Katherine Bianco, MD

Abstract

OBJECTIVE: Evaluate simulation-based training (SBT) in low-and-middle-income countries (LMIC) and the long-term retention of knowledge and self-efficacy.METHODS: We conducted a SBT course on the management of post-partum hemorrhage (PPH), shoulder dystocia (SD), and maternal cardiac arrest (MCA) in three governmental teaching hospitals in Guatemala. We evaluated changes in knowledge and self-efficacy using a multiple-choice questionnaire (MCQ) for 46 OB/GYN residents. A paired Student t-test was used to analyze changes at one week and six months after the SBT.RESULTS: There was an increase in scores in clinical knowledge of MCA, P <0. 001, 95% CI [0.81, 1.49], and SD, P<0.001, 95% CI [0.41, 1.02] one week following SBT and a statistically insignificant increase in PPH scores, P= 0.617, 95% CI [-0.96, 0.60]. This increase in scores was maintained after six months, for MCA, P< 0.001, 95% CI [0.69, 1.53], SD, P= 0.02 95% CI [0.07-0.85] and PPH, P=0.04 95% CI [0.01, 1.26]. For MCA and SD levels of self-efficacy were increased one-week following training, P<0.001 95% CI [0.83, 2.30] and P= 0.008 95% CI [0.60, 3.92], respectively, and at six-months P<0.001 95% CI [0.79, 2.42] and P= 0.006 95% CI [0.66, 3.81], respectively. There was a slight increase in PPH self-efficacy scores one-week after SBT, P=0.73, 95% CI [-6.05, 4.41], maintained after six-months P= 0.38 95% CI [-6.85, 2.85].CONCLUSION: SBT was found to be an effective and feasible method to increase short and long-term clinical knowledge and self-efficacy of obstetric emergencies in LMIC.

View details for DOI 10.1002/ijgo.13526

View details for PubMedID 33314149

View details for DOI 10.1016/j.ajog.2020.08.001

View details for PubMedID 32771381

View details for Web of Science ID 000525432601113

View details for Web of Science ID 000525432600181

Abstract

Impaired placentation is implicated in poor perinatal outcomes associated with Trisomy 21. Earlier studies revealed abnormal cytotrophoblast differentiation along the invasive pathway as a contributing mechanism. To further elucidate the causes, we evaluated Caspase-2 expression at the protein level (immunolocalization and immunoblot) in samples from Trisomy 21 (n = 9) and euploid (n = 4) age-matched placentas. Apoptosis was investigated via the TUNEL assay. An immunolocalization approach was used to characterize Caspase-3, Fas (CD95), and Fas ligand in the same samples. Caspase-2 was significantly overexpressed in Trisomy 21 placentas, with the highest expression in villous cores and invasive cytotrophoblasts. Immunolocalization showed that Caspase-3 had a similar expression pattern as Caspase-2. Using the TUNEL approach, we observed high variability in the number of apoptotic cells in biopsies from different regions of the same placenta and among different placentas. However, Trisomy 21 placentas had more apoptotic cells, specifically in cell columns and basal plates. Furthermore, Caspase-2 co-immunolocalized with Fas (CD95) and FasL in TUNEL-positive extravillous cytotrophoblasts, but not in villous cores. These results help explain the higher levels of apoptosis among placental cells of Trisomy 21 pregnancies in molecular terms. Specifically, the co-expression of Caspase-2 and Caspase-3 with other regulators of the apoptotic process in TUNEL-positive cells suggests these molecules may cooperate in launching the observed apoptosis. Among trophoblasts, only the invasive subpopulation showed this pattern, which could help explain the higher rates of adverse outcomes in these pregnancies. In future experiments, this relationship will be further examined at a functional level in cultured human trophoblasts.

View details for DOI 10.1007/s43032-019-00002-x

View details for Web of Science ID 000525433300011

View details for PubMedID 32046398

View details for DOI 10.1016/j.ajog.2019.11.569

View details for Web of Science ID 000504997300552

Abstract

The clinical importance of marginal cord insertion (MCI) is currently controversial. In this study, we examined the association between MCI and adverse perinatal outcomes. We also evaluated the ultrasound-measured distance from the site of placental cord insertion (PCI) to the placental margin (PCI distance) and perinatal outcomes.This was a retrospective cohort study of MCI and control pregnancies presenting to a single institution between September 2014 and August 2016. Marginal cord insertion was diagnosed on routine anatomy ultrasound scans at 20weeks' gestation. The primary outcome was fetal intolerance to labor. Secondary outcomes of interest included mode of delivery, gestational age at delivery, Apgar scores at 1 and 5 minutes, birth weight, delivery complications, and neonatal intensive care unit admission. The PCI distance was determined by an ultrasound review. Statistical significance was evaluated by a 2 analysis, descriptive statistics, Wilcoxon tests, and regression models with log-transformed outcomes, the PCI distance, or both as needed.Of 675 abnormal cord insertion cases, we identified 183 that met inclusion criteria. We found no statistically significant association between MCI and fetal intolerance to labor (odds ratio, 1.24 [95% confidence interval, 0.55-2.80]; P = .71) or secondary outcomes. Furthermore, we found no significant correlation between perinatal outcomes and the PCI distance.Our study suggests that MCI pregnancies, regardless of the specific PCI distance, might not be at increased risk of adverse perinatal outcomes. This finding questions the need for heightened antepartum surveillance of this patient population.

View details for DOI 10.1002/jum.15586

View details for PubMedID 33277931

View details for DOI 10.1158/1538-7445.AM2018-5569

View details for Web of Science ID 000468819504548

View details for Web of Science ID 000422946900255

Abstract

Chromosomal aberrations are frequently associated with birth defects and pregnancy losses. Trisomy 13, Trisomy 18 and Trisomy 21 are the most common, clinically relevant fetal aneusomies. This study used a transcriptomics approach to identify the molecular signatures at the maternal-fetal interface in each aneuploidy.We profiled placental gene expression (13-22weeks) in T13 (n=4), T18 (n=4) and T21 (n=8), and in euploid pregnancies (n=4).We found differentially expressed transcripts (2-fold) in T21 (n=160), T18 (n=80) and T13 (n=125). The majority were upregulated and most of the misexpressed genes were not located on the relevant trisomic chromosome, suggesting genome-wide dysregulation. A smaller number of the differentially expressed transcripts were encoded on the trisomic chromosome, suggesting gene dosage. In T21, <10% of the genes were transcribed from the Down syndrome critical region (21q21-22), which contributes to the clinical phenotype. In T13, 15% of the upregulated genes were on the affected chromosome (13q11-14), and in T18, the percentage increased to 24% (18q11-22 region).The trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome-wide phenomena and increased gene dosage from the trisomic chromosome. 2016 John Wiley & Sons, Ltd.

View details for DOI 10.1002/pd.4862

View details for Web of Science ID 000384096800002

View details for PubMedID 27328057

View details for PubMedCentralID PMC5104283

View details for DOI 10.1016/j.ajog.2015.10.666

View details for Web of Science ID 000367092800614

Abstract

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

View details for DOI 10.1038/nature14248

View details for PubMedID 25693563

View details for PubMedCentralID PMC4530010

Abstract

During human pregnancy, a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4%-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) and, in some patients, fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously, we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, we cultured CTBs isolated from PE and control placentas for 48 hours, enabling differentiation and invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation, including upregulation of SEMA3B, which resolved in culture. The addition of SEMA3B to normal CTBs inhibited invasion and recreated aspects of the PE phenotype. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression; the autocrine actions of the upregulated molecules (including SEMA3B) impair CTB differentiation, invasion and signaling; and patient-specific factors determine the signs.

View details for DOI 10.1172/JCI66966

View details for Web of Science ID 000321316700016

View details for PubMedID 23934129

View details for PubMedCentralID PMC3999620

View details for Web of Science ID 000329543100649