Michelle Silasi

Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia.

Preeclampsia is a common complication of pregnancy with potentially devastating consequences to both the mother and the baby.It is the leading cause of maternal deaths in developing countries. In developed countries it is the major cause of iatrogenic premature delivery and contributes significantly to increasing health care cost associated with prematurity. There is currently no known treatment for preeclampsia; ultimate treatment involves delivery of the placenta. Although there are several risk factors (such as multiple gestation or chronic hypertension), most patients present with no obvious risk factors. The molecular pathogenesis of preeclampsia is just now being elucidated. It has been proposed that abnormal placentation and an imbalance in angiogenic factors lead to the clinical findings and complications seen in preeclampsia. Preeclampsia is characterized by high levels of circulating antiangiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin, which induce maternal endothelial dysfunction. These soluble factors are altered not only at the time of clinical disease but also several weeks before the onset of clinical signs and symptoms. Many methods of prediction and surveillance have been proposed to identify women who will develop preeclampsia, but studies have been inconclusive. With the recent discovery of the role of angiogenic factors in preeclampsia, novel methods of prediction and diagnosis are being developed to aid obstetricians and midwives in clinical practice. This article discusses the role of angiogenic factors in the pathogenesis, prediction, diagnosis, and possible treatment of preeclampsia.

Understanding the Complexity of the Immune System during Pregnancy

Progress in our understanding of the role of the maternal immune system during healthy pregnancy will help us better understand the role of the immune system in adverse pregnancy outcomes. In this review, we discuss our present understanding of the ‘immunity of pregnancy’ in the context of the response to cervical and placental infections and how these responses affect both the mother and the fetus. We discuss novel and challenging concepts that help explain the immunological aspects of pregnancy and how the mother and fetus respond to infection.

Viral infections during pregnancy.

Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non‐pregnant women. New knowledge about the ways the maternal–fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be ‘immunosuppressed’, the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy and offer potential mechanisms for the associated adverse pregnancy outcomes.

Human Chorionic Gonadotropin Enhances Trophoblast–Epithelial Interaction in an In Vitro Model of Human Implantation

Embryo implantation, which is an absolute requirement for reproduction, starts with blastocyst apposition to the uterine endometrium, followed by attachment to the endometrial surface epithelium. Recent clinical studies reported an increase in implantation and pregnancy rates among women receiving intrauterine human chorionic gonadotropin (hCG) prior to embryo transfer suggesting that, at least in some cases, female infertility is a result of inadequate secretion of hCG. In this study, we characterized the effect of hCG on trophoblast–epithelial interaction by further developing our recently described in vitro model of implantation. Here, we confirmed hCG increased attachment of trophoblast to epithelial cells, using a single-cell trophoblast–epithelial coculture system in addition to a blastocyst-like spheroid–epithelial coculture system. Furthermore, we discovered that the source and concentration was pivotal; the first preparation of hCG affected 2 molecules related to implantation, MUC16 and osteopontin, while the second preparation required additional cytokines to mimic the effects. Using this system, we can develop a comprehensive knowledge of the cellular and gene targets of hCG and other factors involved in embryo apposition and implantation and potentially increase the number of therapeutic targets for subfertile patients.

Robotic Versus Abdominal Hysterectomy for Very Large Uteri

Robotic hysterectomy for very large uteri requires longer operative times but results in shorter hospital stays and decreased intraoperative blood loss.

Placental expression of angiogenic factors in Trisomy 13.

OBJECTIVE Increased levels of soluble fms-like tyrosine kinase (sFlt-1) in Trisomy 13 pregnancies are thought to be mediated by the placenta. This study aimed to compare sFlt-1 expression in Trisomy 13 (n = 7) placentas with that in control placentas (Trisomy 21, n = 11, and euploid, n = 6). STUDY DESIGN This was a retrospective case-control study analyzing paraffin-embedded placental blocks that were stained with hematoxylin and eosin and antibodies to sFlt-1. Their staining intensity was compared using a semiquantitative technique. The Kruskal-Wallis test and Wilcox rank sum test were used for statistical analysis. RESULTS The median staining was significantly higher in Trisomy 13 compared with control specimens (P = .008) (for Trisomy 13 vs Trisomy 21, P = .003, and Trisomy 13 vs euploid, P = .004). CONCLUSION Our study demonstrates that Trisomy 13 placentas express more sFlt-1 than control placentas. These results strengthen the hypothesis that the increased incidence of preeclampsia in Trisomy 13 pregnancies is secondary to placental up-regulation of sFlt-1.

A pregnant female with a large intracranial mass: Reviewing the evidence to obtain management guidelines for intracranial meningiomas during pregnancy

Introduction: Non-obstetric surgery for intracranial meningioma is uncommon during pregnancy and poses significant risks to both the mother and the fetus. We present a case of a parturient that presented with acute mental status changes and we illustrate the decision making process that resulted in a best-possible outcome. Case Description: A woman at 29-week gestation presented with acute language and speech deficits and deteriorating mental status after 2 weeks of headache. Imaging demonstrated a large intracranial mass. A multidisciplinary meeting was held to determine the best treatment plan. The decision was to proceed with caesarean delivery under epidural anesthesia to allow intraoperative monitoring of neurological function. Six hours after successful delivery, the patient had acute mental status changes and she was taken to the operating room immediately for resection of her tumor, which turned out to be a clear cell meningioma. Discussion: Cerebral meningioma is usually a slow-growing tumor; however, during pregnancy, the mass may expand rapidly due to hormonal receptor expression. The presentation of this patient would have normally led to urgent resection of the mass. But the complicating factor was her 29-week pregnancy as standard intraoperative treatment during neurosurgery is known to adversely affect the fetus. A multidisciplinary meeting was critical for this patient’s care, and is recommended by us when treating such patients.

Placental Origins of Angiogenic Dysfunction in Mirror Syndrome

Background. Mirror syndrome is characterized by preeclampsia-like syndrome in pregnancies complicated by fetal hydrops. We describe a case of mirror syndrome associated with angiogenic dysfunction in maternal plasma and the placenta. Case. A pregnant patient with known fetal hydrops presented at 22 weeks gestation with features of severe preeclampsia. Measurements of plasma anti- and proangiogenic factors were consistent with a profound antiangiogenic state. Immunohistochemistry of the placenta for antiangiogenic proteins showed a pattern similar to that seen in patients with severe preeclampsia. Conclusion. Angiogenic imbalance may also be responsible for the preeclampsia-like condition seen in mirror syndrome.

Decidual Stromal Cells as Regulators of T-Cell Access to the Maternal–Fetal Interface

A recent study in the journal Science offers insights into the mechanism behind feto‐maternal tolerance, as evidenced by changes in the immuno‐logical environment of the uterus and decidua. They also provide a rich area of research for the understanding of the regulation of the immune system in other complicated medical conditions, including cancer and pregnancies affected by infection or autoimmunity.

Transient tachypnea of the newborn: is labor prior to cesarean delivery protective?

Transient tachypnea of the newborn (TTN) is a common respiratory problem in newborns. This study aims to determine if cesarean delivery (CD) is a risk factor for TTN, and if labor prior to CD decreases this risk. A linked data set consisting of Arizona birth certificates (1994 to 1998) and infants enrolled in a high-risk perinatal program provided 800 TTN cases and 800 controls, stratified by year. The relationships of CD and labor to TTN were examined using logistic regression. CD was associated with an increased risk of TTN, whether it was accompanied by labor (odds ratio [OR] 2.68; 95% confidence interval [CI] 1.62 to 4.45) or not accompanied by labor (OR 2.88; 95% CI 2.01 to 4.13), even after adjusting for confounding variables. Labor did not affect the development of TTN, nor did it modify the association of CD with increased risk for TTN. CD is a risk factor for TTN. Labor prior to CD is not protective for TTN.