The psychosocial impact of inpatient management of monoamniotic twin gestations.

OBJECTIVE: Monoamniotic twins require unique considerations in clinical management that challenge both clinicians and patients. The aim of this study was to assess the psychosocial impact of inpatient antepartum versus outpatient management for these patients. METHODS: Women with a history of a monoamniotic twin pregnancy between 2002 and 2012 were identified through a social media group and invited to participate in an original survey regarding their clinical management and psychological well-being during gestation. Results between patients managed with inpatient versus outpatient protocols were compared using the Fisher exact test. RESULTS: Participants (n = 197) were multinational. Planned inpatient management after 23 weeks gestation was reported in 76.2% of respondents. Participants in both groups endorsed persistent feelings of hopelessness or despair related to their pregnancies (42.4% of inpatients versus 24.1% of outpatients, p = 0.089). Relationship strain between participants and their partners was similar in both the groups. Participants in the outpatient group were more likely to report feelings of guilt related to their infrequent monitoring (p = 0.01). Patient satisfaction with care was higher in the inpatient group. CONCLUSIONS: Inpatient management did not significantly increase measures of psychosocial stress as compared to outpatient management. Participants in the outpatient group reported feelings of guilt about their infrequent monitoring. Our findings provide increased understanding of the patient experience in these rare and challenging clinical circumstances.

Prenatally diagnosed single umbilical artery: The role and relationship of additional risk factors in the fetus for congenital heart disease.

PURPOSE: Single umbilical artery (SUA) has been associated with an increased risk of congenital heart disease (CHD). Women carrying fetuses with an SUA are often referred for fetal echocardiography, but data to support the need for this testing remain controversial. METHODS: A retrospective review of the records for all women carrying fetuses with an SUA who had undergone fetal echocardiography between 2009 and 2012 at our center was performed. Data on the maternal and fetal risk factors for CHD were collected, and the fetuses were categorized into three groups: low risk (LR; an SUA with no additional risk factors for CHD), moderate risk (MR; an SUA with one additional risk factor for CHD), and high risk (HR; an SUA with two or more additional risk factors for CHD). RESULTS: In total, 101 such patients were identified: 69 LR, 26 MR, and 6 HR. No fetuses in the LR group, three in the MR group, and two in the HR group had CHD (p = 0.0005). CONCLUSIONS: An SUA in an LR fetus did not increase the risk of CHD in our cohort, whereas an SUA in the presence of additional risk factors was associated with significantly increased risk for CHD. Our results suggest that referral for a fetal echocardiogram is indicated for women carrying fetuses with an SUA when additional risk factors for CHD are present. In an LR fetus with an SUA, however, echocardiography may not provide additional benefit unless CHD is suggested on screening obstetric sonography.

Downregulation of apelin in the human placental chorionic villi from preeclamptic pregnancies.

The role of the endogenous apelin system in pregnancy is not well understood. Apelin's actions in pregnancy are further complicated by the expression of multiple forms of the peptide. Using radioimmunoassay (RIA) alone, we established the expression of apelin content in the chorionic villi of preeclamptic (PRE) and normal pregnant women (NORM) at 36-38 wk of gestation. Total apelin content was lower in PRE compared with NORM chorionic villi (49.7±3.4 vs. 72.3±9.8 fmol/mg protein; n=20-22) and was associated with a trend for lower preproapelin mRNA in the PRE. Further characterization of apelin isoforms by HPLC-RIA was conducted in pooled samples from each group. The expression patterns of apelin peptides in NORM and PRE villi revealed little or no apelin-36 or apelin-17. Pyroglutamate apelin-13 [(Pyr1)-apelin-13] was the predominant form of the peptide in NORM and PRE villi. Angiotensin-converting enzyme 2 (ACE2) activity was higher in PRE villi (572.0±23.0 vs. 485.3±24.8 pmol·mg(-1)·min(-1); n=18-22). A low dose of ANG II (1 nM; 2 h) decreased apelin release in NORM villous explants that was blocked by the ANG II receptor 1 (AT1) antagonist losartan. Moreover, losartan enhanced apelin release above the 2-h baseline levels in both NORM and PRE villi (P<0.05). In summary, these studies are the first to demonstrate the lower apelin content in human placental chorionic villi of PRE subjects using quantitative RIA. (Pyr1)-apelin-13 is the predominant form of endogenous apelin in the chorionic villi of NORM and PRE. The potential mechanism of lower apelin expression in the PRE villi may involve a negative regulation of apelin by ANG II.

Hemodynamic responses to angiotensin-(1-7) in women in their third trimester of pregnancy.

BACKGROUND: To understand the role of Angiotensin-(1-7) (Ang-(1-7)) in vasculature of pregnant women, we compared cardiac output (CO), total peripheral resistance (TPR) and forearm blood flow (FBF) responses to Ang-(1-7) infusion between normotensive pregnant women in their third trimester and healthy age matched non-pregnant women. The responses of skin microcirculation to Ang-(1-7) were tested in preeclamptic, normotensive pregnant and non-pregnant women. Responses to Angiotensin II (Ang II) were also determined. METHODS: Non-invasive methods for systemic (bioimpedance and VascuMAP), FBF (venous occlusion strain gauge plethysmography), and skin (laser Doppler) hemodynamics assessments were used. RESULTS: Compared to non-pregnant women, systemic infusion of Ang-(1-7) (2000 pmol/min) resulted in a greater increase in CO (9.4 ± 6.4 versus -3.3 ± 2.1%, n = 9-10) in normotensive pregnant women. Brachial local infusion of Ang-(1-7) had no effect on FBF in either group. In non-pregnant and normotensive pregnant women, local Ang II induced a dose-dependent decrease in FBF and increase in forearm resistance at 50 and 100 pmol/min (p < 0.05 versus corresponding baseline, n = 7-10). Following iontophoretic application of 5 mmol/l dose of Ang-(1-7), the change in skin flow was higher in normotensive pregnant versus preeclamptic women (182.5 ± 93 versus 15.76 ± 19.46%, n = 14-15). Skin flow was lower in normotensive pregnant versus preeclamptic women (-46.5 ± 48.7 versus 108.7 ± 49.1%, n = 14-15) following Ang II infusion at 1.0 pmol/min. CONCLUSION: In the third trimester of pregnancy, Ang-(1-7) induces alterations in CO and differentially regulates micro- and macro-circulations, depending on the dose. Dysregulation in skin vasculature may contribute to the development of vascular dysfunction and hypertension in preeclampsia.

Pregnancy increases myometrial artery myogenic tone via NOS- or COX-independent mechanisms.

Myogenic tone (MT) is a primary modulator of blood flow in the resistance vasculature of the brain, kidney, skeletal muscle, and perhaps in other high-flow organs such as the pregnant uterus. MT is known to be regulated by endothelium-derived factors, including products of the nitric oxide synthase (NOS) and/or the cyclooxygenase (COX) pathways. We asked whether pregnancy influenced MT in myometrial arteries (MA), and if so, whether such an effect could be attributed to alterations in NOS and/or COX. MA (200-300 µm internal diameter, 2-3 mm length) were isolated from 10 nonpregnant and 12 pregnant women undergoing elective hysterectomy or cesarean section, respectively. In the absence of NOS and/or COX inhibition, pregnancy was associated with increased MT in endothelium-intact MA compared with MA from nonpregnant women (P < 0.01). The increase in MT was not due to increased Ca(2+) entry via voltage-dependent channels since both groups of MA exhibited similar levels of constriction when exposed to 50 mM KCl. NOS inhibition (N(ω)-nitro-L-arginine methyl ester, L-NAME) or combined NOS/COX inhibition (L-NAME/indomethacin) increased MT in MA from pregnant women (P = 0.001 and P = 0.042, respectively) but was without effect in arteries from nonpregnant women. Indomethacin alone was without effect on MT in MA from either nonpregnant or pregnant women. We concluded that MT increases in MA during human pregnancy and that this effect was partially opposed by enhanced NOS activity.

MRI of pregnancy-related issues: abnormal placentation.

OBJECTIVE: In this article, we review the clinical significance of abnormal placentation and the role of MRI in diagnosis and management of this potentially morbid condition. We present our clinical perspective on diagnosing this challenging problem with MRI and review the imaging findings that can lead to a correct diagnosis. CONCLUSION: As abnormal placentation becomes more prevalent, in large part due to the markedly rising rates of cesarean delivery, there is a need for accurate antenatal diagnosis of this condition to prevent maternal morbidity and mortality. Maternal and fetal outcomes can be optimized through multidisciplinary planning to achieve accurate diagnosis and anticipation of the extent of abnormal placentation in the antenatal period. Imaging findings of abnormal placentation have been described for both ultrasound and MRI, although limitations exist for each technique. Although ultrasound remains the primary screening modality for the detection of abnormal placentation, MRI is a complementary technique that should be considered when ultrasound is inconclusive or incomplete. Familiarity with MRI techniques to assess the placenta, MRI appearance of normal placenta, and imaging findings that suggest abnormal placentation can help radiologists contribute to a successful maternal outcome.

Successful treatment of severe sepsis with recombinant activated protein C during the third trimester of pregnancy.

BACKGROUND: Severe sepsis in pregnancy is associated with multiorgan failure and a high risk of death for the mother and fetus. CASE: We present the case of a pregnant patient at 26 weeks of gestation with severe sepsis secondary to pneumonia. She was admitted to the intensive care unit and started on combination antibiotics and bilevel positive airway pressure. Her condition continued to deteriorate, and she was treated with recombinant activated protein C (drotrecogin alfa). She improved and delivered at 28 weeks of gestation after preterm labor; neither the patient nor the neonate had evidence of drug-related complications. CONCLUSION: This report describes a case of severe sepsis at 26 weeks of gestation secondary to pneumonia, with successful maternal and fetal outcome after use of drotrecogin alfa (activated).

Robotic-assisted laparoscopic repair of symptomatic cesarean scar defect: a report of two cases.

BACKGROUND: Symptomatic cesarean scar defect is one of the commonly reported long-term complications of cesarean section. CASES: We present two cases of symptomatic cesarean scar defect treated conservatively by robotic-assisted laparoscopy at our institution. Both patients presented with hematocele, pelvic discomfort and secondary infertility. Transvaginal ultrasound revealed hematocele measuring 3.7 x 1.9 x 3.8 cm and 3.0 x 2.0 x 1.6 cm in the lower uterine segments, respectively. After surgery normal menses resumed in both patients, and their childbearing potential was preserved. The patients conceived 3 and 11 months after surgery, respectively. CONCLUSION: Recognition of cesarean scar defect is important in the explanation of certain menstrual disorders since surgical intervention can result in improvement of symptoms and prevent the related secondary obstetric and gynecologic complications. Robotic-assisted laparoscopic approach is a good minimally invasive alternative for the repair of cesarean scar defect.

Placental endothelial nitric oxide synthase in multiple and single dose betamethasone exposed pregnancies.

OBJECTIVE: To compare endothelial nitric oxide synthase expression and capillary density (CDS) in placentas exposed to single or multiple courses of betamethasone. STUDY DESIGN: Placental specimens exposed to single vs repeat courses of betamethasone were analyzed through immunohistochemistry and digital image quantification for endothelial nitric oxide synthase and CD34. Quantified endothelial nitric oxide synthase staining, calculated capillary density, ratio of endothelial nitric oxide synthase to capillary density, and clinical characteristics were compared. Linear regression was performed with these as dependent variables. RESULTS: Mean and maximum capillary density were increased (P = .013 and .005) and the ratio of endothelial nitric oxide synthase to capillary density decreased (P = .016) in specimens exposed to 4 courses of betamethasone compared with 1 to 3 courses. Exposure to 4 courses of betamethasone was associated with increased capillary density, but not with endothelial nitric oxide synthase expression. CONCLUSION: Exposure to 4 courses of betamethasone is associated with increased placental capillary density. The placental effects of multiple courses of betamethasone are unrelated to endothelial nitric oxide synthase expression.

Migraine during pregnancy: is it more than a headache?

Migraine headaches have a female predominance with a peak in prevalence in the third and fourth decades of life. Women of reproductive age are liable to develop their first migraine while pregnant or exhibit changes in the character, frequency or severity of their headaches during pregnancy and the puerperium. The purpose of this Review is to examine the pathophysiology underlying the development of migraine headaches and the association of this pathophysiology with pregnancy-related complications. We also discuss the diagnosis and management of migraine headaches that precede pregnancy or develop de novo during pregnancy, placing an emphasis on the distinction between primary migraine headache and headache secondary to pre-eclampsia--a relatively frequent complication of pregnancy and the puerperium. We present the case of a woman with a history of migraine headaches before pregnancy, whose symptoms progressed during pregnancy in part because of increasing exposure to narcotic medications. We also review the options for migraine evaluation and treatment, and provide an overview of the risks associated with the different treatment options.

Lepirudin for treatment of acute thrombosis during pregnancy.

BACKGROUND: Thromboprophylaxis during pregnancy can be challenging when heparin is contraindicated. Limited data exist regarding alternative anticoagulants in the setting of pregnancy. CASE: We present a patient with antiphospholipid syndrome who developed heparin-induced thrombosis in the third trimester of pregnancy. She was treated with therapeutic doses of intravenous lepirudin until delivery. Induction of labor, regional anesthesia, and forceps-assisted vaginal delivery were performed with no fetal, neonatal, or maternal complications. Postpartum, the patient was transitioned to warfarin therapy, and at 6 weeks postdelivery neither the patient nor her infant had developed any new problems. CONCLUSION: Intravenous lepirudin use at therapeutic doses in late gestation as an alternative to heparin was accomplished with minimal maternal and fetal morbidity.

Identifying risk factors for uterine rupture.

Uterine rupture, whether in the setting of a prior uterine incision or in an unscarred uterus, is an obstetric emergency with potentially catastrophic consequences for both mother and child. Numerous studies have been published regarding various risk factors associated with uterine rupture. Despite the mounting data regarding both antepartum and intrapartum factors, it currently is impossible to predict in whom a uterine rupture will occur. This article reviews the data regarding these antepartum and intrapartum predictors for uterine rupture. The author hopes that the information presented in this article will help clinicians assess an individual's risk for uterine rupture.

Intrapartum predictors of uterine rupture.

This case-controlled study reviewed 26 cases of uterine rupture at an academic medical center. Controls were selected in a 2:1 design by reviewing the immediate successful vaginal birth after cesarean delivery (VBAC) before and after each case of uterine rupture. At less than 2 hours before delivery or acute uterine rupture, mild and severe variable decelerations, persistent abdominal pain, and hyperstimulation were more common in cases of uterine rupture as compared to controls and had statistically significant positive likelihood ratios (LR). Mild and severe variable fetal heart rate decelerations, especially in the presence of persistent abdominal pain, may predict uterine rupture in patients attempting VBAC.

Utilizing cryogenic grips for dynamic tension testing of human placenta tissue.

Computational models are used to investigate placental abruption in motor vehicle crashes, which is the leading cause of traumatic fetal injury mortality in the United States. Material parameters for computational modeling of pregnant occupant kinematics come from early research on placenta tissue at quasi-static loading rates. The purpose of this research is to develop a methodology for using cryogenic grips to test placenta specimens in uniaxial tension at a rate normally seen in a motor vehicle crash. For dynamic testing of placental tissue, implementing and adapting a cryogenic grip mechanism provides the ability to grip the tissue throughout the thickness and eliminates potential slipping of the tissue in the grip during the dynamic test. The validation for using the cryogenic grips is presented with video images of a typical test event showing the tissue failing in the active area. Additionally, local and global strain measures are compared to confirm the tissue strain is similar throughout the specimen. The cryogenic grips provide a low-cost and effective method of gripping and pulling a thick soft tissue in uniaxial tension. As a result, these methods can be used to acquire the material properties of placenta tissue loaded at a dynamic rate to apply in a computational pregnant model.

Fetal laryngeal stenosis/atresia and congenital high airway obstructive syndrome (CHAOS): a case report.

Congenital high airway obstructive syndrome (CHAOS) is a rare but fatal disease with predictably characteristic features including stenotic or atretic upper airway, hyperplastic lungs, elevated diaphragm, massive fetal ascites and fetal hydrops. Diagnosis of CHAOS by ultrasound scan is possible and clinically important since advanced intrauterine surgery to correct the defect is possible. We report a case of fetus of CHAOS with massive ascites, pulmonary hyperplasia and laryngeal stenosis/atresia. We feel that it is important to recognize the entity both by ultrasound scan and by the pathologist so that some cases can be corrected by intrauterine fetal surgery.

Loss of caveolin-1 polarity impedes endothelial cell polarization and directional movement.

The ability of a cell to move requires the asymmetrical organization of cellular activities. To investigate polarized cellular activity in moving endothelial cells, human endothelial cells were incubated in a Dunn chamber to allow migration toward vascular endothelial growth factor. Immunofluorescent staining with a specific antibody against caveolin-1 revealed that caveolin-1 was concentrated at the rear of moving cells. Similarly, monolayer scraping to induce random cell walk resulted in relocation of caveolin-1 to the cell rear. These results suggest that posterior polarization of caveolin-1 is a common feature both for chemotaxis and chemokinesis. Dual immunofluorescent labeling showed that, during cell spreading, caveolin-1 was compacted in the cell center and excluded from nascent focal contacts along the circular lamellipodium, as revealed by integrin beta1 and FAK staining. When cells were migrating, integrin beta1 and FAK appeared at polarized lamellipodia, whereas caveolin-1 was found at the posterior of moving cells. Notably, wherever caveolin-1 was polarized, there was a conspicuous absence of lamellipod protrusion. Transmission electron microscopy showed that caveolae, similar to their marker caveolin-1, were located at the cell center during cell spreading or at the cell rear during cell migration. In contrast to its unphosphorylated form, tyrosine-phosphorylated caveolin-1, upon fibronectin stimulation, was associated with the focal complex molecule phosphopaxillin along the lamellipodia of moving cells. Thus, unphosphorylated and phosphorylated caveolin-1 were located at opposite poles during cell migration. Importantly, loss of caveolin-1 polarity by targeted down-regulation of the protein prevented cell polarization and directional movement. Our present results suggest a potential role of caveolin polarity in lamellipod extension and cell migration.

Inhibition of cyclooxygenase-2: effects on renin secretion and expression in fetal lambs.

The importance of prostaglandins in the regulation of the renin-angiotensin system during development is not known. These experiments were conducted to examine the effects of prostaglandin synthesis inhibitors on basal and isoproterenol-induced plasma renin concentration and renin gene expression in the late-gestation fetal lamb. Eighteen lamb fetuses ranging in gestational age from 129 to 138 days underwent surgical insertion of femoral arterial and venous catheters under general endotracheal anesthesia. After a period of recovery, animals underwent an infusion of isoproterenol after administration of a saline bolus (control experiments); 24-48 h later a second study was performed after administration of NS-398, a cyclooxygenase (COX)-2 inhibitor, or saline for a second control study. Administration of COX-2 inhibitor significantly reduced baseline plasma renin levels and attenuated responses in fetal renin secretion to isoproterenol infusions. Renal cortical cells from animals receiving COX-2 inhibitor had significantly lower levels of renin mRNA compared with animals receiving only saline. Renal cortical cells in culture from animals receiving only saline exhibited increased levels of renin mRNA when treated with isoproterenol, forskolin, or IBMX. Only forskolin increased renin mRNA levels in renal cortical cells in culture from animals receiving COX-2 inhibitor. We conclude that prostaglandins play a stimulatory role in the regulation of the renin-angiotensin system and are necessary for beta-adrenergic stimulation of renin secretion and gene expression in the late-gestation fetal lamb.