Reproductive and developmental safety evaluation of Thymelaea hirsuta (L.) leaves aqueous extract in Wistar albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The popularity of herbal medicine is expanding globally due to the common belief that herbal products are natural and nontoxic. Thymelaea hirsuta leaves are traditionally used for the treatment of recurrent abortion in humans and animals. However, a lack of safety evaluation of the plant, particularly in pregnant women, raises serious concerns regarding its potential embryotoxic effects. AIM OF THE STUDY: Therefore, the present study investigated the safety of Thymelaea hirsuta leaves aqueous extract (THLE) during pregnancy and lactation following maternal rat treatment. MATERIALS AND METHODS: THLE phytochemical compounds were identified using high-performance liquid chromatography (HPLC). THLE was orally administered to pregnant rats and lactating dams at dosages of 0, 250, 500, and 1000 mg/kg/day. At the end of the study, dam s' and pups' body weights, serum biochemical and hematological indices, and histopathological changes were investigated. For the fetal observation and histopathological changes were also evaluated. RESULTS: Our findings revealed that THLE is rich in different phenolic and flavonoid compounds. However, biochemical and hormonal parameters such as ALT, AST, and prolactin were significantly increased in dams treated with a higher dosage of THLE when compared to the control dams (P ≤ 0.05). Additionally, external, visceral and skeletal examinations of fetuses revealed a marked increase of malformation rates in treated fetuses. CONCLUSIONS: The results revealed that higher oral dosing of THLE during pregnancy could affect embryonic development in rats, while lower doses are safe and can be used during pregnancy and lactation to attain its beneficial effects.

Anti-D Alloimmunization in Index Pregnancy after Appropriate Rho(D) Immune Globulin Injection in Two Obese Rh-Negative Patients.

Background The rhesus factor D (RhD)-negative patients who give birth to an RhD-positive newborn or who are otherwise exposed to RhD-positive red blood cells are at risk of developing anti-D antibodies. These antibodies may cause hemolytic disease of the fetus and newborn (HDFN). During pregnancy, prevention of alloimmunization is completed with a Rho(D) immune globulin (RhIg). Cases We report two cases, where obese patients developed alloimmunization, with high neonatal titers, after appropriate RhIG prophylaxis during the index pregnancy. Conclusion Our cases demonstrate cases of anti D-alloimmunization in an index pregnancy, with high neonatal titers. Both patients are obese, with BMI > 35 mg/m 2 . Key Points RhIG can be administered via intramuscular or intravenous formulations. Overall, it appears that both formulations are equally effective. The optimal administration, especially with obese women, is not clearly established.Our cases demonstrate that obesity is a risk factor for failure of RhIG, and could lead to an increase in HDFN.

Effect of mild gestational diabetes mellitus on histological, ultrastructural, and quantitative morphometric alterations of rat fetal liver.

Objectives: Gestational diabetes mellitus (GDM), one of the most common metabolic disorders in pregnancy, impacts maternal and fetal health. This study was designed to assess the effects of mild GDM on the histology, ultrastructure, and morphometry of fetal liver tissue. Materials and Methods: In this experimental study, twenty pregnant rats were randomly allocated into control and streptozotocin (STZ)-induced diabetic groups. Mild hyperglycemia was induced by intraperitoneal injection of STZ (40 mg/kg/bw) on the 5th day of gestation. At day 19 of gestation, fetal livers were separated and subjected to histological, transmission electron microscopic, and quantitative morphometric examinations. Results: In the GDM group, PAS staining was positive, revealing scattered eosinophilic inclusions in some hepatocytes. Masson trichrome staining was also positive and showed some fibrous tissue as fine fibers in the portal spaces that extended to the central vein. Reticulin staining in the GDM group was focally positive in the areas of fibrosis and the portal spaces. Ultrastructural examination showed pyknotic nuclei, karyolysis, degranulation and vesiculation of the rough endoplasmic reticulum, and degeneration of mitochondria in the GDM group. The morphometric examination demonstrated that the mean area of hepatocytes was significantly lower in the GDM group than in the control group (P<0.05). Moreover, the mean diameter of the central vein and the density of megakaryocytes were significantly higher in the GDM group than in the control group (P<0.05). Conclusion: Uncontrolled mild GDM induced the histological, ultrastructural and morphometric alterations in the fetal liver.

A challenging case of hemolytic disease of the fetus and newborn (HDFN) due to anti-Ku in a K0 (Kellnull) mother.

Hemolytic disease of the fetus and newborn (HDFN) due to an antibody in the Kell blood group system can be associated with severe fetal anemia. This case report details the challenges of managing a Kellnull mother with anti-Ku that affected her fetus/newborn. A gravida 4 para 3 woman at term underwent an emergency lower caesarean section because of fetal distress. The baby was intubated because of low oxygen saturation. An urgent request for a hematology workup showed severe anemia and erythroblastosis fetalis. Unfortunately, no compatible blood was found, and the baby died. The case was referred to the National Blood Centre, and anti-Ku was confirmed in a sample sent from the mother. When she presented with her fifth pregnancy, meticulous planning was used to manage this pregnancy. Her family screening revealed one brother with a matching phenotype. Three blood donations were planned for the brother-for freezing, for intrauterine transfusion, and for standby during delivery. Serial anti-Ku titrations of maternal samples were performed, and the fetus was monitored for anemia through middle cerebral artery Doppler scans. Although the anti-Ku titers reached as high as 1024, fetal anemia was never diagnosed. The neonate was delivered safely but was diagnosed with severe pathologic jaundice and anemia secondary to HDFN and congenital pneumonia. The baby was transfused with K0 packed red blood cells and later discharged to home.

Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health.

Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cell mass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear.

International expert consensus statement on physiological interpretation of cardiotocograph (CTG): First revision (2024).

The first international consensus guideline on physiological interpretation of cardiotocograph (CTG) produced by 44 CTG experts from 14 countries was published in 2018. This guideline ensured a paradigm shift from classifying CTG by arbitrarily grouping certain features of the fetal heart rate into different "categories", and then, randomly combining them to arrive at an overall classification of CTG traces into "Normal, Suspicious and Pathological" (or Category I, II and III) to a classification which is based on the understanding of fetal pathophysiology. The guideline recommended the recognition of different types of fetal hypoxia, and the determination of features of fetal compensatory responses as well as decompensation to ongoing hypoxic stress on the CTG trace. Since its first publication in 2018, there have been several scientific publications relating physiological interpretation of CTG, especially relating to features indicative of autonomic instability due to hypoxic stress (i.e., the ZigZag pattern), and of fetal inflammation. Moreover, emerging evidence has suggested improvement in maternal and perinatal outcomes in maternity units which had implemented physiological interpretation of CTG. Therefore, the guideline on Physiological Interpretation of CTG has been revised to incorporate new scientific evidence, and the interpretation table has been expanded to include features of chorioamnionitis and relative utero-placental insufficiency of labour (RUPI-L).

Fetal Vertebral Chondrostasis-Significance of Excessive Cartilage in Vertebral Bodies of Newborns.

INTRODUCTION: We describe an abnormality in fetal and neonatal vertebral bodies whose most conspicuous characteristic is an increase in cartilaginous matrix within cancellous osseous trabeculae. We have termed this finding fetal chondrostasis (FC). METHODS: We initiated a retrospective review of autopsy reports in which this condition had been prospectively diagnosed during a 36-year period. The Chalkley point counting method was applied to histologic sections of vertebral bodies to assess the relative components of cartilage, bone, and bone marrow. The results were compared to those of three control groups whose causes of death were prematurity, birth trauma, and infection. RESULTS: We found that on average, the cartilaginous content in the FC group was considerably greater in both preterm and term infants when compared to controls. FC seemed to evolve from diminished activity in the cartilaginous growth zone resulting in formation of excessively broad cartilaginous columns. These subsequently suffered from delayed resorption following their incorporation within cancellous bony trabeculae. CONCLUSION: Excess cartilage within cancellous bone of vertebral centra in newborns is merely one aspect of disturbed intrauterine osseous development but is seemingly more readily discernible than other features at this site. The most common clinical correlates for FC were multiple congenital anomalies, congenital heart disease, intrauterine growth retardation, prematurity, and certain maternal factors.

A multicenter multinational study to evaluate different aspects of the relationship between MS and pregnancy.

BACKGROUND: To investigate the pregnancy-related issues in females with multiple sclerosis (MS) from Turkiye, Egypt, Kuwait, and Iran. METHODS: 1692 pregnancies of 701 females with MS were evaluated in this retrospective multicenter, international project. Demographics, clinical features, pregnancy outcomes, relapses, effects of exposure to disease-modifying drugs on pregnancy and fetus, and worries about pregnancy decisions were investigated. RESULTS: 85.9 % of females were diagnosed with relapsing-remitting multiple sclerosis. The mean age was 39.0 ± 9.0 years (min 20, max 68). The mean EDSS score was 2.26 ± 1.8. The number of conceptions was inversely correlated with the level of education with significance (p<0.05). Among the concerns related to pregnancy, 31.7 % pertain to disability progression, 14.4 % are associated with relapses, and 7.3 % involve the cessation of treatment. Additionally, 82.3 % of females with MS experienced no relapses during both pregnancy and the postpartum period. Most of the relapses (22.9 %) occurred in the postpartum period. Higher EDSS scores were detected in patients who have higher numbers of pre-MS period pregnancies (p= 0.042; r:0.2591). A similar correlation was found between the total number of pregnancies and higher EDSS levels (p=0.003, r:0.2614). Considering the relationship between EDSS score and the number of pregnancies after MS diagnosis, no significance was found (p = 0.595). The age at first pregnancy did not affect the onset age of MS. Significant positive correlation was found between the age of onset and the total number of pregnancies and pre-MS pregnancies. As the number of pregnancies increased, the disease onset was at a later age (correlation = 0.4258). CONCLUSION: Presence of pre-MS pregnancies increased the age of onset of MS and caused more disability. The reduction in the number of pregnancies following the diagnosis of MS was related with a consistent hesitancy among patients in this regard.

Expanding MNS1 Heterotaxy Phenotype.

MNS1 (meiosis-specific nuclear structural protein-1 gene) encodes a structural protein implicated in motile ciliary function and sperm flagella assembly. To date, two different homozygous MNS1 variants have been associated with autosomal recessive visceral heterotaxy (MIM#618948). A French individual was identified with compound heterozygous variants in the MNS1 gene. A collaborative call was proposed via GeneMatcher to describe new cases with this rare syndrome, leading to the identification of another family. The first patient was a female presenting complete situs inversus and unusual symptoms, including severe myopia and dental agenesis of 10 permanent teeth. She was found to carry compound heterozygous frameshift and nonsense variants in MNS1. The second and third patients were sibling fetuses with homozygous in-frame deletion variants in MNS1 and homozygous missense variants in GLDN. Autopsies revealed a complex prenatal malformation syndrome. We add here new cases with the ultra-rare MNS1-related disorder and provide a review of all published individuals.

Intra-abdominal retroperitoneal fetus in fetu: A case report.

Fetus in fetu (FIF) is a rare abnormality where a vertebrate parasitic fetus develops inside the body of another normally developing fetus. It is distinct from teratomas, tumors composed of cells from multiple germ layers and have malignant potential. Symptoms of FIF arise from the mass effect, causing abdominal distension, feeding difficulties, and pressure effects on organs. FIF is commonly found in the retroperitoneal region but can also occur in other locations. It often includes certain organs such as the vertebral column, limbs, central nervous system, gastrointestinal tract, vessels, and genitourinary tract. Early diagnosis of FIF by ultrasound, computed tomography, and magnetic resonance imaging can improve patient outcomes. Surgical resection is the primary treatment approach, aiming to alleviate symptoms, and molecular analysis helps differentiate FIF from malignant teratomas. Regular follow-up is necessary due to the potential recurrence of teratomas.

Major reduction in occurrence of anti-c and anti-E in pregnancy after more than 10 years of preventive matched transfusion with most benefit for c-matching.

Extension with cE-matching of the transfusion policy for women under 45 years to prevent alloimmunization and hemolytic disease of the foetus and newborn (HDFN) was evaluated. After implementation of cEK-matching, anti-c occurrence decreased from 46.8 to 30.4 per 100 000 pregnancies (RR 0.65, 95% CI 0.54-0.79), while anti-E occurrence decreased from 122.1 to 89.9 per 100 000 pregnancies (RR 0.74, 95% CI 0.66-0.84). The c-negative women showed a higher anti-E occurrence before cEK-matching and a more pronounced decline with the new policy. This indicates that cEK-matched transfusion effectively reduces alloimmunization, and that a cK-matched approach could prevent most transfusion-related alloimmunization and HDFN.

Increased prevalence of negative pregnancy and fetal outcomes in women with primary adrenal insufficiency. A systematic review and meta-analysis.

Maternal primary adrenal insufficiency (PAI) during pregnancy, due to either Addison disease (AD) or congenital adrenal hyperplasia (CAH), is rare. Only few studies have examined the subsequent important outcomes of maternal glucocorticoid and mineralocorticoid deficiencies during pregnancy upon the fetus and the neonate. Therefore, this systematic review and meta-analysis evaluated the impact of these deficiencies, with data from PubMed/Medline, Cochrane/CENTRAL, and Google Scholar. A total of 31 studies were included for qualitative analysis and 11 for quantitative analysis. Studies examining the prevalence of spontaneous abortion, preterm birth, the occurrence of small for gestational age (SGA) neonates, as well as the neonatal birth weight were included. The systematic review revealed a substantial number of spontaneous abortions, preterm births and SGA neonates in pregnant women with PAI. The meta-analysis showed a mean spontaneous abortion prevalence of 18%, 18% and 17% in women with PAI, AD or CAH, respectively. The mean preterm birth prevalence was 11% when women with AD or CAH were analyzed together, and 13% and 9% in women with AD or CAH, respectively, when these women were analyzed separately. The mean prevalence of SGA neonates was 8% when women with AD or CAH were analyzed together, and 5% and 10% in women with AD or CAH, respectively, when these women were analyzed separately. The mean fetal birth weight was within normalcy in all women with PAI, as well as in women with AD or CAH. In conclusion the executed systematic review of 31 studies followed by a meta-analysis of 11 studies in pregnant women with PAI has shown a greater prevalence of pregnancies with negative outcome (spontaneous abortion, preterm birth) and of negative fetal outcome (SGA) in women with either AD or CAH, as compared to control pregnant women.

Fetus descent simulation with the active uterine contraction during the vaginal delivery: MRI-based evaluation and uncertainty quantification.

Finite element models ranging from single to multiscale models have been widely used to gain valuable insights into the physiological delivery process and associated complication scenarios. However, the fetus descent simulation with the active uterine contraction is still challenging for validation and uncertainty quantification issues. The present study performed a fetus descent simulation using the active uterine contraction. Then, simulation outcomes were evaluated using theoretical and in vivo MRI childbirth data. Moreover, parameter uncertainty and propagation were also performed. A maternal pelvis model was developed. The active uterine contraction was modeled using a transversely isotropic Mooney-Rivlin material. Displacement trajectories were compared between simulation, theoretical and in vivo MRI childbirth data. Monte Carlo (M.C) and Polynomial Chaos Expansion (PCE) methods were applied to quantify uncertain parameters and their propagations. Obtained results showed that fetal descent behavior is consistent with the MRI-based observation as well as the theoretical trajectory (curve of Carus). The head downward vertical displacement ranges from 0 to approximately 47 mm. A reduction of 50% in uterine size was observed during the simulation. Three high-sensitive parameters (C1,C2,Ca0) were also identified. Our study suggested that the use of the active uterine contraction is essential for simulating vaginal delivery but the global parameter sensitivity, parameter uncertainty, and outcome evaluation should be carefully performed. As a perspective, the developed approach could be extrapolated for patient-specific modeling and associated delivery complication simulations to identify risks and potential therapeutic solutions.

Efficient decellularization of human fetal kidneys through optimized SDS exposure.

Chronic kidney disease poses a significant threat to public health. Renal replacement therapy is the primary treatment option for end-stage kidney disease. However, there is a promising and relatively new method in regenerative medicine for creating a functional organ known as whole kidney decellularization. This method uses the intrinsic vasculature to perfuse the decellularizing agent into the tissue, effectively penetrating and removing cellular material. The regenerated bioscaffolds could serve as a source of organ donation. This study is focused on evaluating the effectiveness of various SDS exposures in decellularizing human fetal kidneys. The study included human fetal kidneys harvested from fetuses terminated before 14 weeks of gestational age. Kidneys were divided into six treatment groups based on SDS concentration and duration of perfusion. Decellularization, scanning electron microscopy, histopathological staining, immunofluorescent staining, and immunohistochemistry staining were performed to evaluate the adequacy of the process. The statistical analysis revealed that the SDS 0.1% treatment group had the highest collagen deposition after 24 h, significantly greater than the SDS 0.5% treatment group at 24 and 48 h. No significant differences were observed among the other treatment groups. The study concludes that the SDS 0.1% treatment group for 24 h was the most effective in terms of ECM content preservation and effective cell removal. This treatment showed better results than the other treatment groups and can be considered for future whole kidney decellularization studies.

Giant placental chorioangioma: A rare case report.

INTRODUCTION AND IMPORTANCE: Chorioangioma is benign, non-trophoblastic vascular neoplasms of the placenta with an estimated incidence of 1 %. It originates from placental blood vessels. Giant chorioangiomas, larger than 4 cm in diameter, are rare with an incidence ranging between 1/3500 and 1/9000 pregnancies. Giant chorioangiomas easily detected by prenatal ultrasound and are associated with a series of pregnancy and fetal complications. CASE PRESENTATION: A 34-year-old multigravida woman, with twin pregnancy presented with notation of reduced fetal movement. On sonographic examination, first fetus was Intrauterine Growth Restriction (IUGR), stage 1 and the second fetus was small-for gestational age and a well-defined, hypoechoic lesion with increased vascularity measuring 5.8 × 4.7 × 2.5 cm on the fetal surface of the placenta was seen. However, at 35 + 3 weeks, the patient presented with pain in the lower abdomen. Maternal vital signs were within normal ranges. On Physician team discussion, cesarean section was performed. Two female neonates weighing 2260 g and 2400 g were delivered, with normal APGAR scores and physical examinations. And physical examination. The placenta was sent to pathology laboratory. In histopathology numerous proliferative blood vessels was found that confirm with immunohistochemical analysis. Finally, the patient was diagnosed with placental chorioangioma. DISCUSSION: Placental chorioangioma is a rare anomaly in villous capillary development, with uncertain pathogenesis. It is often linked to twin pregnancies, gestational diabetes, maternal hypertension, and female fetal sex. Prenatal sonographic scans are valuable for its identification, revealing a hypoechoic, highly vascular mass confirmed via Doppler ultrasound. In contrast, chorangiocarcinoma, a malignant placental tumor, comprises chorioangioma and proliferating trophoblast cells with distinct histological features. Close monitoring and sonographic evaluations are vital during pregnancy when managing chorioangioma, especially giant ones, known to cause various fetal and pregnancy complications. The decision-making process for delivery in cases of giant chorioangioma should consider fetal complications and gestational age. While some interventions like laser ablation are available, the challenging nature of the patient's response may warrant conservative management in certain instances. CONCLUSION: We report a rare case of giant placental chorioangioma in a 34-year-old twin pregnant patient. Chorioangioma benign vascular neoplasms of the placenta may cause pregnancy and fetal complications.

A fetus with a mass in the oral cavity: A rare case of large oral immature teratoma.

Oral teratoma is a congenital neoplastic lesion with an incidence of 2%-9% of all teratomas. It comprises variable amounts of all three germ cell layers. The lesion is graded on histology depending upon the presence of immature components. The most common sites of presentation are the sacrococcygeal area and head and neck with slight female predominance. Our report is based on a case that was received for histopathological evaluation. It consisted of a 20-week fetus with a huge mass protruding from oral orifice measuring 10.8 × 6.7 cm. Histological examination of the tumor revealed immature teratoma-oropharynx.

Factors related to the occurrence of fetal birth defects and the construction of a Nomogram model.

Objective: To explore the influencing factors of fetal birth defects (BD) and construct a nomogram model. Methods: A total of 341 newborns admitted to Meizhou people's hospital from September 2021 to September 2023 were randomly grouped into a modeling group (239 cases) and a validation group (102 cases). The modeling group fetuses were separated into BD and non-BD groups. Multivariate logistic regression analyzed risk factors for BD; R software constructed a nomogram model; Receiver operating characteristic (ROC) curve evaluated the model's discrimination for BD. Results: The top 5 types of BD were congenital heart disease, polydactyly/syndactyly, cleft lip/palate, ear malformation, and foot malformation, with incidence rates of 23.81%, 20.63%, 12.70%, 11.11%, and 7.94%, respectively. BD incidence was 26.36% (63/239). Significant differences between BD and non-BD groups were found in maternal age, gestational age, history of adverse pregnancy/childbirth, gestational hypertension, adverse emotions during pregnancy, and folic acid intake duration (P<0.05). Logistic regression showed maternal age (OR: 4.125), gestational age (OR: 3.066), adverse pregnancy history (OR: 10.628), gestational hypertension (OR: 5.658), adverse emotions (OR: 5.467), and folic acid intake duration (OR: 4.586) were risk factors for BD (P<0.05). The modeling group's ROC AUC was 0.938, calibration curve slope close to 1, H-L test =8.342, P=0.692; external validation AUC was 0.961, calibration slope close to 1, H-L test =7.634, P=0.635. Conclusion: Identified risk factors include maternal age, gestational age, adverse pregnancy history, gestational hypertension, adverse emotions, and folic acid intake duration. The nomogram model shows good discrimination and consistency for evaluating neonatal BD risk.

A postmortem high-resolution MRI study of the development of cochlear nerve-related structures in the second and third trimesters of pregnancy.

Background: Magnetic resonance imaging (MRI) is used to determine whether cochlear nerve development is normal in infants and adults, but it has not yet been used to evaluate cochlear nerve development or measure cochlear nerve-related structures in the fetus. This study sought to provide imaging data for clinical evaluations concerning cochlear nerve development in the fetus using MRI. Methods: Postmortem 3.0-Tesla MRI of inner ear was performed in 51 fetuses with normal temporal bones at 25 to 40 weeks of gestation. The continuous scanning protocol incorporated axial three-dimensional (3D) sampling perfection with application-specific contrasts using different flip angle evolution sequences. The images were evaluated to measure the structures of the cochlear aperture (CA), internal auditory canal (IAC), and vestibulocochlear and facial nerves in the cerebellopontine angle (CPA), which have been reported to be associated with cochlear nerve development. We also calculated the ratio between the diameters of the vestibulocochlear and facial nerves. The measurable parameters were compared between the right and left sides. The threshold for statistical significance was set at P<0.05. Results: The inner ear anatomy was discernible on MRI in all the fetal specimens, and growth of the CA, IAC, vestibulocochlear nerve, and facial nerve in the CPA was observed as fetal age increased. There was no significant difference in the measurements of these structures between the right and left sides (all P>0.05). Conclusions: MRI can be used to help evaluate the anatomy and development of the cochlear nerve in the fetus. These normative measurements could be valuable for clinical evaluations of the cochlear nerve.