pregnancy.

OBJECTIVES: The aim of this study was to establish the frequency and associations of single umbilical artery (SUA) diagnosed until the first vs second or third trimester. METHODS: A retrospective cohort study was conducted on singleton pregnancies at a tertiary perinatal center. All women underwent both the first and second trimester scans in which the number of arteries in the umbilical cord was routinely documented. SUA was classified as aplastic type when the diagnosis was made in the first trimester and as occlusion type when diagnosed in the second or third trimester. Adverse perinatal outcome was calculated as occurrence of fetal death, birthweight centile < 10th , or Apgar score at 5 minutes < 7. RESULTS: A total of 8675 women underwent ultrasound examinations during the study period. Of the 32 SUA cases, 17 (0.2%) were of the aplastic type and 15 (0.2%) of the occlusion type. Congenital anomalies were more in aplastic than in occlusive SUA (58.8% vs 20%, .043). The occlusive SUA had higher postnatal coiling index (0.3 vs 0.2, .034) and diagnosis of hypercoiled cord (46.7% vs 5.9%, .013) than the aplastic type. CONCLUSIONS: The different gestational age at diagnosis and coiling characteristics suggest two types of SUA, namely, aplastic and occlusion types, which are associated with differences in perinatal outcomes.

Cross-cultural, population-based study on adolescent body image and eating distress in Japan and Finland.

This cross-sectional population-based survey compares the prevalence of self-reported body image and eating distress symptoms among adolescents in Japan and Finland, and associations between emotional/behavioral problems, body image and eating distress from a cross-cultural perspective. The study included 1,840 Japanese and 1,135 Finnish 8th grade students. The self-reported questionnaire included the Body Image and Eating Distress Scale and Strengths and Difficulties Questionnaire (SDQ). The female adolescents from both Finland and Japan reported much greater dissatisfaction with, and concern about, their bodies than the males and Japanese females expressed even higher distress than Finnish females. High levels of body image and eating distress were associated with psychiatric problems measured with the SDQ. There was a significant three-way interaction effect of body image and eating distress, gender and country with SDQ peer problems and prosocial behavior.

Outcomes in the absence of the ductus venosus diagnosed in the first trimester.

PURPOSE: To clarify the outcomes of the absence of the ductus venosus (DV) diagnosed in fetuses suspected to have a structural abnormality during a morphological assessment in the first trimester. METHODS: Infants in whom ultrasound fetal morphological assessments were attempted in the first trimester (11 to 13-6 weeks of gestation) and who were subsequently delivered between 2013 and 2015 at Showa University Hospital were enrolled. In cases in which the absence of the DV was diagnosed in the first trimester, the prognosis was assessed. RESULTS: First-trimester ultrasound screening was performed in a total of 2610 cases between 2013 and 2015. Fetal edema (n = 38), hydrops (n = 16), abnormal four-chamber view findings (n = 2), and tricuspid regurgitation (n = 1) were observed in a total of 52 cases (2.0%). In 4 of the 52 cases with abnormal ultrasound findings, the absence of the DV was detected. CONCLUSION: If fetal edema or hydrops in early pregnancy is found without any other structural abnormalities, not only chromosomal abnormalities should be suspected but also an evaluation for the absence of the DV should be included. In addition, absence of the DV with fetal edema may be associated with the outcomes of cardiac dysfunction, chromosome abnormalities, and intrauterine sudden death. Severe fetal edema is associated with a poor prognosis, and the family must be carefully informed of the potential outcomes.

Association between bullying behavior, perceived school safety, and self-cutting: a Japanese population-based school survey.

BACKGROUND: No previous population-based studies have examined associations between self-cutting, perceived school safety, and bullying behavior among East Asian adolescents. METHOD: We examined whether bullying, victimization, and perceived school safety were associated with self-cutting by getting 1865 students with a mean age of 13.9 years (standard deviation 0.2 years) to complete questions on these variables. Psychiatric problems were assessed with the Strengths and Difficulties Questionnaire. RESULTS: About 5.6% of males and 11.9% females had practiced self-cutting and when we controlled these results for psychiatric symptoms, self-cutting was associated with being both a bully and a victim among males and females. In addition, self-cutting was independently associated with perceived school safety among females. Those who felt unsafe at school and were victimized were much more likely to engage in self-cutting. CONCLUSIONS: Self-cutting among Japanese adolescents was linked with bullying behavior and feeling unsafe at school. Secure school environments and school-based antibullying programs could help to prevent adolescent self-injurious behavior.

Can umbilical artery Doppler findings at 36 weeks' gestation predict maternal hypertension at later gestation?

OBJECTIVES: To clarify whether ultrasonographic evaluations of fetoplacental underperfusion using umbilical artery (UmA) Doppler indices at 36 weeks' gestation can predict maternal hypertension at later gestation. METHODS: Normotensive pregnant women who underwent an ultrasound scan at 36 weeks' gestation and delivered singleton infants at term between 2012 and 2013 were prospectively enrolled. UmA Doppler and maternal blood pressure results at 36 weeks' gestation in cases with pregnancy-induced hypertension (PIH) at later gestation were compared with a control group. RESULTS: Thirty-nine and 775 cases were classified into the PIH and control group, respectively. The UmA pulsatility index (PI) and maternal systolic blood pressure (SBP) at 36 weeks' gestation were higher in the PIH group than in control group (UmA-PI: 0.88 vs. 0.80, p = 0.002; SBP: 126 mmHg vs. 112 mmHg, p < 0.001). The area under the ROC curve for the prediction of PIH by combining the UmA-PI and SBP was 0.867 (95% confidence interval (CI): 0.781, 0.954). The detection rate for PIH was 64.0% with a 10% false-positive rate. CONCLUSIONS: An increased UmA-PI at 36 weeks' gestation is associated with the occurrence of PIH at later gestation. This result may indicate the possibility to detect fetoplacental underperfusion ultrasonically.

Comparison of perinatal outcomes between long-term and short-term use of tocolytic agent: a historical cohort study in a single perinatal hospital.

AIM: The aim of this study was to evaluate the effect of long-term use of tocolytic agents to prevent preterm delivery and improve perinatal outcome. METHODS: A historical cohort study was performed in a single perinatal center. The maternal characteristics, frequency of preterm labor and prescribed dose of tocolytic agents were compared before and after changing the management protocol for threatened premature delivery. RESULTS: A total of 1548 deliveries were carried out before changing the protocol for the use of tocolytic agents for threatened premature delivery and 1444 deliveries afterwards. There was no significant difference in the maternal characteristics before and after the revision except for maternal age. The total number of ritodrine hydrochloride ampules used was reduced from 4654 to 514, and the total vials of magnesium sulfate used were reduced from 1574 to 193, but perinatal outcomes, such as rate of preterm birth, neonatal weight, and rate of NICU hospitalization were not different between the groups. CONCLUSION: There was no significant change in the frequency of preterm delivery before and after changing of the protocol for threatened premature delivery. Because a decrease in the given dose of tocolytic agents did not affect the timing of delivery and neonatal outcomes, long-term tocolysis in patients with threatened premature delivery should be restricted to prevent maternal and fetal adverse side-effects.

Perinatal Management for a Pregnant Woman with an MYH9 Disorder.

We diagnosed a primipara woman with an MYH9 disorder during her pregnancy. A peripheral blood smear with an immunofluorescence analysis is the established method of diagnosing MYH9 disorders. We provided genetic counseling, as required, which included apprising the woman of the inheritance pattern, the importance of a genetic analysis, and the potential delivery risks for the patient and her offspring. Given that the potential delivery risks are reportedly low, special perinatal management is not necessary for patients with an MYH9 disorder whose platelet count is above 5.0 × 10(4)/µL, except for rapid blood access.

Usefulness of antenatal ultrasound fetal morphological assessments in the first and second trimester: a study at a single Japanese university hospital.

OBJECTIVE: To assess the usefulness of antenatal ultrasound examinations for detecting fetal morphological abnormalities in the first and second trimesters. METHODS: A prospective cohort study was conducted at a single Japanese university hospital in the period from February 2011 to September 2013. Patients in whom ultrasound was attempted at both 11 to 13 + 6 and 18 to 20 + 6 weeks' gestation and who were delivered at our hospital were enrolled. After delivery, neonatal congenital abnormalities were reviewed and compared with the ultrasound findings in the first and second trimesters. RESULTS: The subjects were 2028 singleton babies. Abnormal fetal morphological findings were found in the first trimester in 28 cases. In these patients, fetal anomalies detected as diagnostic findings were anencephaly (2 cases) and endocardial cushion defect (2 cases). Findings suggestive of fetal anomalies were observed in 24 cases in the first trimester. Twelve cases with ultrasound findings in the first trimester, including fetal edema, anencephaly, endocardial cushion defect, exhibited an abnormal chromosome after amniocentesis. Ultrasound findings in the first trimester disappeared until 18 weeks of gestation in eight cases, and they were preserved in three cases. Fetal anomalies were primarily noted in the second trimester in 10 cases. However, after delivery, morphological abnormalities were primarily observed in 18 cases. CONCLUSION: Major congenital abnormalities were identified in the first trimester morphological assessment. We think the use of a combination of the first trimester ultrasound screening and the second trimester ultrasound scan for detecting fetal anomalies was effective.