placenta are, however, unknown.We aimed to describe placental histology in eoFGR after sildenafil treatment or placebo.Methods: The Dutch STRIDER study was a randomised controlled trial of sildenafil versus placebo in singleton pregnancies between 20 +0 and 29 +6 weeks of gestation with placental eoFGR.We analysed all available cases for placental pathology.Lesions were classified independently, following the international criteria as defined in the Amsterdam Placental Workshop Group Consensus Statement, by three perinatal pathologists blinded for clinical data.Disagreement was solved by consensus from joint evaluation.Results: 158 cases were available, 81 treated with sildenafil and 77 with placebo.Baseline characteristics were similar.The presence of massive perivillous fibrin deposition (MPVFD) and chronic histiocytic intervillositis (CHIV) were lower in sildenafil compared to placebo (p = 0.026 and p = 0.043).Signs of fetal hypoxia (placental chorangiosis plus fetal nucleated red blood cells) were seen more in the placebo group (p = 0.040).There were no differences for occurrence of MVM, FVM and VUE.Conclusions: The equal distribution of MVM, FVM and VUE in eoFGR treated with sildenafil or placebo suggest that sildenafil had no effect on the most common placental pathology.The finding of a lower incidence of MPVFD and CHIV in the sildenafil group merits more research on the interaction between sildenafil and the maternal immune system, since these lesions are thought to originate from a maternal reaction to fetal antigens.

Prenatal diagnosis for fetal small bowel atresia (SBA) has been known as multiple cysts of the dilated bowel on ultrasound images, however the accurate diagnosis of SBA is challenging. Our objective was to evaluate the prenatal ultrasound findings from the postnatal surgical outcome to accomplish a more accurate diagnosis in SBA. We retrospectively evaluated 11 cases diagnosed as fetal SBA and performed postnatal surgery at our institute from 2019 to 2022. Meconium peritonitis was excluded from this study. The dilation of the bowel on prenatal ultrasound images was evaluated on the axial and coronal plane, then the longest and largest parts were compared at the diagnosis and before birth. The postnatal outcome was confirmed from the operational records. There were 6 jejunal atresias (JA), 3 ileal atresias (IA), and 2 cases that did not require postnatal surgery. The timing of the diagnosis was at 28 (22-32) weeks in JA, and 28 (24-30) weeks in IA. In SBA, there were 5 polyhydramnios (5/6 JA, 0/3 IA), and 6 preterm birth (5/6 JA, 1/3 IA). Regarding prenatal ultrasound findings, the number of bubbles was 3.5 (1-7) in JA, and 6.5 (5-8) in IA. The dilation of the bowel showed 28.65mm (10-30.4) in JA, 30.9mm (21.4-38.8) in IA, the length of the dilated bowel was 83.85mm (35.5-149.6) in JA, 71.95mm (66.8-77.1) in IA. There was no significant correlation between the obstruction site and dilated condition on ultrasound. In the case with no postnatal surgery, one case was diagnosed with chronic constipation at a newborn. The other was idiopathic bowel dilation. It was difficult to evaluate the position of the obstructed site according to the combined dilation and length of the bowel on ultrasound, but the number of bubbles on ultrasound and clinical symptoms might be helpful in distinguishing between JA and IA.

Electronic poster abstracts39 persistent right umbilical vein (PRUV) and 7 others.The group 3 had 7 fetuses (7/7,255; 0.10%).Six fetuses had two different venous disorders.Thus, the prevalence of fetal venous malformations was 1.35% (98/7255).The occurrence of group 1 was higher in twin (8/414; 1.93%) than in singleton (43/6,841; 0.63%) fetuses (P = 0.008).The group 2 had the most favourable outcome characterised by the youngest maternal age, the latest gestational age (GA) at delivery, the highest birthweight and the lowest incidence of associated cardiac or multiple anomalies.Compared with PRUV, more PLSVC fetuses had associated cardiac defects (43.8% vs. 7.7%; P < 0.001).Furthermore, the group 3 had the worst outcome.Conclusions: The 6-plane, systematic 2D ultrasound approach helps in the description of the fetal venous system in a simpler way.An additional 3D/4D-based STIC rendering algorithm is complementary.The presence of a fetal venous disorder is a marker for other serious abnormalities.The prognosis depends on the presence of the associated anomalies or the venous disorders itself.

Global longitudinal strain (GLS) is one of practical parameter for systolic function in adults. GLS in fetal heart is also useful and the detailed evaluation gives further information. The aim of this study was to analyse development of systolic modality in fetal heart by using GLS and the position data with speckle tracking. We evaluated 127 normal fetuses prospectively collected in 18–40 weeks of gestation. GLS in both atriums and ventricles was obtained from four chamber view with speckle tracking. Position data was obtained from GLS analysis by using our original algorithm (figure 1). Subsequently shortening rate (SR) of the long axis and the transverse diameters of apex, middle, and basis in both ventricles were calculated. We defined p < 0.05 was significant. In GLS analysis, only GLS in right ventricle (RV-GLS) slightly decreased across gestation (ρ = 0.35), while GLS in others remained stable. As for SR in RV, the long-axis SR decreased (ρ = 0.39) with gestation, and apical SR was significantly smaller than the others. In left ventricle (LV), middle and basal SRs decreased with gestation (ρ = 0.24, 0.47 respectively), and the values of SR were apex > middle and basis > long axis, in order. Decrease in RV-GLS with gestation might result from the decrease in long-axis SR which might be due to the increased pulmonary circulation or relatively reduced right to left shunting with gestation. Indeed, different SR in RV and LV showed the different systolic modalities in each ventricle from fetal stage. The analysis of position data with speckle tracking clarified the difference of systolic modality of fetal RV and LV. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The intraventricular pressure differences (IVPD) IVPD using color M-mode is a specific marker in infants of mothers with gestational diabetes mellitus (GDM). (Circulation R 2019, 378–388). This study investigated the myocardial performance of fetuses in mothers with GDM under the new GDM definition. The study population comprised of 27 mothers with GDM and the fetus. Women with GDM were defined as those with a glucose metabolism abnormality that existed before or began during the current pregnancy and was diagnosed using OGTTs. The 5 mothers with type 1 or type 2 DM were receiving insulin before their pregnancy. Fetal echo measurements were performed about median gestational age 35 weeks. The primary outcomes were comparisons of the fetal myocardial performance of GDM with insulin administration and without administration using echocardiography with IVPD, and IVPG. The secondary outcome has investigated the relationships between echocardiography parameters, IVPD, and IVPG, and maternal factors. For all statistical analyses, P<0.05 was considered significant. In the insulin group was higher RV output (Fig. 2A). Maternal max HbA1c was observed to have a positive correlation with fetal RV output, significantly (Fig. 2B). Maternal max fasting blood glucose was observed to have a negative correlation with the Total, Basal and Mid to apical IVPD, significantly, respectively. Serial change of LV Total IVPD from fetal to after birth shown in Slide. In both groups, LV Total IVPD was increasing from fetal and after birth significantly. The mechanism associated with the favorable systolic and diastolic performances in IGDMs is suggested to involve metabolic adaptations in the heart. In diabetic mice, these adaptations seem to prevent the heart from failing during conditions of pressure overload, suggesting a restoration of the balance between glucose and fatty acid utilization is beneficial for cardiac function. In fetal LV and RV-IVPD might be interacted the mother's blood sugar control. These indexes can predict the sensitive fetal and infant's cardiac dysfunction for GDM. Type of funding sources: None.

Fetal cardiac axis after first trimester in normal heart is 45 +/- 20 degrees. With progressed ultrasound imaging and increased experiences of first trimester studies, it would be necessary to re-evaluate the change of cardiac axis in normal fetuses at early gestation. The purpose of this study was to evaluate the cardiac axis in normal fetuses during the first trimester, which lead to the early detection of congenital heart diseases (CHD). Indeed, it would lead to better understanding of early fetal heart. This retrospective study was performed at our hospital from 2019 to 2021. The fetal cardiac axis was evaluated between 11.1–13.6 weeks of gestation in 142 fetuses. The cardiac axis in a 4-chamber view was measured as the angle between the line tracing the long axis of the heart and the line bisecting the thorax in the anteroposterior direction. These data were evaluated in Spearman rank-difference correlation analysis. There was a very weak positive correlation between Crown–rump length (CRL) and cardiac axis in 142 fetuses (r = 0.199, p-value = 0.022). Regarding to gestational age, there was a positive trend with the cardiac axis (r = 0.162, p-value = 0.063). At earlier gestation such as 11 weeks, the cardiac axis was slightly smaller than others at later first trimester. The change of fetal cardiac axis at early first trimester might be from the midline to the left. With these nomograms, fetal cardiac axis can be an additional information for prenatal detection of CHD in the first trimester. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Intraventricular pressure difference (IVPD) is an active suction from the basal to the apex during early diastole which contribute to rapid filling of the ventricle. IVPD plays an important role in diastolic function. Fetuses with Twin–twin transfusion syndrome (TTTS) show dramatic changes in cardiac function before and after fetoscopic laser photocoagulation (FLP). Our objective of this study was to evaluate these circulatory dynamics including IVPD in TTTS fetuses treated with FLP. Fetal echocardiogram was performed in 14 TTTS pregnancies, including seven stage 1, three stage 2 and four stage 3 pregnancies. IVPD was obtained with colour M mode subsequently analysed by our own program. Total and segmental (basal and mid-apical) IVPD was measured and converted to z-score to compare the groups. Additionally, Doppler parameters including myocardial performance index (MPI), E/A ratio, inflow time and ejection time (ET) were evaluated. Statistical analysis was performed with Mann-Whitney test or paired t test, and p value <0.05 was significant. In donors, total IVPD in left ventricle (LV) was significantly improved after FLP (p = 0.02). Mid-apical IVPD and basal IVPD also significantly increased after FLP in LV (p = 0.03, 0.01, respectively). There were no differences in right ventricle (RV). In recipients, there were no significances in IVPD before and after FLP. Before FLP, total IVPD and mid-apical IVPD was significantly lower in donors compared with recipients (p = 0.02, p = 0.02, respectively). In other functional parameters, there were no statistically significances for these comparisons. IVPD detected the cardiac changes with FLP in LV in donors which might be mostly affected by increased preload after FLP. IVPD is one of useful parameter which have a different insight to evaluate the changes in fetal circulation complicated with TTTS.

Fetal growth restriction (FGR) is associated with an adverse impact on fetal circulation and fetal cardiac function due to placental insufficiency. Intraventricular pressure difference (IVPD) is known as a parameter for diastolic function which represents the early active diastolic suction from the basal to the apex. Our objective was to elucidate the effects on fetal circulation and cardiac function in FGR fetuses. We prospectively recruited 57 FGR cases at our hospital from 2015 to 2021. FGR was confirmed as the birth weight (BW) less than -2.0SD. IVPD was collected with colour M-mode which was subsequently analysed with our own program on Matlab. Fetal Doppler data such as middle cerebral artery (MCA) pulsatility index (PI), umbilical arterial (UA) PI, ductus venosus (DV) PI and cardiac functional parameters (Tei index, E/A ratio, isovolumetric relaxation time (IRT)) were collected. The relationship between BW and each parameter was analysed with Spearman correlation coefficient. IVPD in right ventricles (RV) showed a positive correlation to BW (P = 0.009, r = 0.475), but not IVPD in left ventricles (LV). Indeed, there was a negative correlation between DV-PI and BW (p < 0.001, r = -0.501). Cerebral placental ratio (CPR) was calculated by UA-PI/MCA-PI. There was no significant correlation between CPR and BW. About cardiac function, there was a negative correlation between E/A ratio and BW (P = 0.007, r = -0.480). Other cardiac parameters did not show significant correlations. DV-PI was the most effective parameter to predict severe FGR cases as previously described. IVPD in RV might be one marker for cardiac function to evaluate severe FGR.

Genetic testing based on next-generation sequencing (NGS) analysis has recently been used to diagnose hereditary diseases. In this study, we explored the usefulness of our custom amplicon panel that targeted 23 genes related to hereditary tumors given in the American College of Medical Genetics and Genomics recommendations. We applied our custom NGS panel to samples from 12 patients previously diagnosed by Sanger sequencing as having the diseases or diagnosed clinically by meeting the diagnostic criteria in this study. Our gene panel not only successfully identified all variants detected by Sanger sequencing but also identified previously unrecognized variants that resulted in confirmation of the disease, or even in the revision of the diagnosis. For instance, a patient identified with an SDHD gene mutation actually had von Hippel-Lindau (VHL) syndrome, as determined by the presence of a pathogenic VHL gene variant. We also identified false-positive results that were generated by amplification of genome regions that are not intended to be investigated. In conclusion, NGS-based amplicon sequencing is a highly effective method to detect germline variants, as long as they are also carefully reviewed by manual inspection.

Intraventricular pressure difference (IVPD), which is a suction force between the apex and the base during early diastole, has been known to a useful marker to evaluate diastolic function. Our objective is to elucidate the cardiac functional change including IVPD in fetal growth restriction (FGR) fetuses. 38 FGR cases were prospectively recruited to this study at our university hospitals in 2015- 2018. We divided two groups as severe FGR (birth weight (BW) ≦-3.0SD: sFGR, n=14) and mild FGR (-1.6SD < BW < -3.0SD, mFGR, n=24), and the fetal cardiac function were compared with bilateral Tei index, E/A ratio, isovolumetric relaxation time and IVPD. IVPD was converted to z-score from published data. Intra ventricular pressure gradient (IVPG) was calculated as IVPD/ventricular length. The study timing of this evaluation was almost same (sFGR=29.61±3.93 weeks, FGR=31.94±4.97 weeks). E/A in left ventricle (LV) showed significantly higher in sFGR compared to mFGR (p < 0.01). Indeed total IVPD in right ventricle (RV) was significantly lower (-1.50±1.09) in sFGR (p < 0.05). IVPG in RV showed a decreased trend in sFGR group (p = 0.07). Although total IVPD in LV decreased in both groups (p = 0.61, sFGR=-1.45±1.03, mFGR=-1.20±0.96), there was no significant difference in comparison of the groups. With progression of FGR, we found increased E/A and decreased IVPD and IVPG in RV. Significant decrease of IVPD in RV might be due to RV dominance in fetal circulation. Since main part of ventricular suction is LV, total IVPD in LV decreased in FGR fetuses. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Congenital pulmonary airway malformation (CPAM) is known as a lung mass with relatively good prognosis unless fetal hydrops is complicated. Compared to other lung related lesions such as congenital diaphragmatic hernia (CDH) or congenital high airway obstruction syndrome, lungs in CPAM grow well even though other lungs were compressed prenatally. In case with pulmonary hypoplasia such as CDH, decreased acceleration time/ ejection time ratio (AT/ET), increased peak early diastolic reverse flow (PEDRF) and lower pulsatility index (PI) have been seen with increased pulmonary vascular resistance. Indeed smaller pulmonary artery size is expected. Our objective of this study was to better understand a natural history of CPAM with pulmonary arterial (PA) Doppler change. We evaluated 11 CPAM cases retrospectively from 2017 to 2019. Branch PA size, branch PA Doppler and lung mass size was collected. As for PA Doppler, AT/ET, PEDRF and PI were compared between ipsilateral and contralateral PA. CPAM type was classified as follow; type 1 = 1, type 2 = 4, type 3 = 6. There was no significant difference in PA size z-score between ipsilateral PA (0.64± 1.04) and contralateral PA (0.51±0.79). AT/ET in ipsilateral PA (0.18±0.02) was slightly higher compared to the ones in contralateral PA (0.16±0.02) although it was not significant (p = 0.08). PEDRF or PI did not show any significance between the lungs. Although CPAM is an occupied lesion in the lungs, the rest of lung grow and sometimes compensate for the mass. Slightly increased AT/ET in ipsilateral PA might show the change of flow distribution in CPAM fetuses. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Aboveground parts of mizuna plants were sprayed with 100 μg/ml L-methionine solution 3 or 10 days before inoculation. These plants were replanted in soil including Fusarium oxysporum f. sp. conglutinans (FOC). Disease severity scored at 14 days post-inoculation (dpi) was lower on L-methionine-treated plants than on untreated plants. No effect of L-methionine on mycelial growth of FOC was visible microscopically. Quantitative RT-PCR analyses of marker genes for plant defense responses (BrPR1, BrBGL2, BrLOX2, BrVSP2) in root tissues at 2 dpi showed that expression of these genes was higher in treated plants than in control plants.

The prognosis of the babies with congenital pulmonary airway malformation (CPAM) has been evaluated with CPAM volume ratio (CVR). Some lesions diminish and it is difficult to measure at late gestation, but some cases need neonatal emergency surgery. In latter case, it is better to deliver the baby at tertiary centre. We examined whether prenatal evaluation can predict the postnatal outcome. Twenty-two CPAM cases from 2012 to 2017 were included. 5 cases had a neonatal surgery (NS group), and 17 cases had an elective surgery (ES group). Prenatal condition was evaluated longitudinally with mass volume/EFW and CVR, Postnatal CT volume and the duration to the surgery were evaluated. The timing of diagnosis was not significantly different between NS group (20.43±2.18) and ES group (22.32±2.13). The volume/EFW at diagnosis was significantly higher in NS group (p=0.015: NS group 4.33±2.82, ES group 1.59±1.39). Indeed the volume/EFW at diagnosis was significantly correlated with the postnatal mass volume by CT (p<0.01, r=0.61). The cut-off value of volume/EFW at diagnosis as a prediction for neonatal operation was 0.0205 (AUC 0.85, sensitivity 0.833, specificity 0.687). There was no significant difference between the groups in CVR at diagnosis, volume/EFW or CVR at late gestation. Although 36% cases were difficult to measure the mass accurately after 34 weeks, only 1 case completely diminished after birth, and only 2 cases did not need the surgery. In fetal CPAM, the volume/EFW at diagnosis is a useful marker to predict neonatal surgery. Indeed even if the mass diminish at late gestation, most of the cases need surgery at later life.