Kara Nerenberg

A case series of LMWH use in pregnancy: should trough anti-Xa levels guide dosing?

INTRODUCTION Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing. MATERIALS/METHODS This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/-trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes. RESULTS/CONCLUSION Women with MHV (N=4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N=12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P<0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.

Why are adult women physically active? A systematic review of prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants.

This study aims to systematically review available evidence from prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants of moderate‐to‐vigorous intensity physical activity (MVPA) among working‐age women.

Cardiovascular Risk Reduction and Weight Management at a Hospital-Based Postpartum Preeclampsia Clinic

OBJECTIVE Women who develop preeclampsia during pregnancy are at high risk of developing future chronic diseases, including premature cardiovascular disease. We have established an interdisciplinary clinic that aims to prevent cardiovascular disease through educational counselling focused on lifestyle modifications in the early postpartum period. The objective of this study was to evaluate changes in weight and cardiovascular risk factors in participating women after six months of attendance at the clinic. METHODS We conducted a retrospective chart review of women who had a pregnancy complicated by preeclampsia, and who subsequently attended the Postpartum Preeclampsia Clinic. Study subjects had baseline assessments of lifestyle, physical, and laboratory parameters. Individualized goals for cardiovascular risk reduction and lifestyle were established, centering on physical activity and dietary modifications. The primary outcome was change in weight. RESULTS Over the study period, 21 women were seen for a minimum of six months of follow-up. At an average (± SD) of 4.4 ± 1.4 months postpartum, subjects showed a non-significant improvement in weight (mean weight loss of 0.4 ± 4.5 kg) and BMI (mean decrease in BMI 0.1 ± 1.7 kg/m2). Physical activity improved significantly, from 14% of subjects participating in physical activity before pregnancy to 76% at a mean of 4.4 months postpartum. CONCLUSION This study has demonstrated the early benefits of a longitudinal interdisciplinary intervention with counselling about lifestyle modifications for prevention of cardiovascular disease in women with recent preeclampsia. A study with a larger sample size and longer duration of follow-up is planned to confirm these findings.

Hypertension Canada's 2018 Guidelines for the Management of Hypertension in Pregnancy

We present Hypertension Canadas inaugural evidence-based Canadian recommendations for the management of hypertension in pregnancy. Hypertension in pregnancy is common, affecting approximately 7% of pregnancies in Canada, and requires effective management to reduce maternal, fetal, and newborn complications. Because of this importance, these guidelines were developed in partnership with the Society of Obstetricians and Gynaecologists of Canada with the main common objective of improving the management of women with hypertension in pregnancy. Guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children are published separately. In this first Hypertension Canada guidelines for hypertension in pregnancy, 7 recommendations for the management of nonsevere and severe hypertension in pregnancy are presented. For nonsevere hypertension in pregnancy (systolic blood pressure 140-159 mm Hg and/or diastolic blood pressure 80-109 mm Hg), we provide guidance for the threshold for initiation of antihypertensive therapy, blood pressure targets, as well as first- and second-line antihypertensive medications. Severe hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg) requires urgent antihypertensive therapy to reduce maternal, fetal, and newborn adverse outcomes. The specific evidence and rationale underlying each of these guidelines are discussed.

Canadian stroke best practice consensus statement: Secondary stroke prevention during pregnancy:

The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy, is the first of a two-part series devoted to stroke in pregnancy. This document focuses on unique aspects of secondary stroke prevention in a woman with a prior history of stroke or transient ischemic attack who is, or is planning to become, pregnant. Although stroke is relatively rare in this cohort, several aspects of pregnancy can increase stroke risk during or immediately after pregnancy. The rationale for the development of this consensus statement is based on the premise that stroke in this group requires a specifically-tailored management approach. No other broad-based, stroke-specific guidelines or consensus statements exist currently. Underpinning the development of this document was the concept that maternal health is vital for fetal wellbeing; therefore, management decisions should be based on the confluence of two clinical considerations: (a) decisions that would be made if the patient was not pregnant and (b) decisions that would be made if the patient had not had a stroke. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include general management considerations for secondary stroke prevention, the use of antithrombotics, blood pressure management, lipid management, diabetes care, and management for specific ischemic stroke etiologies in pregnancy. The focus is on maternal and fetal health while minimizing risks of a recurrent stroke, through counseling, monitoring, and the safety of select pharmacotherapy. These statements are appropriate for health care professionals across all disciplines.

Obesity Prevention from Conception: A Workshop to Guide the Development of a Pan-Canadian Trial Targeting the Gestational Period

This report summarizes a meeting, Obesity Prevention from Conception, held in Ottawa in 2012. This planning workshop was funded by the Canadian Institutes of Health Research (CIHR) to bring together researchers with expertise in the area of maternal obesity (OB) and weight gain in pregnancy and pregnancy-related disease to attend a one-day workshop and symposium to discuss the development of a cross-Canada lifestyle intervention trial for targeting pregnant women. This future intervention will aim to reduce downstream OB in children through encouraging appropriate weight gain during the mothers pregnancy. The workshop served to (i) inform the development of a lifestyle intervention for women with a high pre-pregnancy body mass index (BMI), (ii) identify site investigators across Canada, and (iii) guide the development of a grant proposal focusing on the health of mom and baby. A brief summary of the presentations as well as the focus groups is presented for use in planning future research.

Long-term Risk of a Seizure Disorder After Eclampsia

OBJECTIVE To evaluate the incidence rate and relative risk of a seizure disorder after eclampsia. METHODS We evaluated 1,565,733 births in a retrospective data linkage cohort study in Ontario, Canada, from April 1, 2002, to March 31, 2014. We included females aged 15-50 years and excluded patients with epilepsy, conditions predisposing to seizure, and those who died within 30 days of the delivery discharge date. The exposure was defined as a hypertensive disorder of pregnancy, namely 1) eclampsia, 2) preeclampsia, or 3) gestational hypertension. The referent was an unaffected pregnancy. The primary outcome was the risk of seizure disorder starting 31 days after a hospital birth discharge. Risk was expressed as an incidence rate and a hazard ratio (HR) with 95% CI. The predefined study hypothesis was that women with eclampsia would have an increased risk of future seizure disorder. RESULTS There were 1,615 (0.10%) pregnancies exclusively affected by eclampsia, 17,264 (1.1%) with preeclampsia, 60,863 (3.9%) with gestational hypertension, and 1,485,991 (94.9%) unaffected. A future seizure disorder was significantly more likely after a pregnancy with eclampsia (4.58/10,000 person-years) than a pregnancy without a hypertensive disorder of pregnancy (0.72/10,000 person-years; crude HR 6.09, 95% CI 2.73-13.60). The adjusted HR was minimally attenuated from 6.09 to 5.42 (95% CI 2.42-12.12) after multivariable adjustment for confounders at the index birth as well as adjusting for traumatic brain injury, stroke, cerebral tumor, aneurysm or hemorrhage, and multiple sclerosis. The risk of seizure disorder was doubled in pregnancies affected by preeclampsia (adjusted HR 1.96, 95% CI 1.21-3.17), but not by gestational hypertension (adjusted HR 1.01, 95% CI 0.71-1.43). CONCLUSION Women with eclampsia should be reassured that, although the relative risk of a seizure disorder is higher than unaffected women, the absolute risk is extremely low (approximately one seizure/2,200 person-years).

Adherence to Canada's Food Guide Recommendations during Pregnancy: Nutritional Epidemiology and Public Health

Abstract Background: In Canada, pregnant women are typically referred to Canadas Food Guide (CFG), a set of national dietary recommendations designed to promote adequate nutrient intake. Pregnant women are also advised to gain weight within the Institute of Medicine guidelines, which differ by prepregnancy body mass index (BMI). However, CFG recommendations do not account for prepregnancy BMI and provide no guidance on “less healthy” (LH) foods. Objective: The aim of this study was to score womens diets according to adherence to CFG recommendations and consumption of LH foods and to examine differences between these diet scores by prepregnancy BMI. Methods: Participants enrolled in the APrON (Alberta Pregnancy Outcomes and Nutrition) prospective cohort study completed a 24-h recall in their second trimester (n = 1630). A score was created on the basis of each daily dietary CFG recommendation met, ranging from 0 to 9. The distribution of consumption (grams per day) of 8 LH food groups was given a score of 0 (none) or 1, 2, or 3 (representing the lowest, middle, or highest tertiles, respectively) and summed giving a total LH score of 0–24. Results: There were few differences in CFG recommendations met by prepregnancy BMI status, although fewer women who were overweight or obese prepregnancy met the specific recommendation to consume 7–8 servings of fruit or vegetables/d than did those who were under- or normal weight (47% and 41% compared with 50% and 54%, respectively). Although differences were small, women who were obese prepregnancy had lower CFG scores (β = −0.28; 95% CI:−0.53, −0.02) and higher LH scores (β = 0.45; 95% CI: 0.04, 0.86) than did those who were normal weight. Conclusion: The study results suggest that more attention may need to be paid to individualized counseling on dietary recommendations that take account of prepregnancy BMI.

Letter by Ahmed et al Regarding Article, “Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial”

We read with great interest the recent article by Saito and colleagues.1 In their prospective observational cohort study after the conclusion of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes randomized controlled trial, they found that after a median 10-year follow-up, low-dose aspirin did not affect the risk for cardiovascular events or hemorrhagic stroke but was associated with an increased risk for gastrointestinal bleeding. Use of aspirin in primary prevention is less clear in women compared with men. …

Hypertensive Disorders of Pregnancy and Cardiovascular Diseases: Current Knowledge and Future Directions

Purpose of the reviewCardiovascular diseases (CVDs) are the principal killers of women. In this review, we summarize data regarding CVD and mortality after hypertensive disorders of pregnancy (HDP), and highlight clinical, research and policy needs to mitigate this risk.Recent findingsRobust data indicate that women with HDP have substantially higher risk of future CVD, with a 3.7-fold increase in the risk of chronic hypertension, a 4.2-fold increase in the risk of heart failure, an 81% increase in the risk of stroke, and double the risk of atrial arrhythmias, coronary heart disease, and mortality when compared to women with normotensive pregnancies. Potential explanations include (1) the effect of pregnancy as a “stress test” in women destined to develop CVD, (2) mediation by conventional risk factors, (3) long-term vascular damage sustained during the preeclamptic episode, and (4) preexisting abnormalities in arterial health predisposing women to HDP, and, subsequently, CVD.SummaryWomen with HDP have significantly increased risk of CVD and mortality. Risk scores including obstetric history are necessary to better estimate a woman’s cardiovascular risk. In addition, comprehensive policies promoting systematic risk assessment and modification after HDP are critically needed to improve health, wellness, and survival of affected women.