STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Seven novel COL7A1 mutations identified in patients with recessive dystrophic epidermolysis bullosa from Mexico.

Recessive dystrophic epidermolysis bullosa (RDEB; OMIM #226600) is one of the most devastating subtypes of epidermolysis bullosa, a group of skin and mucous membrane blistering disorders often associated with extracutaneous manifestations. RDEB is caused by mutations in COL7A1, the gene encoding type VII collagen (C7), and to date over 700 different mutations in the 8835 nucleotides constituting the open reading frame or adjacent exon-intron boundaries of COL7A1 have been described. We used targeted next-generation sequencing to identify seven previously unreported mutations in a cohort of 17 Mexican patients who were diagnosed with RDEB based on clinical presentation and immunoepitope mapping. Our study expands the spectrum of mutations identified in this cohort, including those suitable for emerging therapies reliant on precise genotyping.

Maternal mortality in Spain and its association with country of origin: cross-sectional study during the period 1999-2015.

BACKGROUND: The available literature suggests that there are significant differences in maternal mortality according to maternal origin in high income countries. The objective of this study was to quantify the risk of maternal death by maternal origin and region of Spain where the birth occurred and to identify the most important causes of maternal death in our country. METHODS: An ecological cross-sectional study was conducted that included all deliveries that resulted in maternal survival and cases of maternal death during 1999-2015 in Spain. A descriptive analysis of the maternal mortality rate by maternal origin, region and year of birth was performed. The risk of maternal death was calculated using univariate and multivariate logistic regression analysis, with adjustment for the variables included in the descriptive analysis. RESULTS: There were 272 maternal deaths during this period, most of which were due to haemorrhage (63 cases, 23.16%).Women whose continent of origin was South America had the highest adjusted risk of maternal death, with an OR of 3.92 (95% CI 2.75-5.58). The region of Spain with the highest risk of maternal death was Ceuta, with an OR of 12.11 (95% CI 2.02-72.68). CONCLUSIONS: This study shows that there are inequalities in maternal mortality according to maternal origin and region where labour occurred. These findings highlight the need to establish strategies at the national and European levels to analyse the most relevant causes and risk factors associated with maternal mortality in order to reduce it and pay closer attention in identifying and carefully managing pregnant women from this at risk groups.

[CASE REPORT OF FETAL ASCITES CAUSED BY PRENATAL PERFORATION OF BOWEL].

The detection of isolated ascites is a rare ultrasound finding. A precise examination should be undertaken in all cases fetal ascites. This include following a systematic protocol for diagnosis. The prognosis of the newborn in case of prenatal diagnosed ascites, depends on the etiology of the ascites. This is a case report of 40 years old pregnant women, at 34 weeks of gestation. During routine ultrasound examination at 33 weeks of gestation fetal ascites, has been diagnosed. The aim of our team was to examine the etiology of the ascites. We performed systematic diagnostic test and series of ultrasound examination, which helped us to diagnose fetal ascites, caused by bowel perforation. The good timing of delivery and postnatal surgical treatment were associated with good neonatal outcome. In cases of prenatal diagnosed ascites, the desirable good neonatal outcome requires multidisciplinary approach and team work of obstetric consultant, fetal medicine consultants, neonatologists and pediatric surgeons. However the parents should be counselled that not all of the associated anomalies could be diagnosed prenatally.

[ACUTE ABDOMEN CAUSED BY COMPLICATED FIBROID IN PREGNANCY. CASE REPORT].

With the advancing maternal age the rate of fibroids in pregnancy is also growing. A small part of fibroids in pregnancy are complicated and in about 2.6% necessitate urgent surgical treatment. We present a clinical case of subserose fibroid at 20 gestational weeks complicated with acute abdomen treated urgently with normal continuation of pregnancy.

[OPEN LAPAROSCOPY--A MODIFIED HASSON TECHNIQUE].

The open technique was first described by Hasson in 1970. This technique consists of creating a small umbilical incision under direct visualization to enter the abdominal cavity followed by the introduction of a blunt trocar. Pneumoperitoneum is then rapidly created. Hasson proposed its potential benefits to be the avoidance of blind insertion of the Veress needle and bladed trocar, prevention of visceral and vascular injuries, preperitoneal insufflation and gas embolism, guaranteed pneumoperitoneum, and a more anatomical repair of the abdominal wall. Since that time, many surgeons have made some modifications to first Hasson technique. Here we described the way we do the open laparoscopy in our hospital and different positive and useful details we put to original Hasson version.

Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y.

OBJECTIVE: To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms. METHODS: Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13 weeks. Maternal blood was collected before chorionic villus sampling and sent to Natera (San Carlos, CA, USA). cfDNA was isolated from maternal plasma, and targeted multiplex PCR amplification followed by sequencing of 19 488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm that determines the copy number and calculates a sample-specific accuracy for each of the five chromosomes tested. Laboratory personnel were blinded to fetal karyotype. RESULTS: Results were provided for 229 (94.6%) of the 242 cases. Thirty-two cases were correctly identified as aneuploid, including trisomy 21 [n = 25; sensitivity = 100% (CI: 86.3-100%), specificity = 100% (CI: 98.2-100%)], trisomy 18 (n = 3), trisomy 13 (n = 1), Turner syndrome (n = 2), and triploidy (n = 1), with no false positive or false negative results. Median accuracy was 99.9% (range: 96.0-100%). CONCLUSIONS: cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy.

[Impact of the multiple births on the postnatal iron indices in premature infants].

PURPOSE: To investigate the impact of the multiple births on the iron metabolism indices in premature infants. MATERIAL AND METHODS: 102 premature infants, born before 33rd gestational week (GW), are investigated, divided in two groups: control group 1 - singletons (n 69), and case group 2 - twins (n 33). The serum levels of ferritin (Ferr), transferrin (Tf), soluble transferrin receptors (sTfR), iron (Fe), total iron binding capacity (TIBC) and transferrin saturation (SatTf) are examined from the birth to the term. RESULTS: The singletons are complicated more frequently by nosocomial infections also they require more often early haemotransfusions. Their initial levels of Ferr are higher; but sTfR - lower, especially in 36th week corrected age (WCA). Levels of Tf of the twins are elevated sharply after 33rd WCA, but to term are above upper limit of norm. The sTfR levels are higher and above normal value through whole observational period. Fe-curve is upward, but TIBC is on the lower limit through that period. Calculating SatTf, we established that twins are iron deprived at birth, but 1/3 of singletons are iron overloaded. Despite neonatal complications, 80% from singletons are with normal SatTf at term, but iron overload in twins are twice higher (42 vs. 20%). CONCLUSION: The multiple births are a risk factor concerning iron homeostasis in the infants, born before 33rd GW.

[Impact of the multiple births on the postnatal blood count indices in premature infants].

PURPOSE: To investigate the impact of the multiple births on the blood count indices in premature infants. MATERIAL AND METHODS: 299 premature infants, born before 33rd gesta-tional week (GW), are investigated, divided in 2 groups according to the ges-tational age at birth (< or = 29 GW and 30-33 GW). These groups are divided addi-tionally in 2 subgroups: 1- singletons, and 2- twins. Hemoglobin (Hgb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular Hgb concentration (MCHC), peripheral reticulocytes (Ret) are examined at birth and in 27th, 30th, 33rd, 36th and 39th week corrected age (WCA). RESULTS: The congenital infections are more often in group 1 of the newborns 5 29 GW. The twins 30th-33rd GW are with lower average weight and higher frequency of late blood transfusions. Comparing to singletons less mature twins are with initial higher levels of Hgb, Hct, MCV and lower levels of MCHC in 33rd and 36th WCA. They also show high-variable bone marrow answer with high levels of Ret in 30th, 33rd and 36th WCA. Initial values of Hgb, Hct are higher in more mature twins, MCHC also, but in 33rd and 39th WCA. Ret decrease permanently after elevation in 33rd WCA. The MCV levels are under the lower limit of normal in the both age groups. CONCLUSIONS: The multiple births are risk factor for hematological condition in premature infants but the risk is proportional to the duration of the intrauterine stay.

[Borderline ovarian tumours: a challenge for clinicians].

A retrospective analysis of surgical procedures for ovarian tumours, performed in the Department of General and Oncological Gynaecology at the Military Medical Academy (Sofia, Bulgaria) specified 81% of the tumour cases as benignant ones, 15.6% as malignant ones, and 3.4% as borderline ovarian tumours (BOT). The histological type of BOT was assessed as serous in 62% and as mucinous in 38%. The incidence of BOT was found to increase with increasing age. Most patients with BOT were parous (60%). Serum levels of CA 125 were within normal values in all patients with BOT.

IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer.

Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.

[Low Apgar score in term newborn infants and delivery pattern].

OBJECTIVE: Examine the influence of delivery pattern over neonatal condition in the first minutes of life. MATERIALS AND METHODS: We have studied 3624 term newborns of single pregnancies for period of 2 years in the city of Pleven. The patients were divided in 4 groups by the delivery pattern: vaginal delivery with head presentation (2497 infants), vaginal delivery with instrumental assist (45 infants), per vias naturales in breech presentation (44 infants), delivery via Caesarean section (1038 infants). RESULTS: According to our results the Apgar score differs itself from the pathology of a given newborn. Neonatal deaths are significantly higher in the newborns with low Apgar score than deaths in the general population. From all cases of low Apgar score without other clinical problems the highest is the percentage in the infants delivered via Caesarean section. CONCLUSIONS: The goal of the Apgar score is to focus attention on the infant's condition in the first few minutes of its life and the need of resuscitation. Low Apgar score is an important predictor of the newborn morbidity and death rate. The Apgar score alone is not a proof for intrapartal asphyxia and is not associated with long-term neurological damage.

[Diagnosis and prevention of neural tube defects--where are we? (Data based on the registry of congenital anomalies in the Pleven region)].

AIMS: to present some clinical and epidemiological data, concerning diagnosis and prevention of neural tube defects (NTDs), based on the registry of congenital anomalies (CAs) in the Pleven region; to analyse our data comparing with the data of other registries in Europe. MATERIALS AND METHODS: The source of the data was the regional population-based registry of Cas (in live births, stillbirths and terminations of pregnancy following prenatal diagnosis) using criteria according to EUROCAT recommendations. During the study period 1988-2006, 47 622 births were surveyed in the University hospital, City of Pleven. RESULTS: A total of 107 cases of NTDs were ascertained. About 20% of the cases with isolated NTDs were in terminations of pregnancy following prenatal diagnosis, in 80% of the case the diagnosis was ascertained in liveborn and stillborn fetus. The isolated NTDs were among the most common CAs, with a proportion of 8% of all registered cases and a prevalence of 2 per 1000 births. The genetic counseling revealed familial data (other affected child/pregnancy) in 7% of families with NTDs. Prenatal diagnosis was provided to the subsequent risk pregnancies in the affected families and NTDs were detected in 7% of the pregnancies. CONCLUSION: Neural tube defects are a common type of congenital defects that demonstrated a relatively high prevalence in the Pleven region. The data of the study indicates that there is a need to develop an official government policy regarding prevention of NTDs (pericoceptional folic acid supplementation and antenatal screening of CAs).

[Adrenal hemorrhage in a newborn with factor V Leiden--a clinical case].

Neonatal adrenal hemorrhage is frequently associated with birth trauma, perinatal asphyxia, septicemia, coagulation defects and thromboembolism. We report a case of bilateral adrenal hemorrhage in newborn baby with perinatal asphyxia. Ultrasound findings of subacute adrenal hemorrhage draw attention to its presumable antenatal genesis. DNA analysis for thrombophilic mutations identifies factor V Leiden.

[Our experience with linesolid usage in newborn children].

The Gram-positive infections are a problem with increasing significance in the newborn period. LINEZOLID is the first member of the new group antibiotics--oxazolidinones. The most Gram-positive infections, including the resistant of vancomycin, influence by LINEZOLID. We treated twenty newborn babies with LINEZOLID during the period from April 2005 to April 2006. Initial empiric antibiotic therapy appointed all those children. Various Gram-positive cocci were isolated from different biological materials. Five assays were sterile, but the clinical signs were suspect for Gram-positive infection. The treatment with LINEZOLID initialized immediately after the identification of the microbiological agent or when was suspect the resistant of initial antibiotics gram-positive infection. Duration of therapy was determined by the elimination of the microbiological agent or by the involution of the clinical signs, which we observed in the all cases of the treatment with LINEZOLID. Our results received up to date demonstrate the effectiveness and the safety of the LINEZOLID treatment in the newborn period.