TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

Hematologic characteristics and coagulopathy in pregnancy with COVID-19 succeeding the first wave: a multicenter retrospective cross-sectional study.

Background: Early reports have demonstrated an association of COVID-19 infection during pregnancy and postpartum period with coagulopathy and bleeding complications and indicated that pregnant people with COVID-19 are more likely to experience coagulopathy and venous thromboembolism. A recent report concerning such complications during the first wave of the pandemic was reassuring; however, no publications have evaluated these issues in the context of increased illness severity with the emergence of SARS-CoV-2 variants of concern. Objectives: We performed a retrospective, multinational cohort study in Canada, Romania, and the United Kingdom, aiming to provide a comprehensive analysis of the hematologic test characteristics of pregnancies affected by COVID-19 after the first wave of the pandemic. Results: Three-hundred-seventy patients were evaluated. Markers of inflammation and endothelial dysfunction were significantly elevated, in keeping with observations in the nonpregnant population. Reassuringly, despite more severe disease noted in succeeding waves of the pandemic, there was no significant evidence of COVID-19-associated coagulopathy, and overall, no association was demonstrated between isolated coagulation abnormalities and bleeding risk. Notably, fibrinogen below 2g/L was again linked with the risk of postpartum hemorrhage. Finally, venous thromboembolism risk was low but noted more frequently in those with severe illness despite thromboprophylaxis. Conclusion: Our findings add valuable insights into the nature of hematologic test characteristics, bleeding, and thrombotic complications for those affected with COVID-19 in pregnancy, reassuring readers of the low incidence of bleeding and thrombotic complications but inviting further debate as to the degree of thromboprophylaxis that may benefit the subgroup with severe disease.

Spontaneous Fistula and Abdominal Wall Endometriosis Due to Occult Existence of Unicornuate Right Uterus with Rudimentary Non-Communicating Functioning Left Horn.

Accurate diagnosis of Müllerian duct anomalies (MDA) remains a clinical challenge even by direct surgical inspection. Although obstetrical complications are more frequent in women with MDA, some subtypes allow normal reproduction, further delaying the diagnosis. Unicornuate uterus with a rudimentary non-communicating functioning horn is a rare form of MDA, susceptible to many gynecologic and obstetric complications such as miscarriages, premature birth, hematosalpinx, endometriosis, and chronic pelvic pain. We present an entire case pictorial assay including preoperative imaging as well as the surgical correction of the uterine anomaly and the associated complication of an occult unicornuate right uterus with rudimentary non-communicating functioning left horn (Class U4aC0V0/ European Society of Human Reproduction and Embryology/European Society of Gastrointestinal Endoscopy Classification) and its natural evolution following a previous incomplete surgical treatment. The patient had an emergency left adnexectomy for hematosalpinx and ovarian endometrioma at her local county hospital. After five years, the patient presented with severe dysmenorrhea and abdominal endometriosis due to blocked retrograde menstruation from a rudimentary, non-communicating functioning horn. Surgical treatment with the resection of the rudimentary uterine horn, together with the abdominal wall endometriosis lesions, was carried out with good outcomes.

Neonatal Hemochromatosis: Systematic Review of Prenatal Ultrasound Findings-Is There a Place for MRI in the Diagnostic Process?

Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.

Ultrasound Placental Remodeling Patterns and Pathology Characteristics in Patients with History of Mild SARS-CoV-2 Infection during Pregnancy.

Introduction: This research aims to describe a progressive pattern of ultrasound placental remodeling in patients with a history of SARS-CoV-2 infection during pregnancy. Materials and Methods: This was a longitudinal, cohort study which enrolled 23 pregnant women with a history of former mild SARS-CoV-2 infection during the current pregnancy. Four obstetricians analyzed placental ultrasound images from different gestational ages following COVID infection and identified the presence and degree of remodeling. We assessed the inter-rater agreement and the interclass correlation coefficients. Pathology workup included placental biometry, macroscopic and microscopic examination. Results: Serial ultrasound evaluation of the placental morphology revealed a progressive pattern of placental remodeling starting from 30-32 weeks of gestation towards term, occurring approximately 8-10 weeks after the SARS-CoV-2 infection. Placental changes-the "starry sky" appearance and the "white line" along the basal plate-were identified in all cases. Most placentas presented normal subchorionic perivillous fibrin depositions and focal stem villi perivillous fibrin deposits. Focal calcifications were described in only 13% of the cases. Conclusions: We identified two ultrasound signs of placental remodeling as potential markers of placental viral shedding following mild SARS-CoV-2. The most likely pathology correspondence for the imaging aspect is perivillous and, respectively, massive subchorionic fibrin deposits identified in most cases.

Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population.

(1) Background: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing (NGS) is becoming a standard in medical care. There are insufficient genetic studies reported on breast cancer (BC) patients from Romania and most of them are focused only on BRCA 1/2 genes (Breast cancer 1/2). (2) Methods: NGS was performed in 255 consecutive cases of BC referred for management in our clinic between 2015-2019. (3) Results: From the 171 mutations identified, 85 were in the high-penetrance BC susceptibility genes category, 72 were pathogenic genes, and 13 genes were in the (variants of uncertain significance) VUS genes category. Almost half of the mutations were in the BRCA 1 gene. The most frequent BRCA1 variant was c.3607C>T (14 cases), followed by c.5266dupC (11 cases). Regarding BRCA-2 mutations we identified c.9371A>T (nine cases), followed by c.8755-1G>A in three cases, and we diagnosed VUS mutations in three cases. We also identified six pathogenic variants in the PALB2 gene and two pathogenic variants in (tumor protein P 53) TP53. (4) Conclusions: The majority of pathogenic mutations in the Romanian population with BC were in the BRCA 1/ 2 genes, followed by PALB2 (partner and localizer of BRCA2) and TP53, while in the CDH1 (cadherin 1) and STK11 (Serine/Threonine-Protein Kinase) genes we only identified VUS mutations.

Umbilical Cord Biometry and Fetal Abdominal Skinfold Assessment as Potential Biomarkers for Fetal Macrosomia in a Gestational Diabetes Romanian Cohort.

Backgroundand Objectives: Gestational diabetes mellitus (GDM) is a pregnancy-associated pathology commonly resulting in macrosomic fetuses, a known culprit of obstetric complications. We aimed to evaluate the potential of umbilical cord biometry and fetal abdominal skinfold assessment as screening tools for fetal macrosomia in gestational diabetes mellitus pregnant women. Materials and methods: This was a prospective case−control study conducted on pregnant patients presenting at 24−28 weeks of gestation in a tertiary-level maternity hospital in Northern Romania. Fetal biometry, fetal weight estimation, umbilical cord area and circumference, areas of the umbilical vein and arteries, Wharton jelly (WJ) area and abdominal fold thickness measurements were performed. Results: A total of 51 patients were enrolled in the study, 26 patients in the GDM group and 25 patients in the non-GDM group. There was no evidence in favor of umbilical cord area and WJ amount assessments as predictors of fetal macrosomia (p > 0.05). However, there was a statistically significant difference in the abdominal skinfold measurement during the second trimester between macrosomic and normal-weight newborns in the GDM patient group (p = 0.016). The second-trimester abdominal circumference was statistically significantly correlated with fetal macrosomia at term in the GDM patient group with a p value of 0.003, as well as when considering the global prevalence of macrosomia in the studied populations, 0.001, when considering both populations. Conclusions: The measurements of cord and WJ could not be established as predictors of fetal macrosomia in our study populations, nor differentiate between pregnancies with and without GDM. Abdominal skinfold measurement and abdominal circumference measured during the second trimester may be important markers of fetal metabolic status in pregnancies complicated by GDM.

Krukenberg tumor in pregnancy: a rare case and review of the literature.

Krukenberg's tumor diagnosed in pregnancy is an uncommon situation that raises both diagnosis and medical management issues. We performed a review of the existing literature regarding this pathology, diagnostic means and therapeutic approaches, motivated by a case in our own practice. A 35-year-old primigravida was diagnosed with an adnexal mass during the first trimester prenatal ultrasound. Ultrasound revealed a 10 cm right adnexal mass with multiple septae, richly vascularized, whose presence and characteristics were confirmed by magnetic resonance imaging. Due to the progressively increasing tumor size, laparoscopy was performed with right adnexectomy and peritoneal biopsies. Histopathology diagnosed a metastatic ovarian tumor from a mucinous colorectal adenocarcinoma. After delivery the patient was further investigated and diagnosed with sigmoid cancer. Even though ovarian cancer in pregnancy is rare, adnexal ultrasound is mandatory when scanning during the first trimester to rule out the presence of associated fallopian or ovarian masses.

Imaging diagnosis and legal implications of brain injury in survivors following single intrauterine fetal demise from monochorionic twins - a review of the literature.

Brain injury of the surviving twin from monochorionic pregnancies following intrauterine fetal demise during the second and third trimesters is a rare but severe complication. Monochorionicity and gestational age at the time of stillbirth seem to be decisive factors in terms of long-term neurologic outcome prediction for the survivor. Magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) in particular, seem to bring the earliest and most accurate diagnosis. Ultrasound detection of brain damage is possible in later stages of fetal brain injury. It is essential to provide early diagnosis and multidisciplinary counsel to the parents to ensure informed decision making. For couples who choose to terminate pregnancy legislation related to late abortion might lead to further distress. Our paper aims to stress the importance of MRI DWI in the evaluation of surviving twins following single intrauterine fetal demise in monochorionic pregnancies and the delicate context of the medical professionals and parents facing this clinical situation, sometimes complicated by legal constraints.

Predictive role of altered leptin, adiponectin and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid secretion in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, leading to considerable maternal and fetal risks. The main aim of this study was to determine the predictive value of the levels of adiponectin (AN), leptin (L) and CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid) in the development of GDM. We conducted a prospective longitudinal study on 68 pregnant women that were not at risk of developing GDM, in whom we determined AN, L, CMPF levels at 11-13 weeks +6 days of pregnancy during the first trimester screening. Twenty-one of all the patients included in the study developed GDM during pregnancy. Oral glucose tolerance test (OGTT)/75 g was performed at 24-28 weeks of gestation. L levels were significantly higher in patients who developed GDM than in those who did not develop diabetes (P<0.001). The AN/L ratio was significantly lower in patients with GDM (P=0.03). AN and CMPF levels were not associated with GDM. The probability of developing gestational diabetes was higher in patients with L levels above the L cut-off value of 16 ng/ml [area under the curve (AUC), 0.775; 95% confidence interval (CI) 0.658-0.867], sensitivity 100% (95% CI 83.9-100), specificity 48.9% (95% CI 34.1-63.9) (P<0.001). Advanced maternal age and higher L levels were found to be predictive factors [odds ratio (OR)=1.16 and OR=1.06, respectively] independently associated with gestational diabetes. In as far as general factors are concerned, the patient BMI (body mass index) at the beginning of the pregnancy and smoking were found to be the main risk factors for the onset of GDM. This study showed that elevated L levels are a strong predictor of GDM, while AN and CMPF levels are not, as they failed to show a significant association.

Congenital dacryocystocele diagnosed by antenatal ultrasonography with spontaneous resolution.

Dacryocystocele is a rare benign facial abnormality of the nasolacrimal system, which may be detected at the antenatal workup during the third trimester of pregnancy. Ultrasound is the method of choice for this examination. However, magnetic resonance imaging may also be used in selected cases. Dacryocystocele is mostly a transient finding; it may resolve spontaneously in utero or postnatally. When the defect is bilateral and persists in neonatal life, it may lead to respiratory complications. We report a case of a fetus with bilateral dacryocystocele diagnosed by prenatal ultrasound at the beginning of the third trimester of pregnancy with spontaneous postpartum resorption.

Congenital dacryocystocele diagnosed by antenatal ultrasonography with spontaneous resolution / Dacriocistocele congênita diagnosticada por ultrassonografia pré-natal com resolução espontânea

ABSTRACT Dacryocystocele is a rare benign facial abnormality of the nasolacrimal system, which may be detected at the antenatal workup during the third trimester of pregnancy. Ultrasound is the method of choice for this examination. However, magnetic resonance imaging may also be used in selected cases. Dacryocystocele is mostly a transient finding; it may resolve spontaneously in utero or postnatally. When the defect is bilateral and persists in neonatal life, it may lead to respiratory complications. We report a case of a fetus with bilateral dacryocystocele diagnosed by prenatal ultrasound at the beginning of the third trimester of pregnancy with spontaneous postpartum resorption.

RESUMO A dacriocistocele é uma anormalidade facial benigna rara do sistema nasolacrimal, que pode ser detectada na rotina pré-natal durante o terceiro trimestre da gravidez. O ultrassom é o método de escolha, mas a ressonância magnética também pode ser usada em casos específicos. Na maioria das vezes, a dacriocistocele é um achado temporário, que pode se resolver espontâneamente ainda no útero ou após o nascimento. Quando a anormalidade é bilateral e persiste na vida neonatal, pode levar a complicações respiratórias. Este é o relato do caso de um feto com dacriocistocele bilateral diagnosticada por ultrassom pré-natal no início do terceiro trimestre da gravidez, com reabsorção espontânea após o nascimento.

Hypertriglyceridemia triggered acute pancreatitis in pregnancy - diagnostic approach, management and follow-up care.

Acute pancreatitis is a pregnancy complication potentially lethal for both the mother and fetus, occurring most frequently in the third trimester or early postpartum. Hypertriglyceridemia may be the cause of important disease in pregnant patients. Patients with triglyceride levels exceeding 1000 mg/dL are at increased risk of developing severe pancreatitis. Diagnostic criteria and management protocols are not specific for pancreatitis complicating pregnancy. Other causes of acute abdominal pain must be considered in the differential diagnosis. Decision-making in the obstetric context is challenging and bears potential legal implications. Pre-pregnancy preventive measures and prenatal antilipemic treatment are mandatory in high risk patients.

The role of imaging techniques in the diagnosis, staging and choice of therapeutic conduct in pregnancy associated breast cancer.

Breast cancer diagnosed during pregnancy is at increasing incidence due to the increased frequency of obesity, the postponement of the first pregnancy to later decades of life and the advances of diagnostic techniques. Clinical and imaging diagnosis is difficult during gestation due to adaptive changes of the maternal organism , the mammary glads in particular. Furthermore, the therapeutic approach is limited both by the possible side effects on the fetus and by the skepticism of the couple over these therapeutic regimens.The present paper aims to review the main diagnostic steps to confirm pregnancy associated breast cancer, as well as the therapeutic possibilities during this period, related to the potential adverse effects concerning pregnancy.

The influence of reproductive factors on breast cancer risk in women with pathogenic mutations.

PURPOSE: To assess the influence of reproductive factors in the occurrence of breast cancer in women, taking into account the presence/absence of genetic predisposing mutations. METHODS: 100 patients with breast cancer were included. The genetic testing was conducted through a multigene panel. Reproductive characteristics were noted for all patients: age of menarche, age of the patient at first full term pregnancy, number of pregnancies, number of full-term pregnancies, breastfeeding interval, number of abortions, and menopausal status at the time of diagnosis. The patients were divided into three groups according to their mutations: BRCA1, positive for mutations other than BRCA1 and negative. RESULTS: The risk of breast cancer was not influenced by the number of abortions, parity, age at first pregnancy, age at menarche and menopausal status, or by oral contraceptive use in carriers of pathogenic mutations group in the BRCA1 group. The present study has demonstrated the protective effect of breastfeeding only in patients without genetic risk (p=0.0344). In contrast, breastfeeding did not influence breast cancer occurrence in BRCA1 mutation carriers' group (p=0.2321). CONCLUSIONS: Breastfeeding represents a protective mechanism only in patients without genetic breast cancer predisposing mutations. Environmental and reproductive factors can impact the risk and the age of onset of breast cancer in patients carrying pathogenic mutations, but the mechanisms of action are not fully understood.

Recurrent intrahepatic cholestasis of pregnancy. A case report.

Intrahepatic cholestasis of pregnancy (ICP) represents a rare but severe pathology with serious consequences on the outcome of pregnancy. We present the cases of two sisters that came to our clinic with ICP in successive pregnancies. The fetus from a pregnancy with cholestasis can be affected by preterm birth, respiratory distress syndrome, intrauterine death in the third trimester and a possible cerebral damage. Early diagnosis and prednisone treatment have allowed an improvement of the neonatal outcome in the following pregnancies.

Acute pancreatitis in a pregnant woman with acute fatty liver dystrophy. A case report.

Acute fatty liver and acute pancreatitis rarely complicate pregnancy. Acute pancreatitis may appear isolated but when it is subsequent to acute fatty liver of pregnancy the evolution is in many cases fatal. We report the case of a 26-year-old primigravida, at 25 weeks' gestation, who developed acute fatty liver of pregnancy and acute pancreatitis after an acute viral upper respiratory tract infection, with an unfavorable evolution to death. Establishing the diagnosis was very difficult and it was confirmed only at laparotomy.