Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma. METHODS: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed. RESULTS: 46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively. CONCLUSION: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.

Counseling About Cannabis Use During Pregnancy and Lactation: A Qualitative Study of Patient and Clinician Perspectives.

INTRODUCTION: Legalization in many jurisdictions has increased the prevalence of cannabis use, including during pregnancy and lactation. Accordingly, clinicians providing perinatal and infant care are increasingly required to counsel about this topic, even if they do not feel comfortable or prepared for this conversation. The aim of this research was to explore how prenatal clinicians and pregnant and lactating women interact with cannabis consumption. METHODS: Using qualitative description, we conducted semi-structured interviews with 75 individuals in Canada: 23 clinicians who provide pregnancy and lactation care, and 52 individuals who made cannabis consumption decisions during pregnancy and/or lactation. Data were analyzed using inductive content analysis. RESULTS: Three phases of the clinical encounter influenced decision-making about cannabis consumption: initiation of a discussion about cannabis, sense-making, and the outcome of the encounter. Patients and clinicians described similar ideals for a counseling encounter about cannabis consumption during pregnancy or lactation: open, patient-centered conversation grounded in an informed decision-making model to explore the benefits, risks, and alternatives to cannabis. While clinicians described these values as reflecting real clinical interactions, patients reported that in their experience, actual interactions did not live up to these ideals. CONCLUSION: Clinicians and pregnant and lactating people report desiring the same things from a counseling interaction about cannabis: sharing of information, identification of values, and facilitation of a decision. Both groups endorse an open, nonjudgemental counseling approach that explores the reasons why a patient is considering cannabis consumption and reflects these reasons against available evidence and alternatives known to be safe.

Poor data stewardship will hinder global genetic diversity surveillance.

Genomic data are being produced and archived at a prodigious rate, and current studies could become historical baselines for future global genetic diversity analyses and monitoring programs. However, when we evaluated the potential utility of genomic data from wild and domesticated eukaryote species in the world's largest genomic data repository, we found that most archived genomic datasets (86%) lacked the spatiotemporal metadata necessary for genetic biodiversity surveillance. Labor-intensive scouring of a subset of published papers yielded geospatial coordinates and collection years for only 33% (39% if place names were considered) of these genomic datasets. Streamlined data input processes, updated metadata deposition policies, and enhanced scientific community awareness are urgently needed to preserve these irreplaceable records of today's genetic biodiversity and to plug the growing metadata gap.

Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma. METHODS: This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18-60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once-daily inhaled ecleralimab or placebo. Primary end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV1) during the late asthmatic response (LAR) measured by area under the curve (AUC3-7h) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide (F ENO) were secondary and exploratory end-points. RESULTS: 28 subjects were randomised to ecleralimab (n=15) or placebo (n=13). On day 84, ecleralimab significantly attenuated LAR AUC3-7h by 64% (p=0.008), LAR% by 48% (p=0.029), and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC0-2h (p=0.097) and EAR% (p=0.105). F ENO levels were significantly reduced from baseline throughout the study (p<0.05), except at 24 h post-allergen (day 43 and day 85). Overall, ecleralimab was safe and well tolerated. CONCLUSION: Ecleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation, and was safe in subjects with mild atopic asthma.

Sounding the alarmins-The role of alarmin cytokines in asthma.

The alarmin cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 are epithelial cell-derived mediators that contribute to the pathobiology and pathophysiology of asthma. Released from airway epithelial cells exposed to environmental triggers, the alarmins drive airway inflammation through the release of predominantly T2 cytokines from multiple effector cells. The upstream positioning of the alarmins is an attractive pharmacological target to block multiple T2 pathways important in asthma. Blocking the function of TSLP inhibits allergen-induced responses including bronchoconstriction, airway hyperresponsiveness, and inflammation, and subsequent clinical trials of an anti-TSLP monoclonal antibody, tezepelumab, in asthma patients demonstrated improvements in lung function, airway responsiveness, inflammation, and importantly, a reduction in the rate of exacerbations. Notably, these improvements were observed in patients with T2-high and with T2-low asthma. Clinical trials blocking IL-33 and its receptor ST2 have also shown improvements in lung function and exacerbation rates; however, the impact of blocking the IL-33/ST2 axis in T2-high versus T2-low asthma is unclear. To date, there is no evidence that IL-25 blockade is beneficial in asthma. Despite the considerable overlap in the cellular functions of IL-25, IL-33, and TSLP, they appear to have distinct roles in the immunopathology of asthma.

Respiratory System Dynamics.

While static mechanical forces govern resting lung volumes, dynamic forces determine tidal breathing, airflow, and changes in airflow and lung volume during normal and abnormal breathing. This section will examine the mechanisms, measurement methodology, and interpretation of the dynamic changes in airflow and lung volume that occur in health and disease. We will first examine how the total work of breathing can be described by the parameters of the equation of motion, which determine the pressure required to move air into and out of the lung. This will include a detailed description of airflow characteristics and airway resistance. Next, we will review the changes in pressure and flow that determine maximal forced inspiration and expiration, which result in the maximal flow-volume loop and the clinically important forced expired volume in 1 second. We will also assess the mechanisms and interpretation of bronchodilator responsiveness, dynamic hyperinflation, and airways hyperresponsiveness.

Mediating expectations and experiences that influence birth experiences in Canada's first Alongside Midwifery Unit.

BACKGROUND: Globally, midwifery-led birthing units are associated with excellent maternal and neonatal outcomes, and positive childbirth experiences. However, little is known about what aspects of midwife-led units contribute to favorable experiences and overall satisfaction. Our aim was to explore and describe midwifery service user experiences at Canada's first Alongside Midwifery Unit (AMU). METHODS: We used a qualitative, grounded theory approach using semi-structured interviews with recipients of midwifery care at the AMU. FINDINGS: Data were collected from twenty-eight participants between September 2018 and March 2020. Our generated theory explains how birth experiences and satisfaction were influenced by how well the AMU aligned with expectations or desired experiences related to the following four themes: (1) maintaining the midwifery model of care, (2) emphasizing control and choice, (3) facilitating interprofessional relationships, and (4) appreciating the unique AMU birthing environment. CONCLUSION: Canada's first AMU met or exceeded service-user expectations, resulting in high levels of satisfaction with their birth experience. Maintaining core elements of the midwifery model of care, promoting high levels of autonomy, and facilitating positive interprofessional interactions are crucial elements contributing to childbirth satisfaction in the AMU environment.

Exploring patients' perspectives of gestational diabetes mellitus screening and counselling in Ontario: A grounded theory study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Approaches to screening for GDM continue to evolve, introducing potential variability of care. This study explored the impact of these variations on GDM counselling and screening from the perspectives of pregnant individuals. METHODS: Following a Corbin and Strauss approach to qualitative, grounded theory we recruited 28 individuals from three cities in Ontario, Canada who had a singleton pregnancy under the care of either a midwife, family physician or obstetrician. Convenience and purposive sampling techniques were used. Semi-structured telephone interviews were conducted and transcribed verbatim between March and December 2020. Transcripts were analysed inductively resulting in codes, categories and themes. RESULTS: Three themes were derived from the data about GDM screening and counselling: 'informing oneself', 'deciding' and 'screening'. All participants, regardless of geographical region, or antenatal care provider, moved through these three steps during the GDM counselling and screening process. Differences in counselling approaches between pregnancy care providers were noted throughout the 'informing' and 'deciding' stages of care. Factors influencing these differences included communication, healthcare autonomy and patient motivation to engage with health services. No differences were noted within care provider groups across the three geographic regions. Participant experiences of GDM screening were influenced by logistical challenges and personal preferences towards testing. CONCLUSION: Informing oneself about GDM may be a crucial step for facilitating decision-making and screening uptake, with an emphasis on information provision to facilitate patient autonomy and motivation. PATIENT OR PUBLIC CONTRIBUTION: Participants of our study included patients and service users. Participants were actively involved in the study design due to the qualitative, patient-centred nature of the research methods employed. Analysis of results was structured according to the emergent themes of the data which were grounded in patient perspectives and experiences.

Allergen provocation tests in respiratory research: building on 50†years of experience.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review.

Effect of daily dosing with tiotropium against methacholine induced bronchoconstriction in asthmatics.

INTRODUCTION: Loss of bronchoprotection against direct and indirect acting stimuli following regular use of inhaled beta2-agonists occurs with both short and long-acting formulations. Comparatively little is known about the development of tolerance following regular use of inhaled muscarinic receptor antagonists. Two investigations with the short-acting muscarinic receptor antagonist ipratropium bromide have reported no tolerance after regular use against inhaled methacholine. To our knowledge, there are no data regarding loss of bronchoprotection following regular use of long-acting muscarinic receptor antagonist. We therefore looked at the effect of daily dosing with tiotropium on methacholine induced bronchoconstriction in a population of mild asthmatics. METHODS: We performed a randomized, double-blind, placebo-controlled cross-over study comparing tiotropium Respimat® 5 µg to placebo in adult asthmatics. Each treatment arm began with baseline methacholine challenge followed immediately by treatment administration. One hour later a post treatment methacholine challenge was performed. Participants dosed daily (two puffs) at home for the next six days and returned to the lab on Day 8 for a final dose of treatment 1 h prior to methacholine challenge. RESULTS: The average doubling dose increase in methacholine PD20 following a single dose of tiotropium was 3.9 doubling doses whereas that following placebo was 0.93 (p = 0.003). After regular use, methacholine PD20 was further increased to 6.4 doubling doses following tiotropium whereas that following placebo decreased by 0.57 doubling doses (p < 0.001). CONCLUSION: LAMA are indicated for use as add-on monotherapy or in triple therapy combination for poorly controlled asthma. It may be reassuring to know therefore, that regular use does not result in loss of bronchoprotection like that which occurs with beta2-agonist bronchodilators.

Clinician responses to cannabis use during pregnancy and lactation: a systematic review and integrative mixed-methods research synthesis.

BACKGROUND: Perinatal cannabis use is increasing, and clinician counselling is an important aspect of reducing the potential harm of cannabis use during pregnancy and lactation. To understand current counselling practices, we conducted a systematic review and integrative mixed-methods synthesis to determine "how do perinatal clinicians respond to pregnant and lactating patients who use cannabis?" METHODS: We searched 6 databases up until 2021-05-31. Eligible studies described the attitudes, perceptions, or beliefs of perinatal clinician about cannabis use during pregnancy or lactation. Eligible clinicians were those whose practice particularly focusses on pregnant and postpartum patients. The search was not limited by study design, geography, or year. We used a convergent integrative analysis method to extract relevant findings for inductive analysis. RESULTS: Thirteen studies were included; describing perspectives of 1,366 clinicians in 4 countries. We found no unified approach to screening and counselling. Clinicians often cited insufficient evidence around the effects of perinatal cannabis use and lacked confidence in counselling about use. At times, this meant clinicians did not address cannabis use with patients. Most counselled for cessation and there was little recognition of the varied reasons that patients might use cannabis, and an over-reliance on counselling focussed on the legal implications of use. CONCLUSION: Current approaches to responding to cannabis use might result in inadequate counselling. Counselling may be improved through increased education and training, which would facilitate conversations to mitigate the potential harm of perinatal cannabis use while recognizing the benefits patients perceive.

Cannabis use during pregnancy and breastfeeding is common and understanding current physician counselling approaches is important to identify gaps and to make suggestions for practice. We conducted a systematic review of the literature to understand how physicians respond to pregnant or breastfeeding patients who use cannabis. We found 13 eligible articles in our review and our analysis showed that there was no common approach to screening and counselling patients. Physicians often described needing more training and education to support their confidence. Additionally, physicians often did not address the various medical reasons for which patients might use cannabis during pregnancy and breastfeeding. We suggest that counselling approaches may be improved through increased education and training. This could facilitate conversations to help mitigate the potential harm of cannabis use while recognizing the benefits patients perceive and thus establish strong patient­physician relationships.

Muscarinic Receptor Antagonism and Allergen Induced Airway Responses in Allergic Asthma: A Scoping Review.

PURPOSE: The purpose of this scoping review was to identify existing clinical and basic science knowledge surrounding the effect of muscarinic receptor antagonism on allergen-induced airway responses to inform future clinical research in this area. METHODS: Multiple advanced searches were performed using the National Library of Medicine PubMed search engine. Each search began with two terms; for example, "atropine and asthma" or "tiotropium and airway inflammation". Results were then further refined to include terms such as "allergen" or "ovalbumin (OVA)". Abstracts of refined searches were reviewed for relevance to allergic asthma and allergen-induced airway responses including the early and late asthmatic responses, airway inflammation and tissue remodelling. There was no restriction regarding publication date. Reference lists of selected papers were also reviewed for relevant publications. RESULTS: Nine human clinical trial publications and fourteen animal model publications were identified. In humans, single dose atropine (n=4), ipratropium (n=4) or oxitropium (n=1) administered pre-challenge produced equivocal effects on allergen-induced early asthmatic responses as reported but favored inhibition in eight of nine studies after re-analyses. Animal model investigations (n=14) showed mostly favorable results, especially with respect to airway inflammation and tissue remodelling, although two studies were negative, and one study showed a worsening in allergen induced airway inflammation following muscarinic receptor antagonism. CONCLUSION: Existing human and animal model data suggest muscarinic receptor antagonism may be beneficial in preventing allergen induced airway responses in those with allergic asthma. Additional human research utilizing current standardized methodologies is required.

Association of the Cerebro-Placental Ratio With Adverse Outcomes in Pregnancies Affected by Gestational Diabetes Mellitus.

OBJECTIVES: Cerebro-placental ratio (CPR) is a doppler tool contributes to clinical decision-making in pregnancies affected by small for gestational age weight (SGA). Pregnancies affected by gestational diabetes mellitus (GDM) tend to have higher newborn weight, but greater risk of adverse perinatal outcomes. We hypothesized that in GDM-complicated-pregnancies CPR will be associated with adverse perinatal outcomes even in the absence of SGA. METHODS: This prospective single-center cohort study included non-anomalous singleton pregnancies in women with GDM. Those with pre-pregnancy diabetes mellitus, hypertensive disorder or suspected SGA were excluded. Routine fetal sonographic assessment included CPR-defined as middle cerebral artery pulsatilty index/umbilical artery pulsatilty index. Masked CPR measurement closest to birth was used, classified as >10th (normal) or ≤10th centile (low). Primary outcome was a composite, consisting of stillbirth, Caesarean birth due to abnormal fetal heart rate pattern, 5-minute Apgar <7, cord arterial pH < 7.0, hypoxic ischemic encephalopathy, or NICU admission >24 hours. RESULTS: Of 281 participants, 24 (8.5%) had low CPR, at a mean gestational age of 36.3 weeks (IQR 34.0-37.4). Birthweight percentile was significantly lower among the low CPR group (35th [IQR 16-31] versus 60th [IQR 31-82]; P = .002). There was no statistically difference in the primary composite outcome between the groups (8.3% versus 7.0%, P = .68). Low CPR was significantly associated with a higher risk of neonatal hypoglycemia (adjusted odds ratio 3.2, 95% CI 1.2-8.3). CONCLUSION: In pregnancies affected by GDM, CPR ≤10th percentile was not associated with adverse perinatal outcome but was associated with neonatal hypoglycemia.

How Do Health Schemas Inform Healthy Behaviours During Pregnancy? Qualitative Findings from the Be Healthy in Pregnancy (BHIP) Study.

OBJECTIVE: Excess gestational weight gain (GWG) is associated with adverse long and short-term outcomes for both woman and child, yet evidence demonstrates pregnant women are frequently not engaging in healthy behaviours linked to appropriate weight gain. The purpose of the current study was to explore women's values and beliefs related to weight, nutrition and physical activity during pregnancy and to describe how these beliefs influence their behaviours. METHODS: As part of a larger randomized controlled trial, we conducted 20 focus groups with 66 pregnant women between 16 and 24-weeks gestation using a semi-structured interview guide. Focus groups were recorded and transcribed verbatim and analyzed using a grounded theory approach. RESULTS: Three personal health schemas emerged from the findings which illustrated women's diverging beliefs about their health behaviours in pregnancy. 'Interconnected health' described beliefs regarding the impact their health had on that of their growing baby and awareness of risks associated with inappropriate weight gain. 'Gestational weight gain as an indicator of health' illustrated perceptions regarding how GWG impacted health and the utility of guidelines. Finally, 'Control in pregnancy' described the sense of agency over one's body and health. CONCLUSIONS FOR PRACTICE: Our results showed that health-related behaviours in pregnancy are driven by personal health schemas which are often discordant with clinical evidence. Interventions and health care provider advice aimed at behaviour modification would benefit from first understanding and addressing these schemas. Tackling the conflict between beliefs and behaviour may improve health outcomes associated with appropriate weight gain in pregnancy.

Direct and indirect bronchoprovocation tests in dose-response studies of inhaled corticosteroids: Past, present, and future directions.

Inhaled corticosteroids (ICS) are a mainstay of treatment in eosinophilic asthma. Many studies have explored the dose-response effect of different formulations of ICS through direct or indirect bronchoprovocation testing. Such studies are important for investigating efficacy and identifying the relative potency between formulations. However, lack of consistency in methods and designs has hindered the comparability of study findings. This review discusses current knowledge of the dose-response, or lack thereof, of different formulations of ICS through direct and indirect bronchoprovocation testing. The strengths and weaknesses of past studies inform recommendations for future methodological considerations in this field, such as utilizing a randomized double-blind crossover design, enrolling participants likely to respond to ICS therapy, and carefully selecting treatment durations and washout periods to assess incremental improvement in airway hyperresponsiveness while reducing the likelihood of a carryover effect.

Maternal weight gain and pregnancy outcomes in twin gestations.

BACKGROUND: Data on the optimal gestational weight gain in twin pregnancies are limited. As a result, the Institute of Medicine currently provides only provisional recommendations on gestational weight gain in this population. OBJECTIVE: This study aimed to identify the optimal range of gestational weight gain in twin pregnancies and to estimate the association between inappropriate gestational weight gain and adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of all women with twin pregnancies that were followed up in a single, tertiary center between 2000 and 2014. We used 2 approaches to identify the optimal range of gestational weight gain: a statistical approach (the interquartile range of gestational weight gain in low-risk pregnancies with normal outcomes) and an outcome-based approach (by identifying thresholds of gestational weight gain below or above which the rate of adverse outcomes increases). The primary outcome was preterm birth. Associations of gestational weight gain below or above the normal range with the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence intervals. These associations were stratified by prepregnancy body mass index group. RESULTS: A total of 1274 women with twin pregnancies met the study criteria: 43 were classified as underweight, 777 were normal weight, 278 were overweight, and 176 were obese. Our estimates of the optimal gestational weight gain range were similar to those recommended by the Institute of Medicine except for the obese category, in which our optimal gestational weight gain range at 37 weeks (9.3-16.3 kg) was lower than in the provisional Institute of Medicine recommendations (11.3-19.1 kg). Nearly half of our cohort experienced inappropriate gestational weight gain: 30% (n=381) gained weight below and 17% (n=216) gained weight above current Institute of Medicine recommendations. In the normal weight group, gestational weight gain below recommendations was associated with an increased risk of preterm birth and birthweight at the <10th centile and with a reduction in the risk of hypertensive disorders, whereas gestational weight gain above recommendations was associated with an increased risk of hypertensive disorders and a reduction in the risk of birthweight at the <10th centile. Associations were less consistent in the overweight and obese groups. CONCLUSION: These findings identify gestational weight gain as a potentially modifiable risk factor for preterm birth and other pregnancy complications in twin gestations. Further prospective studies are needed to determine whether interventions aimed at optimizing gestational weight gain can improve the outcomes of these high-risk pregnancies.

Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study.

BACKGROUND: People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies. METHODS: We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992-2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP. RESULTS: The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7-20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72-1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04-1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57-0.97]), when compared directly. INTERPRETATION: In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.

Changes in rate of preterm birth and adverse pregnancy outcomes attributed to preeclampsia after introduction of a refined definition of preeclampsia: A population-based study.

INTRODUCTION: Since 2013, various guidelines for hypertension in pregnancy have been refined, no longer requiring proteinuria as a requisite criterion for preeclampsia. We aimed to evaluate the impact of the new definition on preterm birth (PTB) and adverse pregnancy outcomes. MATERIAL AND METHODS: Women delivering in Ontario between April 2012 and November 2016 were included. Delivery <24+0/7 weeks, major fetal anomalies or preexisting renal disease were excluded. The primary outcome was livebirth <37, <34 or <32 weeks. Rates, adjusted rate ratios (aRR) and ratio of the rate ratio (RRR) were used to compare outcomes in the 2 years after the new Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline (December 2014-November 2016; period 2) vs the 2 years before (April 2012-March 2014; period 1), among women with and without preeclampsia. RESULTS: In all, 268 543 and 267 964 births in periods 1 & 2, respectively, were included. Respective preeclampsia rates increased significantly from 3.9% to 4.4% (p < 0.001), with no change in maternal morbidity rates. In preeclamptic women, respective rates of PTB <37 weeks were 21.0% and 20.7% (aRR 1.01, 95% confidence interval [CI] 1.00-1.02), with significant aRR for PTB <34 (0.86, 95% CI 0.77-0.96) and <32 weeks (0.79, 95% CI 0.67-0.94). A similar aRR was observed in women without preeclampsia. In preeclamptic women, composite severe neonatal morbidity decreased after guideline change (aRR 0.95, 95% CI 0.91-0.99), a finding not observed in women without preeclampsia (RRR 0.95, 95% CI 0.91-0.99). CONCLUSIONS: The new definition of preeclampsia was associated with increased disease rates, a modest reduction in adverse neonatal outcomes and no change in maternal outcomes.

Investigating the normalization and normative views of gestational weight gain: Balancing recommendations with the promotion and support of healthy pregnancy diets.

OBJECTIVES: Gestational weight gain (GWG) is increasingly monitored in the United States and Canada. While promoting healthy GWG offers benefits, there may be costs with over-surveillance. We aimed to explore these costs/benefits. METHODS: Quantitative data from 350 pregnant survey respondents and qualitative focus group data from 43 pregnant/post-partum and care-provider participants were collected in the Mothers to Babies (M2B) study in Hamilton, Canada. We report descriptive statistics and discussion themes on GWG trajectories, advice, knowledge, perceptions, and pregnancy diet. Relationships between GWG monitoring/normalization and worry, knowledge, diet quality, and sociodemographics-namely low-income and racialization-were assessed using χ2 tests and a linear regression model and contextualized with focus group data. RESULTS: Most survey respondents reported GWG outside recommended ranges but rejected the mid-20th century cultural norm of "eating for two"; many worried about gaining excessively. Conversely, respondents living in very low-income households were more likely to be gaining less than recommended GWG and to worry about gaining too little. A majority had received advice about GWG, yet half were unable to identify the range recommended for their prepregnancy BMI. This proportion was even lower for racialized respondents. Pregnancy diet quality was associated with household income, but not with receipt or understanding of GWG guidance. Care-providers encouraged normalized GWG, while worrying about the consequences of pathologizing "abnormal" GWG. CONCLUSIONS: Translation of GWG recommendations should be done with a critical understanding of GWG biological normalcy. Supportive GWG monitoring and counseling should consider clinical, socioeconomic, and community contexts.

Be Healthy in Pregnancy: Exploring factors that impact pregnant women's nutrition and exercise behaviours.

Excess gestational weight gain is associated with short- and long-term pregnancy complications. Although a healthy diet and physical activity during pregnancy are recommended and shown to reduce the risk of complications and improve outcomes, adherence to these recommendations is low. The aims of this study were to explore women's view of nutrition and physical activity during pregnancy and to describe barriers and facilitators experienced in implementing physical activity and nutrition recommendations. In a substudy of the Be Healthy in Pregnancy randomized trial, 20 semistructured focus groups were conducted with 66 women randomized to the control group when they were between 16 and 24 weeks gestation. Focus groups were recorded, transcribed verbatim, coded and thematically analysed. The results indicate that women felt motivated to be healthy for their baby, but competing priorities may take precedence. Participants described limited knowledge and access to information on safe physical activity in pregnancy and lacked the skills needed to operationalize both physical activity and dietary recommendations. Women's behaviours regarding diet and physical activity in pregnancy were highly influenced by their own and their peers' beliefs and values regarding how weight gain impacted their health during pregnancy. Pregnancy symptoms beyond women's control such as fatigue and nausea made physical activity and healthy eating more challenging. Counselling from care providers about nutrition and physical activity was perceived as minimal and ineffective. Future interventions should address improving counselling strategies and address individual's beliefs around nutrition and activity in pregnancy.