Clinical value of serum SIRT1 combined with uterine hemodynamics in predicting disease severity and fetal growth restriction in preeclampsia.

Background: To investigate the effect and correlation of serum SIRT1 combined with uterine hemodynamic parameters on disease severity and fetal uterine growth restriction in the progression of preeclampsia, and to evaluate its clinical value as potential markers. Methods: A total of 100 patients with preeclampsia who were hospitalized in Qufu Normal University Hospital from June 2017 to June 2021 were selected as the research objects. According to the severity, they were divided into Mild group (62 cases) and Severe group (38 cases), and according to whether the fetal growth restriction was combined or not, they were divided into the Combined fetal growth restriction group (56 cases) and the Uncomplicated fetal growth restriction group (44 cases). Serum SIRT1 levels and uterine artery hemodynamic parameters were detected, and spearman analysis was used to evaluate the association of serum SIRT1 levels and uterine artery hemodynamic parameters (peak-to-trough ratio of arterial blood velocity, pulsatility index, resistance index) with disease severity (systolic blood pressure, diastolic blood pressure, and random urinary protein levels) and fetal growth restriction (femoral length, biparietal diameter, head circumference and neonatal weight); unsupervised PCA analysis, supervised PLS-DA analysis, Cluster heat map analysis, ROC curve and AUC analysis were used to evaluate the diagnostic value of serum SIRT1 levels combined with uterine artery hemodynamic parameters in the severity of disease and fetal growth restriction in patients with preeclampsia. Results: Serum SIRT1 levels was decreased in patients with severe preeclampsia (p < 0.0001), arterial blood flow velocity peak-to-trough ratio, pulsatility index and resistance index were increased (p < 0.001; p < 0.0001), and serum SIRT1 levels and uterine artery hemodynamic parameters were closely related to disease severity (p < 0.001; p < 0.0001). In addition, the levels of serum SIRT1 in patients with preeclampsia combined with fetal growth restriction was decreased (p < 0.0001), the peak-to-trough ratio of arterial blood flow velocity, pulsatility index and resistance index were increased (p < 0.0001), and serum SIRT1 levels and uterine artery hemodynamics were closely related to fetal growth restriction (p < 0.0001). Unsupervised PCA analysis and supervised PLS-DA analysis showed that patients with different severity of disease and patients with or without fetal growth restriction were similar within groups, and there were significant differences between groups; cluster heat map analysis showed that mild and severe groups were stratified clustering, the combined fetal growth restriction group and the uncombined group were hierarchically clustered; ROC curve and AUC analysis showed that serum SIRT1 levels combined with uterine artery hemodynamic parameters had a significant effect on the severity of preeclampsia and whether combined with fetal growth restriction high diagnostic value. Conclusions: Serum SIRT1 combined with uterine hemodynamic parameters in preeclampsia is closely related to disease severity and fetal growth restriction, and is expected to become potential biomarkers for early clinical intervention in patients.

Comparative Transcriptome Analysis of Human and Mouse Canalicular Lungs in Fetal Diaphragmatic Hernia.

BACKGROUND: The nitrofen model of congenital diaphragmatic hernia (CDH) is widely used in translational research. However, the molecular pathways associated with pulmonary hypoplasia in this model compared to the human CDH phenotype have not been well described. The aim of this study was to investigate differentially expressed genes (DEG) and signaling pathways in early stage fetal lungs in mouse and human CDH. METHODS: CDH lung tissue was obtained from human fetuses (21-23 weeks gestation) and nitrofen mouse pups (E15.5). NovaSeq Flowcell RNA-seq was performed to evaluate differentially expressed transcriptional and molecular pathways (DEGs) in fetal mice with CDH, compared with age-matched normal mouse lungs and human CDH samples. RESULTS: There were thirteen overlapping DEGs in human and mouse CDH lung samples compared to controls. These genes were involved in extracellular matrix, myogenesis, cilia, and immune modulation pathways. Human CDH was associated with an upregulation of collagen formation and extracellular matrix reorganization whereas mouse CDH was associated with an increase in muscular contraction. The most common cell types upregulated in human and mouse CDH samples were ciliated airway cells. CONCLUSIONS: This study highlights the unique gene transcriptional patterns in early fetal mouse and human lungs with CDH. These data have implications when determining the translational potential of novel therapies in CDH using nitrofen-based animal models. LEVEL OF EVIDENCE: Level IV. STUDY TYPE: Basic science/case series.

Altered circadian expression of clock genes and clock-regulatory epigenetic modifiers in saliva of children with fetal alcohol spectrum disorders.

Prenatal alcohol-exposed (AE) infants and children often demonstrate disrupted sleep patterns, including more frequent awakenings, reduced total sleep time, and more night-to-night sleep variability. Despite the strong connection between sleep patterns and circadian rhythmicity, relatively little is known about circadian rhythm disruptions in individuals with AE. Recently, several reports demonstrated that evaluating the expression patterns of human clock genes in biological fluids could reveal an individual's circadian phenotype. Human saliva offers an emerging and easily available physiological sample that can be collected non-invasively for core-clock gene transcript analyses. We compared the expression patterns of core-clock genes and their regulatory genes in salivary samples of children aged 6-10 years-old with and without AE during the light cycle between ZT0-ZT11. We isolated the RNA from the samples and measured the expression patterns of core clock genes and clock regulating genes using the human specific primers with quantitative real-time PCR. Analysis of core clock genes expression levels in saliva samples from AE children indicates significantly altered levels in expression of core-clock BMAL1, CLOCK, PER1-3 and CRY1,2, as compared to those in age-matched control children. We did not find any sex difference in levels of clock genes in AE and control groups. Cosinor analysis was used to evaluate the rhythmic pattern of these clock genes, which identified circadian patterns in the levels of core clock genes in the control group but absent in the AE group. The gene expression profile of a salivary circadian biomarker ARRB1 was rhythmic in saliva of control children but was arhythmic in AE children. Altered expression patterns were also observed in clock regulatory genes: NPAS2, NFL3, NR1D1, DEC1, DEC2, and DBP, as well as chromatin modifiers: MLL1, P300, SIRT1, EZH2, HDAC3, and ZR1D1, known to maintain rhythmic expression of core-clock genes. Overall, these findings provide the first evidence that AE disturbs the circadian patten expression of core clock genes and clock-regulatory chromatin modifiers in saliva.

A customised fetal growth and birthweight standard for Qatar: a population-based cohort study.

OBJECTIVES: Customized birthweight centiles have improved the detection of small for gestational age (SGA) and large for gestational age (LGA) babies compared to existing population standards. This study used perinatal registry data to derive coefficients for developing customized growth charts for Qatar. METHODS: The PEARL registry data on women delivering in Qatar (2017-2018) was used to develop a multivariable linear regression model predicting optimal birthweight. Physiological variables included gestational age, maternal height, weight, ethnicity, parity, and sex of the baby. Pathological variables such as hypertension, preexisting and gestational diabetes and smoking were calculated and excluded to derive the optimal weight at term. RESULTS: The regression model found a term optimal birthweight of 3,235 g for a Qatari nationality mother with median height (159 cm), booking weight (72 kg), parity (1) and gestation at birth (276 days) at the end of an uncomplicated pregnancy. Constitutional coefficients significantly affecting birthweight were gestational age, height, weight, and parity. The main pathological factors were preexisting diabetes (increase by +175.7 g) and smoking (decrease by -190.9 g). The SGA and LGA rates in the entire cohort after applying the population-specific customized centiles were 11.1 and 12.2 %, respectively (contrasting with the Hadlock standard: SGA-26.3 % and LGA-1.8 %, and Fenton standard: SGA-12.9 % and LGA-4.0 %). CONCLUSIONS: Constitutional and pathological variations in fetal growth and birthweight apply in the maternity population in Qatar and have been quantified to allow the generation of customised charts for better identification of pregnancies with abnormal growth. Currently in-use population standards may misdiagnose many SGA and LGA babies.

Effects of Maternal Anemia Affecting Fetal Outcomes: A Narrative Review.

This review's main objective was to assess the obstacles to anemia prevention, as well as the attitudes and behaviors of anemic women toward their condition. Since iron is crucial for neurodevelopment, iron deficiency anemia (IDA) accounts for the majority of pregnant mothers having anemia. In India and other developing countries, anemia is a serious health problem. More than half of pregnant women have anemia. The search strategy was conducted in PubMed. Few of the articles were searched without using MeSH terms. Strong correlations between mothers' anemia and that of their offspring point to intergenerational anemia with lasting consequences. Children who were underweight at birth and those who were malnourished had a higher risk of having anemia. Clinicians usually evaluate anemia, and the criteria for determining the cause of anemia are outlined in this brief review.

Artificial intelligence in fetal echocardiography: Recent advances and future prospects.

In the past few decades, great progress has been made in prenatal diagnosis of congenital heart disease (CHD). Fetal echocardiography is recognized as the main prenatal screening and diagnostic tool that can accurately detect approximately 85 % of fetal cardiac abnormalities. Evaluation of the fetal heart remains a major challenge in prenatal ultrasound screening and diagnosis due to fetal position, involuntary movement, small and complex fetal cardiac anatomy, maternal abdominal wall conditions, and lack of expertise in fetal echocardiography by some physicians engaged in obstetric ultrasound. Artificial intelligence (AI) can automate and standardize the display of each diagnostic section of the fetal heart and thus contribute to accurate diagnosis, which significantly optimizes the clinical application of fetal echocardiography. In this review, we not only clarify the role of AI but also highlight its significance and future solutions in the field of fetal echocardiography.

Attempted suicide by hanging in a pregnant adolescent with psychiatric illness: A case report.

Cases of mental illnesses and suicide attempts while pregnant are of grave concern because they negatively affect both the mother and her fetus. Here we report a case of an 18-year-old woman, who was found at 35 weeks into her pregnancy. She was unconscious when her sister-in-law rescued her. Upon arrival, she was agitated and had respiratory distress. She went into spontaneous labor the next day and delivered a premature infant who succumbed within 24 h. She had a history of mental illness in the past and previous suicide attempts. The reason for her suicide stemmed from conflicts within her family and disagreement with her husband. Various psychosocial elements play a role in suicide risk, such as young age, having a history of mental health issues, experiencing trauma facing domestic violence, and dealing with financial stress. This underlines the need for mental health screening in the course of antenatal visits for a complete risk assessment.

Fetal-BET: Brain Extraction Tool for Fetal MRI.

Goal: In this study, we address the critical challenge of fetal brain extraction from MRI sequences. Fetal MRI has played a crucial role in prenatal neurodevelopmental studies and in advancing our knowledge of fetal brain development in-utero. Fetal brain extraction is a necessary first step in most computational fetal brain MRI pipelines. However, it poses significant challenges due to 1) non-standard fetal head positioning, 2) fetal movements during examination, and 3) vastly heterogeneous appearance of the developing fetal brain and the neighboring fetal and maternal anatomy across gestation, and with various sequences and scanning conditions. Development of a machine learning method to effectively address this task requires a large and rich labeled dataset that has not been previously available. Currently, there is no method for accurate fetal brain extraction on various fetal MRI sequences. Methods: In this work, we first built a large annotated dataset of approximately 72,000 2D fetal brain MRI images. Our dataset covers the three common MRI sequences including T2-weighted, diffusion-weighted, and functional MRI acquired with different scanners. These data include images of normal and pathological brains. Using this dataset, we developed and validated deep learning methods, by exploiting the power of the U-Net style architectures, the attention mechanism, feature learning across multiple MRI modalities, and data augmentation for fast, accurate, and generalizable automatic fetal brain extraction. Results: Evaluations on independent test data, including data available from other centers, show that our method achieves accurate brain extraction on heterogeneous test data acquired with different scanners, on pathological brains, and at various gestational stages. Conclusions:By leveraging rich information from diverse multi-modality fetal MRI data, our proposed deep learning solution enables precise delineation of the fetal brain on various fetal MRI sequences. The robustness of our deep learning model underscores its potential utility for fetal brain imaging.

Dose Sildenafil Citrate Reduce the Incidence of Emergency Cesarean Section and Fetal Distress During Labor? A Randomized Double-Blinded Clinical Trial.

Background: Fetal distress (FD) is one of the most frequent causes of emergency cesarean section (CS) due to the insufficient uteroplacental blood supply during labor. There is a theory that Sildenafil citrate (SC) may improve the uteroplacental blood supply and decrease fetal hypoxia and FD. Methods: In a randomized double-blinded clinical trial, a total of 208 low-risk subjects who met our stringent inclusion criteria were randomly assigned into two groups: the Sildenafil citrate group (n=104) and the placebo group (n=104). These participants were referred to our referral gynecology and obstetrics department for delivery between July 2022 to September 2022. The SC group received oral SC at a dose of 50 mg every 6 hr, up to a maximum of three times. The final maternal-fetal-neonatal results were recorded and all data were analyzed using SPSS version 23. Results: The mean age of mothers was 28.98±5.6 years and 120 cases were primigravid (57.7%). Out of a total of 208 pregnant subjects, 168 subjects delivered through normal vaginal delivery (80.8%) and 40 cases underwent emergency CS (19.2%). The number of NVD in Sildenafil group was significantly more than placebo group (87.5% vs. 74%) and SC decreased the rate of emergency CS to 87.5% (RR=2.46%, 95%CI 1.19-5.08). Also, SC decreased the rate of FD to 53.8% (RR=2.83%, 95%CI of 1-8.24). Conclusion: The results showed that SC can effectively decrease the rate of emergency CS and FD during labor.

Modulatory Effects of Vitamin D: A Possible Approach to Mitigate Air Pollution Related Pregnancy Complications.

Approximately 99% of people on the planet breathe air that exceeds the World Health Organization's permitted threshold for pollution. South Asia is home to the world's most polluted cities. Population-based studies have suggested that women's reproductive health outcomes are worsening due to air pollution. Preeclampsia, miscarriage, gestational diabetes, high blood pressure, and unfavorable birth outcomes, including preterm birth, low birth weight, or even stillbirth are all linked to exposure to air pollution during pregnancy. It is estimated that 0.61 million deaths in India alone were related to indoor air pollution. Females frequently cook in the household using solid fuel as a primary combustion source. Women in the regions with the highest population density are disproportionately affected by high levels of poor-quality indoor air. Recently, it has been proposed that air pollution has a distinct role in the onset of vitamin D deficiency. Numerous studies have explored associations between low vitamin D level and various female reproductive health conditions since the discovery of the vitamin D receptor. It is worthy to note that some of these reproductive health conditions positively correlate with the severity of air pollution. In this study, the evidence has been synthesized on vitamin D's protective properties and dietary and pharmaceutical interventions have been discussed to show their beneficial effects in decreasing the long-term negative impacts of air pollution on women's health.

Sexually dimorphic DNA methylation and gene expression patterns in human first trimester placenta.

BACKGROUND: Fetal sex and placental development impact pregnancy outcomes and fetal-maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies. METHODS: Pregnant subjects were recruited in late first trimester (weeks 10-14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births. DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip array (n = 56). Differential methylation analysis compared 25 females versus 31 males using a generalized linear model on 743,461 autosomal probes. Gene expression sex differences were analyzed with RNA-sequencing (n = 74). An integrated analysis was performed using linear regression to correlate gene expression and DNA methylation in 51 overlapping placentas. RESULTS: Methylation analysis identified 151 differentially methylated probes (DMPs) significant at false discovery rate < 0.05, including 89 (59%) hypermethylated in females. Probe cg17612569 (GABPA, ATP5J) was the most significant CpG site, hypermethylated in males. There were 11 differentially methylated regions affected by fetal sex, with transcription factors ZNF300 and ZNF311 most significantly hypermethylated in males and females, respectively. RNA-sequencing identified 152 genes significantly sexually dimorphic at false discovery rate < 0.05. The 151 DMPs were associated with 18 genes with gene downregulation (P < 0.05) in the direction of hypermethylation, including 2 genes significant at false discovery rate < 0.05 (ZNF300 and CUB and Sushi multiple domains 1, CSMD1). Both genes, as well as Family With Sequence Similarity 228 Member A (FAM228A), showed significant correlation between DNA methylation and sexually dimorphic gene expression, though FAM228A DNA methylation was less sexually dimorphic. Comparison with other sex differences studies found that cg17612569 is male-hypermethylated across gestation in placenta and in human blood up to adulthood. CONCLUSIONS: Overall, sex dimorphic differential methylation with associated differential gene expression in the first trimester placenta is small, but there remain significant genes that may be regulated through methylation leading to differences in the first trimester placenta.

Fetal sex and placenta development affect pregnancy outcomes for both the fetus and mother throughout pregnancy, including risk of miscarriages, preterm birth, preeclampsia, and other outcomes. Epigenetics, the "overlay" of regulatory signals on DNA which affects how DNA is read, is not well understood in early pregnancy when critical placenta developments are happening that affect the rest of pregnancy. Here, we use leftover placenta biopsy samples (n = 56) donated by Cedars-Sinai patients with informed consent to learn about first trimester human placenta DNA methylation differences due to fetal sex. Out of the total 743,461 sites analyzed, we identified 151 sites significantly affected by fetal sex after correcting p-values to reduce false positives (false discovery rate < 0.05). We also performed an analysis to look at multiple sites and identified 11 regions across the genome with significant DNA methylation changes due to fetal sex. Furthermore, because DNA methylation is a regulatory mark on DNA which typically dampens gene expression, we also compared the DNA methylation sex differences to placental RNA-sequencing gene expression analysis using the same tissue from a mostly overlapping patient group (n = 74 total sequenced, n = 51 overlap). We identify 18 genes which show both significant DNA methylation differences and gene expression changes. The most significant gene was transcription factor ZNF300 with higher DNA methylation in males and reduced gene expression in males (and thus higher gene expression in females). This study identifies some sex differences that continue until later pregnancy and others that are unique to first trimester.

Contraindications in national guidelines for vaginal breech delivery at term: Comparison, consensus, and controversy.

INTRODUCTION: The optimal mode of delivery for vaginal breech presentation remains a clinical dilemma. Planned vaginal delivery offers maternal advantages because it avoids major abdominal surgery and has no consequences for following pregnancies, while elective cesarean delivery proves advantageous for the neonate because adverse outcomes are less frequent. Patient selection for vaginal breech delivery is important based on the individual risk balance. A lack of consensus exists regarding the specific contraindications for vaginal breech delivery, largely due to limited scientific evidence. This systematic review aims to give an overview of contraindications for vaginal breech delivery, as presented in guidelines, analyze relevant literature, and offer evidence-based recommendations for the contraindications stated in the guidelines. MATERIAL AND METHODS: To identify national guidelines PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, NICE, UpToDate, and ClinicalKey were searched using two keywords: "breech presentation" and "vaginal delivery." We systematically reviewed the literature for existing evidence for contraindications for term vaginal breech delivery. The following databases were searched: PubMed (April 2024), the Cochrane Central Register of Controlled Trials, and EMBASE (1947 to 2024). RESULTS: Our search identified eight guidelines that stated a total of 11 contraindications for vaginal breech delivery. Among these guidelines, agreement was limited, with the sole consensus in all guidelines on the contraindication of footling breech. Our comprehensive literature search yielded 43 articles discussing 14 potential contraindications. We found supportive evidence for 7 of 11 contraindications from the guidelines, with only substantial and satisfactory evidence for two contraindications. CONCLUSIONS: The findings of this study underscore the lack of consensus among national guidelines regarding contraindications for term vaginal breech delivery. Furthermore, we found a notable lack of substantial scientific evidence to support these contraindications. In light of these findings, we suggest a reduced list of contraindications in vaginal breech deliveries.

Effects of prenatal small-quantity lipid-based nutrient supplements on pregnancy, birth and infant outcomes: a systematic review and meta-analysis of individual participant data from randomized controlled trials in low- and middle-income countries.

BACKGROUND: Undernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNS) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies. OBJECTIVES: We examined effects of SQ-LNS provided during pregnancy, compared to a) iron and folic acid or standard of care (IFA/SOC) or b) multiple micronutrient supplements (MMS), and identified characteristics that modified the estimates of effects of SQ-LNS on birth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNS provided during pregnancy (n = 5,273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether results differed depending on methods for gestational age dating, birth anthropometry, or study design. RESULTS: SQ-LNS (vs IFA/SOC) increased birth weight (mean difference: +49g; 95% CI: 26, 71g) and all birth anthropometric z-scores (+0.10-0.13 SD); it reduced risk of low birthweight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNS and MMS; p-values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age +0.11; 95% CI: -0.01, 0.23). Effect estimates for SQ-LNS vs IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index < 20 kg/m2, inflammation, malaria, or household food insecurity. Effect estimates for SQ-LNS vs MMS were greater for certain outcomes among female infants, first-born infants, and mothers < 25 y. CONCLUSIONS: SQ-LNS had positive impacts on multiple outcomes compared to IFA/SOC, but further research directly comparing SQ-LNS and MMS is needed. Targeting SQ-LNS to vulnerable subgroups may be worth considering. Analysis registered at www.crd.york.ac.uk/PROSPERO (CRD42021283391). REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: Registered at www.crd.york.ac.uk/PROSPERO as CRD42021283391 on 11 April 2021.

The legal rights of the fetus: Nepali perspective.

This article provides an analysis of the legal rights and protection accorded to fetuses under the Nepali law and the comparative common statues. It also analyses the abortion law in Nepal, which aims to balance the needs of women seeking abortion with limited protections for late-term fetuses. The article considers the case, "Lakshmi Dhikta v. the Government of Nepal," which held that access to abortion was a constitutionally formed right. However, barriers to this right still exist, especially among disadvantaged women. Globally, the debate continues between those who advocate for the rights of the fetus and those who put the autonomy of the women first. While some countries grant the fetus limited legal rights, others grant the fetus personhood rights. It is therefore pertinent to discuss the ethics of prenatal harm, sex-selective abortion, and the possible conflict between maternal and fetal interests. The multifaceted law should regulate maternal health, the interest of the fetus, and discrimination while ensuring feasible and affordable abortion.

Assessment of Fetal Ventricular Size and Shape in Women With Intrahepatic Cholestasis of Pregnancy Using Speckle Tracking.

OBJECTIVE: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. METHODS: This case-control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24-segment spherical indices (SIs) were measured and compared between groups. RESULTS: The routine fetal cardiac parameters, global and right-ventricular SIs did not differ between the ICP and control groups. The left-ventricular apical (segments 16-24) SIs were lower in the ICP group than in the control group (P < .05), with no significant difference in the other left-ventricular segments. CONCLUSIONS: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty-four-segment SIs can be used to effectively evaluate these changes.

Dynamics of HSD17B3 expression in human fetal testis: implications for the role of Sertoli cells in fetal testosterone biosynthesis.

Introduction: Androgens play a pivotal role in shaping male sexual characteristics, with testosterone being an essential hormone in orchestrating various developmental processes. Testosterone biosynthesis involves a series of enzymatic reactions, among which the 17ß-hydroxysteroid dehydrogenase type 3 (HSD17B3) holds significance. While its role in adult Leydig cells is well established, its localization and importance during the fetal period remain less known, especially in humans. This study aims to delineate the dynamics of HSD17B3 expression in human fetal testes to clarify the contribution of specific cell types to testosterone biosynthesis. Methods: Using immunofluorescence staining, we investigated the expression pattern of HSD17B3 in human fetal and adult testicular tissues. Results and discussion: The findings of this study revealed a distinct temporal and cellular expression pattern of HSD17B3 protein in the fetal period. We detected its expression exclusively in Sertoli cells, the highest during the second trimester. This unique localization suggests the inclusion of fetal Sertoli cells in testosterone production during the critical masculinization-programming window. Furthermore, we demonstrated a shift in HSD17B3 expression from Sertoli cells to Leydig cells in adulthood, corroborating findings from rodent studies. This study sheds light on the intricate, still underexplored regulation of steroidogenesis during fetal development, whose disturbance might lead to testicular dysgenesis. Further research is warranted to elucidate the regulatory pathways governing the expression of HSD17B3 and its transition between Sertoli and Leydig cells, potentially paving the way for novel therapeutic interventions in disorders of sexual development.

How to prevent rubella epidemics and congenital rubella syndrome: lessons from 42 years of longitudinal epidemiology in Osaka Prefecture, Japan (1982-2023).

BACKGROUND: Despite the introduction of rubella-containing vaccine into routine immunization in 1977, rubella has not been eliminated in Japan. This study aimed to validate the immunization strategy and to highlight the crucial elements of elimination program. METHODS: We scrutinized cases of rubella and congenital rubella syndrome (CRS). Additionally, we analyzed the national vaccination coverage, seroprevalence, and number of maternal rubella-related spontaneous or artificial fetal deaths. RESULTS: The shift from selective to universal immunization significantly reduced rubella cases coupled with increased seroprevalence in children. However, rubella resurged in 2012-2013 and 2018-2019, which was virologically and serologically confirmed to be associated with imported rubella virus (RuV) and susceptible males. Although the disease burden of CRS may have been suppressed in the past by the large number of spontaneous or artificial fetal deaths, the incidence rate of CRS was comparable to that of the 1960s to 1980s. Cases of breakthrough infection and CRS were identified in females who were considered to have a history of single-dose vaccination. CONCLUSIONS: Even with universal immunization, future epidemics and severe outcomes cannot be prevented unless immunization gaps are closed. Furthermore, CRS and breakthrough infection are not completely prevented by single-dose vaccination, indicating the need for second-dose vaccination.

A deep learning approach to identify the fetal head position using transperineal ultrasound during labor.

OBJECTIVES: To develop a deep learning (DL)-model using convolutional neural networks (CNN) to automatically identify the fetal head position at transperineal ultrasound in the second stage of labor. MATERIAL AND METHODS: Prospective, multicenter study including singleton, term, cephalic pregnancies in the second stage of labor. We assessed the fetal head position using transabdominal ultrasound and subsequently, obtained an image of the fetal head on the axial plane using transperineal ultrasound and labeled it according to the transabdominal ultrasound findings. The ultrasound images were randomly allocated into the three datasets containing a similar proportion of images of each subtype of fetal head position (occiput anterior, posterior, right and left transverse): the training dataset included 70 %, the validation dataset 15 %, and the testing dataset 15 % of the acquired images. The pre-trained ResNet18 model was employed as a foundational framework for feature extraction and classification. CNN1 was trained to differentiate between occiput anterior (OA) and non-OA positions, CNN2 classified fetal head malpositions into occiput posterior (OP) or occiput transverse (OT) position, and CNN3 classified the remaining images as right or left OT. The DL-model was constructed using three convolutional neural networks (CNN) working simultaneously for the classification of fetal head positions. The performance of the algorithm was evaluated in terms of accuracy, sensitivity, specificity, F1-score and Cohen's kappa. RESULTS: Between February 2018 and May 2023, 2154 transperineal images were included from eligible participants across 16 collaborating centers. The overall performance of the model for the classification of the fetal head position in the axial plane at transperineal ultrasound was excellent, with an of 94.5 % (95 % CI 92.0--97.0), a sensitivity of 95.6 % (95 % CI 96.8-100.0), a specificity of 91.2 % (95 % CI 87.3-95.1), a F1-score of 0.92 and a Cohen's kappa of 0.90. The best performance was achieved by the CNN1 - OA position vs fetal head malpositions - with an accuracy of 98.3 % (95 % CI 96.9-99.7), followed by CNN2 - OP vs OT positions - with an accuracy of 93.9 % (95 % CI 89.6-98.2), and finally, CNN3 - right vs left OT position - with an accuracy of 91.3 % (95 % CI 83.5-99.1). CONCLUSIONS: We have developed a DL-model capable of assessing fetal head position using transperineal ultrasound during the second stage of labor with an excellent overall accuracy. Future studies should validate our DL model using larger datasets and real-time patients before introducing it into routine clinical practice.