Search

Subfertility and infertility treatment can be stressful experiences, but it is unknown whether each predisposes to postpartum mental illness. We sought to evaluate associations between subfertility or infertility treatment and postpartum mental illness.We conducted a population-based cohort study of individuals without pre-existing mental illness who gave birth in Ontario, Canada, from 2006 to 2014, stratified by fertility exposure: subfertility without infertility treatment; noninvasive infertility treatment (intrauterine insemination); invasive infertility treatment (in vitro fertilization); and no reproductive assistance. The primary outcome was mental illness occurring 365 days or sooner after birth (defined as ≥ 2 outpatient visits, an emergency department visit or a hospital admission with a mood, anxiety, psychotic, or substance use disorder, self-harm event or other mental illness). We used multivariable Poisson regression with robust error variance to assess associations between fertility exposure and postpartum mental illness.The study cohort comprised 786 064 births (mean age 30.42 yr, standard deviation 5.30 yr), including 78 283 with subfertility without treatment, 9178 with noninvasive infertility treatment, 9633 with invasive infertility treatment and 688 970 without reproductive assistance. Postpartum mental illness occurred in 60.8 per 1000 births among individuals without reproductive assistance. Relative to individuals without reproductive assistance, those with subfertility had a higher adjusted relative risk of postpartum mental illness (1.14, 95% confidence interval 1.10-1.17), which was similar in noninvasive and invasive infertility treatment groups.Subfertility or infertility treatment conferred a slightly higher risk of postpartum mental illness compared with no reproductive assistance. Further research should elucidate whether the stress of infertility, its treatment or physician selection contributes to this association.

The prevalence of maternal cardiovascular disease (CVD) has risen throughout the developed world, reflecting an increase in acquired cardiovascular risk factors, such as hypertension and diabetes, and the improved life expectancy of those living with congenital CVD due to advances in care. Because many cardiovascular risk factors or cardiovascular conditions are associated with infertility, reproductive-aged women with CVD may increasingly seek reproductive assistance. The worldwide use of assisted reproductive technologies (ART), such as in-vitro fertilization (IVF) with or without intracytoplasmic sperm injection, or intrauterine insemination following pharmacological ovulation induction have increased steadily over the last several decades. It is incumbent among providers who care for reproductive-aged women with pre-existing CVD or CVD risk factors to understand and appreciate the types of treatments offered and inherent risks related to infertility treatments, in order to guide their patients to making safe reproductive choices in line with their values and preferences. While infertility treatments increase the risk of complicated pregnancy, whether these risks are compounded among individuals with pre-existing CVD is less well known. In this review, we summarize current available evidence regarding short-term and long-term cardiovascular implications of ART among individuals with and without CVD, as well as treatment considerations for these women. Existing knowledge gaps and priority areas for further study are presented.

Background: Electroencephalography (EEG) -based motor-imagery brain-computer interface (MI-BCI) systems can facilitate training of wilful modulation of sensorimotor oscillations in patients with prolonged disorders of consciousness, potentially enabling empirical assessment of awareness and movement independent responses and question answering. Methods: A multistage, ten session, protocol was evaluated with twenty-four (N = 24) patients who have prolonged disorders of consciousness (PDoC) (unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS)) or locked-in syndrome (LIS). Phase one assessed capacity to modulate brain activity and thus detect awareness, phase two involved motor-imagery training with neurofeedback, and phase three assessed patients’ motor-imagery response to closed questions, categorised to assess biographical, numerical, logical, and situational awareness. Results: Patients from all groups show significant capacity to modulate brain activity and respond to closed questions with motor imagery. A conservative approach to statistical testing was necessarily taken, due to a limited sample size and uneven groups. However, significant group differences were observed indicating patients with LIS outperform patients with PDoC. As patients diagnosed with UWS present evidence of command following in this protocol and thus could have MCS, significant differences between UWS and MCS across a range of tests were inconclusive although, in general, group performances are correlated with the level of awareness associated with clinical diagnosis. Conclusions: We conclude that the proposed multistage protocol involving progression from motor imagery training with neurofeedback to closed question responses under the correct conditions may be effective for movement-independent consciousness profiling in prolonged disorders of consciousness.

Background: In the midst of the North American opioid crisis, identifying and intervening on drivers of high-risk opioid prescriptions is an important step towards reducing iatrogenic harm. Objectives: We aimed to identify factors associated with variations in high-risk opioid discharge prescriptions, following select surgical procedures, to guide future quality improvement initiatives. Methods: This retrospective cohort study analyzed 1322 patients who underwent select open pelvic and open abdominal surgeries between January 1 and December 31, 2017, in a tertiary health care centre in Montreal. Results: Patients who underwent open abdominal surgeries were prescribed significantly higher daily doses of morphine milligram equivalents (MME) (45 mg; interquartile range, 30-60), than patients who underwent either a caesarean delivery (20 mg, 20-20) or a hysterectomy (30 mg, 22-30). After adjustment for multiple potential confounders, abdominal surgery was associated with 4 times the odds of receiving more than 50 MME at hospital discharge compared with pelvic surgeries (odds ratio, 3.96; 95% confidence interval, 1.31-11.97). The availability of postoperative preprinted order sets with fixed high doses of opioids was also highly associated with the outcome. Conclusion: In our institution, some surgeries were more likely to receive high-risk opioid prescriptions at discharge. Efforts to optimize safer prescribing practices should address the creation and/or updating of preprinted order sets to reflect current best practice guidelines. This initiative could be overseen by hospital pharmacy and therapeutics committees.

Objective We assessed whether bariatric surgery before pregnancy lowers the risk of severe maternal morbidity to a level comparable to no obesity. Summary of background data Obesity is a risk factor for severe maternal morbidity, but the potential for bariatric surgery to reduce the risk has not been studied. Methods We analyzed a retrospective cohort of 2,412,075 deliveries between 1989 and 2019 in Quebec, Canada. The main exposure measures were bariatric surgery before pregnancy and obesity without bariatric surgery, compared with no obesity. The outcome was severe maternal morbidity, a composite of life-threatening pregnancy complications. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between bariatric surgery and severe maternal morbidity, adjusted for maternal characteristics. Results A total of 2654 deliveries (0.1%) were in women who had bariatric surgery, and 70,041 (29.0 per 1000) were in women who had severe maternal morbidity. Risk of severe maternal morbidity was not significantly elevated for bariatric surgery (RR 1.20; 95% CI 0.98-1.46), but was greater for obesity compared with no obesity (RR 1.60; 95% CI 1.55-1.64). Bariatric surgery was not associated with morbidities such as severe preeclampsia, sepsis, and cardiac complications compared with no obesity, but obesity was associated with elevated risks of these and other severe morbidities. Bariatric surgery was associated, however, with intensive care unit admission, compared with no obesity. Conclusions Pregnant women with prior bariatric surgery have similar risks as nonobese women for most types of severe maternal morbidity, except for intensive care unit admission.

Objective To examine long-term risks of mortality after a pregnancy complicated by severe maternal morbidity. Methods We analyzed a longitudinal cohort of 1,229,306 women who delivered in the province of Quebec, Canada from 1989 through 2016. Severe maternal morbidity included conditions such as cerebrovascular accidents, acute renal failure, severe preeclampsia, and other life-threatening complications. The outcome was in-hospital mortality after the last pregnancy, categorized as postpartum (42 days or fewer after delivery) and long-term (43 days to 29 years after delivery). We estimated hazard ratios (HRs) ofr mortality with 95% CI for severe maternal morbidity compared with no severe morbidity, using Cox regression models adjusted for maternal characteristics. Results Severe maternal morbidity occurred in 2.9% of women. The mortality rate associated with severe maternal morbidity was 0.86 per 1,000 person-years compared with 0.41 per 1,000 person-years for no morbidity. Compared with no morbidity, severe maternal morbidity was associated with two times the rate of death any time after delivery (95% CI 1.81-2.20). Severe cardiac complications (HR 7.00, 85% CI 4.94-9.91), acute renal failure (HR 4.35, 95% CI 2.66-7.10), and cerebrovascular accidents (HR 4.03, 95% CI 2.17-7.48) were the leading morbidities associated with mortality after 42 days. Conclusion Women who experience severe maternal morbidity have an accelerated risk of mortality beyond the postpartum period compared with women who do not experience severe morbidity. More intensive clinical follow-up may be merited for women with serious pregnancy complications.

Time-related biases, such as immortal time and time-window bias, frequently occur in pharmacoepidemiologic research. However, the prevalence of these biases in perinatal pharmacoepidemiology is not well understood.To describe the frequency of time-related biases in observational studies of medications commonly used during pregnancy (antibiotic, antifungal, and antiemetic drugs) via systematic review.We searched Medline and EMBASE for observational studies published between January 2013 and September 2020 and examining the association between antibiotic, antifungal, or antiemetic drugs and adverse pregnancy outcomes, including spontaneous abortion, stillbirth, preterm delivery, small-for-gestational age, pre-eclampsia, and gestational diabetes. The proportion of studies with time-related biases was estimated overall and by type (immortal time bias, time-window bias).Our systematic review included 20 studies (16 cohort studies, 3 nested case-control studies, and 1 case-control study), of which 12 examined antibiotic, 6 antiemetic, and 2 anti-fungal drugs. Eleven studies (55%) had immortal time bias due to the misclassification of unexposed, event-free person-time between cohort entry and exposure initiation as exposed. No included study had time-window bias. The direction of effect varied for both studies with and without time-related bias, with many studies reporting very wide confidence intervals around the effect estimates, thus making the direction of effect less interpretable. However, studies with time-related bias were more likely to show protective or null associations compared with studies without time-related bias.Time-related biases occur frequently in observational studies of drug effects during pregnancy. The use of appropriate study design and analytical approaches is needed to prevent time-related biases and ensure study validity.

Women with a history of preeclampsia (PE) have increased risk of cardiovascular disease (CVD) later in life. However, the molecular determinants underlying this risk remain unclear. We sought to understand how circulating miRNA levels are affected by prior PE, and related to biological pathways underpinning cardiovascular disease. RNA sequencing was used to profile plasma levels of 2578 miRNAs in a retrospective study of women with a history of PE or normotensive pregnancy, in two independent cohorts with either acute coronary syndrome (ACS) (n = 17–18/group) or no ACS (n = 20/group). Differential miRNA alterations were assessed in relation to a history of PE (within each cohort) or ACS (across cohorts), and compared with miRNAs previously reported to be altered during PE. A history of PE was associated with altered levels of 30 and 20 miRNAs in the ACS and non-ACS cohorts, respectively, whereas ACS exposure was associated with alterations in 259 miRNAs. MiR-206 was identified at the intersection of all comparisons relating to past/current PE and ACS exposure, and has previously been implicated in atherogenic activities related to hepatocytes, vascular smooth muscle cells and macrophages. Integration of all differentially altered miRNAs with their predicted and experimentally validated targets in silico revealed a number of highly targeted genes with potential atherogenic functions (including NFAT5, CCND2 and SMAD2), and one significantly enriched KEGG biological pathway (Wnt signaling) that was shared between all exposure groups. The present study provides novel insights into miRNAs, target genes and biological pathways that may underlie the long-term cardiovascular sequelae of PE.

Hypertensive disorders of pregnancy occur in approximately 7%-10% of pregnancies and are associated with adverse maternal cardiovascular health outcomes across the lifespan. In contrast, breastfeeding has been associated with a reduction in cardiovascular risk factors in a dose-dependent manner. Despite the potential protective effects of lactation on cardiovascular risk, how hypertensive disorders of pregnancy relate to breastfeeding practices and experiences is not well understood. The aim of this study was to investigate the association between hypertensive disorders of pregnancy and breastfeeding outcomes in the first year postpartum.We conducted a secondary analysis of prospective data from the All Our Families Cohort, a population-based study conducted in Calgary, Alberta, Canada. Women with a singleton pregnancy (n = 1418) who completed self-report questionnaires at25 weeks and 34-36 weeks of gestation, and 4 months and 12 months postpartum, and provided consent to link to electronic medical records that identified diagnoses of hypertensive disorders of pregnancy (n = 122). Logistic and multiple linear regression analyses were used to model associations between hypertensive disorders of pregnancy and breastfeeding outcomes. Outcomes included breastfeeding intention, intended duration, exclusive breastfeeding at 4 months, breastfeeding duration at 12 months and breastfeeding difficulties.Hypertensive disorders of pregnancy were not associated with breastfeeding intention (odds ration [OR] 1.30, 95% confidence interval [CI] 0.47-3.03, P = 0.57), intended breastfeeding duration (b = -3.28, 95% CI -7.04 to 0.48, P = 0.09), or initiation (OR = 0.64, 95% CI 0.29- 1.65, P = 0.32), but were associated with an increase in the odds of non-exclusive breastfeeding at 4 months postpartum (OR = 2.11, 95% CI 1.39-3.22, P 0.001). Women with hypertensive disorders breastfed for 6.26 (95% CI -10.00 to -2.51, P 0.001) weeks less over 12 months postpartum, had significantly higher odds of reporting insufficient milk supply (OR = 1.75, 95% CI 1.19-2.46, P 0.05) and had lower odds of breast and/or nipple pain (OR = 0.66, 95% CI 0.44-0.92, P 0.05) compared with those without hypertensive disorders of pregnancy.Hypertensive disorders of pregnancy are associated with altered breastfeeding practices and experiences during the first year postpartum. Further research is needed to examine biopsychosocial mechanisms through which hypertensive disorders associate with shorter breastfeeding duration, and to examine whether greater breastfeeding duration, intensity or exclusivity reduces short- or long-term maternal cardiovascular risk.

STUDY QUESTION Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception? SUMMARY ANSWER Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment. WHAT IS KNOWN ALREADY Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear. STUDY DESIGN, SIZE, DURATION This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006–2014. Outcomes were assessed up to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm MAIN RESULTS AND THE ROLE OF CHANCE The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4–8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16–1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01–1.17) in the OI/IUI group and 1.12 (95% CI 1.04–1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males. LIMITATIONS, REASONS FOR CAUTION Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding. WIDER IMPLICATIONS OF THE FINDINGS Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study. STUDY FUNDING/COMPETING INTEREST(s) This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

To synthesize existing evidence on Black-White disparities in the prevalence of severe cardiovascular maternal morbidity.We searched MEDLINE, EMBASE, and CINAHL for observational studies published before July 31, 2021 that compared the risk of severe cardiovascular maternal morbidity between Black and White women. The outcome was severe cardiovascular maternal morbidity, including acute myocardial infarction, peripartum cardiomyopathy, and stroke during pregnancy, delivery, or postpartum. We extracted relevant information including adjusted and unadjusted effect estimates. We used random-effects models to estimate the pooled association between race and severe cardiovascular maternal morbidity, presented as odds ratios with 95% confidence intervals for the comparison of Black women relative to White women.We included 18 studies that met the eligibility criteria for systematic review and meta-analysis. All studies were conducted in the United States and included a total of 7,656,876 Black women and 26,412,600 White women. Compared with White women, Black women had an increased risk of any severe cardiovascular maternal morbidity (adjusted odds ratio, 1.90; 95% confidence interval, 1.54-2.33). Black women were at risk of acute myocardial infarction (adjusted odds ratio, 1.38; 95% confidence interval, 1.14-1.68), peripartum cardiomyopathy (adjusted odds ratio, 1.71; 95% confidence interval, 1.51-1.94), and stroke (adjusted odds ratio, 2.13; 95% confidence interval, 1.39-3.26).Black women have a considerably higher risk of severe cardiovascular maternal morbidity than White women, including acute myocardial infarction, peripartum cardiomyopathy, and stroke. Reducing inequality in adverse cardiovascular outcomes of pregnancy between Black and White women should be prioritized.

Background: Severe maternal morbidity is rising, yet the association with cardiovascular disease is not clear. We examined the risk of cardiovascular hospitalization up to 3 decades after having a pregnancy complicated by severe maternal morbidity. Methods: We analyzed a longitudinal cohort of 1 336 846 women who were pregnant between 1989 and 2019 in Quebec, Canada. The main exposure measure was severe maternal morbidity in any pregnancy, including severe preeclampsia, acute renal failure, sepsis, and other life-threatening conditions. Using time-varying Cox regression models, we compared the adjusted risk of hospitalization for cardiovascular disease up to 3 decades after pregnancy for women with severe maternal morbidity relative to women without severe morbidity. Results: Five percent of women had severe maternal morbidity. Overall, there were 68 287 cardiovascular hospitalizations during 21 725 672 person-years of follow-up in the cohort. Compared with no morbidity, women with any severe morbidity had a greater risk of cardiovascular hospitalization (hazard ratio [HR], 1.77 [95% CI, 1.72–1.82]). The association was the greatest within the first year of delivery (HR, 4.42 [95% CI, 3.77–5.19]) but persisted beyond 15 years (HR, 1.44 [95% CI, 1.37–1.51]). Having a cardiac complication (HR, 5.37 [95% CI, 4.65–6.20]), cerebrovascular accident (HR, 3.82 [95% CI, 2.94–4.96]), or acute renal failure (HR, 2.60 [95% CI, 2.15–3.14]) during pregnancy was strongly associated with future cardiovascular hospitalization. Conclusions: Women with severe maternal morbidity have a greater risk of cardiovascular disease after pregnancy, both in the short and long term. These women may benefit from active surveillance for cardiovascular disease.

The aim of this systematic review was to assess dysregulated miRNA biomarkers in coronary artery disease (CAD). Dysregulated microRNA (miRNAs) have been shown to be linked to cardiovascular pathologies including CAD and may have utility as diagnostic and prognostic biomarkers. We compared miRNAs identified in acute coronary syndrome (ACS) compared with stable CAD and control populations. We conducted a systematic search of controlled vocabulary and free text terms related to ACS, stable CAD and miRNA in Biosis Previews (OvidSP), The Cochrane Library (Wiley), Embase (OvidSP), Global Health (OvidSP), Medline (PubMed and OvidSP), Web of Science (Clarivate Analytics), and ClinicalTrials.gov which yielded 7370 articles. Of these, 140 original articles were appropriate for data extraction. The most frequently reported miRNAs in any CAD (miR-1, miR-133a, miR-208a/b, and miR-499) are expressed abundantly in the heart and play crucial roles in cardiac physiology. In studies comparing ACS cases with stable CAD patients, miR-21, miR-208a/b, miR-133a/b, miR-30 family, miR-19, and miR-20 were most frequently reported to be dysregulated in ACS. While a number of miRNAs feature consistently across studies in their expression in both ACS and stable CAD, when compared with controls, certain miRNAs were reported as biomarkers specifically in ACS (miR-499, miR-1, miR-133a/b, and miR-208a/b) and stable CAD (miR-215, miR-487a, and miR-502). Thus, miR-21, miR-133, and miR-499 appear to have the most potential as biomarkers to differentiate the diagnosis of ACS from stable CAD, especially miR-499 which showed a correlation between the level of their concentration gradient and myocardial damage. Although these miRNAs are potential diagnostic biomarkers, these findings should be interpreted with caution as the majority of studies conducted predefined candidate-driven assessments of a limited number of miRNAs (PROSPERO registration: CRD42017079744).

Background Peripartum cardiomyopathy (PPCM) and preeclampsia are strongly associated, yet a description of risk factors for PPCM among women with preeclampsia is currently lacking. Additionally, the effect of preeclampsia on PPCM-related outcomes is not well known. Methods We constructed a cohort of delivery admissions from 2011 to 2014 using a large US administrative database (Marketscan). We assessed risk factors for the development of PPCM among women with preeclampsia. We compared the risks of major adverse cardiovascular events (MACE) at 6 months between PPCM with co-incident preeclampsia (pePPCM) and PPCM without preeclampsia (npePPCM). Results We included 1,024,035 pregnancies, of which 64,503 (6.3%) had preeclampsia. A total of 874 had PPCM (283 with preeclampsia and 591 without preeclampsia). Among women with preeclampsia, clinical risk factors for PPCM consisted in chronic kidney disease (OR 3.18, 95% CI [1.51, 6.69]), multiple pregnancy (OR 2.11, 95% CI [1.49, 2.98]), chronic hypertension (OR 1.88, 95% CI [1.43, 2.47]), advanced maternal age (OR 1.82, 95% CI [1.42, 2.33]), and type 2 diabetes (OR 1.58, 95% CI [1.00, 2.48]). Women with pePPCM had a higher risk of MACE than women with npePPCM (adjusted RR 1.29, 95% CI [1.06, 1.57]) due to increased rates of clinical heart failure and pulmonary embolism in the pePPCM group. Mortality did not differ between groups. Conclusion Preeclamptic women with risk factors for PPCM and women with pePPCM at increased risk of MACE should be followed closely. Further studies are required to determine whether preeclampsia affects the long-term prognosis of women with PPCM.

BACKGROUND: The extent to which infertility treatment predicts severe maternal morbidity is not well known. We examined the association between infertility treatment and severe maternal morbidity in pregnancy and the postpartum period. METHODS: We conducted a cohort study using population-based registries from Ontario between 2006 and 2012. Pregnancies achieved using infertility treatment (ovulation induction, intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection) were compared with unassisted pregnancies using propensity score matching, based on demographic, reproductive and obstetric factors. The primary outcome was a validated composite of severe maternal morbidity or maternal death from 20 weeks’ gestation to 42 days postpartum. We also calculated the odds ratio of a woman having 1, 2, or 3 or more severe maternal morbidity indicators in relation to invasive (e.g., in vitro fertilization) or noninvasive (e.g., intrauterine insemination) infertility treatment. RESULTS: We matched 11 546 infertility treatment pregnancies with 47 553 untreated pregnancies. Severe maternal morbidity or maternal death occurred in 356 infertility-treated pregnancies (30.8 per 1000 deliveries) versus 1054 untreated pregnancies (22.2 per 1000 deliveries); relative risk 1.39 (95% confidence interval [CI] 1.23–1.56). The likelihood of a woman having 3 or more severe maternal morbidity indicators was increased in women who received invasive infertility treatment (odds ratio [OR] 2.28, 95% CI 1.56–3.33) but not in those who received noninvasive infertility treatment (OR 0.99, 95% CI 0.57–1.72). INTERPRETATION: Women who undergo infertility treatment, particularly in vitro fertilization, are at somewhat higher risk of severe maternal morbidity or death. Efforts are needed to identify patient- and treatment-specific predictors of severe maternal morbidity that may influence the type of treatment a woman is offered.

Background Multiple hypertension guidelines recommend out-of-office measurements for the diagnosis of hypertension in non-pregnant adults, whereas pregnancy guidelines recommend in-office blood pressure measurements. The objective of our study was to determine how Canadian Obstetric Medicine and Maternal Fetal Medicine specialists measure blood pressure in pregnancy. Methods An email survey was sent to 69 Canadian Obstetric Medicine and Maternal Fetal Medicine specialists in academic centers across Canada to explore the practice patterns of blood pressure measurement in pregnant women. Results The response rate was 48%. The majority of respondents (63.6%) preferred office blood pressure measurement for diagnosing hypertension, but relied on home blood pressure readings for ongoing monitoring and management of hypertension during pregnancy (59.4%). The preferred method of out-of-office blood pressure measurement was home monitoring; 24-hour ambulatory blood pressure monitoring was not used due to limited availability and cost. Conclusions There is wide practice variation in methods of measuring blood pressure among Canadian specialists managing hypertension in pregnancy.

Hypertensive disorders of pregnancy (HDP) are associated with future cardiovascular disease (CVD), which may be mediated by diminished cardiorespiratory fitness (CRF). In this systematic review and meta-analysis, we summarize evidence linking CRF with HDP before, during, and after pregnancy. We searched relevant databases to identify observational or randomized studies that measured CRF (VO2 max or peak, VO2 at anaerobic threshold, or work rate at peak VO2) in women with and without HDP. We pooled results using random effects models. Fourteen studies (n = 2406 women) reporting on CRF before, during, and after pregnancy were included. Before pregnancy, women who developed HDP had lower CRF (e.g., VO2max < 37 vs. ≥37 mL O2/min) than those without HDP (two studies, 811 women). VO2max at 14–18 weeks of pregnancy was marginally lower among women who developed preeclampsia vs. normotensive women (three studies, 275 women; mean difference 0.43 mL/kg/min [95% CI 0.97, 0.10]). Postpartum, there was a trend towards lower VO2peak in women with previous preeclampsia (three studies, 208 women; 0.26 mL/kg/min [−0.54, 0.02]). While exploratory, our findings raise the possibility that CRF can identify women at risk for HDP, and furthermore, that HDP confers a hit to a woman’s cardiorespiratory reserve.

The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.

Background Pelvic vein thrombosis (PVT) is a rare complication of pregnancy that can lead to life-threatening complications, such as pulmonary embolism (PE). Objective To describe characteristics of PVT and its treatment in pregnancy in the province of Quebec, Canada. Patients/methods We developed a province-wide case series of PVT in pregnancy including four tertiary care centers and the Registry of Rare Diseases of the Groupe d'Etude en Medecine Obstetricale du Quebec. Using diagnostic codes, we included cases with confirmed PVT on imaging during pregnancy or within 6 weeks postpartum from July 2003 to June 2018. Results A total of 47 cases were identified. PVT diagnosis was generally made in the early postpartum period (median of 9 [interquartile range (IQR) 4.5-12] days postpartum). Most PVT (94%) included in this series were symptomatic. Women presented primarily with abdominal pain (77%) and fever (55%), often prolonged despite antibiotics (mean 4.45 ± 2.39 days, with 39% having fever for more than 5 days). The most common risk factor was surgery (57%) and peripartum infections (54%). Thirty-eight (83%) women received antibiotics and 41 (89%) were anticoagulated. Three cases of PE (7%) occurred concomitantly, 11% of women required intensive care, and 19% had inferior vena cava (IVC) clot extension. The episode resulted in prolonged hospitalization (median 6 [IQR 3-10.75] days), with 48% being hospitalized more than 7 days. Conclusion Symptomatic PVT has significant clinical implications with prolonged fever and risks of extension in the IVC and PE, leading to prolonged hospitalization including in the intensive care unit. Therapeutic anticoagulation and antibiotics, when infection is documented, should be considered for management.

Objective: To improve the prediction of maternal end-organ injury or death using routinely-collected variables from the pre-pregnancy and the early pregnancy period. Design: Population-based cohort study using linked administrative health data. Setting: Ontario, Canada, April 1, 2006 to March 31, 2014. Sample: Women aged 18-60 years with a livebirth or stillbirth, of which one birth was randomly selected per woman. Methods and main outcome measures: We constructed a CPM for the primary composite outcome of any maternal end-organ injury or death, arising between 20 weeks’ gestation and 42 days after the birth hospital discharge date. Our CPM included variables collected from 12 months before estimated conception until 19 weeks’ gestation. We developed a separate CPM for parous women to allow for the inclusion of factors from previous pregnancy(ies). Results: Of 634,290 women, 1969 experienced the primary composite outcome (3.1 per 1000). Predictive factors in the main CPM included maternal world region of origin, chronic medical conditions, parity, and obstetrical/perinatal issues – with moderate model discrimination (C-statistic 0.68, 95% CI 0.66-0.69). Among 333,435 parous women, the C-statistic was 0.71 (0.69-0.73) in the model using variables from the current (index) pregnancy as well as pre-pregnancy predictors and variables from any previous pregnancy. Conclusions: A combination of factors ascertained early in pregnancy through a basic medical history help to identify women at risk for severe morbidity, who may benefit from targeted preventive and surveillance strategies including appropriate specialty-based antenatal care pathways. Further refinement of this model would enable clinical use.

Objective To investigate the association between obstetric haemorrhage and cardiovascular disease up to three decades after pregnancy. Design Population-based cohort study. Setting and population All women who delivered between 1989 and 2016 in Quebec, Canada. Methods Using hospital admissions data, 1 224 975 women were followed from their first delivery until March 2018. The main exposure measures were antenatal (placenta praevia, placental abruption, peripartum haemorrhage) or postpartum haemorrhage, with or without transfusion. Adjusted Cox regression models were used to assess the association between obstetric haemorrhage and future cardiovascular disease. Main outcome measure Cardiovascular hospitalisation. Results Among 104 291 (8.5%) women with haemorrhage, 4612 (4.4%) required transfusion. Women with haemorrhage had a higher incidence of cardiovascular hospitalisation than women without haemorrhage (15.5 versus 14.1 per 10 000 person-years; 2437 versus 28 432 events). Risk of cardiovascular hospitalisation was higher for obstetric haemorrhage, with or without transfusion, compared with no haemorrhage (adjusted hazard ratio [aHR] 1.06, 95% CI 1.02-1.10). Women with haemorrhage and transfusion had a substantially greater risk of cardiovascular hospitalisation (aHR 1.47, 95% CI 1.23-1.76). Among transfused women, placental abruption (aHR 1.79, 95% CI 1.06-3.00) and postpartum haemorrhage (aHR 1.38, 95% CI 1.13-1.68) were both associated with risk of cardiovascular hospitalisation. Antenatal haemorrhage with transfusion was associated with 2.46 times the risk of cardiovascular hospitalisation at 5 years (95% CI 1.59-3.80) and 2.14 times the risk at 10 years (95% CI 1.47-3.12). Conclusions Obstetric haemorrhage requiring transfusion is associated with maternal cardiovascular disease. The benefit of cardiovascular risk prevention in pregnant women with obstetric haemorrhage requires further investigation. Tweetable abstract Risk of future cardiovascular disease is increased for women with obstetric haemorrhage who require transfusion.

Pulmonary embolism (PE) complicates 5.4 per 10 000 pregnancies and remains a significant cause of maternal mortality. Prompt diagnosis and treatment of PE are key to ensuring optimal outcomes, but are not without risks associated with over-testing. Given the paucity of evidence informing PE diagnosis in pregnancy, marked heterogeneity exists among different societies in their recommendations. Here we provide an overview of existing recommendations and novel evidence informing the diagnosis of PE in pregnancy, including the use of d-dimers, the choice of diagnostic imaging modality, and the potential for breast cancer risk among women exposed to ionizing radiation from computed tomography pulmonary angiography (CTPA).

OBJECTIVE Data regarding low maternal haemoglobin concentration and severe maternal morbidity (SMM) are limited and potentially biased. This study evaluated the relation between early maternal haemoglobin concentration and SMM or maternal mortality. DESIGN Population-based cohort study. SETTING Ontario, Canada, in a public healthcare system. POPULATION 737 393 births with a routine outpatient haemoglobin measured at a calculated gestational age of 2-16 weeks. METHODS The relation between early-pregnancy outpatient blood haemoglobin concentration and each study outcome was expressed as adjusted relative risks (aRR) and absolute risk differences (aRD), with 95% confidence intervals (CI), generated by modified Poisson regression. MAIN OUTCOME MEASURES The primary outcome was SMM or maternal mortality, from 23 weeks' gestation to 42 days postpartum. RESULTS The mean (SD) haemoglobin concentration was 126.9 (9.3) g/l. Overall, SMM or death occurred in 13 514 pregnancies (1.8%). Relative to a haemoglobin level of 125-129 g/l, the aRR was 1.07 (95% CI 1.02-1.13) and aRD (0.09%, 95% CI 0.01-0.18) at 120-124 g/l; aRR 1.31 (95% CI 1.17-1.46) and aRD 0.47% (95% CI 0.24-0.69) at 105-109 g/l; and aRR 4.53 (95% CI 3.59-5.72) and aRD 5.94% (95% CI 4.12-7.76) at

Preeclampsia increases a woman’s risk of stroke and leads to short-term cognitive complaints. Our objective was to assess the impact of preeclampsia on long-term cognitive performance. This is a retrospective cohort study using data from the Coronary Artery Risk Development in Young Adults cohort of healthy individuals (18–30 years) recruited from the general population in 3 cities in the United States, followed for 25 years (1985–2010). Psychomotor speed (Digit Symbol Substitution Test), executive function (Stroop Test), and memory (Rey Auditory Verbal Learning Test) were contrasted between women with and without preeclampsia using multivariate linear regression. We included 568 parous women (193 with preeclampsia and 375 with normotensive pregnancy) without baseline neurological disease or depression matched according to delivery period. Approximately 18 years after delivery, preeclamptic women scored significantly lower on Digit Symbol Substitution Test than women with normotensive pregnancy (73.21±14.79 versus 75.87±15.22; P =0.047) and on the third trial of Stroop Test (correct answers: 38.85±3.62 versus 39.42±1.87; P =0.014; completion time: 44.02±10.48 versus 41.62±10.61 seconds; P =0.01), but there were no differences in Rey Auditory Verbal Learning Test. These differences were attenuated after adjustment for age, body mass index, hypertension, education, and depression. Similar differences in neurocognitive scores were noted between women with other hypertensive disorders of pregnancy and normotensive pregnancy. Hypertension in pregnancy does not seem to be independently associated with neurocognitive impairment later in life.

STUDY QUESTION Is there a synergistic risk of severe maternal morbidity (SMM) in overweight/obese women who conceived by IVF compared to normal-weight women without IVF? SUMMARY ANSWER SMM was more common in IVF pregnancies, and among overweight/obese women, but we did not detect a synergistic effect of both factors. WHAT IS KNOWN ALREADY While much is known about the impact of overweight and obesity on success rates after IVF, there is less data on maternal health outcomes. STUDY DESIGN, SIZE, DURATION This is a population-based cohort study of 114 409 singleton pregnancies with conceptions dating from 11 January 2013 until 10 January 2014 in Ontario, Canada. The data source was the Canadian Assisted Reproductive Technologies Register (CARTR Plus) linked with the Ontario birth registry (BORN Information System). PARTICIPANTS/MATERIALS, SETTING, METHODS We included women who delivered at ≥20 weeks gestation, and excluded those younger than 18 years or with twin pregnancies. Women were classified according to the mode of conception (IVF or unassisted) and according to pre-pregnancy BMI (high BMI (≥25 kg/m2) or low-normal BMI (

Objective We aimed to describe opioid prescribing practices after obstetric delivery and to evaluate how these practices compare with national opioid prescribing guidelines. Methods A closed survey was developed, evaluated for validity and reliability, and distributed by email to obstetrician members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) in December 2018. Descriptive statistics were used to summarize respondent demographics, pharmaceutical pain management strategies, and opioid prescribing practices. Logistic regression was used to measure associations between respondent characteristics and high-risk opioid prescribing practices (e.g., prescribing >50 mg morphine equivalent dose per day, prescribing >5 days, not screening for substance/opioid use disorder before prescribing). Results Our survey had high content validity (content validity index 0.89; 95% CI 0.78–1.00) and adequate reliability (Kappa 0.70; 95% CI 0.63–0.84 and intraclass correlation coefficient 0.70; 95% CI 0.67–0.81). Of the 1019 SOGC members reached, 243 initiated the survey (response rate, 24%). Among respondents, 235 (92%) completed the survey. Among opioid prescribers, 47% reported at least 1 high-risk opioid prescribing practice, the most frequent being a lack of substance/opioid use disorder screening. In the adjusted logistic regression model, being in practice more than 20 years (adjusted odds ratio [aOR] 0.53; 95% CI 0.29–0.93) and practising in a non-central area of Canada (aOR 0.49; 95% CI 0.28–0.84) reduced the odds of high-risk prescribing. Conclusion Further research on barriers to screening are needed to support and enhance safer opioid prescribing practices among Canadian obstetricians.

Background The longer term cardiovascular effects of fertility therapy are unknown. Objectives The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes. Methods We systematically searched published reports for studies addressing the question “does fertility therapy increase the risk of longer term cardiovascular outcomes?” We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not. Results Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I2 = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I2 = 0%). Results were not pooled for hypertension (I2 = 95.0%) and venous thromboembolism (I2 = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I2 = 0%). Conclusions The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area.

Objectives To investigate the short-term effects of breastfeeding on hypertension, metabolic syndrome, serum glucose and cholesterol profile among postpartum women 6 months after a pregnancy complicated by hypertensive disorders of pregnancy, gestational diabetes, intrauterine growth restriction, abruption, and preterm delivery. Methods Our cross-sectional analysis includes 622 women with a pregnancy complication seen at 6 months postpartum between November 2011 and December 2017 at a tertiary care centre. We compared systolic and diastolic blood pressure, serum cholesterol profile, serum glucose, and estimated cardiovascular risk in women who did not breastfeed (n=100, 16%), who breastfed for less than 6months (n=315, 51%), and who breastfed for 6 months or more (n=207, 33%) using descriptive statistics and multivariate linear and logistic regression. Results Adjusted models showed that increasing breastfeeding duration significantly decreased the odds of metabolic syndrome (Odds Ratio [95% Confidence Interval]; 0.88 [0.80, 0.98]), a high lifetime risk score (0.92 [0.80, 0.99]), elevated (0.92 [0.84, 0.99]) or hypertensive systolic blood pressure (0.90 [0.82, 0.99]), abnormal fasting glucose (0.80 [0.67, 0.95]), triglycerides (0.88 [0.79, 0.97]), and ratio of total cholesterol to HDL-C (0.86 [0.79, 0.94]). BMI, waist circumference and non-HDL-C decreased (estimated coefficients [95%CI]; of -0.11 [-0.19, -0.03], -0.32 [-0.60, -0.04], -0.04 [-0.88, -0.07]; respectively) while HDL-C increased (0.03 [-0.02, -0.04]). Conclusions Our findings suggest that breastfeeding for at least 6 months is associated with decreased indicators of cardiovascular disease risk in a cohort of women with a recent pregnancy complication and should encourage breastfeeding support and interventions in this population.

Background and aim: Hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM) are common complications in pregnancy. The risk of developing premature cardiovascular disease (CVD) is increased in women with a history of these disorders. However, more nuanced risk stratification is needed to identify women who would derive the greatest benefit from early risk reduction. We investigated demographic and clinical factors associated with future CVD in women with a history of HDP or GDM. Method: Women who were aged 15 to 45 years at the time of delivery were identified from among all hospital deliveries in Quebec between 1989 and 2016. Criteria for inclusion in the study were HDP, defined as pre-existing hypertension, gestational hypertension, pre-eclampsia, and superimposed pre-eclampsia, or GDM. Women with HDP or GDM were followed until age 60 years for CVD events, death, or loss to follow-up. CVD events included heart disease, cerebrovascular disease, heart and blood vessel procedures, coronary care unit admission, or mortality prior to age 60 years. We examined the association (hazard ratio, HR; 95% confidence interval, CI) between potential predictor variables and future CVD using Cox proportional hazard regression models. Risk factor variables included sociodemographic, pregnancy-related and perinatal factors recorded at the time of delivery. Results: Hypertension in pregnancy or gestational diabetes occurred in 173,430 (14%) of 1,229,278 women admitted for hospital delivery during the study. CVD events occurred in 3.3% of women with hypertensive disorders of pregnancy or gestational diabetes, of which death occurred in 903 (0.5%) women. The median time to event was 12 years. Neonatal death and stillbirth had the strongest associations with CVD. HRs for CVD were 2.29 (95% CI: 1.62-3.25) for neonatal death vs none, and 2.01 (95% CI: 1.556-2.60) for stillbirth vs none. Maternal age, substance use, low socioeconomic status, tobacco use, and obesity were also associated with increased risk of CVD (Table 1). Conclusion: Future studies should investigate whether these identified factors can reliably predict the risk of CVD and mortality in women with a history of hypertensive disorders of pregnancy and gestational diabetes.

Women with prior hypertensive disorders of pregnancy (HDP) are at twice the risk of cardiovascular disease compared with women with prior normotensive pregnancy, possibly because of sustained vascular dysfunction after delivery. The aim of this systematic review and meta-analysis is to summarize evidence of vascular dysfunction at least 3 months after HDP. Articles in all languages were retrieved from principal databases. Studies included were observational, with HDP as the main exposure and measurements of vascular dysfunction via imaging modalities or serum biomarkers as the main outcome, assessed at least 3 months postpartum. We pooled results of modalities reported in >3 studies using a random effects model. Of 6109 potentially relevant studies, 72 were included that evaluated 10 imaging modalities and 11 serum biomarkers in 8702 women. There was evidence of vascular dysfunction in women post HDP compared with women with prior normal pregnancy when measured by carotid-femoral pulse wave velocity (0.64 m/s [0.17–1.11]), carotid intima–media thickness (0.025 mm [0.004–0.045]), and augmentation index (5.48% [1.58–9.37]), as well as mean levels of soluble fms-like tyrosine kinase (6.12 pg/mL [1.91–10.33]). Between-groups differences in measures of vascular dysfunction were more pronounced when assessments were performed in younger women (

Background Following an episode of hypertensive disorder of pregnancy (HDP) women have an increased risk of cardiovascular disease over their lifetime. At the time of acute coronary syndrome we compared clinical information between women with and without a history of hypertension in pregnancy to gain further insight into the pathophysiology of cardiovascular disease in this population. Methods GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond—PRemature Acute Coronary SYdrome) is a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome. Results The median age was 50years (IQR 6) and HDP was common; 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) preeclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of preeclampsia (aOR 3.12, 95% CI 1.22–8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60–3.26) nor preeclampsia (aOR 0.63, 95% CI 0.23–1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease. Conclusion In this study of women with premature cardiovascular disease, ST-elevation myocardial infarction was associated with a history of preeclampsia possibly because of persistent endothelial dysfunction. High-risk coronary lesions on angiography did not appear to have an association with preeclampsia or gestational hypertension despite a high burden of traditional risk factors.