Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia

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

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Gender-Specific Differences in Fetal Cardiac Troponin T in Pregnancies Complicated by Placental Insufficiency

Background: Placental insufficiency and fetal growth restriction may lead to fetal hypoxia and acidemia, which result in fetal cardiac injury. Objective: The goal of this study was to compare the levels of fetal cardiac troponin T (cTnT) at birth and fetal Doppler parameters according to fetal gender in pregnancies complicated by placental insufficiency before 34 weeks` gestation. Methods: Between March 2007 and November 2010, singleton pregnancies with placental insufficiency characterized by abnormal umbilical artery Doppler results were prospectively studied. All the patients delivered by cesarean section, and Doppler examinations were performed up to 48 hours before birth. Immediately after delivery, umbilical artery blood samples were obtained for fetal cTnT measurements. Results: Fifty high-risk pregnant women met the study criteria. The study groups were as follows: group 1 consisted of 23 male fetuses (46%) and group 2 consisted of 27 female fetuses (54%). cTnT levels were significantly higher in the group of male fetuses (median, 0.14; range, 0.01-0.85) compared with the group of female fetuses (median, 0.05; range, 0.01-0.27) (P = 0.039). In the group of male fetuses, Doppler results of the ductus venosus assessment revealed values of pulsatility index for veins >= 1.0 in 15 male fetuses (65.2%) and 9 female fetuses (33.3%) (P = 0.032). Conclusions: Fetal gender was associated with cTnT level at birth in pregnancies complicated by placental insufficiency before 34 weeks` gestation, although the Doppler findings did not support gender differences. The fetal cardiac compromise and cardiac injury may be influenced by fetal gender, suggesting differences in the cardiovascular response to fetal hypoxia. (Gend Med. 2011;8:202-208) (C) 2011 Elsevier HS Journals, Inc. All rights reserved

Changes in Amniotic Fluid Index after Maternal Oral Hydration in Pregnancies with Fetal Gastroschisis: Initial Observations

Objective: To evaluate the effect of maternal oral hydration on amniotic fluid index (AFI) in pregnancies with fetal gastroschisis. Methods: AFI was evaluated at 24-hour intervals, during 4 consecutive days, under a continuous maternal oral water hydration regimen, in singleton pregnancies with isolated fetal gastroschisis. Results: Nine pregnancies were examined at a mean gestational age of 31.6 weeks (+/-1.4) and mean maternal daily oral water intake was 3,437 (+/-810) ml. Mean AFI on days 0-3 were 13.2 (+/-2.9), 14.8 (+/-3.3), 14.5 (+/-3.1) and 14.8 (+/-2.6), respectively. AFI on day 0 was significantly lower compared to all the other 3 days (p = 0.01 and 0.02). Significant correlation was found in relative difference in AFI between day 0 and day 1 and gestational age (r = -0.67, p = 0.05) and the amount of water intake in the previous 24 h (r = 0.76, p = 0.02). Conclusion: Maternal oral water hydration significantly increases AFI in pregnancies with isolated fetal gastroschisis. Copyright (C) 2010 S. Karger AG, Base

Computerized cardiotocography in pregnancies complicated by maternal asthma

Objective: The aim of the present study was to investigate the FHR parameters in term pregnancies complicated by asthma. Study design: prospective cross-sectional study performed between July 2008 and November 2009. Twenty-one singleton pregnancy between 36 and 40 weeks gestation with diagnosis of maternal asthma and no current use of oral corticosteroids were compared with 30 pregnancies without morbidities at the same gestational age. The computerized cardiotocography (System 8002, Sonicaid) was performed and 30 min analysis was studied. Statistical analysis included Student's t-test or Mann-Whitney U test for comparisons between groups. Categorical data were compared using the chi(2)-test or Fisher's exact test. Results: There were no significant differences in FHR parameters analyzed by computerized cardiotocography: basal FHR (p = 0.80), number of accelerations >10 bpm (p = 0.08) or >15 bpm (p = 0.20), duration of high episodes (p = 0.70), duration of low episodes (p = 0.46) and STV (p = 0.66). Asthmatic mothers presented mean number of fetal movement per hour significantly lower than control group (34.6 +/- 28.2 vs. 60.6 +/- 43.1, p = 0.02). Conclusion: Computerized cardiotocography demonstrates no association between the abnormal parameters of FHR and maternal asthma in term pregnancies. Maternal asthma was associated with less fetal movements per hour, suggesting further studies on the counting of fetal movements in pregnant women with asthma.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Prediction of intrauterine death and severe preterm delivery in twin pregnancies discordant for major fetal abnormality

Objective: To investigate predictors of spontaneous fetal death and preterm delivery in twin pregnancies with one fetus affected by a major structural malformation.Study design: Retrospective study (1999-2012) conducted at a tertiary teaching hospital involving 51 twin pregnancies (dichorionic = 31, monochorionic diamniotic = 15, monochorionic monoamniotic = 4, not established = 1) with a major fetal abnormality, enrolled before 26 weeks and managed expectantly. Primary outcomes: spontaneous fetal death, and/or delivery before 32 weeks. Prediction was examined with stepwise logistic regression analysis, and independent variables included: maternal age, gestational age at diagnosis, chorionicity, fetal gender, number and type of fetal abnormalities. Significance level was set at 0.15.Results: Fetal abnormalities were diagnosed at a mean gestation of 21.5 3.7 weeks: cardiac abnormalities were observed in 31.4% of abnormal fetuses, abdominal wall defects in 29.4%, central nervous system 21.5%, spine 17.6%, effusions 17.6%, noncardiac thoracic abnormalities 15.7%, genital and urinary system 13.7%, limbs and soft tissue 3.9%, intestinal 1.9% and facial defects 1.9%. Fetal death occurred in 15 (29.4%) abnormal fetuses and was significantly correlated with the number of fetal malformations (p = 0.02, OR = 2.54, 95% CI = 1.14-5.62), presence of effusion/hydrops (p = 0.06, OR = 4.7, 95% CI = 0.95-24) and monochorionic placenta (p = 0.11, OR= 2.8, 95% CI = 0.78-9.8). Normal co-twin fetal death occurred in four cases (7.8%) and was related to monochorionic pregnancies (p = 0.14, OR = 5.8, 95% CI = 0.56-61). Delivery before 32 weeks was observed in 14 (27.5%) pregnancies and was related to presence of effusion/ hydrops (p = 0.04, OR = 5.5, 95% CI = 1.07-28).Conclusion: Spontaneous fetal death and/or delivery before 32 weeks in twin pregnancies with one fetus affected by a major structural malformation are related to the number of abnormalities diagnosed and presence of fetal effusion or hydrops. 2014 Elsevier Ireland Ltd. All rights reserved.Univ São Paulo, Sch Med, Dept Obstet & Gynecol, São Paulo, BrazilUniv São Paulo, Sch Med, Hosp Clin, Dept Pediat, São Paulo, BrazilWeb of Scienc

Transplacental Total IgG Transfer in Twin Pregnancies

ProblemIn twin pregnancies, factors that influence total umbilical cord IgG concentration and IgG transfer ratio are not well known.MethodBlood samples were prospectively collected from 57 twin pregnancies. Stepwise multivariate regression analysis was used to evaluate the association between total IgG levels in the umbilical cord blood and IgG transfer ratio according to serum IgG concentration, pregnancy chorionicity, the presence of abnormal umbilical artery pulsatility index, intrauterine growth restriction, gestational age at delivery (GAD), birthweight, and placental weight.ResultsUmbilical cord IgG concentration showed a positive correlation with serum IgG concentration and GAD; levels were significantly lower in monochorionic compared with dichorionic pregnancies. IgG transfer ratio also increased with GAD but was inversely correlated with serum IgG concentration levels.ConclusionIn twin pregnancies, besides serum IgG concentration and GAD, chorionicity also influences umbilical cord IgG concentration. Monochorionic twins have lower IgG cord concentration than dichorionic twins.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Sch Med, Dept Obstet & Gynecol, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Pediat, São Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilFAPESP: 2011/13587-4Web of Scienc

Should We Measure Fetal Omphalocele Diameter for Prediction of Perinatal Outcome?

Objective: To evaluate the fetal omphalocele diameter/abdominal circumference ratio (OD/AC) as a predictor of adverse perinatal outcome. Methods: Analysis involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and absence of other major abnormalities. the OD/AC ratio was determined antenatally by ultrasound and the best cutoff for the prediction of neonatal death was determined by receiver operating characteristic curve analysis. Additional secondary outcomes included need for oral intubation in the first 24 h of life, two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and need for respiratory assistance >21 days, time to first oral feed, and time to hospital discharge. Results: Fetal OD/AC did not change significantly with gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff for prediction was an OD/AC ratio >= 0.26 in pregnancies with the first ultrasound evaluation performed before 31 weeks' gestation and an OD/AC >= 0.26, the likelihood ratio for needing intubation in the first 24 h of life was 2.6 (95% CI: 1.2-5.7), needing two-step surgery or use of mesh was 4.9 (95% Cl: 1.9-14.4), and postnatal death was 4 (95% Cl: 1.9-7.5). Conclusion: A fetal ultrasound OD/AC ratio >= 0.26 is associated with increased postnatal morbidity and mortality. (C) 2013 S. Karger AG, BaselUniv São Paulo, Sch Med, Hosp Clin, Dept Obstet & Gynaecol, São Paulo, BrazilUniv São Paulo, Sch Med, Hosp Clin, Dept Pediat Surg, São Paulo, BrazilUniv São Paulo, Sch Med, Hosp Clin, Dept Pediat, São Paulo, BrazilWeb of Scienc

Feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation

Objective: this study investigated the feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation. The aim of this study was to present the decision making process of women that chose for pregnancy termination and to present selected speeches of women about their feelings. Design: open psychological interviews conducted by a psychologist immediately after the diagnosis of fetal malformation by ultrasound. Analysis of the results was performed through a content analysis technique. Setting: the study was carried out at a public university hospital in Brazil. Participants: 249 pregnant women who had received the diagnosis of a severe lethal fetal malformation. Findings: fetal anencephaly was the most frequent anomaly detected in 135 cases (54.3%). Termination of pregnancy was decided by 172 (69.1%) patients and legally authorised by the judiciary (66%). The reason for asking for termination was to reduce suffering in all of them. In the 77 women who chose not to terminate pregnancy (30.9%), the reasons were related to feelings of guilt (74%). Key conclusions: the results support the importance of psychological counselling for couples when lethal fetal malformation is diagnosed. The act of reviewing moral and cultural values and elements of the unconscious provides assurance in the decision-making process and mitigates the risk of emotional trauma and guilt that can continue long after the pregnancy is terminated. (C) 2011 Elsevier Ltd. All rights reserved