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We compared levels of cannabis and other substance use before and after the legalization of cannabis in the obstetric population of the Kingston General Hospital (KGH). Urine samples were collected from patients admitted to KGH labour and delivery in September/October 2018 and September/October 2019. Urine was anonymously screened for cannabis and other substances. Approximately 9.5%-10% of patients screened positive for cannabis. We found no difference in the prevalence of cannabis use in our sample after legalization. Health care providers should discuss cannabis with patients who are pregnant or planning a pregnancy.

Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman’s reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.

Objective At the Maternal Health Clinic (MHC), women with certain pregnancy complications are seen for appointments focusing on lifestyle modification and future pregnancy counselling. This study's objective is to determine whether women who attended the MHC following a pregnancy complicated by gestational diabetes mellitus (GDM) or a hypertensive disorder of pregnancy (HDP) have improved interpregnancy and subsequent pregnancy outcomes, compared with non-attendees. Methods A retrospective cohort study was conducted including all pregnancies ≥20 weeks gestation at Kingston Health Sciences Centre (KHSC) from April 2010 to Dec 2019. Women with ≥2 deliveries were eligible for inclusion, with 2 pregnancies per woman included. These criteria identified 178 patients who attended the MHC and 133 who did not. Continuous variables with normal distribution were assessed with independent sample t tests. Continuous variables without normal distribution and ordinal variables were assessed with Mann–Whitney U tests. Categorical variables were assessed with Pearson's χ2 tests. Preterm delivery, HDP and GDM recurrence, HDP and GDM progression, and change in first-trimester blood pressure and pre-pregnancy weight were examined using multivariate regression modelling. Probability values Results MHC attendance was associated with improvements in interpregnancy weight reduction (P = 0.002), fewer interpregnancy type II diabetes diagnoses (P Conclusion In our examination of MHC outcomes, we found improvements in certain interpregnancy and subsequent pregnancy outcomes. These results support the continued development and funding of these clinics.

OBJECTIVE Caesarean section (CS) is more common following infertility treatment (IT) but the reasons why remain unclear and confounded. The Robson 10-Group Classification System (TGCS) may further explain variation in CS rates. We assessed the association between mode of conception and CS across Robson groups. DESIGN Population-based cohort study. SETTING Ontario, Canada, in a public healthcare system. POPULATION 921 023 births, 2006-2014. METHODS Modified Poisson regression produced relative risks (RR) and 95% confidence intervals, comparing the risk of CS among women with (1) subfertility without IT, (2) non-invasive IT (OI, IUI) or (3) invasive IT (IVF)-each relative to (4) spontaneous conception (SC). MAIN OUTCOME MEASURES CS rate according to one of four modes of conception, overall and stratified by each of the TGCS groups. RESULTS Relative to SC (26.9%), the risk of CS increased in those with subfertility without IT (RR 1.17, 95% CI 1.16-1.18), non-invasive IT (RR 1.21, 95% CI 1.18-1.24) and invasive IT (RR 1.39, 95% CI 1.36-1.42). Within each Robson group, similar patterns of RRs were seen, but with markedly differing rates. For example, in Group 1 (nulliparous, singleton, cephalic at ≥37 weeks, with spontaneous labour), the respective rates were 15.0, 19.4, 18.7 and 21.9%; in Group 2 (nulliparous, singleton, cephalic at ≥37 weeks, without spontaneous labour), the rates were 35.9, 44.4, 43.2 and 54.1%; and in Group 8 (multiple pregnancy), they were 55.9, 67.5, 65.0 and 69.3%, respectively. CONCLUSIONS CS is relatively more common in women with subfertility and those receiving IT, an effect that persists across Robson groups. TWEETABLE ABSTRACT Caesarean delivery is more common in women with infertility independent of demographics and prenatal conditions.

This study compared pregnancy-related cardiovascular disease risk indicators between women who attended 2 different postpartum screening and education clinics: 1 at an urban tertiary care centre and 1 at a northern, rural community hospital. Risk differences associated with ethnicity were also examined.We conducted a retrospective record review that compared data from an urban clinic in Kingston, Ontario (n = 675) with those from a rural clinic in Prince Rupert, British Columbia (n = 65). Patients who had a hypertensive disorder of pregnancy, gestational diabetes, intrauterine growth restriction, idiopathic preterm birth, or placental abruption attended the clinics at 6 months postpartum. Demographic information, personal and family history, physical examination findings, and laboratory results were collected and used to generate cardiovascular risk estimates using validated scoring systems. These estimates were compared between clinic populations and between ethnic subsets.Fifty-five percent of the Prince Rupert cohort were Indigenous, while 87% of the Kingston cohort were White (P0.001). A greater proportion of the Kingston cohort had experienced hypertensive disorders of pregnancy (P = 0.002), while a greater proportion of the Prince Rupert cohort had developed gestational diabetes (P=0.010). The Prince Rupert population had higher lifetime and 30-year cardiovascular disease risk scores (P = 0.008 and P = 0.005, respectively). Indigenous patients had more major cardiovascular risk factors as well as higher lifetime and 30-year cardiovascular risk scores (P = 0.001 and P = 0.008, respectively) than White and Asian patients.The increased cardiovascular disease risk in both rural and Indigenous women supports the need for better postpartum care, long-term follow-up, and early promotion of cardiovascular health in these populations.

Background/Objective Previous studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to the paucity of studies in which fathers were assessed prior to pregnancy. Thus, we established a cohort of preconception couples to prospectively evaluate the associations of maternal and paternal weight prior to pregnancy with infant birthweight at delivery. Methods In this prospective observational cohort study, 1292 newly-married women and their partners in Liuyang, China, were assessed at median of 23.3 weeks before a singleton pregnancy, thereby enabling concomitant assessment of preconception maternal and paternal body mass index (BMI) in relation to infant birthweight. Results Mean birthweight was 3294 ± 450 g with 147 neonates (11.4%) born large-for-gestational-age (LGA) and 94 (7.3%) small-for-gestational-age (SGA). After adjustment for maternal and paternal factors prior to conception (age, education, smoking, BMI, household income), length of gestation, total gestational weight gain, gestational diabetes, preeclampsia, and infant sex, it was noted that infant birthweight increased by 42.2 g (95% CI 29.5–54.8; p p = 0.04) per unit increase in paternal pregravid BMI. Maternal pregravid BMI explained 6.2% of the variance in birthweight whereas paternal BMI explained only 0.7%. Independent predictors of LGA delivery were maternal pregravid BMI (aOR = 1.91, 95% CI 1.50–2.44), maternal age (aOR = 1.48, 95% CI 1.09–2.00), and gestational weight gain (aOR = 1.80, 95% CI 1.40–2.30). Paternal pregravid BMI was not independently associated with LGA or SGA. Conclusion Paternal BMI prior to conception is associated with infant birthweight but only modestly so, in contrast to the dominant impact of maternal weight.

Severe maternal morbidity and mortality continue to increase in the United States, largely owing to chronic and newly diagnosed medical comorbidities. Interconception care, or care and management of medical conditions between pregnancies, can improve chronic disease control before, during, and after pregnancy. It is a crucial and time-sensitive intervention that can decrease maternal morbidity and mortality and improve overall health. Despite these potential benefits, interconception care has not been well implemented by the primary care community. Furthermore, there is a lack of guidelines for optimizing preconception chronic disease, risk stratifying postpartum chronic diseases, and recommending general collaborative management principles for reproductive-age patients in the period between pregnancies. As a result, many primary care providers, especially those without obstetric training, are unclear about their specific role in interconception care and may be unsure of effective methods for collaborating with obstetric care providers. In particular, internal medicine physicians, the largest group of primary care physicians, may lack sufficient clinical exposure to medical conditions in the obstetric population during their residency training and may feel uncomfortable in caring for these patients in their subsequent practice. The objective of this article is to review concepts around interconception care, focusing specifically on preconception care for patients with chronic medical conditions (eg, chronic hypertension, chronic diabetes mellitus, chronic kidney disease, venous thromboembolism, and obesity) and postpartum care for those with medically complicated pregnancies (eg, hypertensive disorders of pregnancy, gestational diabetes mellitus, excessive gestational weight gain, peripartum cardiomyopathy, and peripartum mood disorders). We also provide a pragmatic checklist for preconception and postpartum management.

Patients with a hypertensive disorder of pregnancy are more likely to have underlying cardiovascular risk factors and are at increased risk of future cardiovascular disease. These patients are more likely to be diagnosed with new-onset chronic hypertension and meet the criteria for metabolic syndrome postpartum. High-sensitivity C-reactive protein is a marker of general inflammation and may be used to identify increased risk for cardiovascular disease.This collaborative data-sharing study between Yale University, United States (Yale Hearts Moms study) and Queen's University, Canada (Maternal Health Clinic) aimed to study the utility of high-sensitivity C-reactive protein in postpartum cardiovascular risk screening, as determined by 30-year risk (Framingham) and metabolic syndrome 6 to 12 months postpartum.Patients with a hypertensive disorder of pregnancy (n=478) or an uncomplicated, term pregnancy (n=90) had cardiovascular risk screening and risk scoring performed at 6 to 12 months postpartum. Patients were excluded if they had a multiple gestation or chronic hypertension, diabetes mellitus, or cardiovascular disease diagnosed before pregnancy. Patients were categorized according to high-sensitivity C-reactive protein (mg/L) into Normal (3.0), High (3.1 to10.0), and Acute (≥10.0) groups. The primary outcome of the study was risk for future cardiovascular events, calculated through surrogate measures such as hypertension and cholesterol. Kruskal-Wallis and chi-square tests were used to compare groups, with post hoc tests corrected using the Bonferroni method. Multivariable logistic regression was used to assess the association between high-sensitivity C-reactive protein and cardiovascular risk, adjusting for relevant medical and sociodemographic variables. Analysis was completed with IBM SPSS Statistics, version 27.Patients in the High and Acute high-sensitivity C-reactive protein groups were more likely to have a body mass index ≥30, to have experienced a hypertensive disorder of pregnancy, to have a lower household income, and to have not breastfed or to have breastfed for6 months, when compared with the Normal high-sensitivity C-reactive protein group (all P.05). Patients in the High and Acute high-sensitivity C-reactive protein groups had higher 30-year cardiovascular risk scores and were more likely to have metabolic syndrome when compared with the Normal high-sensitivity C-reactive protein group (all P.05). Patients with High high-sensitivity C-reactive protein had 2-fold odds of metabolic syndrome 6 to 12 months after delivery, compared with those in the Normal high-sensitivity C-reactive protein group (adjusted odds ratio, 2.85 [95% confidence interval, 1.66-4.91]), adjusting for hypertensive disorder of pregnancy, body mass index, clinic site, breastfeeding, income, and family history of cardiovascular disease. Those with Acute high-sensitivity C-reactive protein also seemed to have elevated odds of metabolic syndrome compared with the Normal high-sensitivity C-reactive protein group (adjusted odds ratio, 2.52 [95% confidence interval, 1.24-5.12]). The odds of chronic hypertension were significantly higher (P.05) in the High high-sensitivity C-reactive protein group (adjusted odds ratio, 1.72 [95% confidence interval, 1.12-2.65]) compared with the Normal group.Individuals with elevated postpartum high-sensitivity C-reactive protein are at increased risk of cardiovascular disease 6 to 12 months postpartum after a pregnancy complicated by a hypertensive disorder of pregnancy. Future research is critical to determine the most comprehensive and accurate method and timing of postpartum cardiovascular risk screening to decrease the incidence of preventable cardiovascular mortality among women.

Background Periconceptional folic acid (FA) supplementation is recommended to prevent the occurrence of neural tube defects. Currently, most over-the-counter FA supplements in Canada and the United States contain 1 mg FA and some women are prescribed 5 mg FA/d. High-dose FA is hypothesized to impair 1-carbon metabolism. We aimed to determine folate and 1-carbon metabolism biomarkers in pregnant women exposed to 1 mg or 5 mg FA. Objectives This was an ancillary study within the Folic Acid Clinical Trial (FACT), a randomized, double-blinded, placebo-controlled, phase III trial designed to assess the efficacy of high-dose FA to prevent preeclampsia. Methods For FACT, women were randomized at 8-16 gestational weeks to receive daily 4.0 mg FA (high dose) or placebo (low dose) plus their usual supplementation (≤1.1 mg). Women were recruited from 3 Canadian FACT centers and provided nonfasting blood samples at 24-26 gestational weeks for measurement of RBC and serum total folate, serum unmetabolized FA (UMFA), tetrahydrofolate (THF), 5-methylTHF, 5-formylTHF, 5,10-methenylTHF, and MeFox (pyrazino-s-triazine derivative of 4α-hydroxy-5-methylTHF, a 5-methylTHF oxidation product); total vitamins B-12 and B-6; and plasma total homocysteine. Group differences were determined using χ2, Fisher exact, and Wilcoxon rank-sum tests. Results Nineteen (38%) women received high-dose FA and 31 (62%) received low-dose FA. The median RBC folate concentration was 2701 (IQR: 2243-3032) nmol/L and did not differ between groups. The high-dose group had higher serum total folate (median: 148.4 nmol/L, IQR: 110.4-181.2; P = 0.007), UMFA (median: 4.6 nmol/L, IQR: 2.5-33.8; P = 0.008), and 5-methylTHF (median: 126.6 nmol/L, IQR: 98.8-158.6; P = 0.03) compared with the low-dose group (median: 122.8 nmol/L, IQR: 99.5-136.0; median: 1.9 nmol/L, IQR: 0.9-4.1; median: 108.6 nmol/L, IQR: 96.4-123.2, respectively). Other biomarkers of 1-carbon metabolism did not differ. Conclusions High-dose FA supplementation in early pregnancy increases maternal serum folate but not RBC folate concentrations, suggesting tissue saturation. Higher UMFA concentrations in women receiving high-dose FA supplements suggest that these doses are supraphysiologic but with no evidence of altered 1-carbon metabolism.

We examine maternal microvascular function after preeclampsia, identifying heightened endothelium-dependent and endothelium-independent microvascular reactivity following severe disease. Our study represents a noteworthy addition to the existing literature with the use of a novel imaging modality, vascular perturbation, postpartum time point, and patient population with differentiation of preeclampsia into severe and nonsevere subtypes. These results represent a novel addition to the growing clinical and academic understanding of maternal health outcomes following preeclampsia.

Background: Women with a history of certain adverse outcomes in pregnancy (preterm birth, delivery of a small-for-gestational age [SGA] infant, preeclampsia, and gestational diabetes mellitus [GDM]) have an elevated lifetime prevalence of metabolic syndrome (MetS) and cardiovascular disease, compared with their peers. However, it is not known if MetS precedes the index pregnancy in young, nulliparous women who experience these antepartum outcomes. Thus, we sought to evaluate the relationship between pregravid cardiovascular risk factor profile and these pregnancy outcomes in low-risk women. Methods: In this prospective preconception cohort study, 1183 newly married women underwent systematic assessment of cardiovascular risk factors (anthropometry, blood pressure, lipids, glucose) at median 24.7 weeks before pregnancy, whereupon they were followed for the outcomes of preterm birth, SGA delivery, preeclampsia, and GDM. Results: Women who had pregravid MetS (harmonized definition) (n = 49) were more likely to have a Caesarean delivery than their peers (61.4% vs. 38.6%, p = 0.003). However, they did not have a higher incidence of preterm delivery, SGA, preeclampsia, or GDM. Similarly, women who had at least one of these adverse pregnancy outcomes (n = 141) did not have a higher prevalence of MetS or any of its component disorders before pregnancy. Indeed, before pregnancy, there were no significant differences between these women and their peers in waist circumference, body mass index, blood pressure, fasting glucose, triglycerides, low-density-lipoprotein, or high-density-lipoprotein cholesterol. Conclusions: The adverse cardiovascular risk factor profile that is seen in women with a history of preterm birth, SGA, preeclampsia, or GDM does not necessarily manifest before their pregnancy.

Preeclampsia is a hypertensive pregnancy complication with an unknown etiology and high maternal burden worldwide. Burgeoning research has linked preeclampsia to adverse maternal health outcomes remote from pregnancy; however, the intermediary mechanisms responsible for this association have not been sufficiently established. In the present narrative review, we summarize leading evidence of structural and functional cardiovascular changes associated with prior preeclampsia, and how these changes may be linked to future maternal disease. KEY POINTS: · Prior preeclampsia is associated with subclinical structural and functional vascular changes remote from pregnancy.. · Maternal cardiac adaptations to preeclampsia may have long-term implications on cardiovascular health.. · Clinicians have an opportunity to minimize maternal disease risk following preeclampsia..

Heart disease is the leading cause of mortality in adult women. Beyond the traditional risk factors of obesity, diabetes, and hypercholesterolemia, women with the pregnancy complications of preeclampsia, gestational diabetes, prematurity, and low birth weight for gestational age (fetal growth restriction) are at higher risk for later development of cardiovascular disease. Education of women and providers about the association of pregnancy complications and cardiovascular disease should begin in the postpartum period. Postpartum cardiovascular risk screening and lifestyle modifications should be considered standard of care and are essential to improving cardiac health as a preventive strategy.

Resume Objectif La maladie de Lyme est une infection emergente au Canada. Causee par une bacterie appartenant au complexe d'especes Borrelia burgdorferi sensu lato, elle est transmise par la morsure d'une tique a pattes noires infectee. Les populations de tiques a pattes noires continuent de se propager et sont maintenant etablies dans differentes regions du Canada. Il faut habituellement plus de 24 heures de temps d'attachement de la tique pour que la B. burgdorferi soit transmise a l'humain. Le diagnostic de la maladie de Lyme au stade localise precoce est pose au moyen d'une evaluation clinique, puisque les analyses de laboratoire ne sont pas fiables a ce stade. La plupart des patients atteints de la maladie de Lyme au stade localise precoce manifestent une lesion cutanee (c.-a-d. erytheme migrant) qui s'etend a partir du site de la morsure et/ou des symptomes non specifiques qui rappellent l'influenza (p. ex. arthralgie, myalgie et fievre). Les signes et symptomes peuvent se manifester de 3 a 30 jours apres la morsure de tique. Il y a lieu de prendre en charge les patientes enceintes qui presentent une morsure de tique ou une maladie de Lyme soupconnee en leur prodiguant des soins semblables a ceux de la population adulte non enceinte, ce qui implique d'envisager le recours aux antibiotiques pour la prophylaxie et le traitement. L'objectif principal de la presente opinion du comite est de renseigner les praticiens sur la maladie de Lyme et de fournir une facon d'aborder la prise en charge des soins prodigues aux femmes enceintes qui pourraient avoir ete infectees par une morsure de tique a pattes noires. Utilisateurs concernes Les fournisseurs de soins de sante qui prodiguent des soins aux patientes enceintes ou aux femmes en âge de procreer. Population cible Les femmes en âge de procreer. Donnees probantes En novembre 2018, des recherches ont ete effectuees dans les bases de donnees Medline, EMBASE, PubMed et CENTRAL relativement a deux categories principales : (1) maladie de Lyme, (2) autres maladies transmises par les tiques. Puisque la recherche etait principalement axee sur la maladie de Lyme et compte tenu du nombre limite d'articles a ce sujet, aucun filtre supplementaire n'a ete applique pour la date de publication ou le type d'etude. Pour ce qui est des autres maladies transmises par les tiques, les resultats ont ete restreints a une date de publication qui s'inscrit dans les 10 dernieres annees (2008–2018). Les termes de recherche ont ete determines au moyen des termes de recherche MeSH et de mots cles : Lyme Disease, Pregnancy, Pregnant Women, Pregnancy Complications, Ehrlichiosis, Anaplasmosis, Rocky Mountain Spotted Fever, Babesiosis, Tularemia, Powassan Virus, Encephalitis Viruses, Tick-Borne, Tick-Borne Diseases, Colorado Tick Fever, Q Fever, Relapsing Fever, et Southern Tick-Associated Rash Illness. Tous les articles portant sur la maladie de Lyme et autres maladies transmises par les tiques comprenant une population cible de femmes enceintes ont ete inclus; les autres groupes et populations ont ete exclus. Methodes de validation Le contenu et les recommandations de la presente opinion du comite ont ete rediges et acceptes par les auteurs. Le conseil d'administration de la Societe des obstetriciens et gynecologues du Canada a approuve la version definitive aux fins de publication.

Carbon monoxide (CO), an endogenously produced gasotransmitter, regulates inflammation and vascular tone, suggesting that delivery of CO may be therapeutically useful for pathologies like preeclampsia where CO insufficiency is implicated. Our strategy is to identify chemicals that increase the activity of endogenous CO-producing enzymes, including cytochrome P-450 oxidoreductase (CPR). Realizing that both riboflavin and pyrroloquinoline quinone (PQQ) are relatively nontoxic, even at high doses, and that they share chemical properties with toxic CO activators that we previously identified, our goal was to determine whether riboflavin or PQQ could stimulate CO production. Riboflavin and PQQ were incubated in sealed vessels with rat and human tissue extracts and CO generation was measured with headspace-gas chromatography. Riboflavin and PQQ increased CO production ∼60% in rat spleen microsomes. In rat brain microsomes, riboflavin and PQQ increased respective CO production approximately fourfold and twofold compared to baseline. CO production by human placenta microsomes increased fourfold with riboflavin and fivefold with PQQ. In the presence of recombinant human CPR, CO production was threefold greater with PQQ than with riboflavin. These observations demonstrate for the first time that riboflavin and PQQ facilitate tissue-specific CO production with significant contributions from CPR. We propose a novel biochemical role for these nutrients in gastransmission.

Adverse pregnancy outcomes including hypertensive disorders of pregnancy and gestational diabetes are significant causes of maternal mortality. There is substantial evidence of an association between adverse events during pregnancy and long‐term maternal cardiovascular risk. It is therefore important to understand the role of risk modification prior to, during, and after pregnancy to reduce adverse outcomes. These efforts include risk assessment, routine screening for cardiovascular risk factors, and potential pharmacotherapeutic risk reduction. In this manuscript, we aim to highlight the current evidence in the areas of cardiovascular risk assessment and risk modification, and the role for potential risk reduction therapies before, during, and after pregnancy.

Objective:Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.Design:Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.Setting:Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.Participants:Women were recruited when presenting for prenatal care in the early second trimester.Results:In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.Conclusions:We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.

Preeclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) in later life. Postpartum cardiovascular risk screening could identify patients who would benefit most from early intervention and lifestyle modification. However, there are no readily available methods to identify these high-risk women. We propose that placental lesions may be useful in this regard. Here, we determine the association between placental lesions and lifetime CVD risk assessed 6 months following PE. Placentas from 85 PE women were evaluated for histopathological lesions. At 6 months postpartum, a lifetime cardiovascular risk score was calculated. Placental lesions were compared between CVD risk groups and the association was assessed using odds ratios. Multivariable logistic regression was used to develop prediction models for CVD risk with placental pathology. Placentas from high-risk women had more severe lesions of maternal vascular malperfusion (MVM) and resulted in a 3-fold increased risk of screening as high-risk for CVD (OR 3.10 (1.20–7.92)) compared to women without these lesions. MVM lesion severity was moderately predictive of high-risk screening (AUC 0.63 (0.51, 0.75); sensitivity 71.8% (54.6, 84.4); specificity 54.7% (41.5, 67.3)). When clinical parameters were added, the model’s predictive performance improved (AUC 0.73 (0.62, 0.84); sensitivity 78.4% (65.4, 87.5); specificity 51.6% (34.8, 68.0)). The results suggest that placenta pathology may provide a unique modality to identify women for cardiovascular screening.

Background Ontario’s birth Registry (BORN) was established in 2009 to collect, interpret, and share critical data about pregnancy, birth and the early childhood period to facilitate and improve the provision of healthcare. Since the use of routinely-collected health data has been prioritized internationally by governments and funding agencies to improve patient care, support health system planning, and facilitate epidemiological surveillance and research, high quality data is essential. The purpose of this study was to verify the accuracy of a selection of data elements that are entered in the Registry. Methods Data quality was assessed by comparing data re-abstracted from patient records to data entered into the Ontario birth Registry. A purposive sample of 10 hospitals representative of hospitals in Ontario based on level of care, birth volume and geography was selected and a random sample of 100 linked mother and newborn charts were audited for each site. Data for 29 data elements were compared to the corresponding data entered in the Ontario birth Registry using percent agreement, kappa statistics for categorical data elements and intra-class correlation coefficients (ICCs) for continuous data elements. Results Agreement ranged from 56.9 to 99.8%, but 76% of the data elements (22 of 29) had greater than 90% agreement. There was almost perfect (kappa 0.81–0.99) or substantial (kappa 0.61–0.80) agreement for 12 of the categorical elements. Six elements showed fair-to-moderate agreement (kappa 0.50). Conclusion Overall, the data elements we evaluated in the birth Registry were found to have good agreement with data from the patients’ charts. Data elements that showed moderate kappa or low ICC require further investigation.

Objective: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at 7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. Results: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. Conclusions: In preterm neonates of

Background: Women with a history of certain pregnancy complications are at higher risk for cardiovascular (CVD) disease. However, most clinical guidelines only recommend postpartum follow-up of those with a history of preeclampsia, gestational diabetes mellitus, or preterm birth. This systematic review was undertaken to determine if there is an association between a broader array of pregnancy complications and the future risk of CVD. Methods: We systematically searched PubMed, MEDLINE and EMBASE (via Ovid), CINAHL, and the Cochrane Library from inception to September 22, 2017, for observational studies of the association between the hypertensive disorders of pregnancy, placental abruption, preterm birth, gestational diabetes mellitus, low birth weight, small-for-gestational-age birth, stillbirth, and miscarriage and subsequent CVD. Likelihood ratio meta-analyses were performed to generate pooled odds ratios (OR) and 95% intrinsic confidence intervals (ICI). Results: Our systematic review included 83 studies (28 993 438 patients). Sample sizes varied from 250 to 2 000 000, with a median follow-up of 7.5 years postpartum. The risk of CVD was highest in women with gestational hypertension (OR 1.7; 95% ICI, 1.3–2.2), preeclampsia (OR 2.7; 95% ICI, 2.5–3.0), placental abruption (OR 1.8; 95% ICI, 1.4–2.3), preterm birth (OR 1.6; 95% ICI, 1.4–1.9), gestational diabetes mellitus (OR 1.7; 95% ICI, 1.1–2.5), and stillbirth (OR 1.5; 95% ICI, 1.1–2.1). A consistent trend was seen for low birth weight and small-for-gestational-age birth weight but not for miscarriage. Conclusions: Women with a broader array of pregnancy complications, including placental abruption and stillbirth, are at increased risk of future CVD. The findings support the need for assessment and risk factor management beyond the postpartum period.

Essentials Low-molecular-weight heparin (LMWH) is used to prevent venous thromboembolism (VTE) in pregnancy. We evaluated the association between LMWH and large for gestational age (LGA) infants. We found no significant associations between LMWH use and LGA. LMWH does not appear to increase the risk for the delivery of an LGA infant. SUMMARY: Background Low-molecular-weight heparin (LMWH), an anticoagulant, is the recommended drug for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy. During pregnancy, LMWH is routinely prescribed to mothers with an increased risk of VTE or with a history of thrombosis. Although clinical reports of larger offspring born to women administered LMWH have been noted, no studies to date have evaluated or associated the use of LMWH and large for gestational age (LGA) infants. Objectives To determine whether there is an association between LMWH usage in mothers and the prevalence of LGA. Patients/Methods We performed an analysis of the Ottawa and Kingston (OaK) Birth Cohort and report characteristics of LMWH and association LGA (> 10%ile). We used coarsened exact matching (CEM) methods to account for bias and confounding. Results A total of 7519 women from the OaK Birth Cohort were included; 59 were administered LMWH during pregnancy (0.78%). Mothers prescribed LMWH had significantly greater BMI (P = 0.0001), age (P = 0.0001) and parity (P = 0.02). Gestational length was shorter among women administered LMWH compared to those without treatment (37.7 ± 2.0 vs. 39.2 ± 2.0, P

Women who experience a hypertensive disorder of pregnancy (HDP) are amongst those at the highest risk of premature cardiovascular diseases (CVD). In Canada, effective CVD prevention interventions tailored specifically for this high-risk population are urgently needed. The objective of this review is to summarize a broad range of mechanistic and clinical studies examining the association of HDP with future CVD to inform postpartum clinical follow-up strategies focused on improving women's cardiovascular health. The current state of the science (animal model, observational and intervention studies) largely support two main hypotheses explaining the epidemiological link between HDP and long-term risk of CVD. First, that the complicated pregnancy “unmasks” women who were predisposed to CVD prior to pregnancy (i.e., women with subclinical atherosclerosis or pre-pregnancy CVD risk factors). Second, that HDP causes vascular dysfunction and/or worsens preexisting, subclinical CVD risk factors. Despite this strong evidence, several knowledge gaps remain in the understanding of specific mechanisms linking these two theories and the impacts of other important contributors (e.g., intersectional factors). From a clinical perspective, given the consistent data demonstrating a high prevalence of CVD risk factors after HDP, routine care after pregnancy at minimum should include: 1) standardized assessment of pregnancy-associated CV risks (P-CVRs); 2) early and regular screening of traditional CVD risk factors; 3) education and support for health behaviours as first line therapy (including breastfeeding); 4) individualized pharmacotherapy (i.e., statins, antihypertensives or antiglycemic agents as clinically indicated); and 5) consideration of a woman's health goals, reproductive plans and social context.

Studies show poor maternal and fetal outcomes associated with prenatal cannabis use. With the legalization of cannabis in Canada, it is of timely importance to increase awareness of the effects of its use in pregnancy. An anonymous, online questionnaire was used to assess the pregnant population's knowledge, beliefs, and risk perceptions concerning cannabis. Additionally, educational materials on the effects of prenatal cannabis use were evaluated. A potential knowledge gap was found among 9%-19% of participants, who reported that cannabis posed no risk of harm to the pregnant person or fetus. Moreover, minor changes could improve the effectiveness of educational resources.

IntroductionThe ‘Developmental Origins of Health and Disease’ hypothesis suggests that a healthy trajectory of growth and development in pregnancy and early childhood is necessary for optimal health, development and lifetime well-being. The purpose of this paper is to present the protocol for a randomised controlled trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada). The primary objective of HeLTI Canada is to determine whether a 4-phase ‘preconception to early childhood’ lifecourse intervention can reduce the rate of child overweight and obesity. Secondary objectives include improved child: (1) growth trajectories; (2) cardiometabolic risk factors; (3) health behaviours, including nutrition, physical activity, sedentary behaviour and sleep; and (4) development and school readiness at age 5 years.Method and analysisA randomised controlled multicentre trial will be conducted in two of Canada’s highly populous provinces—Alberta and Ontario—with 786 nulliparous (15%) and 4444 primiparous (85%) women, their partners and, when possible, the first ‘sibling child.’ The intervention is telephone-based collaborative care delivered by experienced public health nurses trained in healthy conversation skills that includes detailed risk assessments, individualised structured management plans, scheduled follow-up calls, and access to a web-based app with individualised, evidence-based resources. An ‘index child’ conceived after randomisation will be followed until age 5 years and assessed for the primary and secondary outcomes. Pregnancy, infancy (age 2 years) and parental outcomes across time will also be assessed.Ethics and disseminationThe study has received approval from Clinical Trials Ontario (CTO 1776). The findings will be published in peer-reviewed journals and disseminated to policymakers at local, national and international agencies. Findings will also be shared with study participants and their communities.Trial registration numberISRCTN13308752; Pre-results.

Women have unique sex- and gender-related risk factors for cardiovascular disease (CVD) that can present or evolve over their lifespan. Pregnancy-associated conditions, polycystic ovarian syndrome, and menopause can increase a woman’s risk of CVD. Women are at greater risk for autoimmune rheumatic disorders, which play a role in the predisposition and pathogenesis of CVD. The influence of traditional CVD risk factors (eg, smoking, hypertension, diabetes, obesity, physical inactivity, depression, anxiety, and family history) is greater in women than men. Finally, there are sex differences in the response to treatments for CVD risk and comorbid disease processes. In this Atlas chapter we review sex- and gender-unique CVD risk factors that can occur across a woman’s lifespan, with the aim to reduce knowledge gaps and guide the development of optimal strategies for awareness and treatment. Résumé: Les femmes présentent des facteurs de risque de maladies cardiovasculaires (MCV) uniques, liés au sexe et au genre, qui peuvent se manifester ou évoluer tout au long de leur vie. Les troubles médicaux associés à la grossesse, le syndrome des ovaires polykystiques et la ménopause peuvent augmenter le risque de MCV chez une femme. Les femmes sont plus exposées aux troubles rhumatologiques auto-immuns, qui jouent un rôle dans la prédisposition et dans la pathogenèse des MCV. L’influence des facteurs de risque traditionnels pour les MCV (par exemple, le tabagisme, l’hypertension, le diabète, l’obésité, la sédentarité, la dépression, l’anxiété et les antécédents familiaux) est plus importante chez les femmes que chez les hommes. Enfin, il existe des différences entre les sexes dans la réponse aux traitements du risque de MCV et des processus pathologiques comorbides. Dans ce chapitre de l’Atlas, nous passons en revue les facteurs de risque de MCV propres au sexe et au genre qui peuvent survenir tout au long de la vie d’une femme, dans le but de réduire les lacunes dans les connaissances et d’orienter l’élaboration de stratégies optimales de sensibilisation et de traitement.

BackgroundCaesarean section rates are higher among pregnancies conceived by assisted reproductive technology (ART) compared to spontaneous conceptions (SC), implying an increase in neonatal and maternal morbidity. We aimed to compare caesarean section rates in ART pregnancies versus SC, overall, by indication (elective versus emergent), and by type of ART treatment (in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), fresh embryo transfer, frozen embryo transfer) in a systematic review and meta-analysis.MethodsWe searched Medline, EMBASE and CINAHL databases using the OVID Platform from 1993 to 2019, and the search was completed in January 2020. The eligibility criteria were cohort studies with singleton conceptions after in-vitro fertilization and/or intracytoplasmic sperm injection using autologous oocytes versus spontaneous conceptions. The study quality was assessed using the Newcastle Ottawa Scale and GRADE approach. Meta-analyses were performed using odds ratios (OR) with a 95% confidence interval (CI) using random effect models in RevMan 5.3, and I-squared (I2) test > 75% was considered as high heterogeneity.ResultsOne thousand seven hundred fifty studies were identified from the search of which 34 met the inclusion criteria. Compared to spontaneous conceptions, IVF/ICSI pregnancies were associated with a 1.90-fold increase of odds of caesarean section (95% CI 1.76, 2.06). When stratified by indication, IVF/ICSI pregnancies were associated with a 1.91-fold increase of odds of elective caesarean section (95% CI 1.37, 2.67) and 1.38-fold increase of odds of emergent caesarean section (95% CI 1.09, 1.75). The heterogeneity of the studies was high and the GRADE assessment moderate to low, which can be explained by the observational design of the included studies.ConclusionsThe odds of delivering by caesarean section are greater for ART singleton pregnancies compared to spontaneous conceptions. Preconception and pregnancy care plans should focus on minimizing the risks that may lead to emergency caesarean sections and finding strategies to understand and decrease the rate of elective caesarean sections.

Background Reports on the adequacy of vitamin D status of pregnant women are not available in Canada. Objectives The objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada. Methods Pregnant women (≥18 years) from 6 provinces (2008–2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n = 1905) and third trimesters (n = 1649) and at delivery (n = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test. Results In the first trimester, 93.4% (95% CI: 92.3%–94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P

Preeclampsia is a severe pregnancy complication with high potential for adverse effects on maternal and fetal health during the perinatal period. It is also associated with an increased risk of maternal cardiovascular disease later in life. Development of preeclampsia can be decreased by prescribing low-dose aspirin to high-risk women. At present, maternal and pregnancy factors are used to assess the risk of preeclampsia. One additional factor that could add to the assessment of risk is a family history of hypertension, cardiovascular disease, or diabetes, especially for nulliparous women who do not have a pregnancy history to inform treatment decisions. Therefore, we conducted a systematic review to assess the association between family history of the aforementioned conditions and preeclampsia. Four databases including MEDLINE, EMBASE, the Cochrane Library, and CINAHL/pre-CINAHL were searched for observational studies that examined a family history of hypertension, cardiovascular disease, or diabetes in women with preeclampsia and in a control population. Studies were evaluated for quality using the Newcastle-Ottawa Scale. A total of 84 relevant studies were identified. A meta-analysis was not conducted due to suspected heterogeneity in the included studies. Most studies reported a positive association between a family history of hypertension or cardiovascular disease and the development of preeclampsia. The majority of studies examining family history of diabetes reported non-significant associations. Overall, family history of hypertension or cardiovascular disease is associated with a higher risk for developing preeclampsia and should be considered when assessing women in the first trimester for low-dose aspirin.

Background Cigarette smokers have a reduced risk of developing preeclampsia, possibly attributed to an increase in carbon monoxide (CO) levels. Carbon monoxide is a gasotransmitter that has been implicated in maintaining vascular tone, increasing angiogenesis, and reducing inflammation and apoptosis at physiological concentrations. Moderately increasing CO concentrations may have therapeutic potential to prevent or treat preeclampsia; however, the effects of CO on pregnancy are under studied. Our objective was to investigate the effect of CO on major angiogenic and inflammatory markers in pregnancy, and to evaluate the effect of CO on indicators of placental health. Findings Pregnant CD-1 mice were constantly exposed to either ambient air or 250 ppm CO from conception until gestation day (GD)10.5 or GD16.5. Using a qRT-PCR array, we identified that CO increased expression of major angiogenic genes at the implantation site on GD10.5, but not GD16.5. Pro-inflammatory cytokines in the plasma and tissue lysates from implantation sites in treated mice were not significantly different compared to controls. Additionally, CO did not alter the implantation site phenotype, in terms of proliferative capacity, invasiveness of trophoblasts, or abundance of uterine natural killer cells. Conclusions This study suggests that CO exposure is pro-angiogenic at the maternal-fetal interface, and is not associated with demonstrable concerns during murine pregnancy. Future studies are required to validate safety and efficacy of CO as a potential therapeutic for vascular insufficiency diseases such as preeclampsia and intrauterine growth restriction.

Purpose The use of assisted reproductive technology (ART) has increased in the last 2 decades and continuous surveillance is needed. This systematic review aims to assess the risk of adverse neonatal outcomes (preterm birth [PTB], low birth weight [LBW], small-for-gestationalage [SGA] and large for gestational-age [LGA]), in singleton pregnancies conceived by fresh or frozen embryo transfer (FET) compared to spontaneous conceptions. Methods Cohort studies were identified from MEDLINE, Embase, Cochrane Library (January 2019), and manual search. Meta-analyses were performed to estimate odds ratios (OR) using random effects models in RevMan 5.3 and I-squared (I2) test > 50% was considered as high heterogeneity. Results After 3142 titles and abstracts were screened, 1180 full-text articles were assessed, and 14 were eligible. For fresh embryo transfer, the pooled ORs were PTB 1.64 (95% CI 1.46, 1.84); I2 = 97%; LBW 1.67 (95% CI 1.52, 1.85); I2 = 94%; SGA 1.46 [95% CI 1.11, 1.92]; I2 = 99%, LGA 0.88 (95% CI 0.80, 0.87); I2 = 80%). For frozen, the pooled ORs were PTB 1.39 (95% CI 1.34, 1.44); I2 = 0%; LBW 1.38 (95% CI 0.91, 2.09); I2 = 98%; SGA 0.83 (95% CI 0.57, 1.19); I2 = 0%, LGA 1.57 (95% CI 1.48, 1.68); I2 = 22%). Conclusions When compared with spontaneous pregnancies, fresh, but not frozen was associated with LBW and SGA. Both fresh and frozen were associated with PTB. Frozen was uniquely associated with LGA. Despite improvements in ART protocols in relation to pregnancy rates, attention is needed towards monitoring adverse neonatal outcomes in these pregnancies.

Infants with restricted growth for age are frequently exposed to insufficient placental circulation and are more likely to develop postnatal complications. Delayed cord clamping at birth for these infants requires further exploration.This study aimed to compare the short-term neonatal outcomes of delayed cord clamping with that of early cord clamping in small for gestational age preterm infants and to explore whether the effects of delayed cord clamping in small for gestational age preterm infants are different from that in non-small for gestational age preterm infants.We conducted a national retrospective cohort study, including infants born at33 weeks' gestation and admitted to the Canadian Neonatal Network units between January 2015 and December 2017. Small for gestational age infants (birthweight of10th percentile for gestational age and sex) who received delayed cord clamping ≥30 seconds were compared with those who received early cord clamping. In addition, non-small for gestational age infants who received delayed cord clamping were compared with those who received early cord clamping. The main study outcomes included composite outcome of mortality or major morbidity, neonatal morbidity rate, mortality rate, peak serum bilirubin, and number of blood transfusions. Multivariable logistic and linear regression models with a generalized estimation equation approach were used to account for the clustering of infants within centers.Overall, 9722 infants met the inclusion criteria. Of those infants, 1027 (10.6%) were small for gestational age. The median (interquartile range) gestational age was 31 weeks (range, 28-32 weeks). After adjusting for potential confounders, delayed cord clamping in small for gestational age infants was associated with a reduction in the composite outcome of mortality or major morbidity (adjusted odds ratio, 0.60; 95% confidence interval, 0.42-0.86) compared with early cord clamping. There was no difference between the 2 groups in peak serum bilirubin. Many associated benefits of delayed cord clamping in small for gestational age infants were similar to those in non-small for gestational age infants.Delayed cord clamping in small for gestational age preterm infants was associated with decreased odds of mortality or major morbidity. Many of the benefits of delayed cord clamping in the small for gestational age preterm infants were similar to those identified in the non-small for gestational age preterm infants.

Smokers have a significantly decreased risk of pre-eclampsia (PE), possibly attributed to an increase in blood carbon monoxide (CO) concentrations. At physiological concentrations, CO has been demonstrated to have placental vasodilatory and anti-inflammatory properties. Increasing endogenous CO production may have therapeutic potential to either prevent or treat PE. Menadione (MD), synthetic vitamin K3, increases CO in rat microsomes. Our objective was to investigate MD's ability to increase endogenous CO concentrations in pregnancy.Three experiments were completed. First, in vitro CO production was measured using isolated GD15 placentas. Second, non-pregnant normotensive mice received no, 1.5, 4.0 or 6.5 g/L MD for 7 days. Lastly, pregnant normotensive mice received either no or 6.5 g/L MD in water from GD10.5 to GD17.5. Consumption was measured as average daily water intake per gram of body weight. Maternal and fetal CO levels in the blood and tissue were quantified using headspace gas chromatography.MD significantly increased CO production in isolated GD15 placentas. In both pregnant and non-pregnant experiments, splenic CO, hepatic CO, and splenic mass were higher in treated mice compared to controls (all p 0.05). Maternal %COHb and Hb in treated dams were not significantly different compared to controls. The fetal:placental mass ratio was significantly lower in the treatment group (p = 0.002).Placental CO production was observed in GD15 placentas after co-incubation with MD. MD administration increased CO in the liver and spleens of pregnant mice. Further investigation into different doses of MD is required to identify one without demonstrable fetal/placental effects.