Heather L. Mertz

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 individuals risk for uterine rupture.

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.

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.

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. Apelins 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.

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.

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.

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

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.

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).