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In plants, serpins are a superfamily of serine and cysteine protease inhibitors involved in stress and defense mechanisms, with potential for controlling agricultural pests, making them important biotechnological tools. The objective of this study was to characterize a serpin from Theobroma cacao , called TcSERPIN, to identify its endogenous targets and determine its function and biotechnological potential. TcSERPIN has 390 amino acid residues and shows conservation of the main active site, RCL. Cis-elements related to light, stress, hormones, anaerobic induction, cell cycle regulation and defense have been identified in the gene's regulatory region. TcSERPIN transcripts are accumulated in different tissues of Theobroma cacao . Furthermore, in plants infected with Moniliophtora perniciosa and Phytophthora palmivora , the expression of TcSERPIN was positively regulated. The protein spectrum, rTcSERPIN, reveals a typical β-sheet pattern and is thermostable at pH 8, but loses its structure with temperature increases above 66°C at pH 7. At the molar ratios of 0.65 and 0.49, rTcSERPIN inhibited 55 and 28% of the activity of papain from Carica papaya and trypsin from Sus scrofa , respectively. The protease trap containing immobilized rTcSERPIN captured endogenous defense proteins from cocoa extracts that are related to metabolic pathways, stress and defense. The evaluation of the biotechnological potential against geohelminth larvae showed that rTcSERPIN and rTcCYS4 ( Theobroma cacao cystatin 4) reduced the movement of larvae after 24 hours. The results of this work show that TcSERPIN has ideal biochemical characteristics for biotechnological applications, as well as potential for studies of resistance to phytopathogens of agricultural crops., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ferreira, Farias, Zugaib, Alves, Amaral, Santos, Freitas, Santana, dos Santos Júnior, Mora-Ocampo, Santos, da Silva, Andrade and Pirovani.)

Plant serpins are a superfamily of protein inhibitors that have been continuously studied in different species and have great biotechnological potential. However, despite ongoing studies with these inhibitors, the biological role of this family in the plant kingdom has not yet been fully clarified. In order to obtain new insights into the potential of plant serpins, this study presents the first systematic review of the topic, whose main objective was to scrutinize the published literature to increase knowledge about this superfamily. Using keywords and the eligibility criteria defined in the protocol, we selected studies from the Scopus, PubMed, and Web of Science databases. According to the eligible studies, serpins inhibit different serine and non-serine proteases from plants, animals, and pathogens, and their expression is affected by biotic and abiotic stresses. Moreover, serpins like AtSerpin1, OSP-LRS, MtSer6, AtSRP4, AtSRP5, and MtPiI4, act in resistance and are involved in stress-induced cell death in the plant. Also, the system biology analysis demonstrates that serpins are related to proteolysis control, cell regulation, pollen development, catabolism, and protein dephosphorylation. The information systematized here contributes to the design of new studies of plant serpins, especially those aimed at exploring their biotechnological potential.

The fungus Moniliophthora perniciosa secretes protein effectors that manipulate the physiology of the host plant, but few effectors of this fungus have had their functions confirmed. We performed functional characterization of a promising candidate effector of M. perniciosa . The inoculation of rBASIDIN at 4 µmol L -1 in the mesophyll of leaflets of Solanum lycopersicum caused symptoms of shriveling within 6 h without the presence of necrosis. However, when sprayed on the plant at a concentration of 11 µmol L -1 , it caused wilting symptoms only 2 h after application, followed by necrosis and cell death at 48 h. rBASIDIN applied to Theobroma cacao leaves at the same concentration caused milder symptoms. rBASIDIN caused hydrogen peroxide production in leaf tissue, damaging the leaf membrane and negatively affecting the photosynthetic rate of Solanum lycopersicum plants. Phylogenetic analysis indicated that BASIDIN has orthologs in other phytopathogenic basidiomycetes. Analysis of the transcripts revealed that BASIDIN and its orthologs are expressed in different fungal species, suggesting that this protein is differentially regulated in these basidiomycetes. Therefore, the results of applying BASIDIN allow the inference that it is an effector of the fungus M. perniciosa , with a strong potential to interfere in the defense system of the host plant.

Introduction: Bacteriuria during pregnancy is a frequent and important cause of morbidity and complications. Data on its occurrence in pregnant adolescents are still scarce., Methods: A cross-sectional study was conducted at a tertiary teaching hospital in São Paulo, Brazil. All adolescents (≤18 years) who came for prenatal care between January 2010 and January 2016 were included. Sociodemographic characteristics, medical history, obstetric history, and the results of laboratory tests were selected. A urine sample was aseptically collected from each patient to undergo microscopic and culture analysis., Results: A total of 388 pregnant adolescents averaging 15.30 ± 1.24 years of age were included. The frequency of bacteriuria in this group was 17.01% (66/388). The lack of sports practice (OR = 8.65; 95% CI, 1.09-68.39), the fact that pregnancy was desired (OR = 2.17; 95% CI, 1.08-4.34), and the use of hormonal methods of contraception (OR = 2.46; 95% CI, 1.04-5.84) turned out to be independent risk factors for bacteriuria. Protective factors were identified as late coitarche (OR = 0.75; 95% CI, 0.57-0.98) and a urine culture analysis at a later gestational age (OR = 0.94; 95% CI, 0.90-0.98). The most often isolated pathogens were Escherichia coli (49%) and Streptococcus agalactiae (18%)., Conclusion: Bacteriuria among pregnant adolescents is a relatively common condition. The infection risk of the urinary tract was increased by physical inactivity and seemingly by the influence of behavioral and sexual factors. Such results can help to identify patients at risk, favoring the early diagnosis of urinary tract infections and optimizing prenatal care., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Preeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded protein responses (UPRs) in placental explants and trophoblast cells lineage. We cultured placental explants from third-trimester term placentas from control non-preeclamptic (NPE) pregnant women with serum from women with PE or controls (NPE). In PE-treated explants, there was a significant increase in gene expression of GADD34 , CHOP , and SDF2 . At the protein level, GRP78, SDF2, p-eIF2α, and p-eIF2α/eIF2α ratio were also augmented in treated explants. Assays were also performed in HTR8/SV-neo trophoblast cell line to characterize the putative participation of trophoblast cells. In PE serum-treated protein levels of p-eIF2a and the ratio p-elF2 α/elF2α increased after 12 h of treatment, while the gene expression of GADD34 , ATF4 , and CHOP was greater than control. Increased expression of SDF2 was also detected after 24 h-cultured HTR8/SV-neo cells. PE serum increased sFLT1 gene expression and decreased PlGF gene expression in placental explants. Morphologically, PE serum increased the number of syncytial knots and reduced placental cell metabolism and viability. Analysis of the serum of pregnant women with PE through Raman spectroscopy showed changes in amino acids, carotenoids, lipids, and DNA/RNA, which may be associated with the induction of ER stress found in chorionic villi treated with this serum. In conclusion, this study provides evidence that the serum of pregnant women with PE may impact placental villi changing its morphology, viability, and secreted functional factors while triggers ER stress and an UPR. The differences between PE and control sera include molecules acting as inducing factors in these processes. In summary, the results obtained in our assays suggest that after the development of PE, the serum profile of pregnant women may be an additional factor that feeds a continuous imbalance of placental homeostasis. In addition, this study may expand the possibilities for understanding the pathogenesis of this disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castro, Prado, Lorenzon, Hoshida, Alves, Francisco, Zugaib, Marques, Silva, Fonseca, Borbely, Veras and Bevilacqua.)

Introduction: Significant bacteriuria is associated with clinical and obstetric complications. The existing studies on the profile of urinary pathogens in pregnant women have widely divergent results and they hardly include data on pregnant adolescents., Methods: This observational retrospective study was conducted in a tertiary hospital in the city of São Paulo with 388 pregnant adolescents and 2547 pregnant low-risk obstetric care adults who began prenatal care between January 2010 and January 2016. They were compared in terms of urine sediment, urine culture, and antibiogram results., Results: The prevalence of bacteriuria was 17.01% (66/388) among adolescents and 10.13% (258/2547) among adults. Adolescence was a risk factor for bacteriuria in pregnancy (OR=1.82, CI95%=1.35-2.44, p=0.08). The most frequently isolated pathogen in urine culture was Escherichia coli , both in adolescents (49%) and in adults (42.18%). In positive urine cultures, urinary leukocytes were present in greater numbers in adolescents than in adults (p<0.001). Resistance to quinolones in general was more frequent among adults (OR=5.86, CI95%=0.78-44.20, p<0.001), but the tendency was not statistically significant., Conclusion: Escherichia coli and the less frequent Streptococcus agalactiae were the etiologic agents most often found in the urine cultures both of adolescents and adults. Higher rates of bacteriuria and of abnormal urine sediments prevailed among adolescents., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Diorio de Souza et al.)

Objective: To compare maternal complications and describe neonatal outcomes in women with severe preeclampsia at ≤ 26+0 weeks in two countries with different management policies: expectant management (Brazil) versus termination of pregnancy (France)., Methods: We conducted a retrospective comparative study by reviewing the medical records of women with severe preeclampsia at ≤ 26+0 weeks, from January 2010 to June 2018, in two centers: Hospital das Clínicas da Faculdade de Medicina, in Sao Paulo, Brazil (where medical abortion is forbidden in this indication) and Hôpital Antoine-Béclère, Clamart, France (where medical termination is accepted). We collected information on maternal characteristics, laboratory tests, maternal complications and fetal and newborn characteristics. We used Student's t-test and the Mann-Whitney U nonparametric test to compare quantitative variables, and Chi-square test or Fisher's exact test to evaluate the associations between the qualitative variables., Results: There was no between-group difference in maternal complications during hospitalization (p = 0.846). In Brazil, the rate of cesarean section was 66.7%, and 20% of patients had vertical incision. The rate of spontaneous fetal death was 35.6% and among the live-born infants 26.6% were discharged from hospital. In France, one patient had a cesarean section with vertical incision., Conclusion: When comparing termination of pregnancy to expectant management in severe preeclampsia before 26 weeks, maternal complications were equivalent but maternal reproductive future might have been compromised in 20% of cases due to a higher risk of uterine rupture in subsequent pregnancies for patients having classic cesarean (vertical incision). 26.6% of children survived the neonatal period when pregnancy was pursued, however we lack information on their long-term follow-up., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Renal development is impaired in fetal growth restriction (FGR). Renal size can be considered a surrogate of renal function in childhood, and could be impaired in that condition. Our aim was to evaluate the ratio of total renal volume, measured by three-dimensional ultrasound, to estimated fetal weight (TRV/EFW) among fetuses with and without growth restriction. Furthermore, we correlated TRV/EFW with fetal Doppler velocimetry and renal vascularization indexes and evaluated the association of renal volume and vascular parameters with adverse neonatal events in growth-restricted fetuses., Methods: In a retrospective cohort, TRV and renal vascularization of growth-restricted and normal fetuses were evaluated by three-dimensional ultrasonography and VOCAL technique. Independent samples t-tests and Mann-Whitney test were used for comparisons between groups. Logistic regression model was applied to evaluate the association between renal characteristics and adverse neonatal events., Results: Seventy-one growth-restricted fetuses were compared to 194 controls. The TRV/EFW was lower in the growth-restricted group (P < .001). In our sample, this ratio did not correlate with Doppler velocimetry parameters, renal vascular indexes or any adverse neonatal events., Conclusion: The TRV/EFW ratio is decreased in FGR. Further studies are needed to investigate the association of this ratio with long-term renal outcomes., (© 2020 John Wiley & Sons, Ltd.)

Objective: To construct individualized fetal growth curves estimated by ultrasound parameters adjusted for maternal and fetal characteristics., Methods: Data were retrospectively assessed from serial ultrasonographic examinations of singleton pregnancies at 12-42 gestational weeks among women without maternal or fetal conditions and full-term delivery at the University Hospital of University of São Paulo between July 1, 2014, and December 31, 2017. Measurements included biparietal diameter, head circumference, abdominal circumference, and femur length. Mixed linear regression was used to model the ultrasound biometric parameters as a function of gestational age, parity, maternal height, pre-pregnancy weight, and fetal sex., Results: In total, data were assessed from 1445 examinations of 434 pregnancies meeting the inclusion criteria. The estimated fetal weight model included gestational age, fetal sex, maternal height, and pre-pregnancy body mass index as covariates. The model enabled the construction of individual estimated fetal weight curves with respective percentiles covering 12-42 gestational weeks using maternal and fetal characteristics., Conclusion: The growth curves, which are based on a sample of the Brazilian population with low risk of maternal or fetal morbidity and mortality, will make it possible to determine whether a fetus is achieving ideal growth potential according to maternal and fetal characteristics., (© 2019 International Federation of Gynecology and Obstetrics.)

Objectives: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia., Methods: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins., Results: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024)., Conclusion: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

Objective: To perform a descriptive analysis of preterm premature rupture of membranes (PPROM) cases attended in a tertiary hospital., Method: Retrospective analysis of medical records and laboratory tests of patients admitted to a Brazilian tertiary hospital between 2006 and 2011, with a confirmed diagnosis of PPROM and gestational age (GA) at delivery <37 weeks., Results: A total of 299 pregnant women were included in the study. Nine patients evolved to abortion, and 290 pregnant women remained for the final analysis. There was initial diagnostic doubt in 17.6% of the cases. The oligohydramnios rate [amniotic fluid index (AFI) <5] was 27.9% on admission. Chorioamnionitis was initially diagnosed in 10.8% of the patients and was retrospectively confirmed in 22.9% of the samples. The latency period had a mean of 9.1 days. The main reasons for interruption were premature labor (55.2%), GA ≥36 weeks (27.2%), and fetal distress (6.9%). The delivery method was cesarean section in 55% of cases. The mean birth weight was 2,124 grams, and 67% of the neonates had a low birth weight (<2500 g). The GA at delivery averaged 33.5 weeks. The stillbirth rate was 5.3%, and the early neonatal mortality rate was 5.6%. There were complications at delivery in 18% of mothers., Conclusion: In one of the few Brazilian reports on the epidemiological profile of PPROM, with GA until 37 weeks and intercurrences generally excluded from assessments (such as twinning and fetal malformations), there is a favorable evolution, with an acceptable rate of complications.

The use of immunosuppressive drugs guarantees the vitality of the graft and allows gestation in spite of intercurrences such as prematurity and intrauterine growth restriction. However, little is known about the direct effects of immunosuppressive drugs on placental cells. We investigated the effects of immunosuppressive drugs in the chorionic villous explants from human term placentas of healthy gestations. Human placental explants from term gestations (37-39 week gestational age, n = 12) were exposed to cyclosporine A (CSA, 0, 62.5, 125, 1250 ng/mL) or azathioprine (AZA, 0, 5, 10, 100 ng/mL) separately or, in combination for up to 48 hours. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed a significant decrease in the explant metabolic activity between AZA and the control group (24 hours, 100 ng/mL, 48 hours, all concentrations, P < .005). Cyclosporin A (CsA) reduced cell activity when associated with AZA (48 hours, P < .005). Fibrinoid deposits increased in AZA-treated explants alone (5 ng/mL, 48 hours; 10 ng/mL, 24-48 hours; P < .005) or when associated with CsA (10 AZA/125 CsA, P < .05), whereas in CsA treatment alone, there was an augment in syncytial knots (24-48 hours, P < .005). The sFLT1 gene (24 hours, P < .05) and protein ( P < .005) expression increased in AZA and CsA-treatments separately or in combination ( P < .05). Placental growth factor increased in AZA (24 hours, 10 ng/mL) and CsA (125 ng/mL; P < .05). In conclusion, our data indicate that AZA primarily acts on the villous metabolism, perturbing placental homeostasis. Since these drugs may alter the balance of angiogenic factors in its selection for clinical application, their impact on the behavior of placental villous should be considered.

Aim: Preterm premature rupture of membranes (PPROM) is responsible for approximately one-third of premature births worldwide, and although the diagnosis is often straightforward, this condition can still present difficulties. The purpose of this research was to compare the accuracy of several PPROM diagnostic tests., Methods: A total of 94 pregnant women with clinical suspicion of PPROM who were between 20 and 36 weeks of pregnancy were examined by vaginal speculum, and tests were performed for phenol, pH, insulin-like growth factor binding protein-1 (IGFBP-1) and placental alpha-microglobulin-1 (PAMG-1). All patients were followed up until the diagnosis was fully defined, and a diagnosis of PROM was confirmed by a definitive evolution of the clinical symptoms (visualization of vaginal amniotic fluid or persistence of oligohydramnios)., Results: After excluding the cases that could not be definitively diagnosed, a good diagnostic performance of the immunochromatographic tests was observed that was superior to that of the clinical tests. Similar accuracies were observed for IGFBP-1 (98.7%) and PAMG-1 (93.9%). However, while the IGFBP-1 test differed from a vaginal pH ≥7 (88.9%) and the phenol test (85.7%), this did not occur for the PAMG-1 test. The performance of the tests was modified only by the presence of bleeding (with lower specificity rates for pH and phenol), without interference of gestational age or maternal morbidities., Conclusion: Immunochromatographic tests are good tools but should be used sparingly in resource-poor settings because they are expensive, and there is no significant difference between PAMG-1 and traditional tests., (© 2019 Japan Society of Obstetrics and Gynecology.)

Background: The gestational and neonatal outcomes of women with early cervical dilatation undergoing emergency cerclage were evaluated and compared with women treated with expectant management and bed rest., Methods: Retrospective analysis of pregnant women admitted between 2001 and 2017 with a diagnosis of early cervical dilatation and/or bulging membranes. Patients with a singleton pregnancy of a fetus without malformations, between 16 and 25 weeks and 6 days, with cervical dilatation of 1 to 3 cm were included; patients who delivered or miscarried within 2 days after admission were excluded., Results: The study enrolled 30 patients: 19 in the cerclage group and 11 in the rest group. There was a significant difference, with the cerclage group showing better results concerning gestational age at delivery (28.7 vs. 23.3 weeks; p=0.031) and latency between hospital admission and delivery (48.6 vs. 16 days; p=0.016). The fetal death rate was lower in the cerclage group (5.3% vs. 54.5%, p=0.004). Considering gestational age at delivery of live newborns, no difference was observed between the cerclage and rest groups (29.13 vs. 27.4 weeks; p=0.857)., Conclusions: Emergency cerclage was associated with longer latency, a significant impact on gestational age at delivery and reduction in the fetal death rate.

Background: Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage., Methods: This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (μALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight., Results: All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and μALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%)., Conclusions: RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.

Objective: The objective of this study is to evaluate risk factors and propose a model for the prediction of insulin requirement during the treatment of early-diagnosed gestational diabetes mellitus (GDM)., Research Design and Methods: Retrospective cohort analysis of all pregnant women who were diagnosed with GDM by abnormal fasting blood glucose at the first prenatal visit. According to the requirement for insulin therapy to achieve good glycemic control (insulin or diet group), women were compared regarding clinical and laboratory variables. The performance of these variables in predicting insulin need for GDM treatment was identified by a logistic regression model, and a nomogram was created based on the model to facilitate clinical interpretation., Results: In total, 408 women were included for analysis. Among them, 135 (33%) needed insulin therapy. In the logistic regression model, maternal age, prepregnancy body mass index, fasting blood glucose (FBG) value, prior GDM, and family history of diabetes were significant independent variables for the prediction of insulin need., Conclusions: The need for insulin therapy in women with early diagnosis of GDM can be predicted by a logistic regression model, which can be converted to a clinically usable nomogram that could help to properly address follow-up strategies for GDM treatment in regions where health resources are limited.

Introduction: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage., Objective: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies., Study Design: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), and microalbuminuria (μALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay., Results: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-β1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients., Discussion: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-β1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group., Conclusions: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to investigate the influence of vaginal progesterone on cervical length (CL) in asymptomatic nonselected twin gestations., Methods: This was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. The CL was examined at six different time periods: 18-21 +6 weeks (T1), 21-23 +6 weeks (T2), 24-26 +6 weeks (T3), 27-29 +6 weeks (T4), 30-32 +6 weeks (T5) and 33-34 +6 weeks (T6). The rate of cervical shortening per week and the percent cervical shortening were compared between the groups, with analyses of the entire cohort and of those who delivered spontaneously according to gestational age at birth., Results: The final analysis included 184 women in the progesterone group and 188 women in the placebo group. The baseline characteristics were similar in both groups. No differences in cervical shortening in terms of absolute value or percent shortening were observed between the groups at each time period or throughout gestation. Furthermore, no difference was found in cervical shortening for those who delivered spontaneously., Conclusion: Cervical shortening in asymptomatic nonselected twin pregnancies occurred at a similar rate, regardless of vaginal progesterone treatment.

Although a rare and challenging condition, cancer during pregnancy should promptly be identified and treated. Not only standards of care guidelines for the underlying disease are taken into account, but also fetal safety might be weighted for clinical decisions. Frequent lack of experience and knowledge about this condition could lead to late diagnosis, imprecise management, suboptimal treatment and fetal and maternal harm. Therefore, this review aims to summarize the current evidence regarding the epidemiology, clinical presentation, diagnostic workup, staging and treatment, including novel treatment modalities for patients diagnosed with cancer during pregnancy., Competing Interests: The authors have no conflicts of interest to disclose related to this paper.

Background: Many factors may influence a woman's decision to start and maintain breastfeeding. Research aim: This study aimed to investigate the factors associated with breastfeeding cessation in twin infants during the first 6 months after birth and to describe the main reasons for weaning cited by mothers of twins., Methods: This is a secondary data analysis of a prospective randomized trial conducted in Brazil. Data were obtained through longitudinal quantitative and qualitative self-reported interviews. One hundred twenty-eight women pregnant with twins and their 256 infants were followed for up to approximately 6 months, during which time breastfeeding data were obtained through face-to-face interviews at three different points after birth: 30 to 40 days (Time 1), 90 days (Time 2), and 180 days (Time 3). The association between weaning and the investigated factors was examined using survival analysis methodologies., Results: Nonexclusive breastfeeding ( p = .004, Cox proportional hazards regression model), a lack of support during the lactation period ( p = .001), difficulty breastfeeding ( p = .003), a breastfeeding duration shorter than 12 months in a previous pregnancy ( p = .001), and infants' birth weight less than 2,300 g ( p < .001) were the factors associated with breastfeeding cessation. The main reasons for weaning cited by mothers of twins were insufficient human milk supply, infants' behavior, and returning to work., Conclusion: We have identified the factors associated with weaning in twin infants during the first 180 days of life. This knowledge can help improve strategies to increase breastfeeding rates in twins.

Objectives: Hospitalized patients with cancer are at high risk of developing venous thromboembolism, and the risk increases with pregnancy. The aim of this study was to apply a thromboprophylaxis protocol with a venous thromboembolism risk score for hospitalized pregnant women with cancer and to evaluate the effects on maternal morbidity and mortality., Methods: A longitudinal and prospective study was conducted from December 2014 to July 2016. The venous thromboembolism risk score was modified from the guidelines of the Royal College of Obstetricians and Gynaecologists. Patients were classified as low (score <3) or high risk (score ≥3). The high-risk group received thromboprophylaxis with low-molecular-weight heparin, unless the patient had a contraindication for anticoagulation. One patient could have undergone more than one evaluation., Results: Fifty-two ratings were descriptively analyzed: 34 (65.4%) were classified as high risk, and 28/34 (82.3%) received low-molecular-weight heparin, 1 received unfractionated heparin, and 5 did not receive intervention. Most patients (23/52; 44.2%) had breast cancer. The main risk factors for venous thromboembolism in the high-risk group were chemotherapy (within 6 months; 22/34; 64.7%). No patient exhibited venous thromboembolism, adverse effects of anticoagulation or death up to three months after hospitalization., Conclusions: Most pregnant women with cancer had a high risk for venous thromboembolism at the time of hospitalization. Breast cancer was the most prevalent cancer, and recent chemotherapy was the main risk factor for anticoagulation. The application of a thromboprophylaxis protocol and determination of a venous thromboembolism risk score for these patients was useful for the prevention of maternal morbidity and mortality due to venous thromboembolism.

Objective: Cervical cerclage is the standard treatment for cervical incompetence (CI); however, there is still a high risk of preterm birth for women who undergo this treatment. The aim of this study was to longitudinally evaluate findings on two-dimensional transvaginal ultrasonography (2DTVUS) and three-dimensional transvaginal ultrasonography (3DTVUS) that could be related to gestational age at birth., Methods: A total of 68 pregnant women who were treated with cerclage were evaluated by 2DTVUS and 3DTVUS in the second and third trimesters of pregnancy. Log-rank tests and Cox regression analyses were used to identify significant findings related to gestational age at delivery., Results: A cervical length lower than 281 mm (p= 0.0083), a proximal cervical length lower than 10 mm (p= 0.0151), a cervical volume lower than 18.17 cm3 (p= 0.0152), a vascularization index (VI) under 2.153 (p= 0.0044), and a vascularization-flow index (VFI) under 0.961 (p= 0.0059) in the second trimester were all related to earlier delivery. In the third trimester, a cervical length lower than 20.4 mm (p= 0.0009), a VI over 0.54 (p= 0.0327) and a VFI over 2.275 (p= 0.0479) were all related to earlier delivery. Cervical funnelling in the second and third trimesters and proximal cervical length in the third trimester were not related to gestational age at birth. The COX regression analyses showed that cervical volume in the second trimester; FI and VFI in the third trimester were significantly associated with gestational age at birth., Conclusion: In women treated with history-indicated cerclage or ultrasound-indicated cerclage, 2nd trimester cervical volume and 3rd trimester FI and VFI are independent significant sonographic findings associated with time to delivery.

Purpose of Review: The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the management of pregnant patients with preexisting resistant hypertension and also of those who develop severe hypertension in gestation and puerperium., Recent Findings: The main cause of severe hypertension in pregnancy is preeclampsia, and differential diagnosis must be done with secondary or primary hypertension. Women with preexisting resistant hypertension may need pharmacological therapy adjustment. Several drugs can be used to treat severe hypertension, with exception of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. The most used drugs are methyldopa, beta-blockers, and calcium channel antagonists. There is a general agreement that severe hypertension must be treated, but there are still debates over the goals of the treatment. Delivery is indicated in viable pregnancies in which blood pressure control is not achieved with three drugs in full doses. Resistant hypertension may arise in postpartum. The management of resistant hypertension in pregnancy must regard the possible etiology, the fetal well-being, and the mother's risk. Good care is mandatory to reduce maternal mortality risk.

Introduction: Pregnancy in women on dialysis is associated with a higher risk of adverse events, and the best care for this population remains to be established., Methods: In this series, we aimed to identify factors associated with the risk of adverse fetal outcomes among 93 pregnancies in women on hemodialysis. Dialysis dose was initially assigned according to the presence of residual diuresis, body weight, and years on dialysis. Subsequent adjustments on dialysis dose were performed according to several parameters., Results: The overall successful delivery rate was 89.2%, with a dialysis regimen of 2.6 ± 0.7 h/d, 15.4 ± 4.0 h/wk, and mean weekly standard urea Kt/V of 3.3 ± 0.6. In the logistic models, preeclampsia, lupus, primigravida, and average midweek blood urea nitrogen (BUN) level were positively related to the risk of a composite outcome of perinatal death or extreme prematurity, whereas polyhydramnios was inversely related to it. In multivariable linear regression, preeclampsia, polyhydramnios, primigravida, average midweek BUN, and residual diuresis remained significantly and independently related to fetal weight, which is a surrogate marker of fetal outcome. An average midweek BUN of 35 mg/dl was the best value for discriminating the composite outcome, and BUN ≥35 mg/dl was associated with a significant difference in a Kaplan-Meier curve ( P  = 0.01)., Conclusion: Our results showed that a good fetal outcome could be reached and that preeclampsia, lupus, primigravida, residual diuresis, polyhydramnios, and hemodialysis dose were important variables associated with this outcome. In addition, we suggested that a midweek BUN <35 mg/dl might be used as a target for adjusting dialysis dose until hard data were generated.

Objective: To evaluate whether thrombophilia worsens maternal and foetal outcomes among patients with severe preeclampsia (PE)., Method: From October 2009 to October 2014, an observational retrospective cohort study was performed on pregnant women with severe PE diagnosed before 34 weeks of gestation and their newborns hospitalized at the Clinics Hospital, FMUSP. Patients who had no heart disease, nephropathies, pre-gestational diabetes, gestational trophoblastic disease, foetal malformation, or twin pregnancy and who underwent thrombophilia screening during the postnatal period were included. New pregnancies of the same patient; cases of foetal morphological, genetic, or chromosomal abnormalities after birth; and women who used heparin or acetylsalicylic acid during pregnancy were excluded. Factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The groups with and without thrombophilia were compared regarding their maternal clinical and laboratory parameters and perinatal outcomes., Results: Of the 127 patients selected, 30 (23.6%) had thrombophilia (hereditary or acquired). We found more white patients in thrombophilia group (p = .036). Analysis of maternal parameters showed a tendency of thrombophilic women to have more thrombocytopenia (p = .056) and showed worsening of composite laboratory abnormalities (aspartate aminotransferase ≥ 70 mg/dL, alanine aminotransferase ≥ 70 mg/dL, platelets < 100,000/mm 3 , serum creatinine ≥ 1.1 mg/dL; p = .017). There were no differences in foetal perinatal outcomes., Conclusion: The presence of thrombophilia leads to worsening of maternal laboratory parameters among patients with severe forms of PE but without worsening perinatal outcomes., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the ultrasound (US) markers predictive of complex gastroschisis (CG), mortality, and morbidity in fetuses with gastroschisis., Materials and Methods: This was a retrospective cohort study of 186 pregnancies with isolated fetal gastroschisis. Eight US markers were analyzed. The predictions and associations of US markers with CG, mortality, and morbidity were assessed. Combinations of US markers predictive of CG were investigated., Results: Extra-abdominal bowel dilatation (EABD), intra-abdominal bowel dilatation (IABD), and polyhydramnios were predictive of CG. EABD between 25 and 28 weeks had a sensitivity of 64%, a specificity of 89%, a positive predictive value (PPV) of 56.2%, and negative predictive value (NPV) of 91.8%. The predictions of IABD were sensitivity = 26.7%, specificity = 96.7%, PPV = 61.5%, and NPV = 86.8%. The odds ratios for CG in the presence of 1 and 2 US markers, compared with the absence of a US marker, were 18.3 (95% CI, 3.83-87.64) and 73.3 (95% CI, 6.14-876), respectively., Conclusion: US markers predictive of CG were established. The combination of these markers increases the probability of CG., (© 2017 S. Karger AG, Basel.)

Aim: Our aim was to investigate the effect of the prophylactic use of vaginal progesterone on the latency period from the initiation of tocolytic therapy to delivery in twin pregnancies with preterm labor., Methods: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies in mothers who were exposed to a 200 mg vaginal progesterone ovule or a placebo ovule daily from 18 to 34 weeks gestation. Patients who were administered tocolysis with Atosiban because of preterm labor were included. The latency from tocolysis to delivery, mean gestational age at delivery and the rates of delivery within 48 h and within seven days were compared between progesterone and placebo groups., Results: The analysis included 27 women in the progesterone group and 30 in the placebo group. The baseline characteristics were similar between the groups. Overall, there were no differences in the latency period to delivery (17.54 ± 13.54 days and 21.58 ± 13.52 days; P = 0.289), rates of delivery within 48 h (14.8% and 6.7%; P = 0.40) or within seven days (29.64% and 23.3%; P = 0.76) or mean gestational age at delivery (32.53 ± 3.33 and 34.13 ± 2.87; P = 0.08) between the progesterone and placebo groups, respectively., Conclusions: Prophylactic use of 200 mg of vaginal progesterone does not influence the latency to delivery in women with twin pregnancies treated with tocolysis because of preterm labor., (© 2017 Japan Society of Obstetrics and Gynecology.)

Objectives:: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory., Method:: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes., Results:: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples., Conclusion:: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.

Objectives:: To analyze the influence of lying in prone position on a specially designed stretcher on the maternal-fetal hemodynamic parameters and comfort of pregnant women., Methods:: A randomized, controlled trial with 33 pregnant women divided into 2 groups: pregnant group sequence 1 and pregnant group sequence 2. The order of positions used in sequence 1 was Fowler's position, prone position, supine position, left lateral, Fowler's position 2, supine position 2, prone position 2 and left lateral 2. The order of positions used in sequence 2 was Fowler's position, prone position, left lateral, supine position, Fowler's position 2, left lateral 2, prone position 2 and supine position 2. Each woman remained in each position for 6 minutes. For the statistical analyses, we used Wilcoxon's test for 2 paired samples when comparing the prone position with the other positions. The variables are presented in graphs showing the means and 95% confidence intervals. Trial Registration: Clinical Trial No. ISRCTN41359519., Results:: All the parameters were within the standards of normality. There were no differences between positions in terms of maternal heart rate, diastolic blood pressure, oxygen saturation and fetal heart rate. However, there were significant decreases in respiratory rate and systolic blood pressure in prone position 2 compared with left lateral 2. There was an increase in oxygen saturation in prone position compared with Fowler's position and supine position 2 in both sequences. All the women reported feeling comfortable in the prone position., Conclusions:: The prone position was considered safe and comfortable and could be advantageous for improving oxygen saturation and reducing the systolic blood pressure and respiratory rate.

Objective:: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins., Methods:: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated., Results:: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p<0.001) twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36) or dichorionic (p=0.68) twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions., Conclusion:: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

Objective: To examine the accuracy of fetal RHD genotype and RHD pseudogene determination in a multiethnical population., Methods: Prospective study involving D-negative pregnant women. Cell-free DNA was extracted from 1 ml of maternal plasma by an automated system (MagNA Pure Compact, Roche) and real-time PCR was performed in triplicate targeting the RHD gene exons 5 and 7. Inconclusive samples underwent RHD pseudogene testing by real-time PCR analysis employing novel primers and probe., Results: A positive result was observed in 128/185 (69.2%) samples and negative in 50 (27.0%). Umbilical cord blood phenotype confirmed all cases with a positive or negative PCR result. Seven (3.8%) cases were found inconclusive (exon 7 amplification only) and RHD pseudogene testing with both conventional and real-time PCR demonstrated a positive result in five of them, while two samples were also RHD pseudogene negative., Conclusion: Real-time PCR targeting RHD exons 5 and 7 simultaneously in maternal plasma is an accurate method for the diagnosis of fetal D genotype in our population. The RHD pseudogene real-time PCR assay is feasible and is particularly useful in populations with a high prevalence of this allele., (© 2016 Wiley Periodicals, Inc.)

Objective: To investigate the effect of antenatal breastfeeding counseling on the breastfeeding rates for women who give birth to twins., Design: Prospective randomized trial., Setting: Multiple Pregnancy Unit, Obstetrics Department, University of São Paulo, Brazil., Participants: A total of 171 mothers of twins and their 342 infants., Methods: The participants were randomized into the prenatal counseling group (PCG) or control group (CG). Breastfeeding data were collected through personal interviews at three times after birth: 30 to 40 days (Time 1), 90 days (Time 2), and 180 days (Time 3). The primary endpoint was a comparison of the mothers' breastfeeding rates between PCG and CG in each analyzed period. The secondary endpoint was the comparison of the overall rates of twin infant breastfeeding between PCG and CG until 180 days after birth., Results: The final analysis included 68 women pregnant with twins in the PCG and 60 in the CG. There was no significant difference in the breastfeeding rates between PCG and CG in the analyzed periods: Time 1 (odds ratio [OR] = 1.87, 95% confidence interval [CI] [0.71, 4.95]), Time 2 (OR = 1.50, 95% CI [0.72, 3.10]), and Time 3 (OR = 1.06, 95% CI [0.51, 2.19]). Also, no difference existed in the overall rates of breastfeeding between PCG and CG at 180 days., Conclusion: In women pregnant with twins, antenatal breastfeeding counseling did not significantly affect the breastfeeding rates. Further research about the best moment to counsel mothers of twins is needed to improve breastfeeding rates., (Copyright © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the antenatal fetal heart rate (FHR) parameters analyzed by computerizedcardiotocography (cCTG) in fetuses with gastroschisis and compare the FHR parameters with ultrasound gastrointestinal markers., Methods: A retrospective analysis of antepartum cCTG records were conducted in 87 pregnant cases with fetal gastroschisis between 28and 36 weeks (plus 6 days). A comparative analysis of the median distribution of the following FHR parameters was performed: basal FHR, short-term variation (STV), FHR accelerations and decelerations, episodes of high and low variations, and variations in low and high episodes. FHR parameters and ultrasound gastrointestinal markers were also compared., Results: The majority of FHR parameters did not present significant changes throughout gestation. An increased number of records with episodes of low variation (p = 0.019) and an increased number of accelerations >15 bpm (p = 0.001) were the only observed changes throughout gestation. Stomach herniation was significantly associated with a lower STV (p = 0.018) and a higher frequency of records with low episodes (p = 0.049)., Conclusions: The cCTG analysis indicated that the FHR parameters in fetuses with gastroschisis presented different patterns from those observed in normal fetuses. Stomach herniation was associated with altered FHR patterns.

Introduction: The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women., Objective: To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy., Method: Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome"., Results: A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities., Conclusion: The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

Objectives: This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations., Study Design: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization., Results: The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation., Conclusions: In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate predictors of perinatal mortality in triplet pregnancies., Methods: Retrospective cohort managed in a tertiary teaching hospital (1998-2012) including all pregnancies with tree live fetuses at the first ultrasound examination, performed after 11 weeks of gestation. Primary end-point was defined as the number of children alive at hospital discharge. Ordinal stepwise regression analysis examined the association with maternal age, parity, pregnancy chorionicity, gestational age at our first ultrasound evaluation, presence of maternal clinical, obstetrical and fetal complications and gestational age at delivery., Results: Sixty-seven triplet pregnancies were first seen at 18.5 ± 6.8 weeks, 33 (49.3 %) were trichorionic, obstetric complications occurred in 34 (50.7 %) and fetal complications were diagnosed in 17 (25.4 %). Perinatal mortality rate was 249 ‰ (95 % CI 189-317) and 138 (73 %) children were discharged alive from hospital (11 pregnancies with no survivors; single and double survival in ten cases each; all children alive in 36). Regression analysis showed that presence of fetal complications (OR 0.10, 95 % CI 0.03-0.36) and gestational age at delivery (OR 1.55, 95 % CI 1.31-1.85) are significant predictors of outcome (p < 0.001)., Conclusions: Perinatal mortality in non-selected triplet pregnancies is high and is related to the presence of fetal complications and gestational age at delivery.

Objective: To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia., Methods: Fetal pulmonary response, prematurity (<37 weeks at delivery) and extreme prematurity (<32 weeks at delivery) were evaluated and compared between survivors and non-survivors at 6 months of life. Multivariable analysis was conducted with generalized linear mixed models for variables significantly associated with survival in univariate analysis., Results: Eighty-four infants were included, of whom 40 survived (47.6%) and 44 died (52.4%). Univariate analysis demonstrated that survival was associated with greater lung response (p=0.006), and the absence of extreme preterm delivery (p=0.044). In multivariable analysis, greater pulmonary response after FETO was an independent predictor of survival (aOR 1.87, 95% CI 1.08-3.33, p=0.023), whereas the presence of extreme prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367)., Conclusion: Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery.

Objective: To analyze the prenatal outcomes in a cohort of fetuses with mild bilateral pyelectasis and determine whether performing serial ultrasounds is a good follow-up strategy., Methods: A prospective longitudinal study was conducted on 62 fetuses with mild bilateral pyelectasis. Fetal mild bilateral pyelectasis was considered when the renal pelvis measured (in millimeters) ≥5.0 to 10.0, ≥7.0 to 10.0, and ≥10.0 to 15 at ≤23 weeks 6 days, 24 to 31 weeks 6 days, and ≥32 weeks, respectively, with no uretero-calyceal dilatation. Ultrasounds were performed every 3 weeks to assess whether the mild bilateral pyelectasis regressed, remained unchanged (Group 1) or progressed (Group 2)., Results: Group 1 consisted of 53 fetuses (85.4%), and progression was observed in 9 cases (Group 2, 14.6%). The initial renal pelvis diameter was significantly larger in fetuses with progression (p=0.028). Statistically significant differences in the renal pelvis diameter were also found at weeks 31 and 35 for both kidneys (p<0.05). The cases requiring intrauterine procedures or early delivery were not observed., Conclusion: Fetal mild bilateral pyelectasis with no calyceal dilatation is a benign condition that can be managed in the postnatal period. The initial renal pelvis diameter and the diameter in week 31 or 35 were valuable parameters for identifying cases that would eventually need specific postnatal procedures., Competing Interests: No potential conflict of interest was reported.

Objective: We aimed to compare sFlt-1 and placental growth factor (PlGF) levels and the sFlt-1/PlGF ratio between women with preeclampsia and superimposed preeclampsia to, respectively, normotensive and chronic hypertensive ones., Study Design: We performed a prospective two-armed cohort in a tertiary teaching hospital in Sao Paulo, Brazil, including 37 normotensive and 60 chronic hypertensive pregnant women. We assessed the serum levels of sFlt-1 and PlGF at 20, 26, 32, and 36 gestational weeks by enzyme-linked immunosorbent assay., Main Outcome Measures: Having preeclampsia and superimposed preeclampsia., Results: Among normotensive and chronic hypertensive pregnancies, 4 (10.8%) and 14 (23.3%) women developed preeclampsia and superimposed preeclampsia, respectively. Compared with those who remained normotensive, the preeclampsia women presented higher sFlt-1 levels at 32 gestational weeks (4323.45 pg/mL vs. 2242.04 pg/mL, p = 0.019), lower PlGF levels at 20 (183.54 pg/mL vs. 337.38 pg/mL, p = 0.034), 32 (169.69 pg/mL vs. 792.53 pg/mL, p = 0.001), and 36 gestational weeks (252.99 pg/mL vs. 561.81 pg/mL, p = 0.029), and higher sFlt-1/PlGF ratios at 26 (9.02 vs. 1.84, p = 0.004), 32 (23.61 vs. 2.55, p = 0.001), and 36 gestational weeks (49.02 vs. 7.34, p = 0.029). On the other hand, compared with those who remained chronic hypertensive, the superimposed preeclampsia women only presented a higher sFlt-1/PlGF ratio at 32 gestational weeks (9.98 vs. 2.51, p = 0.039)., Conclusion: Although angiogenic imbalance is clearly related to preeclampsia, it seems to play a more modest role in superimposed preeclampsia, in which other mechanisms should also be investigated.

Objective: To evaluate the retention of information after participation in multidisciplinary group in patients with gestational diabetes mellitus (GDM) through a phone contact., Method: 122 pregnant women diagnosed with gestational diabetes were included. After diagnosis of gestational diabetes, the patients were referred to the multidisciplinary group where they received medical, nutrition and nursing guidelines related to the disease. After three days these patients received one telephone call from a nurse, who made the same questions regarding the information received. In the statistical analysis, results were presented as absolute and relative frequencies., Results: Most patients 119/122 patients (97.5%) were managing to do self glucose monitoring. Twenty-one patients (17.2%) reported having difficulty performing the blood glucose, especially finger pricking. When questioning whether the woman was following the proposed diet, 24/122 (19.7%) patients said they did not; the meal frequency was not reached by 23/122 (18.9%) of the women, and forty-seven (38.5%) of the women reported having ingested sugar in the days following the guidance in multidisciplinary group., Conclusion: Regarding the proposed treatment, there was good adherence of patients, especially in relation to blood glucose monitoring. As for nutritional control, we observed greater difficulty in following the guidelines demonstrating the need for long-term monitoring, as well as further clarification to the patients about the importance of nutrition in diabetes management.

Introduction: A previous study indicated that progesterone reduces the mean uterine contraction frequency in singleton pregnancy at high risk for preterm birth. The aim of this study was to investigate the effect of vaginal progesterone on the frequency of uterine contractions in twin pregnancies., Material and Methods: This was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. Naturally conceived twin pregnancies with no prior history of preterm delivery, asymptomatic regarding preterm labor, who had undergone uterine contraction frequency monitoring from 24 to 34 weeks and 6 days were included in the study. Comparison of the mean frequency of uterine contractions between the treatment groups was performed. We also examined the influence of cervical length and chorionicity on the mean frequency of uterine contractions according to the group., Results: The final analysis included 166 women in the progesterone and 170 in the placebo group. The baseline characteristics were similar in the two groups. Overall, no difference in the mean frequency of uterine contractions (p = 0.91) was observed between the progesterone (2.54 ± 3.19) and placebo (2.56 ± 3.59) groups. Also, no difference in the mean frequency of uterine contractions was observed between the groups in each week between 24 and 34 weeks and 6 days of gestation. Cervical length and chorionicity did not influence the frequency of contractions according to the progesterone or placebo treatment., Conclusions: Overall, progesterone does not influence the frequency of uterine contractions in twin pregnancies., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

A retrospective study from November 2004 to May 2012, conducted at the Obstetric Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; 95CI=0.27- 0.85, p=0.005). No predictive factors were identified in the T13/18 group. Intra- uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

Aim: To determine the ultrasonographic findings that predict death in fetal ascites., Methods: This was a retrospective cohort study involving pregnancies with ultrasonographic findings related to fetal ascites. The inclusion criteria were as follows: single pregnancy with a live fetus; ultrasound findings of ascites; ascites unrelated to maternal fetal alloimmunization; and pregnancy follow-up at our institution. The χ2-test was used to evaluate the association of ultrasound findings and death. Multiple logistic regression analysis was performed to determine the ultrasound findings that are predictive of death prior to hospital discharge., Results: A total of 154 pregnancies were included in the study. In 8 (5.19%) cases, ascites was an isolated finding, and in 146 cases, other alterations were observed during the ultrasound evaluation. Death before hospital discharge occurred in 117 cases (76.00%). The following ultrasonographic findings were significantly associated with death: gestational age at diagnosis <24 weeks (P<0.0001); stable/progressive ascites evolution (P=0.004); the presence of hydrops (P<0.0001); and the presence of cystic hygroma (P<0.0001). The presence of hydrops, the presence of respiratory tract malformations, and stable/progressive ascites evolution were significantly associated with the prediction of death., Conclusions: Based on ultrasound examination, the presence of hydrops, malformation of the respiratory tract, and stable/progressive evolution of ascites increase the chances of death in cases of fetal ascites.

Purpose: To evaluate the precision of both two- and three-dimensional ultrasonography in determining vertebral lesion level (the first open vertebra) in patients with spina bifida., Methods: This was a prospective longitudinal study comprising of fetuses with open spina bifida who were treated in the fetal medicine division of the department of obstetrics of Hospital das Clínicas of the Universidade de São Paulo between 2004 and 2013. Vertebral lesion level was established by using both two- and three-dimensional ultrasonography in 50 fetuses (two examiners in each method). The lesion level in the neonatal period was established by radiological assessment of the spine. All pregnancies were followed in our hospital prenatally, and delivery was scheduled to allow immediate postnatal surgical correction., Results: Two-dimensional sonography precisely estimated the spina bifida level in 53% of the cases. The estimate error was within one vertebra in 80% of the cases, in up to two vertebrae in 89%, and in up to three vertebrae in 100%, showing a good interobserver agreement. Three-dimensional ultrasonography precisely estimated the lesion level in 50% of the cases. The estimate error was within one vertebra in 82% of the cases, in up to two vertebrae in 90%, and in up to three vertebrae in 100%, also showing good interobserver agreement. Whenever an estimate error was observed, both two- and three-dimensional ultrasonography scans tended to underestimate the true lesion level (55.3% and 62% of the cases, respectively)., Conclusions: No relevant difference in diagnostic performance was observed between the two- and three-dimensional ultrasonography. The use of three-dimensional ultrasonography showed no additional benefit in diagnosing the lesion level in the fetuses with spina bifida. Errors in both methods showed a tendency to underestimate lesion level., (Thieme Publicações Ltda Rio de Janeiro, Brazil.)

Objective: To investigate the changes in fetal left ventricle myocardial performance index (MPI) following intrauterine intravascular transfusion (IUT)., Methods: Prospective study, including 25 IUT performed in 13 singleton pregnancies with maternal Rh D alloimmune disease. Left ventricle MPI was evaluated prior to transfusion and repeated 24 h after each procedure. Delta MPI was calculated as the difference between post- and pre-transfusion MPI z-scores. Multilevel regression analysis was used to examine the association between delta MPI and gestational age at procedure, fetal middle cerebral artery peak velocity MoM, pre- and post-MPI and hemoglobin z-score values, the volume of blood transfused and feto-placental volume percentage expansion. Adjustments were made for repeated measurements within the same fetus, and across different time points. The significance level was set as 0.05., Results: MPI z-score values increased significantly following transfusion (delta MPI = 1.10 ± 2.47, p=0.036). Delta MPI showed a significant correlation with gestational age at transfusion (r= -0.47, p=0.018), pre-transfusion MPI z-score (r= -0.50, p=0.012) and feto-placental volume percentage expansion (r= -0.41, p=0.044)., Conclusion: Left ventricle MPI increases significantly after intrauterine blood transfusion and greater changes are associated with procedures at an earlier gestational age, lower pre-transfusion MPI z-scores and smaller feto-placental volume expansion.

Objective: The aim of this study was to analyze the causes and perinatal outcome related to fetal ductus arteriosus constriction or closure at a single center over a 26-year period., Methods: This was a retrospective analysis of 45 consecutive cases of constriction (n = 41) and closure (n = 4) from 1987 through 2013. Patients were divided into Group A (maternal use of non-steroidal anti-inflammatory drugs (NSAID), n = 29), Group B (idiopathic, n = 8), and Group C (other drugs not previously described, n = 8)., Results: The median gestational age at diagnosis was 34 weeks (range, 27-38), mean systolic and diastolic velocity in the ductus arteriosus was 2.01 ± 0.66 m/s and 0.71 ± 0.46 m/s, respectively. Among the 29 cases of NSAIDs, 27.5% (8/29) have taken a single day use and 75% multiple days/doses. Right ventricular dilatation was present in 82.2% of the fetuses, tricuspid insufficiency in 86.6%, and heart failure in 22.2%. Neonatal persistent pulmonary hypertension occurred in 17.7% of the patients. Late follow-up showed all 43 survivors alive and healthy with only two deaths from unrelated causes., Conclusions: The results of this study indicate that clinically significant ductal constriction may follow maternal exposure to single doses of NSAIDs. Unknown causes or other new substances were also described, such as naphazoline, fluoxetine, isoxsuprine, caffeine and pesticides. Echocardiographic diagnosis of ductal constriction led to an active medical approach that resulted in low morbidity of this group of patients.