Cases in Precision Medicine: A Personalized Approach to Stroke and Cardiovascular Risk Assessment in Women.

Cardiovascular disease is the leading cause of death among women in the United States, and stroke is third. This article uses a case scenario to examine female sex-specific cardiovascular risk factors across the lifespan and describes a precision medicine-based approach to risk factor modification and primary prevention. It also presents recent updates to the role of genetic testing and polygenic risk scores for the prediction of stroke and cardiovascular disease.

Accuracy of Blood Pressure Measurement Devices in Pregnancy: A Systematic Review of Validation Studies.

The accurate measurement of blood pressure (BP) in pregnancy is essential to guide medical decision making that affects both mother and fetus. The aim of this systematic review was to determine the accuracy of ambulatory, home, and clinic BP measurement devices in pregnant women. We searched Ovid MEDLINE, The Cochrane Library, EMBASE, CINAHL EBSCO, ClinicalTrials.gov, International Clinical Trials Registry Platform, and dabl from inception through August 3, 2017 for articles that assessed the validity of an upper arm BP measurement device against a mercury sphygmomanometer in pregnant women. Two independent investigators determined eligibility, extracted data, and adjudicated protocol violations. From 1798 potential articles identified, 41, that assessed 28 devices, met the inclusion criteria. Most articles (n=32) followed a standard or modified American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization, British Hypertension Society, or European Society of Hypertension validation protocol. Several articles described the results of validation studies performed on >1 device (n=7) or in >1 population of pregnant women (n=12), comprising 64 pairwise validity assessments. The device was validated in 61% (32 of 52) of studies which used a standard or modified protocol. Only 34% (11 of 32) of the studies wherein the device was successfully validated were performed without a protocol violation. Given the implications of inaccurate BP measurement in pregnant women, healthcare providers should be aware of and try to use the BP measurement devices which have been properly validated in this population.

Challenges of studying drugs in pregnancy for off-label indications: pravastatin for preeclampsia prevention.

Statins (3-hydroxy-3 methyl-glutaryl coenzyme-A reductase inhibitors) are the most commonly prescribed cholesterol-lowering medications due to their efficacy in reducing cardiovascular mortality and morbidities, tolerability, and safety profiles. Based on pathophysiologic similarities between cardiovascular disease and preeclampsia, a common and dangerous complication of pregnancy, there is an increasing interest in studying this class of medications during pregnancy to prevent and/or treat preeclampsia. Undergoing such a study, which entails the use of a pregnancy class X medication for an off-label indication in pregnancy, requires intensive multidisciplinary involvement of a group of experts in basic and clinical pharmacology, research methods, pregnancy physiology and maternal-fetal medicine, as well as U.S. Food and Drug Administration (FDA) regulatory guidelines and practice. Issues of potential fetal risk, altered maternal-fetal pharmacokinetics and pharmacodynamics, and regulatory challenges are real, and must be carefully considered in the process of research in this arena.

Patterns of use and predictors of receipt of antibiotics in women undergoing cesarean delivery.

OBJECTIVE: Perioperative antibiotics are recommended during cesarean delivery to reduce the risk of postoperative infections and resulting maternal morbidity. We examined the patterns of use and predictors of receipt of antibiotics in women undergoing cesarean delivery. METHODS: We identified a national cohort of women who underwent a cesarean delivery between 2003 and 2010 using a commercial hospitalization database. Women who received antibiotics on the day of cesarean delivery were classified as having received perioperative antibiotics. Multivariable regression models were developed to account for patient, obstetric, physician, and hospital factors on receipt of antibiotics. Between-hospital variation was calculated using generalized linear mixed models. RESULTS: Among 1,137,804 women who underwent cesarean delivery, 59.5% received perioperative antibiotics. The proportion of patients receiving antibiotics increased over time from 52.5% in 2003 to 63.1% in 2010 (P<.001) and varied significantly by geographic region. Women who did not labor were more likely to receive antibiotics than those who had a cesarean delivery after labor (66% compared with 44%, P<.001). Age, race, and insurance status were not major determinants of the use of perioperative antibiotics. CONCLUSION: Among women undergoing cesarean delivery, compliance with the recommendation for universal perioperative antibiotic prophylaxis is poor. Coordinated efforts are needed to enhance use of guideline-based perioperative antibiotic prophylaxis for women undergoing cesarean delivery. LEVEL OF EVIDENCE: III.

The timing of antibiotics at cesarean: a randomized controlled trial.

We compared maternal and neonatal outcomes in women who received prophylactic antibiotics prior to skin incision to those who received antibiotics at cord clamp. We performed a randomized clinical trial at two sites. Eligible women included those undergoing nonemergency cesarean at 36 weeks' gestation or greater. Subjects were randomized (permuted blocks) into one of two treatments: "preoperative antibiotics" (cefazolin 1 g given <30 minutes prior to skin incision) or "intraoperative antibiotics" (cefazolin 1 g at cord clamping). Patients who reported an allergy to penicillin received clindamycin 900 mg. The trial primary outcome was a composite of maternal infectious morbidities, defined as having any one of the following: (1) postoperative fever (defined as oral temperature >38°C on two separate occasions more than 6 hours apart, after the initial 24-hour postoperative period); (2) wound infection (defined as purulent discharge from the incision); (3) endomyometritis (defined as fundal tenderness and fever malodorous lochia, fever); (4) urinary tract infection (defined as fever, positive urine culture). We enrolled a total of 434 subjects in this study, with 217 in each group. Overall, we found no difference in composite maternal infectious morbidity between those who received antibiotics preoperatively and those who received antibiotics at cord clamp (relative risk = 1.2, 95% confidence interval 0.7 to 1.5). Neonatal outcomes were also similar between the two intervention arms. The rate of suspected sepsis was similar between the two groups. There were no cases of antibiotic resistance in the neonates. Either preoperative antibiotic therapy or antibiotic administration after cord clamp is a reasonable clinical method for reducing the risk of postcesarean infectious morbidity.

Cardiopulmonary complications of pre-eclampsia.

Pre-eclampsia affects 3 to 8% of all pregnancies. In the USA, pre-eclampsia remains a leading cause of maternal morbidity and mortality, comprising 17% of maternal deaths in advanced gestations in 1999. The pathophysiologic changes associated with pre-eclampsia can have a profound impact on the uteroplacental unit and fetal and neonatal outcome. Equally important are the adverse effects on the maternal hematologic, cardiovascular and pulmonary, neurologic, renal, and gastrointestinal system. This article aims to review complications of pre-eclampsia as they impact on the cardiovascular and pulmonary systems.

Pre-eclampsia and the kidney.

Pre-eclampsia is a multisystem disorder that is unique to pregnancy, affecting at least 5% of all gravidas. The mainstay of this diagnosis is a combination of new-onset hypertension and proteinuria. The kidney deserves particular attention because of the physiologic as well as pathologic changes that can affect this vital organ in pregnancy. In fact, there is a major interplay between renal disease and pre-eclampsia. Proteinuria is universal to all cases of pre-eclampsia, yet some cases can progress to acute renal failure. Furthermore, it is well-established that the latter is more frequent in women with underlying renal disease. This chapter reviews the physiologic changes that the human kidney adapts during pregnancy, the impact of pre-eclampsia on the kidney and its function, and the risk of pre-eclampsia in women with chronic renal disease. Two groups that warrant special consideration are pregnant women with systemic lupus erythematosus and those with history of renal transplantation.

Thromboprophylaxis after cesarean delivery: a decision analysis.

OBJECTIVE: To compare 4 strategies for managing patients after cesarean delivery. METHODS: Using decision analysis, we compared universal subcutaneous (SC) heparin prophylaxis, heparin prophylaxis only for patients with a genetic thrombophilia, use of pneumatic compression stockings (PCS), and no thromboprophylaxis. Outcomes included heparin-induced thrombocytopenia (HIT), HIT-related thrombosis, major maternal bleeding, and venous thromboembolism (VTE). RESULTS: Use of PCS was the strategy with the lowest number of adverse events. With heparin prophylaxis, 13 cases of HIT-induced thrombosis and hemorrhage would occur per VTE prevented. When heparin prophylaxis is administered only to thrombophilia-positive women, 1.2 cases of HIT-induced thrombosis and bleeding would occur per VTE prevented. In sensitivity analyses, the model was stable across virtually all variable ranges. CONCLUSION: Use of PCS after cesarean delivery is the strategy with the lowest number of adverse events. Universal prophylaxis with SC heparin is associated with an excess risk of HIT-induced thrombosis and bleeding per VTE prevented compared with PCS use. Until future studies are completed, postcesarean thromboprophylaxis with PCS should be used if the clinician elects to provide prophylaxis.

Type-specific screening for asymptomatic herpes infection in pregnancy: a decision analysis.

OBJECTIVE: To evaluate the merits of serum screening for herpes simple virus (HSV) in pregnant women with no history of prior HSV infection. DESIGN: Clinical decision analysis. POPULATION: Hypothetical cohort of pregnant women in first trimester with no clinical history of HSV infection. METHODS: We used decision analysis techniques to compare three strategies for antepartum screening for HSV in women with no history of infection: (1) universal screening; (2) targeted screening in women estimated to be at high risk for infection; and (3) current care (no screening). For the screening strategies, we considered screening at 35 weeks of gestation, with prophylactic antiviral therapy for seropositive women. For all women, we assumed caesarean delivery in the setting of symptomatic infection at delivery. We performed a literature review of English-language publications to derive probability estimates for the rate of HSV seropositivity in asymptomatic pregnant women, and the risks of symptomatic HSV infection and asymptomatic shedding at the time of delivery. We determined the modification of rates of viral shedding, symptomatic lesions and caesarean section with the use of prophylactic suppression therapy for seropositive women based on available data. We chose neonatal herpes with severe sequelae, neonatal death, as well as caesarean delivery as clinically relevant outcomes. MAIN OUTCOME MEASURES: Number of cases of neonatal death, neonatal HSV with severe sequelae, neonatal HSV with moderate sequelae, patients screened, patients treated and caesarean section with each strategy. RESULTS: Universal maternal screening reduced the total number of deaths and severe sequelae secondary to neonatal HSV. Universal screening required treatment of 3849 women to prevent one case of neonatal death or disease with severe sequelae from HSV. Targeted screening of high risk women treatment of 2277 women to prevent one death or case of severe disease. Universal screening reduced the rate of neonatal HSV attributable to recurrent HSV by 79.3%. Caesarean delivery was reduced with both screening strategies. We used one-way sensitivity analyses to evaluate the robustness of our model. CONCLUSIONS: Maternal screening reduced the number of cases of neonatal HSV. Screening also reduced the rate of caesarean delivery. However, employing universal screening will likely result in a significant expenditure of medical resources because the number needed to treat to avert a single case of neonatal herpes is high.