Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance.

Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB.

Review of the Evaluation of Pulmonary Hypoplasia as an Important Determinant of Clinical Outcomes in Infants with Congenital Diaphragmatic Hernia.

Pulmonary hypoplasia is one of main causes of neonatal mortality and morbidity in patients with congenital diaphragmatic hernia. With most cases diagnosed prenatally, the emphasis is put on prediction of the severity of this defect. Several attempts are made to reduce the mortality and provide optimal prenatal and postnatal care. Appropriate estimation of risk of pulmonary hypoplasia also provides an important inclusion criterion for prenatal intervention. The main tool used for the detection and prediction of pulmonary hypoplasia is ultrasound, with an increasing number of available formulas to estimate the risk of occurrence of this phenomenon and complication associated with it. For most of the formulas used in this measurement method, the main limitations are either gestational-age dependency or limited research. Other imaging methods used to assess the risk of pulmonary hypoplasia involve magnetic resonance imaging and vascular assessment of affected lungs. The limitation in these remains the limited accessibility. Currently, the most widely used indexes are observed-to-expected lungs-to-head ratio and presence of liver herniation. These are the 2 most commonly used measurement methods, as they are the basis for patient qualification for fetoscopic endoluminal tracheal occlusion. This article aims to review the evaluation of pulmonary hypoplasia or hypoplastic lung disease as an important determinant of clinical outcomes in infants with congenital diaphragmatic hernia. In this review, we emphasize the importance of early prenatal diagnosis of congenital diaphragmatic hernia and present a summary of different methods of prenatal risk assessment of lung hypoplasia in congenital diaphragmatic hernia.

Intrahepatic cholestasis of pregnancy and theory of inheritance of the disease. Literature review.

Intrahepatic cholestasis during pregnancy is associated with a higher risk of prenatal and maternal complications. There are several new publications and guidelines on the detection and thresholds of intrahepatic cholestasis during pregnancy. However, the genetic background of this disease has rarely been investigated. This is a comprehensive review of the roles of genes in intrahepatic cholestasis during pregnancy.

Poster Session: Optoretinography-based frequency characterization of the retinal response to a chirped flickering light.

In this contribution, we present experimental results of in vivo characterization of the photoreceptor's response to a chirped flickering white light stimulating the retina. We acquire the ORG signal with Spatio-Temporal Optical Coherence Tomography (STOC-T) setup, which combines both temporal and coherence gating to overcome limitations present in Full Field Fourier Domain Optical Coherence Tomography. From the acquired volumes, we extract the changes in optical path length (OPL) between the inner and outer photoreceptor junction (ISOS) and the cone outer segment tips (COST). We perform the measurements for frequencies ranging from 5 Hz to 50 Hz. The chirped flickering facilitates significantly shorter data acquisition time. We present results of in vivo measurement from three volunteers. Our results show that we can measure OPL changes between ISOS and COST occurring in response to a chirped flickering stimulation in a reproducible manner and resolve the amplitude of the response in the function of flicker frequency.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening.

INTRODUCTION: Extreme levels of either PAPP-A or free ß-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. METHODS: A total number of 8591 patients with singleton pregnancies between 11 + 0-13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free ß-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. RESULTS: Values of PAPP-A ≥ 2,0 MoM and free ß-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free ß-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free ß-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free ß-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free ß-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DISCUSSION: Pregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free ß-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free ß-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

Spatio-temporal optical coherence tomography provides full thickness imaging of the chorioretinal complex.

Despite the rapid development of optical imaging methods, high-resolution in vivo imaging with penetration into deeper tissue layers is still a major challenge. Optical coherence tomography (OCT) has been used successfully for non-invasive human retinal volumetric imaging in vivo, advancing the detection, diagnosis, and monitoring of various retinal diseases. However, there are important limitations of volumetric OCT imaging, especially coherent noise and the limited axial range over which high resolution images can be acquired. The limited range prevents simultaneous measurement of the retina and choroid with adequate lateral resolution. In this article, we address these limitations with a technique that we term spatio-temporal optical coherence tomography (STOC-T), which uses light with controlled spatial and temporal coherence and advanced signal processing methods. STOC-T enabled the acquisition of high-contrast and high-resolution coronal projection images of the retina and choroid at arbitrary depths.

Light-adapted flicker optoretinograms captured with a spatio-temporal optical coherence-tomography (STOC-T) system.

For many years electroretinography (ERG) has been used for obtaining information about the retinal physiological function. More recently, a new technique called optoretinography (ORG) has been developed. In one form of this technique, the physiological response of retinal photoreceptors to visible light, resulting in a nanometric photoreceptor optical path length change, is measured by phase-sensitive optical coherence tomography (OCT). To date, a limited number of studies with phase-based ORG measured the retinal response to a flickering light stimulation. In this work, we use a spatio-temporal optical coherence tomography (STOC-T) system to capture optoretinograms with a flickering stimulus over a 1.7 × 0.85 mm2 area of a light-adapted retina located between the fovea and the optic nerve. We show that we can detect statistically-significant differences in the photoreceptor optical path length (OPL) modulation amplitudes in response to different flicker frequencies and with better signal to noise ratios (SNRs) than for a dark-adapted eye. We also demonstrate the ability to spatially map such response to a patterned stimulus with light stripes flickering at different frequencies, highlighting the prospect of characterizing the spatially-resolved temporal-frequency response of the retina with ORG.

Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience.

BACKGROUND: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. METHODS: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. RESULTS: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. CONCLUSIONS: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.

Comparative Genomic Hybridization to Microarrays in Fetuses with High-Risk Prenatal Indications: Polish Experience with 7400 Pregnancies.

The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.

Multimode fiber as a tool to reduce cross talk in Fourier-domain full-field optical coherence tomography.

Fourier-domain full-field optical coherence tomography (FD-FF-OCT) is an emerging tool for high-speed eye imaging. However, cross-talk formation in images limits the imaging depth. To this end, we have recently shown that reducing spatial coherence with a fast deformable membrane can suppress the noise but over a limited axial range and with substantial data processing. Here, we demonstrate that a multimode fiber with carefully chosen parameters enables cross-talk-free imaging over a long axial range and without significant artifacts. We also show that it can be used to image the human retina and choroid in vivo with exceptional contrast.

Quadratus Lumborum and Transversus Abdominis Plane Blocks and Their Impact on Acute and Chronic Pain in Patients after Cesarean Section: A Randomized Controlled Study.

BACKGROUND: Severe postoperative pain is a significant problem after cesarean sections. METHODS: This study was a randomized, controlled trial of 105 patients conducted in two hospitals. All patients were anesthetized spinally for elective cesarean section. Each participant was randomly allocated to one of three study groups: the quadratus lumborum block (QLB) group, the transversus abdominis plane block (TAPB) group, or the control (CON) group. The primary outcome of this study determined acute pain intensity on the visual analog scale (VAS). The secondary outcomes determined morphine consumption and chronic pain evaluation according to the Neuropathic Pain Symptom Inventory (NPSI) after hospital discharge. RESULTS: At rest, the pain intensity was significantly higher in the CON group than in the QLB and TAPB groups at hours two and eight. Upon activity, the pain in the control subjects was more severe than in the QLB and TAPB groups in three and two of five measurements, respectively. Moreover, morphine consumption was significantly lower in the QLB (9 (5-10)) and TAPB (10 (6-14)) groups than in the CON (16 (11-19)) group. Persistent postoperative pain was significantly lower in the QLB group than in the CON group at months one and six following hospital discharge. CONCLUSIONS: Both the QLB and TAPB can improve pain management after cesarean delivery. Moreover, the QLB might reduce the severity of persistent postoperative pain months after cesarean section.

Oxytocin and Misoprostol With Diclofenac in the Preparation for Magnetic Resonance-Guided High-Intensity Ultrasound Treatment of Symptomatic Uterine Fibroids: A Prospective Cohort Study.

Uterine fibroids (UFs) are very common benign tumors of the female reproductive tract. According to recent reports, magnetic resonance-guided high-intensity ultrasound (MR-HIFU) appears to be a well-tolerated and efficient treatment option for UFs. However, MR-HIFU still presents several limitations. The treatment is rarely associated with achieving complete non-perfused volume (NPV). Not all patients are qualified for a final procedure, and selected women obtain very good results in such treatment. The primary objective of this experimental study was to assess the effect of transvaginal misoprostol and intravenous oxytocin preparation on UF volume change, sonication time and NPV after MR-HIFU procedure in women of reproductive age with symptomatic UFs. Secondary outcomes included the effect on the peri-procedural effectiveness of misoprostol and oxytocin. This study enrolled 247 women with symptomatic UFs; based on gynecologic examinations and magnetic resonance imaging (MRI) scans, 128 women qualified for MR-HIFU without pharmacologic treatment, 57 women qualified for the misoprostol/diclofenac group and 62 women qualified for the oxytocin group. Pharmacologic pre-treatment improved NPV compared with non-pharmacologic treatment (average NPV: controls 61.9% ± 25.8%; oxytocin 76.8% ± 20.7%; misoprostol/diclofenac 85.2% ± 15.1%; average sonication time: controls 120 min ± 56.4%; oxytocin 111 min ± 45.4%; misoprostol/diclofenac 80 min ± 47.7%). Statistical analysis did not reveal significant intergroup differences in UF volume changes after 6 mo (controls: n = 40, 37.4% ± 27.5%; oxytocin n = 25, 45.8% ± 31%; misoprostol/diclofenac n = 19, 33.4% ± 23.2%). The misoprostol/diclofenac group, which achieved the highest NPV immediately after the MR-HIFU procedure, was characterized by the lowest UF volume change percentages 6 mo later. The administration of vasoconstrictor drugs (oxytocin and misoprostol/diclofenac) to support MR-HIFU in UF treatment is a new issue that may improve the total effectiveness of this method. Randomized controlled trials are necessary to estimate the real effect of vasoconstrictors on MR-HIFU.

A new approach to study human perivascular adipose tissue of the internal mammary artery by fiber-optic Raman spectroscopy supported by spectral modelling.

Perivascular adipose tissue (PVAT) regulates vascular function and represents a novel therapeutic target in vascular diseases. In this work, a new approach based on fiber-optic Raman spectroscopy and spectral modelling was used to characterize the chemical content of the PVAT of the internal mammary artery (IMA) of patients with advanced coronary atherosclerosis (n = 10) undergoing coronary bypass surgery. Our results showed a high degree of lipid unsaturation and low carotenoid content in the PVAT of the IMA of patients with more advanced coronary artery disease. Moreover, the spectral modelling of the IMA's PVAT composition indicated that glyceryl trioleate was a major PVAT lipid and for patients with relatively low levels of ß-carotene, it was accompanied by arachidonic acid and glyceryl trilinolenate. In summary, our proof-of-concept study suggests that carotenoid content and lipid unsaturation degree may reflect the PVAT functional status and a Raman-based assessment of the PVAT of the IMA could prove useful as a novel diagnostic tool to rapidly define the PVAT phenotype in a grafted artery in patients undergoing coronary bypass.

Polish Society of Gynecology and Obstetrics statement on safety measures and performance of ultrasound examinations in obstetrics and gynecology during the SARS-CoV-2 pandemic.

We present recommendations on performance and safety measures of ultrasound examinations in obstetrics and gynecology during the SARS COV-2 pandemic. The statement was prepared based on the current knowledge on the coronavirus by the Ultrasound Section of the Polish Society of Obstetrics and Gynecology. It has to be noted that the presented guidance is based on limited evidence and is primarily based on experiences published by authors from areas most affected by the virus thus far, such as China, Singapore, Hong Kong, and Italy. We realize that the pandemic situation is very dynamic. New data is published every day. Despite the imposed limitations related to the necessity of social distancing, it is crucial to remember that providing optimal care in safe conditions should remain the primary goal of healthcare providers. We plan to update the current guidelines as the situation develops.

Quantitative and qualitative Ductus Venosus blood flow evaluation in the screening for Trisomy 18 and 13 - suitability study.

OBJECTIVES: The objective of the paper is the suitability assessment of screening for Trisomy 18 and 13 on the basis of nuchal translucency (NT) measurement, Fetal Heart Rate (FHR), double test, quantitative [Ductus Venosus (DV) Pulsatility Index for Veins (PIV)] and qualitative (the A-wave assessment) blood flow evaluation in the DV. MATERIAL AND METHODS: The study was performed in 7296 singleton pregnancies. In each fetus NT, FHR, DV-PIV were examined. Double test from maternal blood was examined. These ultrasound and biochemical factors were in combined screening investigated. Additional doppler ultrasound markers such as abnormal a-wave in Ductus Venosus and Pusatility Index for Veins of Ductus Venosus were and their impact on Trisomies 18 and 13 screening were examined. RESULTS: Two groups of patients were compared - with chromosomal normal and chromosomal abnormalities - Trisomy 18 and 13. Detection Rate of Trisomies 18 and 13 at the risk cutoff 1/300 using combined screening was 90.2% and FPR was 6%. Detection Rates of examined chromosomal abnormalities using contingent screening were: 92.1% using DV abnormal a-wave and 94.84% using DV-PIV. FPR's for booths parameters 5.8% and 5.4% respectively. CONCLUSIONS: Quantitative analysis of the flow - assessment of DV-PIV in the first trimester significantly influences the improvement of screening values focusing on Trisomy 18 and 13 detection.

Computational aberration correction in spatiotemporal optical coherence (STOC) imaging.

Spatiotemporal optical coherence (STOC) imaging is a new technique for suppressing coherent cross talk noise in Fourier-domain full-field optical coherence tomography (FD-FF-OCT). In STOC imaging, the time-varying inhomogeneous phase masks modulate the incident light to alter the interferometric signal. Resulting interference images are then processed as in standard FD-FF-OCT and averaged incoherently or coherently to produce cross-talk-free volumetric optical coherence tomography (OCT) images of the sample. Here, we show that coherent averaging is suitable when phase modulation is performed for both interferometer arms simultaneously. We explain the advantages of coherent over incoherent averaging. Specifically, we show that modulated signal, after coherent averaging, preserves lateral phase stability, enabling computational phase correction to compensate for geometrical aberrations. Ultimately, we employ it to correct for aberrations present in the image of the photoreceptor layer of the human retina that reveals otherwise invisible photoreceptor mosaics.