Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report.

BACKGROUND: Congenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3-9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case. CASE PRESENTATION: A 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses' umbilical cord, third fetus' placenta, and the fourth fetus' blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth. CONCLUSIONS: This report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease.

miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia.

MicroRNAs (miRNAs) are non-coding small RNA molecules that can be secreted into the circulation and which exist in remarkably stable forms. Circulating miRNAs regulate numerous biological process and are aberrantly expressed in pathological conditions. Differentially expressed circulating miRNAs have received attention as potential biomarkers for many diseases. In this study, we revealed that miR-515-5p was significantly upregulated in maternal serum from preeclampsia patients in comparison to normal pregnant women. Bioinformatics prediction and a dual-luciferase reporter gene assay revealed that miR-515-5p directly targets the X-linked inhibitor of apoptosis protein (XIAP) 3'-untranslated region. In addition, the overexpression of miR-515-5p inhibited the proliferation and invasion of HTR-8/SVneo trophoblast cells. The decreased XIAP expression and reduced epithelial-mesenchymal transition (EMT) were observed in the preeclamptic placenta. Collectively, miR-515-5p may play critical roles in the pathogenesis of preeclampsia through suppression of XIAP, and serum miR-515-5p may act as a potential biomarker for preeclampsia.

The Effect of Maternal Coagulation Parameters on Fetal Acidemia in Placental Abruption.

This study aimed to identify factors predicting the probability of serious fetal acidemia at delivery in placental abruption. We identified 5769 women who delivered at >22 weeks' gestation at two institutions in a tertiary referral unit specializing in neonatal infant care between January 2007 and December 2011. Ninety-one abruption cases were identified based on clinical and histological diagnoses. Serious fetal acidemia was defined as a pH < 7.0 in the umbilical arterial blood at delivery. Using a linear discriminant function, we calculated the score to determine the probability of serious fetal acidemia. Serious fetal acidemia was observed in 34 patients (37.4%). A logistic regression model showed that abnormal fetal heart rate patterns (bradycardia and late decelerations), uterine spasm, and maternal plasma concentration of fibrinogen less than 288 ng/dL were significantly associated with the occurrence of serious fetal acidemia. We suggest that the implementation of maternal fibrinogen in patients with placental abruption is a prognostic factor for serious fetal acidemia at delivery.

Use of an artificial intelligence-based rule extraction approach to predict an emergency cesarean section.

OBJECTIVE: One of the major problems with artificial intelligence (AI) is that it is generally known as a "black box". Therefore, the present study aimed to construct an emergency cesarean section (CS) prediction system using an AI-based rule extraction approach as a "white box" to detect the cause for the emergency CS. METHODS: Data were collected from all perinatal records of all delivery outcomes at Osaka Medical College between December 2014 and July 2019. We identified the delivery method for all deliveries after 36 gestational weeks as either (1) vaginal delivery or scheduled CS, or (2) emergency CS. From among these, we selected 52 risk factors to feed into an AI-based rule extraction algorithm to extract rules to predict an emergency CS. RESULTS: We identified 1513 singleton deliveries (1285 [84.9%] vaginal deliveries, 228 emergency CS [15.1%]) and extracted 15 rules. We achieved an average accuracy of 81.90% using five-fold cross-validation and an area under the receiving operating characteristic curve of 71.46%. CONCLUSION: To our knowledge, this is the first study to use interpretable AI-based rule extraction technology to predict an emergency CS. This system appears to be useful for identifying hidden factors for emergency CS.

Possible prevention of post-partum depression by intake of omega-3 polyunsaturated fatty acids and its relationship with interleukin 6.

AIM: This study examined whether the intake of omega-3 polyunsaturated fatty acids (PUFA) prevented post-partum depression and if interleukin 6 (IL-6) was involved in this effect. We hypothesized that omega-3 supplementation has a protective effect against post-partum depression. METHODS: We measured eicosapentaenoic acid (EPA), the arachidonic acid (AA)/EPA ratio, and IL-6 in 80 singleton pregnant women during the first and second trimesters, and post-partum. The women also completed a dietary questionnaire, and post-partum depression was measured using the Edinburgh Postnatal Depression Scale (EPDS). We examined the correlations between the frequency of eating fish and EPA, the AA/EPA ratio and IL-6 in the first and second trimesters, and post-partum. We also investigated the correlation between the EPDS and the EPA, the AA/EPA ratio and IL-6. RESULTS: The frequency of eating fish was significantly correlated with EPA in the second trimester and post-partum and with the AA/EPA ratio in the second trimester. There was no correlation between IL-6 levels and the frequency of eating fish. Post-partum levels of EPA and the AA/EPA ratio were higher in the EPDS >7 group than in the EPDS ≤7 group. In the second trimester, a higher AA/EPA ratio was associated with EPDS >7. IL-6 levels did not differ between the two groups. CONCLUSION: In conclusion, a low dietary intake of omega-3 PUFA during pregnancy was correlated with lower EPA levels, which tended to lead to post-partum depression. The relationship between the IL-6 level and the pathogenesis of post-partum depression was unclear from the results of this study.

Application of deep learning to the classification of uterine cervical squamous epithelial lesion from colposcopy images combined with HPV types.

The aim of the present study was to explore the feasibility of using deep learning, such as artificial intelligence (AI), to classify cervical squamous epithelial lesions (SILs) from colposcopy images combined with human papilloma virus (HPV) types. Among 330 patients who underwent colposcopy and biopsy performed by gynecological oncologists, a total of 253 patients with confirmed HPV typing tests were enrolled in the present study. Of these patients, 210 were diagnosed with high-grade SIL (HSIL) and 43 were diagnosed with low-grade SIL (LSIL). An original AI classifier with a convolutional neural network catenating with an HPV tensor was developed and trained. The accuracy of the AI classifier and gynecological oncologists was 0.941 and 0.843, respectively. The AI classifier performed better compared with the oncologists, although not significantly. The sensitivity, specificity, positive predictive value, negative predictive value, Youden's J index and the area under the receiver-operating characteristic curve ± standard error for AI colposcopy combined with HPV types and pathological results were 0.956 (43/45), 0.833 (5/6), 0.977 (43/44), 0.714 (5/7), 0.789 and 0.963±0.026, respectively. Although further study is required, the clinical use of AI for the classification of HSIL/LSIL by both colposcopy and HPV type may be feasible.

Recombinant human soluble thrombomodulin as an anticoagulation therapy improves recurrent miscarriage and fetal growth restriction due to placental insufficiency - The leading cause of preeclampsia.

INTRODUCTION: Placental insufficiency is one of the major risk factors for growth restriction and preeclampsia. The aim of this study is to investigate whether recombinant human Thrombomodulin(r-TM) improves fetal conditions and physiological outcomes. METHODS: We used CBA/J × BALB/C mice as a control and CBA/J × DBA/2 mice - a well-studied model of recurrent spontaneous miscarriage. Pregnant mice received daily subcutaneous injections of r-TM or saline from day 0-15. The fetal resorption rate, fetal weight, and litter size were calculated at day 15. Additionally, we analyzed the mRNA expression of angiogenic factors and the concentration of soluble Flt-1 (sFlt-1) using the ELISA kit. RESULTS: The rate of fetal resorption in CBA/J × DBA/2 mice treated with r-TM was significantly lower compared with mice without r-TM treatment. Additionally, fetal weight and litter size were also significantly higher in the r-TM treated mice. Fibrinogen deposition in the labyrinth area of the CBA/J × DBA/2 mice treated with r-TM was significantly lower compared with deposits in the mice untreated with r-TM. As well, r-TM significantly increased the gene expression level of VEGF and Flt-1 mRNA in the placentas of the CBA/J × DBA/2 mice. r-TM treatment also significantly decreased the production of sFlt-1 protein in the placentas of preeclampsia-like diseased mice. CONCLUSION: r-TM as an anticoagulation therapy has the potential for the medical treatment of recurrent miscarriage and fetal growth restriction due to improved angiogenic factors. Additionally, r-TM treatment has the potential for the recovery of preeclampsia.

A Case of Intestinal Obstruction in Pregnancy Diagnosed by MRI and Treated by Intravenous Hyperalimentation.

Intestinal obstruction in pregnancy is rare and is mainly caused by prior pelvic surgery. We herein report a case of intestinal obstruction in a pregnant female with a history of laparoscopic myomectomy, who presented with hypogastric pain, abdominal distension, and vomiting at 26 weeks of gestation. A simple intestinal obstruction was diagnosed by MRI. Conservative treatments, including intravenous hyperalimentation and the placement of an ileus tube, were provided and her abdominal symptoms improved for 14 days. After restarting oral intake, she had no abdominal symptoms. She gave birth to a 2,146 g female infant by caesarean section at 37 weeks and 1 day of gestation. Although an area of cicatrization, which was thought to have been the starting point of the occlusion that caused the intestinal obstruction, was found, the excision of the small intestine was not necessary. Her postoperative course was uneventful. Intestinal obstruction requires a prompt diagnosis and aggressive intervention may be necessary to minimize the morbidity and mortality associated with this rare complication of pregnancy. MRI can be safely used during pregnancy to diagnose intestinal obstruction and intravenous hyperalimentation may improve the maternal and fetal prognoses.