Good performance of bioimpedance in early pregnancy to predict preeclampsia.

INTRODUCTION: Preeclampsia (PE) affects 2-8% of pregnancies and is one of the main causes of maternal morbidity and mortality worldwide. Early identification of pregnant women at higher risk for PE would allow the use of interventions to reduce adverse maternal and perinatal outcomes. OBJECTIVE: To assess the ability of bioelectrical impedance analysis (BIA) in pregnancy to predict the development of PE. METHODS: This prospective cohort involved healthy nulliparas who underwent BIA at 17-20 weeks gestation and were followed until delivery. We used univariate and multivariate logistic regression to assess the ability of BIA measures to predict the occurrence of PE. We used an adjusted regression model to estimate the probability of developing PE, the Hosmer-Lemeshow test to assess the adequacy of the final model, and ROC curves to assess the sensitivity and specificity of different BIA measures in the prediction of PE. RESULTS: Twelve (6.1%) of the 196 participants developed PE. In the final multivariate model, the following BIA measures were associated with the occurrence of PE: extracellular water/intracellular water ≤ 0.618, skeletal muscle mass ≥ 25 Kg, and body fat percentage ≥ 44%. The combination of these three measures had a predictive accuracy of 83.7%, a sensitivity of 83.3%, a specificity of 83.7%, and a negative predictive value of 98.7% for PE. CONCLUSION: BIA done on nulliparous women at 17-20 weeks gestation has a good accuracy and high negative predictive value for the risk of developing PE.

Distinct microRNA profiles for complete hydatidiform moles at risk of malignant progression.

BACKGROUND: MicroRNAs are small noncoding RNAs with important regulatory functions. Although well-studied in cancer, little is known about the role of microRNAs in premalignant disease. Complete hydatidiform moles are benign forms of gestational trophoblastic disease that progress to gestational trophoblastic neoplasia in up to 20% of cases; however, there is no well-established biomarker that can predict the development of gestational trophoblastic neoplasia. OBJECTIVE: This study aimed to investigate possible differences in microRNA expression between complete moles progressing to gestational trophoblastic neoplasia and those regressing after surgical evacuation. STUDY DESIGN: Total RNA was extracted from fresh frozen tissues from 39 complete moles collected at the time of uterine evacuation in Brazil. In the study, 39 cases achieved human chorionic gonadotropin normalization without further therapy, and 9 cases developed gestational trophoblastic neoplasia requiring chemotherapy. Total RNA was also extracted from 2 choriocarcinoma cell lines, JEG-3 and JAR, and an immortalized normal placenta cell line, 3A-subE. MicroRNA expression in all samples was quantified using microRNA sequencing. Hits from the sequencing data were validated using a quantitative probe-based assay. Significantly altered microRNAs were then subjected to target prediction and gene ontology analyses to search for alterations in key signaling pathways. Expression of potential microRNA targets was assessed by quantitative real-time polymerase chain reaction and western blot. Finally, potential prognostic protein biomarkers were validated in an independent set of formalin-fixed paraffin-embedded patient samples from the United States (15 complete moles progressing to gestational trophoblastic neoplasia and 12 that spontaneously regressed) using quantitative immunohistochemistry. RESULTS: In total, 462 microRNAs were identified in all samples at a threshold of <1 tag per million. MicroRNA sequencing revealed a distinct set of microRNAs associated with gestational trophoblastic neoplasia. Gene ontology analysis of the most altered transcripts showed that the leading pathway was related to response to ischemia (P<.001). Here, 2 of the top 3 most significantly altered microRNAs were mir-181b-5p (1.65-fold; adjusted P=.014) and mir-181d-5p (1.85-fold; adjusted P=.014), both of which have been shown to regulate expression of BCL2. By quantitative real-time polymerase chain reaction, BCL2 messenger RNA expression was significantly lower in the complete moles progressing to gestational trophoblastic neoplasia than the regressing complete moles (-4.69-fold; P=.018). Reduced expression of BCL2 was confirmed in tissue samples by western blot. Immunohistochemistry in the independent patient samples revealed significantly lower cytoplasmic expression of BCL2 in the villous trophoblasts from cases destined for progression to gestational trophoblastic neoplasia compared with those that regressed, both with respect to staining intensity (optic density 0.110±0.102 vs 0.212±0.036; P<.001) and to the percentage of positive cells (16%±28% vs 49.4%±28.05%; P=.003). CONCLUSION: Complete moles progressing to gestational trophoblastic neoplasia are associated with a distinct microRNA profile. miR-181 family members and BCL2 may be prognostic biomarkers for predicting gestational trophoblastic neoplasia risk.

Women's multisite microbial modulation during pregnancy.

The composition of female microbiome varies with age, physiological and socio-behavior conditions. Also, changes in microbiome composition are observed as pregnancy progresses, especially in the vaginal site. Together with the physiological adaptations of gestation, changes in microbiome composition seem to be fundamental for proper fetal development. This study aimed at simultaneously evaluating the vaginal, gut, and oral microbiome of healthy pregnant women, and comparing it with those observed in healthy non-pregnant women of reproductive age. In a cross-sectional study, vaginal, oral and gut samples were collected from 42 pregnant and 18 non-pregnant women, and the microbiome composition was evaluated by 16S rRNA sequencing, using Illumina platform. In the pregnant group, we observed a positive correlation between Eubacterium and Akkermansia in the gut samples; between Eubacterium and Ruminococcus in the vaginal samples; and between Streptococcus and Gemella in the oral samples. Notwithstanding, we observed a negative correlation between Lactobacillus and Atopobium and between Lactobacillus and Gardnerella in vaginal microbiome. Prevotella was the only genus found in all three sites studied; however, there was no signal of bacterial influence between sites during pregnancy. These results suggest that in addition to hormonal and immunological variations during healthy pregnancy, the female body also undergoes microbiome modulation in multiple sites in order to maintain an eubiotic status.

Neonatal Near Miss among Newborns of Women with Type 1 Diabetes Mellitus.

OBJECTIVE: To investigate the frequency of neonatal near miss (NNM) and associate it with maternal morbidity in newborns of women with type 1 diabetes mellitus (T1DM). METHODS: This was a cross-sectional retrospective study from a secondary analysis of data retrieved from medical records of pregnant women with T1DM cared at a Brazilian university hospital between 2005 and 2015. Maternal near miss (MNM) and potentially life-threatening conditions (PTLC) were classified according to the World Health Organization criteria. NNM was classified according to the Pan American Health Organization Neonatal Near Miss Working Group criteria. Association of maternal morbidity with NNM was assessed using chi-square test. RESULTS: There were 122 newborns (NB) among 137 T1DM pregnancies. Thirty-seven NB presented NNM-incidence of 303 NNM per 1000 live births (37/122). NNM was associated with MNM (P < 0.001, OR (95% CI): 17.15 (1.85-159.12)). PLTC did not increase the odds of NNM (P=0.07; OR (95% CI): 2.1281 (0.92-4.91)). Seven newborns died, six of them from pregnancies without severe maternal morbidity. 71% of the neonatal death (5/7) occurred in malformed neonates. CONCLUSION: MNM was associated with NNM among women with T1DM, and PLTC, paradoxically, did not increase NNM.

Versican silencing in BeWo cells and its implication in gestational trophoblastic diseases.

Versican is a proteoglycan known to interact with cells to influence their ability to proliferate, differentiate, migrate, invade and assemble extracellular matrix, with all of these cell functions present during placentation. In the placenta, cytotrophoblast cells have the ability to differentiate into the syncytiotrophoblast, a mechanism that is greatly increased in gestational trophoblastic diseases (GTD). Nevertheless, the molecular signaling underlying the increased syncytiotrophoblast differentiation are still being unveiled and may result in novel therapeutic targets for GTD. Versican expression was investigated to establish its differential expression among GTD (partial moles, complete moles, invasive moles and choriocarcinoma) and the possible functional outcomes from versican gene silencing. Tissue samples had their versican expression evaluated using immunohistochemistry and RT-PCR. BeWo cells were employed for versican silencing with siRNA and the efficiency was confirmed by RT-PCR, immunofluorescence and flow cytometry. Cell death and forskolin-induced syncytialization were analyzed by a morphological analysis and human chorionic gonadotropin (hCG) production using immunofluorescence. Versican V0 and V1 isoforms were mainly expressed in the syncytiotrophoblast and they were the most expressed in benign rather than in malignant tumors. BeWo cells also expressed V0 and V1 isoforms, but only in cells undergoing syncytial fusion. After versican silencing, cell death was greatly increased, whereas spontaneous and forskolin-induced syncytialization decreased as well as hCG production. Versican is differentially expressed in GTD and is important for hydatidiform moles pathophysiology, protecting trophoblast cells from death and playing a role in their differentiation and functionality.

Experience With the Use of an Online Community on Facebook for Brazilian Patients With Gestational Trophoblastic Disease: Netnography Study.

BACKGROUND: The term gestational trophoblastic disease (GTD) includes both complete and partial moles, which are uncommon nonviable pregnancies with the potential to evolve into a malignancy known as gestational trophoblastic neoplasia. While highly curable, the potential for malignancy associated with molar pregnancies worries the patients, leading them to seek information on the internet. A Facebook page headed by Brazilian specialized physicians in GTD was created in 2013 to provide online support for GTD patients. OBJECTIVE: The objective of our study was to describe the netnography of Brazilian patients with GTD on Facebook (FBGTD) and to evaluate whether their experiences differed depending on whether they received care in a Brazilian gestational trophoblastic disease reference center (BRC) or elsewhere. METHODS: This was a cross-sectional study using G Suite Google Platform. The members of FBGTD were invited to participate in a survey from March 6 to October 5, 2017, and a netnographic analysis of interactions among the members was performed. RESULTS: The survey was answered by 356 Brazilian GTD patients: 176 reference center patients (RCP) treated at a BRC and 180 nonreference center patients (NRCP) treated elsewhere. On comparing the groups, we found that RCP felt safer and more confident at the time of diagnosis of GTD (P=.001). RCP were more likely to utilize FBGTD subsequent to a referral by health assistants (P<.001), whereas NRCP more commonly discovered FBGTD through Web searches (P<.001). NRCP had higher educational levels (P=.009) and were more commonly on FBGTD for ≥ 6 months (P=.03). NRCP were more likely to report that doctors did not adequately explain GTD at diagnosis (P=.007), had more doubts about GTD treatment (P=.01), and were less likely to use hormonal contraception (P<.001). Overall, 89% (317/356) patients accessed the internet preferentially from home and using mobile phones, and 98% (349/354) patients declared that they felt safe reading the recommendations posted by FBGTD physicians. CONCLUSIONS: This netnographic analysis of GTD patients on FBGTD shows that an Web-based doctor-patient relationship can supplement the care for women with GTD. This resource is particularly valuable for women being cared for outside of established reference centers.

Multiple pregnancies with complete mole and coexisting normal fetus in North and South America: A retrospective multicenter cohort and literature review.

OBJECTIVE: To determine the clinical characteristics of multiple gestation with complete mole and coexisting fetus (CHMCF) in North and South America. METHODS: Retrospective non-concurrent cohorts compromised of CHMCF from New England Trophoblastic Disease Center (NETDC) (1966-2015) and four Brazilian Trophoblastic Disease Centers (BTDC) (1990-2015). RESULTS: From a total of 12,455 cases of gestational trophoblastic disease seen, 72 CHMCF were identified. Clinical characteristics were similar between BTDC (n=46) and NETDC (n=13) from 1990 to 2015, apart from a much higher frequency of potentially life-threatening conditions in Brazil (p=0.046). There were no significant changes in the clinical presentation or outcomes over the past 5 decades in NETDC (13 cases in 1966-1989 vs 13 cases in 1990-2015). Ten pregnancies were electively terminated and 35 cases resulted in viable live births (60% of 60 continued pregnancies). The overall rate of gestational trophoblastic neoplasia (GTN) was 46%; the cases which progressed to GTN presented with higher chorionic gonadotropin levels (p=0.026) and higher frequency of termination of pregnancy due to medical complications (p=0.006) when compared to those with spontaneous remission. CONCLUSIONS: The main regional difference in CHMCF presentation is related to a higher rate of potentially life-threatening conditions in South America. Sixty percent of the expectantly managed CHMCF delivered a viable infant, and the overall rate of GTN in this study was 46%. Elective termination of pregnancy did not influence the risk for GTN; however the need for termination due to complications and higher hCG levels were associated with development of GTN in CHMCF.

Decorin and biglycan immunolocalization in non-villous structures of healthy and pathological human placentas.

AIMS: Decorin and biglycan are members of the small leucine-rich proteoglycan family, and constituents of both the extracellular matrix (ECM) and the cell surface. They are recognized as important factors in the control of proliferation, migration and invasion in vivo and in vitro. In this study, the localization patterns of decorin and biglycan were determined in healthy placentas and in highly invasive placental pathologies. METHODS AND RESULTS: The study included immunolocalization of decorin and biglycan in samples of first-trimester and term placentas, placenta accreta, invasive mole, and choriocarcinoma. Extravillous cytotrophoblast (EVT) cells were positive for both proteoglycans in all pathologies and in first-trimester placentas, although not in term placentas. Biglycan was immunolocalized in the ECM of all healthy and pathological placentas, whereas decorin was observed only in term placenta ECM. CONCLUSIONS: The expression of both proteoglycans was cell-specific and gestation time-dependent in healthy placentas, and was associated with invasive EVT cells in pathological placentas. In view of the biological properties of these molecules, it is possible that the biglycan pattern found here is intrinsically implicated in the invasive activity of EVT cells in both healthy and disordered placentas.

Pregnancy follow-up and outcome in a patient with Takayasu's arteritis.

We describe here the pregnancy follow-up and outcome in a patient with Takayasu's arteritis, with a detailed account of the complications during gestation and delivery and the impact of the disease on the newborn's health.

Gestação em portadora de arterite de Takayasu / Pregnancy follow-up and outcome in a patient with Takayasu's arteritis

No presente relato, que descreve a gestação de paciente portadora de arterite de Takayasu, serão avaliadas a interação dessa afecção com a gravidez e as intercorrências materno-fetais, do parto e do recém-nascido.

We describe here the pregnancy follow-up and outcome in a patient with Takayasu's arteritis, with a detailed account of the complications during gestation and delivery and the impact of the disease on the newborn's health.