Expert ultrasonographic evaluation in fetuses with spina bifida: An essential prerequisite to select candidate to fetal surgery.

Suggested management flowchart in presence of a prenatal diagnosis of open spina bifida.

A complete hydatidiform mole and coexisting viable fetus in a twin pregnancy: a case report with literature review.

INTRODUCTION: A twin pregnancy involving a hydatidiform mole (HM) coexisting with a developing fetus is an extremely rare obstetric complication, which typically presents as a complete hydatidiform mole with a coexisting fetus (CHMCF) or a partial hydatidiform mole with a coexisting fetus (PHMCF). CASE PRESENTATION: A 26-year-old woman was admitted to our hospital due to a small volume of vaginal bleeding during the 31st week of pregnancy. The patient was previously healthy, and an intrauterine singleton pregnancy was detected by ultrasound on day 46 of gestation; however, bunch-of-grapes sign was observed in the uterine cavity at 24 weeks. The patient was subsequently diagnosed with CHMCF. As the patient insisted on continuing her pregnancy, she underwent hospital monitoring. Vaginal bleeding occurred in the 33rd week again and received a course of betamethasone, then continued pregnancy after bleeding stopped spontaneously. In the 37th week, a male infant weighing 3090 g was delivered by cesarean section, with an Apgar score of 10 at 1 min and a karyotype of 46XY. Placental pathology confirmed the diagnosis of a complete hydatid tumor. CONCLUSION: In this report, a case of CHMCF was maintained by monitoring of blood pressure, thyroid function, human chorionic gonadotrophin, and fetal condition during pregnancy. A live newborn was delivered by cesarean section. CHMCF is a clinically rare disease with high risks; thus, it should be diagnosed carefully using several tools, including ultrasound, magnetic resonance imaging, and karyotype analysis and dynamically monitored if the patient decides to continue the pregnancy.

De novo mutations disturb early brain development more frequently than common variants in schizophrenia.

Investigating functional, temporal, and cell-type expression features of mutations is important for understanding a complex disease. Here, we collected and analyzed common variants and de novo mutations (DNMs) in schizophrenia (SCZ). We collected 2,636 missense and loss-of-function (LoF) DNMs in 2,263 genes across 3,477 SCZ patients (SCZ-DNMs). We curated three gene lists: (a) SCZ-neuroGenes (159 genes), which are intolerant to LoF and missense DNMs and are neurologically important, (b) SCZ-moduleGenes (52 genes), which were derived from network analyses of SCZ-DNMs, and (c) SCZ-commonGenes (120 genes) from a recent GWAS as reference. To compare temporal gene expression, we used the BrainSpan dataset. We defined a fetal effect score (FES) to quantify the involvement of each gene in prenatal brain development. We further employed the specificity indexes (SIs) to evaluate cell-type expression specificity from single-cell expression data in cerebral cortices of humans and mice. Compared with SCZ-commonGenes, SCZ-neuroGenes and SCZ-moduleGenes were highly expressed in the prenatal stage, had higher FESs, and had higher SIs in fetal replicating cells and undifferentiated cell types. Our results suggested that gene expression patterns in specific cell types in early fetal stages might have impacts on the risk of SCZ during adulthood.

Rupture of a non sinus of Valsalva aneurysm during pregnancy: Case report and review of literatures.

Ruptured Sinus of Valsalva aneurysms during pregnancy is rare and presents a threat both to the mother and the fetus. We report a case of ruptured nonsinus of Valsalva aneurysms in a 26-year-old woman diagnosed at 32+4 weeks of gestation. A successful elective lower-segment cesarean section was conducted under general anesthesia. A successful surgical correction of the ruptured aneurysm under cardiopulmonary bypass (CPB) was performed with patch repair after 13 days. A multidisciplinary approach with respect to the pregnant patient's diagnosis, indications, and timing of surgery is necessary in ensuring the best possible outcomes for both the mother and the child.

Does detection of a large for gestational age (LGA) fetus in fetal anomaly scan (FAS) require an early oral glucose screening test (OGTT) and can LGA fetus be detected at birth?

OBJECTIVE: Gestational diabetes mellitus (GDM) complications increase with late diagnosis and late treatment, so early diagnosis and treatment is one of the most important factors in preventing complications. We tried to find an answer to the question of whether the detection of large for gestational age (LGA) fetus in fetal anomaly scan (FAS) requires earlier oral glucose screening test (OGTT) and predicts LGA fetus at birth. PATIENTS AND METHODS: Pregnant women who underwent fetal anomaly scan and gestational diabetes screening at the Department of Obstetrics and Gynecology, University of Health Sciences, Tepecik Training and Research Hospital between 2018 and 2020 were included in this large retrospective cohort study. FAS was routinely performed between 18-22 weeks in our hospital. 75 grams of OGTT was used for gestational diabetes screening and it was performed between 24-28 weeks. RESULTS: This large retrospective cohort study was performed on 3,180 fetuses, 2,904 appropriate for gestational age (AGA) and 276 LGA, in the second trimester. The prevalence of GDM was significantly higher in the LGA group (OR 2.44, 95% CI 1.66-3.58; p < 0.001). Insulin requirement for blood glucose regulation was significantly higher in the LGA group (OR 3.6, 95% CI 1.68-7.7; p = 0.001). Fasting and 1st hour OGTT values were similar between the groups, but 2nd hour OGTT values were significantly higher in the second trimester LGA group (p = 0.041). The prevalence of LGA newborns at birth was higher in second trimester LGA fetuses than in fetuses with AGA (21.1% vs. 7.1%, p < 0.001). CONCLUSIONS: The fact that the estimated fetal weight (EFW) measured in the second trimester FAS is LGA may be related to GDM in the future and LGA fetus at birth. A more detailed GDM risk questioning should be performed to these mothers and OGTT should be considered when additional risk factors are detected. In addition to all these, glucose regulation may not be possible with diet alone in mothers who have LGA in the second trimester ultrasound and who may have GDM in the future. These mothers should be monitored more closely and more carefully.

Acute recurrent pancreatitis during 3rd trimester of pregnancy.

OBJECTIVE: We present an unusual case report of a pregnant patient with recurrent attacks of acute pancreatitis due to cholecystolithiasis. CONCLUSION: Acute pancreatitis in pregnancy is a rare disease. Unlike the non-pregnant population, it is characterized by a high recurrence rate. Acute pancreatitis during pregnancy has a negative effect on both the mother and the fetus. The treatment is modified depending on the trimester of pregnancy.

Early-onset fetal growth restriction: comparison of two management protocols in a single tertiary center.

OBJECTIVE: Compare the neonatal outcomes of two protocols of diagnosis and surveillance of pregnancies complicated by early-onset FGR in a tertiary hospital. METHODS: This is a retrospective cohort study of pregnant women diagnosed with early-onset FGR between 2017 and 2020. We compared the obstetric and perinatal outcomes between two different management protocols (before and after 2019). RESULTS: Seventy-two cases of early-onset FGR were diagnosed in the forementioned period: 45 (62.5%) were managed according to protocol 1 and 27 (37.5%) according to protocol 2. Mean gestational age at delivery was significantly different between groups: 34.9 ± 3.1 weeks (95% CI 34.0-35.9) in group 1 and 32.3 ± 4.4 weeks (95% CI 30.4-33.9) in group 2. 74.1% (20) of newborns in group 2 were admitted in de NICU, a significant difference when compared with 46.7% of group 1. There were no statistically significant differences in the remaining serious neonatal adverse outcomes. CONCLUSIONS: This is the first study published comparing two different protocols of management of FGR. The implementation of the new protocol seems to have led to a decrease in the number of fetuses labeled as growth restricted and to a decrease in the gestational age of delivery of such fetuses, but without increasing the rate of serious neonatal adverse outcomes. SYNOPSIS: The implementation of the 2016 ISUOG guidelines for the diagnosis of fetal growth restriction seems to have led to a decrease in the number of fetuses labeled as growth restricted and to a decrease in the gestational age of delivery of such fetuses, but without increasing the rate of serious neonatal adverse outcomes.

High Vitamin D Level in Female Mice Increases the Number of Live Fetuses.

Little is known about the impact of high-normal range of 25-hydroxyvitamin D [25(OH)D] on reproductive function. The aim of this study was to investigate the effect of different dose vitamin D supplementation in female mice on the pregnancy outcomes. Three groups of female mice were fed with fodder containing different dose of vitamin D at both pre-gestational and gestational stages. Serum 25(OH)D and calcium concentrations were monitored. The expression levels of vitamin D receptor (VDR) mRNA and protein in placenta were determined by real-time RT-PCR and western blot. Pregnancy outcomes were evaluated and compared among the three groups. Compared with the medium and low dose groups, serum 25(OH)D concentration was significantly increased and approximated to high-normal range in the high dose group (pre-gestational: 81.3±5.75 vs 52.8±6.24 and 25.0±3.99 ng/mL; gestational: 86.8±5.99 vs 52.6±9.29 and 27.9±4.96 ng/mL, respectively; all p<0.001). Interestingly, the average number of live fetuses per litter was much larger in the high dose group than in other two groups (19.8±5.31 vs 13.8±1.30 and 12.8±3.55 respectively, both p<0.05). However, no significant differences of the expression levels of VDR mRNA and protein in placenta were identified among the three groups. Supplementation of high dose vitamin D can enhance the female mice reproductive function. Further study is warranted to explore the mechanism by which high level of 25(OH)D in female mice increases the number of fetuses.

Cytomegalovirus reactivation in a SARS-CoV-2 infected woman experiencing fetal demise in the first trimester with fetal trisomy 21: A case report.

Cytomegalovirus (CMV) is the most common cause of congenital viral infections. Women seropositive for CMV prior to pregnancy can develop a non-primary CMV infection. Here, we present a case of first trimester pregnancy loss during active SARS-CoV-2 infection. There was no evidence of SARS-CoV-2 RNA in placenta and fetal tissue, but there was presence of congenital cytomegalovirus infection by nested PCR. To the best of our knowledge, this is the first report demonstrating association of early congenital CMV infection due to reactivation and fetal demise in a SARS-CoV-2 positive woman with fetal trisomy 21.

Correlation between hypertensive retinopathy and fetal outcomes in patients with preeclampsia in a tertiary care hospital: A prospective cohort study.

Purpose: To study the effect of increasing grades of hypertensive retinopathy (HTR) on neonatal outcomes among preeclamptic women and assess the various maternal risk factors for HTR. Methods: A prospective cohort study was conducted on 258 preeclamptic women. The systolic and diastolic blood pressure (SBP and DBP), liver, and renal function parameters were collected besides basic demographic details. Dilated fundus examination with the Keith-Wagner-Barker classification was used to grade HTR. Following delivery, neonatal outcomes were evaluated. Results: Of the 258 preeclamptic women recruited, 53.1% had preeclampsia (PE), and 46.9% had severe preeclampsia. With increasing grades of HTR, a significant association with low birth weight (LBW) (p = 0.012) and preterm gestational age (p = 0.002) was noted but not with the Appearance, Pulse, Grimace, Activity and Respiration (APGAR) score (p = 0.062). Also, it did not increase the risk of retinopathy of prematurity (ROP), with most babies, even those born to mothers with high grades of HTR, showing no evidence of ROP (p = 0.025). Among the maternal factors, increasing age (p = 0.016), SBP (p < 0.001), DBP (p < 0.001), serum creatinine (p = 0.035), alanine aminotransferase (p = 0.008), lower hemoglobin (Hb) (p = 0.009), lower platelet (p < 0.001), and severe PE (p < 0.001) have been found to significantly affect the grade of HTR. Conclusion: Higher grades of HTR in the preeclamptic mother are associated with preterm delivery and LBW of the neonates but neither affect the APGAR score nor pose the risk of developing ROP.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

Chronic Fetal Leucine Infusion Increases Rate of Leucine Oxidation but Not of Protein Synthesis in Late Gestation Fetal Sheep.

BACKGROUND: Leucine increases protein synthesis rates in postnatal animals and adults. Whether supplemental leucine has similar effects in the fetus has not been determined. OBJECTIVE: To determine the effect of a chronic leucine infusion on whole-body leucine oxidation and protein metabolic rates, muscle mass, and regulators of muscle protein synthesis in late gestation fetal sheep. METHODS: Catheterized fetal sheep at ∼126 d of gestation (term = 147 d) received infusions of saline (CON, n = 11) or leucine (LEU; n = 9) adjusted to increase fetal plasma leucine concentrations by 50%-100% for 9 d. Umbilical substrate net uptake rates and protein metabolic rates were determined using a 1-13C leucine tracer. Myofiber myosin heavy chain (MHC) type and area, expression of amino acid transporters, and abundance of protein synthesis regulators were measured in fetal skeletal muscle. Groups were compared using unpaired t tests. RESULTS: Plasma leucine concentrations were 75% higher in LEU fetuses compared with CON by the end of the infusion period (P < 0.0001). Umbilical blood flow and uptake rates of most amino acids, lactate, and oxygen were similar between groups. Fetal whole-body leucine oxidation was 90% higher in LEU (P < 0.0005) but protein synthesis and breakdown rates were similar. Fetal and muscle weights and myofiber areas were similar between groups, however, there were fewer MHC type IIa fibers (P < 0.05), greater mRNA expression levels of amino acid transporters (P < 0.01), and a higher abundance of signaling proteins that regulate protein synthesis (P < 0.05) in muscle from LEU fetuses. CONCLUSIONS: A direct leucine infusion for 9 d in late gestation fetal sheep does not increase protein synthesis rates but results in higher leucine oxidation rates and fewer glycolytic myofibers. Increasing leucine concentrations in the fetus stimulates its own oxidation but also increases amino acid transporter expression and primes protein synthetic pathways in skeletal muscle.

Fetoscopic endoluminal tracheal occlusion with Smart-TO balloon: Study protocol to evaluate effectiveness and safety of non-invasive removal.

INTRODUCTION: One of the drawbacks of fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to reestablish airway patency. The "Smart-TO" (Strasbourg University-BSMTI, France) is a new balloon for FETO, which spontaneously deflates when positioned near a strong magnetic field, e.g., generated by a magnetic resonance image (MRI) scanner. Translational experiments have demonstrated its efficacy and safety. We will now use the Smart-TO balloon for the first time in humans. Our main objective is to evaluate the effectiveness of prenatal deflation of the balloon by the magnetic field generated by an MRI scanner. MATERIAL AND METHODS: These studies were first in human (patients) trials conducted in the fetal medicine units of Antoine-Béclère Hospital, France, and UZ Leuven, Belgium. Conceived in parallel, protocols were amended by the local Ethics Committees, resulting in some minor differences. These trials were single-arm interventional feasibility studies. Twenty (France) and 25 (Belgium) participants will have FETO with the Smart-TO balloon. Balloon deflation will be scheduled at 34 weeks or earlier if clinically required. The primary endpoint is the successful deflation of the Smart-TO balloon after exposure to the magnetic field of an MRI. The secondary objective is to report on the safety of the balloon. The percentage of fetuses in whom the balloon is deflated after exposure will be calculated with its 95% confidence interval. Safety will be evaluated by reporting the nature, number, and percentage of serious unexpected or adverse reactions. CONCLUSION: These first in human (patients) trials may provide the first evidence of the potential to reverse the occlusion by Smart-TO and free the airways non-invasively, as well a safety data.

Wearable Sensors for the Monitoring of Maternal Health-A Systematic Review.

Maternal health includes health during pregnancy and childbirth. Each stage during pregnancy should be a positive experience, ensuring that women and their babies reach their full potential in health and well-being. However, this cannot always be achieved. According to UNFPA (United Nations Population Fund), approximately 800 women die every day from avoidable causes related to pregnancy and childbirth, so it is important to monitor mother and fetal health throughout the pregnancy. Many wearable sensors and devices have been developed to monitor both fetal and the mother's health and physical activities and reduce risk during pregnancy. Some wearables monitor fetal ECG or heart rate and movement, while others focus on the mother's health and physical activities. This study presents a systematic review of these analyses. Twelve scientific articles were reviewed to address three research questions oriented to (1) sensors and method of data acquisition; (2) processing methods of the acquired data; and (3) detection of the activities or movements of the fetus or the mother. Based on these findings, we discuss how sensors can help effectively monitor maternal and fetal health during pregnancy. We have observed that most of the wearable sensors were used in a controlled environment. These sensors need more testing in free-living conditions and to be employed for continuous monitoring before being recommended for mass implementation.

Immune subset-committed proliferating cells populate the human foetal intestine throughout the second trimester of gestation.

The intestine represents the largest immune compartment in the human body, yet its development and organisation during human foetal development is largely unknown. Here we show the immune subset composition of this organ during development, by longitudinal spectral flow cytometry analysis of human foetal intestinal samples between 14 and 22 weeks of gestation. At 14 weeks, the foetal intestine is mainly populated by myeloid cells and three distinct CD3-CD7+ ILC, followed by rapid appearance of adaptive CD4+, CD8+ T and B cell subsets. Imaging mass cytometry identifies lymphoid follicles from week 16 onwards in a villus-like structure covered by epithelium and confirms the presence of Ki-67+ cells in situ within all CD3-CD7+ ILC, T, B and myeloid cell subsets. Foetal intestinal lymphoid subsets are capable of spontaneous proliferation in vitro. IL-7 mRNA is detected within both the lamina propria and the epithelium and IL-7 enhances proliferation of several subsets in vitro. Overall, these observations demonstrate the presence of immune subset-committed cells capable of local proliferation in the developing human foetal intestine, likely contributing to the development and growth of organized immune structures throughout most of the 2nd trimester, which might influence microbial colonization upon birth.

The Presence of a Single Nuchal Cord in the Third Trimester May Not Affect Tei Index in LGA Fetuses.

(1) Background: The aim of this study was to assess the RV (right ventricle) and LV (left ventricle) Tei index in large for gestational age (LGA) fetuses with a single 360-degree umbilical coil of the umbilical cord around the fetal neck identified by ultrasound in the third trimester of gestation. (2) Methods: The RV and LV Tei index for the cardiac function were measured in 297 singleton pregnancies, and we identified 25 LGA fetuses. There were 48% of LGA fetuses with a nuchal umbilical cord-LGA/NC-larger for gestational age fetuses with a nuchal cord. NC was detected with a color Doppler during a transverse scan of the fetal neck, when the umbilical cord formed a U shape. All fetuses had normal anatomy and normal uterine, placental, umbilical, intracardiac and cerebral Doppler waveforms values for their gestational age. (3) Results: The RV Tei index was significantly higher in the LGA subgroup vs. AGA (0.6 ± 0.2 vs. 0.50 ± 0.2; p value = 0.01), but in LGA fetuses with a single coil of the nuchal cord, there were not any significant changes in the Tei indexes. (4) Conclusions: The Tei index might not be impacted by the presence of the nuchal cord in LGA fetuses.

Impact of additional theoretical training program in the diagnosis of the fetal head position during labor: a prospective observational study.

BACKGROUND: The accuracy of transvaginal digital examination in determining foetal head position is not high enough. This study aimed to evaluate whether an additional training on our new theory could improve the diagnostic accuracy of the foetal head position. METHODS: This was a prospective study conducted at a 3a grade hospital. The study included 2 residents in their first year of training in obstetrics without prior experience in transvaginal digital examination. In the observational study, 600 pregnant women without contraindications to vaginal delivery were included. Two residents were simultaneously trained in the theory of traditional vaginal examination, but resident B received an additional theoretical training program. The pregnant women were randomly assigned to have the foetal head position examined by resident A and resident B. The foetal head position was then confirmed by ultrasound, which was performed by the main investigator. After 300 examinations were independently performed by each resident, the accuracy of foetal head position and perinatal outcomes were compared between the two groups. RESULTS: During the 3-month period, 300 post training transvaginal digital examinations were performed by each resident in our hospital. The two groups were found to be homogeneous for age at delivery, BMI before delivery, parity, gestational weeks at delivery, the rate of epidural analgesia, foetal head position, presence of caput succedaneum, presence of moulding and foetal head station(p > 0.05). The diagnostic accuracy of head position by digital examination was higher for resident B, who was subjected to an additional theoretical training program, than for resident A (75.00% vs. 60.67%, p < 0.001). There were no significant differences in maternal and neonatal outcomes between the two groups (p > 0.05). CONCLUSION: An additional theoretical training program for residents increased the accuracy of vaginal assessment of foetal head position. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry Platform (ChiCTR2200064783), October 17, 2022. https://www.chictr.org.cn/edit.aspx?pid=182857&htm=4.