Evaluation of Vasculogenic Factors in the Developing Embryo at Weeks Five and Seven With a Special Focus on CD133 and TIE2 Markers.

Background Human embryo vasculogenesis (blood vessel development starting from endothelial precursors) includes the ability of mesenchymal cells and pluripotent stem cells to differentiate into endothelial cells. Quantification of endothelial progenitor cells is difficult to assess during the early steps of human embryo development due to several factors, especially due to the paucity of human embryo tissue which is usually discarded after early-stage pregnancy abortive methods. CD133 (Promimin-1) is a general marker of progenitor cells, but combined with other endothelial markers such as CD34, it may identify endothelial progenitor cells during embryonic development. CD34 immunohistochemistry was previously performed by our team to identify human embryo capillaries and comparatively assess microvessel density between different human embryonic tissues. TIE2 is an angiopoietin receptor strongly involved in the newly formed blood vessel maturation due to its expression in some mesenchymal precursors for future pericytes. CD34 assesses the presence of endothelial cells but its single use does not evaluate the endothelial progenitor state as CD133 may do nor vessel maturation as TIE2 may do. Data about the dynamics of CD133/TIE2 expression in the early stages of human embryo development are scarce. Hence, in this study, we aimed to comparatively assess the dynamic of CD133+ endothelial precursors and TIE2 expression on five and seven-week-old human embryonic tissues with a special emphasis on their expression on embryonic vascular beds. Methodology CD133 and TIE2 immunohistochemistry was performed on five and seven-week-old human embryonic tissues followed by their quantification using the Qu Path digital image analysis (DIA) automated method. Results CD133 and TIE2 showed divergent patterns of expression during the initial phases of human embryonic development, specifically in the vascular endothelium of tiny capillaries. The expression of CD133 in endothelial cells lining the perfused lumen gradually decreased from five to seven-week-old embryos. It remained expressed with greater intensity in cells located at the tip of the vascular bud that emerged into pre-existing capillaries. TIE2 was much more specific than CD133, being restricted to the level of the vascular endothelium; therefore, it was easier to quantify using digital image analysis. The endothelium of the embryonic aorta was an exception to the divergent expression, as CD133 and TIE2 were consistently co-expressed in the seven-week-old embryo. The Qu Path DIA assessment increased the accuracy of CD133 and TIE2 evaluation, being the first time they were quantified by using automated software and not manually. Conclusions High heterogeneity of CD133 and TIE2 was observed between five and seven-week-old embryonic tissues as well as between different embryonic regions from the same gestational age. The unique finding of CD133/TIE2 co-expression persistence inside aortic endothelium needs further studies to elucidate the role of this co-expression.

Placental pathology in early-onset fetal growth restriction: insights into fetal growth restriction mechanisms.

BACKGROUND: Early-onset fetal growth restriction (FGR), an identifiable variant of FGR, exhibits divergences in its severity, management, and placental pathologies when juxtaposed with late-onset FGR. The objective of this cross-sectional investigation was to scrutinize placental pathologies in pregnancies afflicted by early-onset FGR, emphasizing a comparative analysis between cohorts with and without preeclampsia (PE). PATIENTS, MATERIALS AND METHODS: The study encompassed a cohort of 85 expectant mothers who received a diagnosis of early-onset FGR. Rigorous histopathological (HP) and immunohistochemical (IHC) assessments were conducted on the placentas. Comparative analyses were performed, distinguishing between individuals diagnosed with both PE and early-onset FGR, and those presenting normotensive early-onset FGR. RESULTS: HP analysis unveiled a multitude of shared placental lesions, encompassing retroplacental hemorrhage, expedited villous maturation, infarctions, and calcification-associated fibrin deposits. IHC investigations displayed affirmative immunoreactivity for anti-hypoxia-inducible factor (HIF) and anti-vascular endothelial growth factor (VEGF) antibodies within the placental infarcted villitis. Moreover, noteworthy variances in placental measurements and distinctive lesions were discerned when comparing the PE and early-onset FGR cohort with the normotensive group. CONCLUSIONS: Maternal malperfusion emerged as a pivotal determinant linked to placental lesions in pregnancies affected by early-onset FGR. Remarkably, the occurrence of infarctions, specifically delayed infarctions, exhibited a noteworthy correlation with PE. These findings accentuate the significance of pursuing additional research endeavors aimed at unraveling the intricate mechanisms governing maternal malperfusion and its consequential influence on placental health in the context of early-onset FGR, with particular attention to the interplay with PE.

Clinical features and management of trophoblastic epithelioid tumors: A systematic review.

BACKGROUND: This study aimed to systematically review the existing literature on epithelioid trophoblastic tumors (ETTs), the rarest type of gestational trophoblastic neoplasia. METHODS: A systematic review according to PRISMA guidelines was performed, using ScienceDirect, Web of Science, and Scopus databases. The only filter used was the English language. Eligibility/inclusion criteria: retrospective observational studies (case reports, case series) including full case description of epithelioid trophoblastic tumor lesions. RESULTS: Seventy studies were assessed for synthesis, including 147 cases. 66.7% of patients with ETT presented with irregular vaginal bleeding. Pretreatment ß-hCG levels ranged up to 1000 mIU/mL in 58.5% patients. Of most patients, 42.2% had stage I disease, 10.9% stage II, 25.2% stage III, and 21.8% of patients had stage IV. The most common sites of metastatic disease were the lungs, followed by the liver and brain. After treatment, complete remission was achieved in 75.5% of patients, partial remission in 10.2% of patients, and 14.3% of patients died. On univariate and multivariate analyses, stage IV disease was an independent prognostic factor for overall and disease-free survival. CONCLUSIONS: Hysterectomy and metastatic lesion resection are essential for controlling ETT. Investigational studies on molecules like EGFR, VEGF, PD-1, CD105, and LPCAT1 are potential therapeutic targets for metastatic ETT.

Prevalence and Risk Factors of Postpartum Depression in Romanian Women during Two Periods of COVID-19 Pandemic.

Postpartum depression is a major mental health disorder that can negatively affect both mother and baby. In addition, the COVID-19 pandemic associated with extreme measures of the lockdown had profound effects on humanity, increasing the rates of anxiety and depression, especially among women in the postpartum period. The aim of this study was threefold: to determine the prevalence of postpartum depression, to compare the prevalence of postpartum depression at two different times during the COVID-19 pandemic, and to assess a possible association between the timing of childbirth in a given period of the pandemic and the risk of postpartum depression. A cross-sectional study involving 154 women who were interviewed immediately postpartum, using the EPDS scale, was conducted at the Timisoara Municipal Hospital, Romania at two different periods during the COVID-19 pandemic (March−April 2020 during the first wave and August−September 2021 during the fourth wave). The overall prevalence of postpartum depression (EPDS score > 13) was 18.8%, with a statistically significantly higher rate among participants surveyed during the fourth wave of the COVID-19 pandemic in Romania; the COVID-19 pandemic represents an impact on women's mental health in the postpartum period, increasing the risk of developing postpartum depression.

The Risk of Spontaneous Abortion Does Not Increase Following First Trimester mRNA COVID-19 Vaccination.

Clinical trials for COVID-19 vaccines initially excluded pregnant women due to safety concerns, and when the vaccines were authorized for emergency use, they were not recommended for this population. However, observational studies discovered that pregnant women infected with COVID-19 have higher risks of negative pregnancy and delivery outcomes compared to non-pregnant women, raising the question of the risks-benefits of administering COVID-19 vaccines to pregnant women. By mid-2021, there was general consensus on the relative safety of COVID-19 vaccination during pregnancy; therefore, it is critical to investigate the safety issues related to these vaccines, considering the increasing acceptance among pregnant women. To address these concerns, we developed a research project to study the short-term effects and outcomes of COVID-19 vaccination during the first trimester of pregnancy. Our research followed an observational retrospective design for 12 months from the beginning of the vaccination campaign, and included 124 cases of spontaneous abortions and 927 ongoing pregnancies. The odds of spontaneous abortion were non-significant for both versions of the mRNA vaccine (Pfizer BNT162b2 AOR = 1.04, CI = 0.91-1.12; Moderna mRNA-1273 AOR = 1.02, CI = 0.89-1.08). Overall, our data indicated that the risk of spontaneous abortion after mRNA COVID-19 immunization during the first trimester of pregnancy is commensurate with the predicted risk in non-vaccinated pregnant women. These findings contribute to the growing body of information regarding the safety of mRNA COVID-19 vaccination during pregnancy.

Immunogenicity Following Administration of BNT162b2 and Ad26.COV2.S COVID-19 Vaccines in the Pregnant Population during the Third Trimester.

Globally, COVID-19 vaccines are currently being used to prevent transmission and to reduce morbidity and death associated with SARS-CoV-2 infection. Current research reveals that vaccines such as BNT162b2 and Ad26.COV2.S are highly immunogenic and have high short-term effectiveness for most of the known viral variants. Clinical trials showed satisfying results in the general population, but the reluctance in testing and vaccinating pregnant women left this category with little evidence regarding the safety, efficacy, and immunogenicity following COVID-19 vaccination. With the worldwide incidence of COVID-19 remaining high and the possibility of new transmissible SARS-CoV-2 mutations, data on vaccination effectiveness and antibody dynamics in pregnant patients are critical for determining the need for special care or further booster doses. An observational study was developed to evaluate pregnant women receiving the complete COVID-19 vaccination scheme using the BNT162b2 and Ad26.COV2.S, and determine pregnancy-related outcomes in the mothers and their newborns, as well as determining adverse events after vaccination and immunogenicity of vaccines during four months. There were no abnormal findings in pregnancy and newborn characteristics comparing vaccinated versus unvaccinated pregnant women. COVID-19 seropositive pregnant women had significantly higher spike antibody titers than seronegative patients with similar characteristics, although they were more likely to develop fever and lymphadenopathy following vaccination. The same group of pregnant women showed no statistically significant differences in antibody titers during a 4-month period when compared with case-matched non-pregnant women. The BNT162b2 and Ad26.COV2.S vaccines are safe to administer during the third trimester of pregnancy, while their safety, efficacy, and immunogenicity remain similar to those of the general population.

The Predictive Role of NLR, d-NLR, MLR, and SIRI in COVID-19 Mortality.

(1) Background: Since its discovery, COVID-19 has caused more than 256 million cases, with a cumulative death toll of more than 5.1 million, worldwide. Early identification of patients at high risk of mortality is of great importance in saving the lives of COVID-19 patients. The study aims to assess the utility of various inflammatory markers in predicting mortality among hospitalized patients with COVID-19. (2) Methods: A retrospective observational study was conducted among 108 patients with laboratory-confirmed COVID-19 hospitalized between 1 May 2021 and 31 October 2021 at Municipal Emergency Clinical Hospital of Timisoara, Romania. Blood cell counts at admission were used to obtain NLR, dNLR, MLR, PLR, SII, and SIRI. The association of inflammatory index and mortality was assessed via Kaplan-Maier curves univariate Cox regression and binominal logistic regression. (3) Results: The median age was 63.31 ± 14.83, the rate of in-hospital death being 15.7%. The optimal cutoff for NLR, dNLR, MLR, and SIRI was 9.1, 9.6, 0.69, and 2.2. AUC for PLR and SII had no statistically significant discriminatory value. The binary logistic regression identified elevated NLR (aOR = 4.14), dNLR (aOR = 14.09), and MLR (aOR = 3.29), as independent factors for poor clinical outcome of COVID-19. (4) Conclusions: NLR, dNLR, MLR have significant predictive value in COVID-19 mortality.

Hysteroscopy as a Primary Tool in Exploration and Treatment of Infertility: Single Center Experience in Western Romania.

(1) Background: Infertility is a disease that affects millions of individuals worldwide. Intrauterine lesions are common in infertile women, hysteroscopy being considered the gold standard for assessing them, even if in routine clinical practice indirect imaging techniques are the first-line investigative tools. The aim of the study was to evaluate hysteroscopic findings among women with unexplained infertility and to analyze fertility outcomes after operative hysteroscopy; (2) Methods: a retrospective cohort study was conducted among 198 women with infertility that had undergone hysteroscopy as the first step of their infertility workup. (3) Results: The median age of the participants was 34 years, 67.7% of them being diagnosed with primary infertility. The most common abnormalities were endometrial polyps, uterine synechiae and uterine fibroids. In addition, pregnancy rates were 23.1% after hysteroscopic polypectomy, 11.1% after hysteroscopic myomectomy and 23.8% after uterine synechiae resection; (4) Conclusions: Endometrial polyps were the most common uterine abnormality found in women with infertility. Hysteroscopic interventions appeared to increase pregnancy rates and outcomes among these women.

Ovarian cancer health politics in Romania and Germany: A comparative study.

Ovarian cancer is known to have a poor prognosis, being the 7th most common cancer type in women with regard to incidence and mortality worldwide. The present study underlines the importance of early diagnosis and prevention management of ovarian cancer. This study is a hospital-based case-control study that was conducted at the same time in two similar hospitals from different countries, Romania and Germany, over three years. The results showed that significant differences were identified for the two groups with regards to the age factor (P<0.001). A risk analysis was performed to determine whether the patients from Romania were exposed to a risk factor. The risk of developing deadly diseases was deemed much higher owing to insufficient protocols or informative programs in Romania. The medical information, early diagnosis and standardized therapy with optimum treatment based on health policy and health care systems, play a key role concerning the management and prognosis of ovarian cancer which are different from country to country.

Treatment Experience and Predictive Factors Associated with Response in Platinum-Resistant Recurrent Ovarian Cancer: A Retrospective Single-Institution Study.

Ovarian cancer (OC) represents the most common and lethal gynecologic malignancy, due to its increased incidence and mortality rate. It is usually diagnosed in advanced stages and, even though surgery and platinum-based treatments are initially efficient, recurrences emerge in over 70% of cases. Although there are multiple options of chemotherapy drugs from which to choose, little is known regarding the best strategy for prolonged survival. Thus, this study aimed to assess the effect that most frequently used chemotherapeutic regimens have upon time-to-treatment-failure (TTF) from the first line and beyond, considering clinical and biological factors which influence the treatment outcome of platinum-resistant recurrent OC. We retrospectively analyzed data from 78 patients diagnosed with platinum-resistant OC, who underwent chemotherapy-based treatment with or without anti-angiogenic therapy at OncoHelp Oncology Center, Romania (January 2016-February 2021). Our study identified positive predictive factors for TTF related to histology (serous carcinoma subtype), anthropometry (age over 60 for patients treated with topotecan with or without bevacizumab), renal function (creatinine levels between 0.65 and 1 mg/dL for patients treated with regimens containing bevacizumab and pegylated liposomal doxorubicin) and treatment choice (bevacizumab in combination with pegylated liposomal doxorubicin or topotecan used from the first line and beyond).

Ovarian dysgerminoma in pregnancy: A case report.

RATIONALE: Although dysgerminomas are relatively uncommon among all ovarian neoplasms, representing for only about 2%, they account for 32.8 percent of malignant ovarian germ cell tumors. Their association with pregnancy is extremely rare; due to the low frequency of occurrence, there are few recommendations regarding pregnancy management; therefore, it is important to discuss and summarize the treatment strategy. PATIENT CONCERNS: We present the case of a 25 years patient, gestation 1, para 1, who was hospitalized in the clinic at 38/39 weeks of gestation at the beginning of labor. Following the ultrasound examination, a hypoechogenic lesion on the uterine fundus was found, suggestive of subterranean fibroid. After caesarean section, right adnexectomy was performed; the histopathological examination revealed, unexpectedly, the diagnosis of dysgerminoma. DIAGNOSES: Dysgerminoma as associated with pregnancy. INTERVENTIONS: Birth by Caesarean section and right adnexectomy. No other medical complications occurred. OUTCOMES: The histopathological and immunohistochemical examinations were consistent with the pure dysgerminoma. Oncology was staged AI, with the monitoring of markers and abdominal and pelvic magnetic resonance imaging at 3, 6, 9, and 12 months. LESSONS: Dysgerminoma is the most common ovarian malignancy associated with pregnancy with a good fetal maternal outcome. If these tumors are discovered accidentally during caesarean section, tumor markers and magnetic resonance imaging scanning should be done postoperatively to plan optimal treatment.

Role of Reconstructive Microsurgery in Tubal Infertility in Young Women.

AIM: Here, we retrospectively analyzed the success rate of reconstructive microsurgery for tubal infertility (RMTI) as a "first-line" approach to achieving tubal reversal and pregnancy after tubal infertility. PATIENTS AND METHODS: During 9 consecutive years (2005-2014), 96 patients diagnosed with obstructive tubal infertility underwent RMTI (tubal reversal, salpingostomy, and/or tubal implantation) in our centre. The outcomes are presented in terms of tubal reversal rate and pregnancy and correlated with age, level of tubal obstruction, and duration of tubal infertility. RESULTS: The overall tubal reversal rate was 87.56% (84 patients). The 48-month cumulative pregnancy rate was 78.04% (64 patients), of which seven ectopic pregnancies occurred (8.53%). The reversibility rate for women under 35 yo was 90.47%, with a birth rate of 73.01%. The reconstruction at the infundibular segments favored higher ectopic pregnancy rates (four ectopic pregnancies for anastomosis at infundibular level-57.14%, two for ampullary level-28.57%, and one for replantation technique-14.28%), with a significant value for p < 0.05. CONCLUSIONS: In the context of IVF "industrialization", reconstructive microsurgery for tubal infertility has become increasingly less favored. However, under available expertise and proper indication, RMTI can be successfully used to restore a woman's ability to conceive naturally with a high postoperative pregnancy rate overall, especially in women under 35 yo.

p16/Ki-67 dual staining has a better accuracy than human papillomavirus (HPV) testing in women with abnormal cytology under 30 years old.

Due to a high rate of transient human papillomavirus (HPV) infection, HPV genotyping has a low specificity for high-grade cervical lesions, especially in young women. p16/Ki-67 dual immunocytochemical staining can also be used for the detection of oncogenic changes in cervical cells. Our aim was to compare the performance of p16/Ki-67 dual staining and HPV genotyping in the detection of high-grade cervical lesions in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We retrospectively analyzed 310 patients with ASCUS/LSIL on Pap smear, who underwent colposcopy. Among these, 161 patients with suspected lesions detected by colposcopy were referred for biopsy. HPV genotyping by LINEAR ARRAY HPV Genotyping Test (CE-IVD) and p16/Ki-67 dual staining by CINtec PLUS Cytology kit was performed prior to cervical biopsy. The overall sensitivity and specificity of HPV genotyping for the detection of cervical intraepithelial neoplasia (CIN) 2-3 was 79% and 72%, respectively in patients with ASCUS, and 85% and 64%, respectively in patients with LSIL. For p16/Ki-67 test, sensitivity and specificity rate was 66% and 93%, respectively in ASCUS and 59% and 79%, respectively in LSIL group. The specificity of p16/Ki-67 staining was significantly higher in both groups in patients aged <30 years compared to patients >30 years old (p < 0.001). Our results showed that p16/Ki-67 dual staining has a higher specificity compared to HPV genotyping, especially in patients under 30 years old. This indicates the usefulness of p16/Ki-67 testing in the triage of patients with ASCUS/LSIL and <30 years old, prior to referral for colposcopy and biopsy.

Spontaneous postnatal complete resolution of an antenatally diagnosed fetal hepatic cyst: A case report.

RATIONALE: Antenatal diagnosis of a fetal hepatic cyst is rare. Since in most cases the lesion is treated after birth by surgery only a few reports present a complete spontaneous resolution of an antenatally diagnosed hepatic cyst. PATIENT CONCERNS: A single hepatic cyst (1.34/1.47 cm) was diagnosed in a fetus at 36 weeks of pregnancy while mother was in labor. After an uneventful vaginal birth, a multidisciplinary evaluation of the newborn confirmed the presence of the cyst. DIAGNOSES: Single hepatic cyst INTERVENTIONS:: Passive approach; periodic ultrasound monitoring of the cyst OUTCOMES:: The latest ultrasound examination performed at 18 months of age confirmed complete resolution of the cyst. No other medical complications occurred before 18 months of age. LESSONS: The management of such a case depends on the cyst dimensions, the types of involved structure and could require urgent prenatal or neonatal treatment. In our case a complete spontaneous resolution of the hepatic cyst was achieved before 18 months of age.

HPV genotyping and p16÷Ki-67 dual staining in the detection of high-grade cervical lesion in patients with LSIL on Pap smear.

p16÷Ki-67 dual-stained cytology, either alone or combined with human papillomavirus (HPV) 16÷18 genotyping, could be a useful tool for triage for colposcopy of HPV-positive patients. Based on this background, we aimed at comparing the diagnostic performance of the p16÷Ki-67 dual staining test, and high-risk HPV test for the detection of high-risk cervical intraepithelial neoplasia (CIN2÷3) in patients diagnosed with low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We performed a retrospective study including 184 patients with LSIL cytology on Pap smear, of which 64 were referred for biopsy after colposcopy. Prior biopsy HPV genotyping and dual staining test were performed on all 64 patients. The mean age of the patients selected for conization was 36 years and seven months. The pathological exam showed that 28.13% (18÷64) from the patients LSIL on cytology were actually having CIN2÷3: 12 cases with CIN2, five cases with CIN3 and one case of in situ cervical carcinoma. HPV positive were 56.25% (36÷64) of the patients with LSIL. The p16÷Ki-67 dual staining test was positive in 29.69% (19÷64) of the patients with LSIL. Among women with LSIL cytology, the sensitivity and specificity of the HPV genotyping test for predicting CIN2÷CIN3 were 94.44% (17÷18) and 58.7% (27÷46), respectively. The sensitivity and specificity of the p16÷Ki-67 dual staining test were 66.67% (12÷18) and 84.78% (39÷46), respectively. Our results agree with other data available in literature and suggest that the p16÷Ki-67 dual staining test could be included in the management protocol of patients with modified cytology as a triage test before referring those patients for colposcopy.

The importance of immunocytochemistry in the detection of high-grade cervical lesions.

Despite the implementation of various screening programs in many countries, cervical cancer continues to be a major health problem. Cervical cytology is the most used screening method, but human papillomavirus (HPV) genotyping, alone or in combination with cytology, has gained ground during the last years. Still, one of the major limitations of HPV-genotyping is the low specificity of HPV as a screening method in young women that are HPV-positive, but with no potential for future disease. Obviously, there is a need for a better screening algorithm. The ideal screening test for cervical high-grade lesions should detect the effect of high-risk (HR)-HPV infection after cell transformation, but not before, and should accurately identify the cases that are more likely to experience disease progression to neoplasia. Solid data regarding the benefit of immunocytochemistry in the evaluation of the patients with modified cervical cytology have been published recently. The use of the dual staining with p16INK4a and Ki-67 could increase specificity of the method for the detection of atypical cells and may perform better in predicting the risk of high-grade dysplasia in the near future.

In vitro fertilization represents a risk factor for vasa praevia.

Vasa praevia is a rare but very dangerous obstetrical condition. The purpose of our article is to evaluate data available in literature that indicate in vitro fertilization as a risk factor for vasa praevia. PubMed Library and Cochrane Database were searched using the keywords vasa praevia, in vitro fertilization, velamentous cord insertion, placenta praevia. The conditions related to in vitro fertilization that increase the risk of vasa praevia formation were identified and discussed. Also, the diagnosis and management options were reviewed. In vitro fertilization represents a risk factor for vasa praevia and all such pregnancies should be screened by transvaginal ultrasound for vasa praevia.

Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.

BACKGROUND/AIM: Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma. MATERIALS AND METHODS: Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells. RESULTS AND CONCLUSION: LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis.

Early pregnancy serum neopterin concentrations predict spontaneous preterm birth in asymptomatic pregnant women.

OBJECTIVE: To investigate if early pregnancy serum neopterin concentrations (EPSN) could predict spontaneous preterm birth (SPB). METHODS: EPSN was measured in 92 sera collected from 46 pregnant women with birth at term and 40 sera from 20 pregnant women with preterm birth. Two sera were collected for each case: in the first and early second trimester. RESULTS: EPSN concentrations correlate with gestational age (ρ=0.275, P=0.001), a correlation which was present in both groups: term and preterm birth. EPSN were higher in pregnancies with SPB compared with normal pregnancies (6.27±1.03 vs. 6.04±0.15, P=0.039). Patients with SPB showed a considerable increase of EPSN in the second trimester compared with patients with birth at term (7.30±1.53 vs. 6.16±0.23, P=0.043). A sharper increase was found in the group with SPB before 32 weeks of pregnancy (wp) (9.83±4.36 vs. 6.16±0.23, P=0.016). Pregnant women with an early second trimester serum neopterin value of above 8 nmol/L are associated with a risk of SPB before 32 wp (odds ratio=14.4, P=0.01) and of SPB before 34 wp (odds ratio=3.6, P=0.05), respectively. CONCLUSIONS: EPSN increases with the gestational age and predicts SPB in asymptomatic pregnant women.

Reversible arterial redistribution in a fetus with true umbilical cord knot: case report and review of literature.

Umbilical cord knot (UCK) affects around 1% of pregnancies and tightening of UCK is a very rare and highly unpredictable complication of pregnancy that can lead to fetal demise or neonatal death. The majority of authors agree that very little could be done to prevent fetal deaths in pregnancies with undiagnosed tight UCK. We herein report the case of a 39-year-old, gravidity five, parity three, pregnant woman at 40 weeks and five days age of pregnancy, whose pregnancy evolved without complications and who was admitted to hospital for the management of the birth. Although the last ultrasound examination before birth showed a reversible arterial redistribution in the fetus dependent on the postural status of the pregnant women and other factors associated with umbilical cord knot were present, the diagnosis was missed because of the factors' non-specificity. After a spontaneous labor without complications a dead male fetus, weight 3300 g, without heartbeat, Apgar score 0 was delivered. Macroscopic and microscopic findings confirmed that the cause of neonatal death was asphyxia caused by a tight UCK. The aim of our paper is to present the dramatic outcome of a pregnancy with a fetus with a tight umbilical cord knot (UCK), to bring to attention the signs that suggested the diagnosis, and to review the literature on this subject.