The Proper Diagnosis of Thrombophilic Status in Preventing Fetal Growth Restriction.

Fetal growth restriction is an important part of monitoring a pregnancy. Because guidelines or diagnostic criteria for either minor or major thrombophilia are scarce, this systematic review aims to summarize the present knowledge in the field. We performed the CRD42022376006 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and with the "thrombophilia AND (pregnancy OR diagnostic criteria) AND fetal growth restriction" criteria. After two researchers extracted the articles of interest, they were assessed using the Newcastle-Ottawa Scale and eight articles were included. The elements from the thrombophilia diagnostic predict IUGR, factor V Leiden mutation, MTHFR C667T mutation, protein S deficiency, antithrombin deficiency, factor VII polymorphism, and antiphospholipid antibodies, while the association of protein C, PAI-1 and certain combinations of mutations are still under debate and require the collection of more data. The present systematic review provides an extensive picture of the actual knowledge about thrombophilia diagnosis and its links with pregnancy complications, such as intrauterine growth restriction, despite its limitation in the inclusion of other actually debated disorders such as PAI-1 mutation, protein C deficiency and other thrombophilia types.

Current Innovative Methods of Fetal pH Monitoring-A Brief Review.

In this study, we explore the "why?", and "how?", monitoring the pH of the fetal scalp is used, and show its limitations. In addition, we review the development of new devices based on the modern physics and nanomaterials serving this topic. Most of the works we found in our search have focused on improving the prognostic of fetal heart rate monitoring, because it is the "golden standard" in determining fetal distress. Although the best-known screening method, it can only provide limited information about the actual status of the fetus. The best predictive assessment, with the highest reproducibility, states that a normal fetal heart rate is indicative of a healthy baby. However, its excellent sensitivity is much reduced when identifying the actual "distress". This is when second-line monitoring methods come into play to guide the diagnostics and direct the obstetrician towards an action plan. Although a historic method, fetal scalp pH sampling is still under review as to its efficiency and place in the current obstetrics. Continuous surveillance of the fetal parameters is important, especially for the fetuses undergoing intrauterine growth restricted (IUGR). Since fetal scalp blood sampling is still under research and is a randomized controlled trial, which compares the relevance of pH and lactates to the obstetrical situation, the maternal-fetal medicine could greatly benefit from the introduction of engineered nanomedicines to the field.

Technical Tips and Tricks after 10 Years of HyFoSy for Tubal Patency Testing.

BACKGROUND: Hysterosalpingo-foam sonography (HyFoSy) has gained popularity in the last decades, as it represents a feasible, well-tolerated, and minimally invasive method of evaluation of tubal patency in cases of infertility. The purpose of this study was to communicate the technical tips and tricks based on our experience in performing HyFoSy, with the aim to improve the feasibility, to reduce the pain, and to evaluate pregnancy-obtaining rate after procedure. METHODS: Our observational study includes 672 patients from infertile couples who underwent HyFoSy for tubal patency evaluation. During HyFoSy, tubal pathway and patency as well as the level of pain were evaluated. A telephonic questionnaire was conducted in order to assess the pregnancy obtaining rate in the first 3 months and more than 3 months after the procedure. RESULTS: The median age in our group was 33.5 years. Most of our patients (61.16%) underwent HyFoSy in the 8-10 days of the menstrual cycle. Tubal patency was present bilaterally in 86% cases, unilaterally in 11% of patients, and was absent in 3% of cases; 75% of patients related absent or tolerable pain, 17% described HyFoSy as a painful procedure, and 8% experienced extreme pain. After HyFoSy, pregnancy was naturally obtained in 10.86% of cases within the first 3 months after HyFoSy. CONCLUSIONS: HyFoSy represents a useful, easy to use, and painless tool in female infertility evaluation and should be considered as a complementary method of the transvaginal ultrasonography, completing the genital tract imaging with information about the hidden part of the standard examination: tubal patency. HyFoSy provides information about patency, caliber regularity, pathway, and occlusion location of the fallopian tubes; therefore, it should be introduced along with transvaginal ultrasound as a first-line infertility exploration method.

Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19.

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.

The Strategy against Iatrogenic Prematurity Due to True Umbilical Knot: From Prenatal Diagnosis Challenges to the Favorable Fetal Outcome.

True umbilical knot (TUK), although not a commonly encountered pathology, hasan important psychological burden on the mother and obstetrician. It has an extremely low prenatal ultrasound diagnosis rate, despite its adverse perinatal outcomes when unknown. We conducted a retrospective observational analytical study on a 7-year period (2015-2021), including all pregnancies overseen by a single fetal-maternal medicine specialist for monitoring and delivery. We analyzed the prenatal detection rate and correlations between prenatal diagnosis of TUK and pregnancy outcome in terms of associated maternal and fetal factors, time and mode of delivery, fetal weight at birth, maternal level of stress, and iatrogenic prematurity. We compared our results with an electronic search of the literature to study the relationship between TUK and prematurity. We prenatally diagnosed 16 TUKs, and there were two false positives and two undiagnosed knots. All of those women had birth at term. The main finding of the review was a small number of studies that included enough cases for analysis. The prematurity rate due to TUK is 14.2%, significantly increased compared to the general population. An umbilical artery flow velocimetry notch in twin pregnancies complicated by TUK was an important ultrasonographic finding. We consider intrauterine fetal death exceptional, and the main adverse neonatal outcome is due to iatrogenic prematurity caused by maternal anxiety of knowing the prenatal diagnosis and mode of delivery. The elective method for diagnosis should be the second-trimester ultrasound scan using three-dimensional (3D) reconstruction and cesarean delivery for a good neonatal outcome. Pregnant women should be counseled to understand the implications of iatrogenic prematurity, especially respiratory distress syndrome, to ensure these infants are delivered at term.

Clinically Relevant Prenatal Ultrasound Diagnosis of Umbilical Cord Pathology.

Umbilical cord abnormalities are not rare, and are often associated with structural or chromosomal abnormalities, fetal intrauterine growth restriction, and poor pregnancy outcomes; the latter can be a result of prematurity, placentation deficiency or, implicitly, an increased index of cesarean delivery due to the presence of fetal distress, higher admission to neonatal intensive care, and increased prenatal mortality rates. Even if the incidence of velamentous insertion, vasa praevia and umbilical knots is low, these pathologies increase the fetal morbidity and mortality prenatally and intrapartum. There is a vast heterogeneity among societies' guidelines regarding the umbilical cord examination. We consider the mandatory introduction of placental cord insertion examination in the first and second trimester to practice guidelines for fetal ultrasound scans. Moreover, during the mid-trimester scan, we recommend a transvaginal ultrasound and color Doppler assessment of the internal cervical os for low-lying placentas, marginal or velamentous cord insertion, and the evaluation of umbilical cord entanglement between the insertion sites whenever it is incidentally found. Based on the pathological description and the neonatal outcome reported for each entity, we conclude our descriptive review by establishing a new, clinically relevant classification of these umbilical cord anomalies.

First-Trimester Diagnosis of Supernumerary Hemivertebra.

Hemivertebra is a common cause of congenital scoliosis and results from a lack of formation of one-half of the vertebral body. This condition is very rare and can present as solitary or as a syndrome component: i.e., the split notochord syndrome, which often implies vertebral defects, from a bifid vertebra to hemivertebrae, or fused vertebrae. We describe a case of supernumerary lateral hemivertebra detected prenatally at 12 weeks of gestation and the ultrasonography specifics that lead to early and accurate diagnosis, monitoring during pregnancy, and follow-up at the 4-year period. The case is presented to specify the importance of an early assessment of fetal spine and diagnosis of various conditions, including hemivertebrae, considering the significant association with other anomalies (cardiovascular, urinary, skeletal, gastrointestinal, and central nervous systems), which are most commonly involved. Moreover, the need to counsel future parents on the risks implied by this anomaly is important for the obstetrician. We underline the inclusion of these types of congenital conditions in high-risk pregnancy because of the frequent association with high cesarean delivery rates, growth restriction, delivery before term, and higher morbidity rates.

Success rate of methotrexate in the conservative treatment of tubal ectopic pregnancies.

An ectopic pregnancy (EP) involves the implantation of the gestational sac outside the uterine cavity. In the event of diagnosing an EP, the current medical approach is to avoid surgery and to preserve fertility whenever possible; therefore, methotrexate (MTX)-based therapy has become prominent in recent years. MTX, a drug usually used to treat severe forms of autoimmune diseases and several types of cancer, has proven its utility in the conservative treatment of EPs. The success rate of MTX correlates with lower values of ß subunit of human chorionic gonadotropin hormone (ß-hCG) serum levels, especially below 2,000 mUI/ml, side effects being insignificant. In the present study, the results obtained concerning the success rate of MTX in the conservative treatment of EPs were obtained at the Department of Obstetrics and Gynecology of the Bucharest University Emergency Hospital from January 2014 to December 2020. The aim of the present study was to highlight the necessity for revising current guidelines for ectopic pregnancy medical treatment in order to manage this pathology optimally and to select carefully the proper treatment, whether medical, surgical or expectant management, so that morbidity is reduced to a minimum.

Polycythemia vera in pregnancy represents a challenge for a multidisciplinary collaboration: A case report and literature review.

Polycythemia vera (PV) is a rare chronic myeloproliferative neoplasm which represents an additional thrombotic factor in pregnancy. PV may be difficult to diagnose, particularly as its incidence is extremely uncommon among young women. The main diagnostic method involves a bone marrow biopsy, and high hemoglobin and platelet counts are usually indicative of the condition, after excluding other more frequent pathologies. PV is associated with a high risk of thrombosis, particularly in pregnancy, and requires anti-platelet treatment. At present, only a limited number of PV cases in pregnancy have been reported in the literature, at least to the best of our knowledge, with the largest case series being a retrospective study that included 25 pregnancies in 15 women. The present study describes the case of a patient diagnosed with JAK2-positive PV and also discusses this rare condition with particular focus on the following: i) The management of PV in pregnancy along with the additional pathologies in this specific case; and ii) the particularities of the pregnancy course. By identifying women suffering from PV superimposed by other possible procoagulant factors and applying the latest standard in healthcare, fetal and maternal prognosis may be significantly improved.

Influence of pemphigoid gestationis on pregnancy outcome: A case report and review of the literature.

Pemphigoid gestationis is considered to be a rare pregnancy exclusive bullous disease, which modifies the course of the pregnancy, with difficulties in the management of the pruritus and skin lesions as well as a possible change in the neonatal outcome. Differential diagnosis of skin lesions and pruritus in pregnancy is challenging, and complementary investigations such as skin biopsy or laboratory tests are indispensable. The correct diagnosis and proper treatment could change the natural course of a pregnancy at risk and could improve maternal and fetal morbidity. We present the case of a patient with pemfigoid gestationis with the aim to highlight: i) the management of this pregnancy-associated skin disorder which transfers this pregnancy into a category of high obstetrical risk pregnancy; ii) the particularities of the course of the pregnancy; and iii) the importance in the differential diagnosis of pregnancy dermatoses. The particularity of this case of pemphigoid gestationis was the acute fetal distress in the absence of intrauterine growth restriction that is frequently found in this pathology, and the management of a rare pregnancy skin condition that currently has no standard treatment.

Diagnosis and Management of Fetal and Neonatal Thyrotoxicosis.

Background and Objectives: Clinical fetal thyrotoxicosis is a rare disorder occurring in 1-5% of pregnancies with Graves' disease. Although transplacental passage of maternal TSH receptor stimulating autoantibodies (TRAb) to the fetus occurs early in gestation, their concentration in the fetus is reduced until the late second trimester, and reaches maternal levels in the last period of pregnancy. The mortality of fetal thyrotoxicosis is 12-20%, mainly due to heart failure. Case report: We present a case of fetal and neonatal thyrotoxicosis with favorable evolution under proper treatment in a 37-year-old woman. From her surgical history, we noted a thyroidectomy performed 12 years ago for Graves' disease with orbitopathy and ophthalmopathy; the patient was hormonally balanced under substitution treatment for post-surgical hypothyroidism and hypoparathyroidism. From her obstetrical history, we remarked a untreated pregnancy complicated with fetal anasarca, premature birth, and neonatal death. The current pregnancy began with maternal euthyroid status and persistently increased TRAb, the value of which reached 101 IU/L at 20 weeks gestational age and decreased rapidly within 1 month to 7.5 IU/L, probably due to the placental passage, and occurred simultaneously with the development of fetal tachycardia, without any other fetal thyrotoxicosis signs. In order to treat fetal thyrotoxicosis, the patient was administered methimazole, in addition to her routine substitution of 137.5 ug L-Thyroxine daily, with good control of thyroid function in both mother and fetus. Conclusions: Monitoring for fetal thyrotoxicosis signs and maternal TRAb concentration may successfully guide the course of a pregnancy associated with Graves' disease. An experienced team should be involved in the management.

Ductus venosus reversed flow in omphalocele: Could it be a prognostic factor for long-term neurological impairment?

Omphalocele (exomphalos) represents one of the most frequent congenital abdominal wall defects. It presents as a defect of inconstant size and is located on the midline, at the base of the umbilical cord, the skin, fascia, and abdominal muscles being absent at this level. Omphaloceles are classified as liver-containing or non-liver-containing, the latter containing primarily bowel loops. We present the case of a 37-year-old pregnant woman with an early diagnosis of liver-containing omphalocele associating ductus venosus reversed flow, with the aim to highlight the importance of the first-trimester morphology scan and to develop a pilot study regarding the neurological development of infants after surgical repair of giant omphaloceles. The particularity of this case consists of a fetus with a positive diagnosis of a giant liver-containing omphalocele but with a small abdominal wall defect during the first-trimester morphology scan at 13 weeks and 3 days of gestation which associated ductus venosus reversed flow, presenting a normal karyotype postabortum. With a small defect, we can speculate the risk of strangling besides the mechanical traction exercised on the ductus venosus generating fetal distress, specifically fetal hypoxia at an early gestational age. In conclusion, the main issue, in this case, was if the fetal omphalocele and ductus venosus reversed flow indicated fetal hypoxia, what was the obstruction effect on the oxygenated blood pathway caused by the abdominal defect, and which were the long-term effects on infants with this complex pathology with an unknown outcome.

Prenatal Ultrasound Diagnosis of Double Aortic Arch versus Right Aortic Arch Variant in Vascular Ring Formation - Case Report and Review of the Literature.

Double aortic arch represents a congenital vascular malformation that is characterized by the development of a complete vascular ring around the esophagus and trachea due to an anomaly in the development of branchial arteries. We present the case of a 31-year-old gravida that was referred for fetal ultrasound anomalies screening at 22 weeks and six days of gestation. Routine ultrasound scanning of the fetus revealed a structural aortic arch anomaly consistent with a double aortic arch, with no other cardiac and diextracardiac congenital structural malformations. Knowledge of embryology and imaging spectrum of aortic arch anomalies that are able to form vascular rings around the trachea and esophagus are essential for an accurate antenatal diagnosis and therefore, for a correct clinical management.

Pregnancy and Delivery in a 27-Year-Old ICD Carrier.

Implantable cardiac devices represent the first line treatment option used not only for secondary prevention of sudden cardiac death but also for primary prevention in patients with cardiac pathologies considered at risk of sudden cardiac death caused by ventricular tachycardia or ventricular fibrillation. The number of women with implantable cardiac devices reaching child bearing age is expected to increase more and more in the next years. Despite this tendency, there are only a few reported cases of pregnancies in implantable cardiac defibrillator carriers, leading to insufficient evidence and clear guideline recommendations on how to manage and monitor pregnancy in patients with this type of cardiac pathology. Closely monitoring within a multidisciplinary team consisting of an obstretician, electrophysiologist and anesthesiologist is required for this group of pregnant patients in order to achieve the best maternal and neonatal results. The present study describes the case of succesful outcome in a 27-year-old implantable cardiac defibrillator carrier implanted after an aborted cardiac arrest and reccurent polymorphic ventricular tachycardia due to myocarditis eight years prior to pregnancy, with an aim to emphasize the monitoring particularities and management during pregnancy.