Development of a Core Outcome Set for Studies on Cardiac Disease in Pregnancy (COSCarP): A study protocol

Background: Clinical studies looking at interventions to optimize pregnancy and long-term outcomes for women with cardiac disease and their babies are inconsistent in their reporting of clinical outcomes, making it difficult to compare results across studies and draw meaningful conclusions. The development of a core outcome set (COS) - a standardized, minimum set of outcomes that must be collected and reported in all studies - is a practical solution to this problem. Methods/design: We will follow a five-step process in developing a COS for studies on pregnant women with cardiac disease. First, a systematic literature review will identify all reported outcomes (including patient-reported outcomes) and definitions. Second, semi-structured interviews with stakeholders involved in the care of pregnant women with cardiac disease will determine their perspective and add new outcomes that they consider important. Third, an international electronic Delphi survey will narrow outcomes obtained through the first two steps, in an attempt to arrive at a consensus. Fourth, a face-to-face consensus meeting will deliberate to finalize the COS. Finally, measurement tools and definitions for included outcomes will be determined through a series of literature reviews and Delphi surveys. Discussion: This protocol provides an overview of the steps involved in the development of a COS that must be reported in studies involving pregnant women with cardiac disease, in an attempt to harmonize outcome reporting and ensure the validity of study results that will not only inform clinical practice and future research but also encourage the development of COS in other areas of medicine. COMET core outcome set registration: http://www.comet initiative.org/studies/details/83

Myasthenia Gravis in pregnancy: Systematic review and case series

Background: Myasthenia gravis is an autoimmune disease which can impact pregnancy. Methods: Six databases were systematically searched for studies with at least five subjects reporting pregnancy outcomes for women with myasthenia gravis in pregnancy. Assessment of bias was performed for all included studies. Forty-eight cases from our own centre were also included in the analysis. Results: In total, 32 publications met inclusion criteria for systematic review, for a total of 33 unique data sets including 48 cases from our institution. Outcome data was available for 824 pregnancies. Spontaneous vaginal delivery occurred in 56.3% of pregnancies. Overall risk of myasthenia gravis exacerbation was 33.8% with a 6.4% risk of myasthenic crisis in pregnancy and 8.2% postpartum. The incidence risk of transient neonatal myasthenia gravis was 13.0%. Conclusions: The current systematic review provides the best estimates of risk currently available to aid in counselling women with myasthenia gravis in pregnancy

Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse

Limfoma de cèl·lules B; Supervivència lliure de malaltiaLinfoma de células B; Supervivencia libre de enfermedadB-cell lymphoma; Disease-free survivalAlthough methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.This work was supported in part by research funding from Fundación Alfonso Martín Escudero to SB. Data from this manuscript were presented at the 61st Annual Meeting of the American Society of Hematology, Orlando, FL, December 7th–10th, 2019

Impact of maternal metabolic abnormalities in pregnancy on human milk and subsequent infant metabolic development: methodology and design

<p>Abstract</p> <p>Background</p> <p>Childhood obesity is on the rise and is a major risk factor for type 2 diabetes later in life. Recent evidence indicates that abnormalities that increase risk for diabetes may be initiated early in infancy. Since the offspring of women with diabetes have an increased long-term risk for obesity and type 2 diabetes, the impact of maternal metabolic abnormalities on early nutrition and infant metabolic trajectories is of considerable interest. Human breast milk, the preferred food during infancy, contains not only nutrients but also an array of bioactive substances including metabolic hormones. Nonetheless, only a few studies have reported concentrations of metabolic hormones in human milk specifically from women with metabolic abnormalities. We aim to investigate the impact of maternal metabolic abnormalities in pregnancy on human milk hormones and subsequently on infant development over the first year of life. The objective of this report is to present the methodology and design of this study.</p> <p>Methods/Design</p> <p>The current investigation is a prospective study conducted within ongoing cohort studies of women and their offspring. Pregnant women attending outpatient obstetrics clinics in Toronto, Canada were recruited. Between April 2009 and July 2010, a total of 216 pregnant women underwent a baseline oral glucose tolerance test and provided medical and lifestyle history. Follow-up visits and telephone interviews are conducted and expected to be completed in October 2011. Upon delivery, infant birth anthropometry measurements and human breast milk samples are collected. At 3 and 12 months postpartum, mothers and infants are invited for follow-up assessments. Interim telephone interviews are conducted during the first year of offspring life to characterize infant feeding and supplementation behaviors.</p> <p>Discussion</p> <p>An improved understanding of the link between maternal metabolic abnormalities in pregnancy and early infant nutrition may assist in the development of optimal prevention and intervention strategies and in the protection of nutritionally vulnerable offspring who are at risk for obesity and diabetes later in life.</p

B-Type Natriuretic Peptide in Pregnant Women With Heart Disease

ObjectivesThe objectives of this study were to examine: 1) B-type natriuretic peptide (BNP) response to pregnancy in women with heart disease; and 2) the relationship between BNP levels and adverse maternal cardiac events during pregnancy.BackgroundPregnancy imposes a hemodynamic stress on the heart. BNP might be a useful biomarker to assess the ability of the heart to adapt to the hemodynamic load of pregnancy.MethodsThis was a prospective study of women with structural heart disease seen at our center. Serial clinical data and plasma BNP measurements were obtained during the first trimester, third trimester, and after delivery (>6 weeks).ResultsSeventy-eight pregnant women were studied; 66 women with heart disease (age 31 ± 5 years), and 12 healthy women (age 33 ± 5 years). During pregnancy, the median peak BNP level was higher in women with heart disease compared with control subjects (median 79, interquartile range 51 to 152 pg/ml vs. median 35, interquartile range 21 to 43 pg/ml, p < 0.001). In women with heart disease, those with subaortic ventricular dysfunction had higher BNP levels (p = 0.03). A BNP >100 pg/ml was measured in all women with events during pregnancy (n = 8). Sixteen women had increased BNP levels during pregnancy but did not have clinical events. None of the women with BNP ≤100 pg/ml had events. BNP ≤100 pg/ml had a negative predictive value of 100% for identifying events during pregnancy.ConclusionsMany pregnant women with heart disease have increased BNP levels during pregnancy. Incorporating serial BNP levels in into clinical practice can be helpful, specifically in adjudicating suspected adverse cardiac events during pregnancy

Cardiac outcomes after pregnancy in women with congenital heart disease

Objective: Women with congenital heart disease (CHD) are at risk for adverse cardiac events during pregnancy; however, the risk of events late after pregnancy (late cardiac events; LCE) has not been well studied. A study was undertaken to examine the frequency and determinants of LCE in a large cohort of women with CHD. Design: Baseline characteristics and pregnancy were prospectively recorded. LCE (\u3e6 months after delivery) were determined by chart review. Survival analysis was used to determine the risk factors for LCE. Setting: A tertiary care referral hospital. Patients: The outcomes of 405 pregnancies were studied (318 women; median follow-up 2.6 years). Main outcome measures: LCE included cardiac death/ arrest, pulmonary oedema, arrhythmia or stroke. Results: LCE occurred after 12% (50/405) of pregnancies. The 5-year rate of LCE was higher in women with adverse cardiac events during pregnancy than in those without (27±9% vs 15±3%, HR 2.2, p=0.02). Women at highest risk for LCE were those with functional limitations/cyanosis (HR 3.9, 95% CI 1.2 to 13.0), subaortic ventricular dysfunction (HR 3.0, 95% CI 1.4 to 6.6), subpulmonary ventricular dysfunction and/or significant pulmonary regurgitation (HR 3.2, 95% CI 1.6 to 6.6), left heart obstruction (HR 2.6, 95% CI 1.2 to 5.2) and cardiac events before or during pregnancy (HR 2.6, 95% CI 1.3 to 4.9). In women with 0, 1 or \u3e1 risk predictors the 5-year rate of LCE was 762%, 2365% and 44610%, respectively (p\u3c0.001). Conclusions: In women with CHD, pre-pregnancy maternal characteristics can help to identify women at increased risk for LCE. Adverse cardiac events during pregnancy are important and are associated with an increased risk of LCE

Borderline gestational diabetes mellitus and pregnancy outcomes

Background: The impact of borderline gestational diabetes mellitus (BGDM), defined as a positive oral glucose challenge test (OGCT) and normal oral glucose tolerance test (OGTT), on maternal and infant health is unclear. We assessed maternal and infant health outcomes in women with BGDM and compared these to women who had a normal OGCT screen for gestational diabetes. Methods: We compared demographic, obstetric and neonatal outcomes between women participating in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS) who had BGDM and who screened negative on OGCT. Results: Women who had BGDM were older (mean difference 1.3 years, [95% confidence interval (CI) 0.3, 2.2], p = 0.01) and more likely to be obese (27.1% vs 14.1%, relative risk (RR) 1.92, [95% CI 1.41, 2.62], p &lt; 0.0001) than women who screened negative on OGCT. The risk of adverse maternal outcome overall was higher (12.9% vs 8.1%, RR 1.59, [95% CI 1.00, 2.52], p = 0.05) in women with BGDM compared with women with a normal OGCT. Women with BGDM were more likely to develop pregnancy induced hypertension (17.9% vs 11.8%, RR 1.51, [95% CI 1.03, 2.20], p = 0.03), have a caesarean for fetal distress (17.1% vs 10.5%, RR 1.63, [95% CI 1.10, 2.41], p = 0.01), and require a longer postnatal hospital stay (mean difference 0.4 day, [95% CI 0.1, 0.7], p = 0.01) than those with a normal glucose tolerance. Infants born to BGDM mothers were more likely to be born preterm (10.7% vs 6.4%, RR 1.68, [95% CI 1.00, 2.80], p = 0.05), have macrosomia (birthweight ≥4.5 kg) (4.3% vs 1.7%, RR 2.53, [95% CI 1.06, 6.03], p = 0.04), be admitted to the neonatal intensive care unit (NICU) (6.5% vs 3.0%, RR 2.18, [95% CI 1.09, 4.36], p = 0.03) or the neonatal nursery (40.3% vs 28.4%, RR 1.42, [95% CI 1.14, 1.76], p = 0.002), and have a longer hospital stay (p = 0.001). More infants in the BGDM group had Sarnat stage 2 or 3 neonatal encephalopathy (12.9% vs 7.8%, RR 1.65, [95% CI 1.04, 2.63], p = 0.03). Conclusion: Women with BGDM and their infants had an increased risk of adverse health outcomes compared with women with a negative OGCT. Intervention strategies to reduce the risks for these women and their infants need evaluation. Trial registration: Current Controlled Trials ISRCTN00416244Hong Ju, Alice R. Rumbold, Kristyn J. Willson and Caroline A. Crowthe