Risk of recurrent severe maternal morbidity: a population-based study.

BACKGROUND: Severe maternal morbidity is a composite indicator of maternal health and obstetrical care. Little is known about the risk of recurrent severe maternal morbidity in a subsequent delivery. OBJECTIVE: This study aimed to estimate the risk of recurrent severe maternal morbidity in the next delivery after a complicated first delivery. STUDY DESIGN: We analyzed a population-based cohort study of women with at least 2 singleton hospital deliveries between 1989 and 2021 in Quebec, Canada. The exposure was severe maternal morbidity in the first hospital-recorded delivery. The study outcome was severe maternal morbidity at the second delivery. Log-binomial regression models adjusted for maternal and pregnancy characteristics were used to generate relative risks and 95% confidence intervals comparing women with and without severe maternal morbidity at first delivery. RESULTS: Among 819,375 women, 43,501 (3.2%) experienced severe maternal morbidity in the first delivery. The rate of severe maternal morbidity recurrence at second delivery was 65.2 vs 20.3 per 1000 in women with and without previous severe maternal morbidity (adjusted relative risk, 3.11; 95% confidence interval, 2.96-3.27). The adjusted relative risk for recurrence of severe maternal morbidity was greatest among women who had ≥3 different types of severe maternal morbidity at their first delivery, relative to those with none (adjusted relative risk, 5.50; 95% confidence interval, 4.26-7.10). Women with cardiac complication at first delivery had the highest risk of severe maternal morbidity in the next delivery. CONCLUSION: Women who experience severe maternal morbidity have a relatively high risk of recurrent morbidity in the subsequent pregnancy. In women with severe maternal morbidity, these study findings have implications for prepregnancy counseling and maternity care in the next pregnancy.

Accuracy of aspirin prophylaxis for preeclampsia prevention documentation within a large administrative dataset.

BACKGROUND: Low-dose aspirin prophylaxis is recommended for women at risk of preeclampsia. Capturing aspirin prophylaxis within administrative databases can be challenging since it is an over-the-counter medication. The Better Outcome Registry and Network (BORN) database, a perinatal health registry in Ontario, Canada, includes a formal variable that captures aspirin prophylaxis for preeclampsia. This variable has not been formally validated. OBJECTIVES: To assess the accuracy of the aspirin prophylaxis variable in the BORN database against an electronic medical record (EMR). METHODS: This validation study comprised 200 randomly selected women who had a livebirth at St. Michael's Hospital (SMH) in Toronto, Ontario, from January 2018 to July 2022. Recorded aspirin prophylaxis in pregnancy and maternal sociodemographic characteristics were independently extracted by two abstractors. Accuracy of aspirin prophylaxis use in the BORN database was compared to that in the SMH EMR, expressed as sensitivity, specificity, positive (PPV) and negative predictive values (NPV), Cohen's kappa (κ), and overall percent agreement, with 95% confidence intervals (CI). Sensitivity analyses were performed to account for missing or unclear aspirin prophylaxis use. RESULTS: Among 200 women, 24 (12.0%) received aspirin prophylaxis - 12.5% within the SMH EMR and 8.0% in the BORN database. Women using aspirin were older (37.0 vs 33.0 years) and had higher median gravidity (3 vs. 2). Sensitivity and specificity of the BORN aspirin prophylaxis variable were 62.5% (95% CI 40.6, 81.2) and 100.0% (95% CI 97.3, 100.0), respectively. The corresponding positive and negative predictive values were 100.0% (95% CI 78.2, 100.0), and 93.8% (95% CI 88.6, 97.1), respectively. Cohen's κ was 0.74 (95% CI 0.58, 0.90), and overall percent agreement was 94.4% (95% CI 87.1, 100.0). CONCLUSIONS: Aspirin use within the BORN database, based on a standard variable field, appears accurate enough for the potential use in epidemiological studies of aspirin prophylaxis for preeclampsia or as a covariate in related studies.

Thrombocytopenia and neonatal outcomes among extremely premature infants exposed to maternal hypertension.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with neonatal hematological disturbances, such as thrombocytopenia. The association of HDP to platelet counts in the context of extreme prematurity, to trends of platelet counts during neonatal hospitalization, and to frequency of platelet transfusions remain to be explored. PROCEDURE: Retrospective study of infants born at less than 29 weeks born between 2015 and 2019. Platelet counts were collected on initial complete blood count, at 2 weeks, 32 weeks post-menstrual age (PMA), 36 weeks PMA, and closest to discharge. We examined the association between HDP and platelet counts at each time point, frequency of platelet transfusions and intraventricular hemorrhage (IVH) grade 3 or more. RESULTS: Total 296 infants were included, 43 exposed to HDP. Infants exposed had lower platelet counts at each time point, as well as a higher prevalence of platelet less than 150 × 109 /L on one of the time points (32% vs. 65%, p < .001). Infants exposed to maternal hypertension were more frequently exposed to platelet transfusions (63% vs. 18%, p < .001). Mixed effect model demonstrated an association between HDP and a lower trend in platelet counts at each time point (ß = -94 × 103 /µl, p < .001). Although initial platelet count was associated with severe IVH, it was not associated to exposure to HDP. CONCLUSION: Premature infants exposed to HDP have a higher prevalence of thrombocytopenia, increased frequency of platelet transfusion, and an altered trend in platelet counts during neonatal hospitalization.

Identifying Targets to Improve the Management of Severe Hypertension in Pregnancy and Postpartum.

OBJECTIVES: To (1) define quality indicators, (2) describe care gaps, and (3) identify process issues in severe hypertension (sustained systolic blood pressure [BP] ≥160 mm Hg or diastolic BP ≥110 mm Hg) management at our tertiary care centre. METHODS: Pregnant and postpartum persons diagnosed with a hypertensive disorder of pregnancy from 2018 to 2019 were identified. A retrospective cohort of patients with severe hypertension was constructed, and data were collected through chart review. Severe hypertension management was assessed according to defined quality indicators. Clinical characteristics were compared between participants with and without time-to-target BP within 60 minutes. Process issues were examined for each severe hypertension occurrence. RESULTS: Of 608 participants with a hypertensive disorder of pregnancy, 90 (15%) experienced severe hypertension. Median time-to-target BP was 76 minutes (interquartile range 47-123 minutes), and target BP (<155/105 mm Hg) was achieved within 60 minutes in 31/90 (34%) participants. Appropriate antihypertensives for severe hypertension were used in 55/90 (61%), and time-to-treatment initiation was within 30 minutes in 42/54 (78%). Chronic hypertension and oral labetalol use were associated with delays in achieving target BP. Process issues related to severe hypertension management included inappropriate treatment (n = 35/90; 39%), failure to recognize severe hypertension as an emergency (n = 21/90; 23%), and delayed treatment initiation (n = 12/54; 22%). CONCLUSION: We defined quality indicators for severe hypertension management. Time-to-target BP within 60 minutes was achieved in a minority of patients, and chronic hypertension was associated with delayed severe hypertension resolution. Process issues in severe hypertension management were described.

Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC Registry.

AIMS: Hypertensive disorders of pregnancy (HDP) occur in 10% of pregnancies in the general population, pre-eclampsia specifically in 3-5%. Hypertensive disorders of pregnancy may have a high prevalence in, and be poorly tolerated by, women with heart disease. METHODS AND RESULTS: The prevalence and outcomes of HDP (chronic hypertension, gestational hypertension or pre-eclampsia) were assessed in the ESC EORP ROPAC (n = 5739), a worldwide prospective registry of pregnancies in women with heart disease.The overall prevalence of HDP was 10.3%, made up of chronic hypertension (5.9%), gestational hypertension (1.3%), and pre-eclampsia (3%), with significant differences between the types of underlying heart disease (P < 0.05). Pre-eclampsia rates were highest in women with pulmonary arterial hypertension (PAH) (11.1%), cardiomyopathy (CMP) (7.1%), and ischaemic heart disease (IHD) (6.3%). Maternal mortality was 1.4 and 0.6% in women with vs. without HDP (P = 0.04), and even 3.5% in those with pre-eclampsia. All pre-eclampsia-related deaths were post-partum and 50% were due to heart failure. Heart failure occurred in 18.5 vs. 10.6% of women with vs. without HDP (P < 0.001) and in 29.1% of those with pre-eclampsia. Perinatal mortality was 3.1 vs. 1.7% in women with vs. without HDP (P = 0.019) and 4.7% in those with pre-eclampsia. CONCLUSION: Hypertensive disorders of pregnancy and pre-eclampsia rates were higher in women with CMP, IHD, and PAH than in the general population. Adverse outcomes were increased in women with HDP, and maternal mortality was strikingly high in women with pre-eclampsia. The combination of HDP and heart disease should prompt close surveillance in a multidisciplinary context and the diagnosis of pre-eclampsia requires hospital admission and continued monitoring during the post-partum period.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Screening and Testing Pregnant Patients for SARS-CoV-2: First-Wave Experience of a Designated COVID-19 Hospitalization Centre in Montréal.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) may present asymptomatically in a large proportion of cases in endemic areas. Accordingly, universal testing has been suggested as a potential strategy for reducing transmission in the obstetrical setting. We describe the clinical characteristics of patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy at a designated COVID-19 hospitalization centre in Montréal, Québec. METHODS: A single-centre retrospective cohort was constructed to include all pregnant patients who tested positive for SARS-CoV-2 between March 22 and July 31, 2020, and received care at the Jewish General Hospital. Initially, testing was restricted to at-risk patients, identified through the use of a screening questionnaire. Beginning on May 15, 2020, universal testing was implemented, and all pregnant patients admitted to the hospital were tested. Data were collected through chart review. RESULTS: Of 803 patients tested for SARS-CoV-2 during the study period, 41 (5%) tested positive. Among those patients who were symptomatic, the most commonly reported symptoms were cough (53%), fever (37%), dyspnea (30%), and anosmia and/or ageusia (20%). Before the implementation of universal testing, 13% (3 of 24) of patients with SARS-CoV-2 were asymptomatic. After implementation of universal testing, 80% (8 of 10) of patients with SARS-CoV-2 were asymptomatic. CONCLUSION: Our findings suggest that most pregnant patients with SARS-CoV-2 are asymptomatic or have mild symptoms of COVID-19. Particularly in endemic areas, universal testing of pregnant patients presenting to the hospital should be strongly considered as an important measure to prevent in-hospital and community transmission of COVID-19.

Obstetrical and Newborn Outcomes Among Patients With SARS-CoV-2 During Pregnancy.

We report on the perinatal outcomes of pregnant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 2 hospitals in Montréal, Québec. Outcomes of 45 patients with SARS-CoV-2 during pregnancy were compared with those of 225 patients without infection. Sixteen percent of patients with SARS-CoV-2 delivered preterm, compared with 9% of patients without (P = 0.28). Median gestational age at delivery (39.3 (interquartile range [IQR] 37.7-40.4) wk vs. 39.1 [IQR 38.3-40.1] wk) and median birth weight (3250 [IQR 2780-3530] g vs. 3340 [IQR 3025-3665] g) were similar between groups. The rate of cesarean delivery was 29% for patients with SARS-CoV-2. Therefore, we did not find important differences in outcomes associated with SARS-CoV-2. Our findings may be limited to women with mild COVID-19 diagnosed in the third trimester.

Thrombotic Microangiopathy in a Pregnant Woman With Kidney Transplantation: A Case Report.

BACKGROUND: The differential diagnosis of thrombotic microangiopathy (TMA) in pregnancy includes common conditions, such as preeclampsia. In women with kidney transplantation, additional causes of TMA must be considered. CASE: A 22-year-old primigravid woman with a transplanted kidney presented with fetal growth restriction, hypertension, acute kidney injury, and hemolysis at 28 weeks gestation. While her clinical presentation was initially consistent with preeclampsia, hemolysis persisted beyond 1 week postpartum. Diagnoses of TMA associated with tacrolimus and antibody-mediated rejection were considered. An elevated tacrolimus level likely contributed to her TMA and a decrease in dosage improved her clinical picture and laboratory markers. CONCLUSION: We report the case of a pregnant kidney transplant recipient with TMA. A multidisciplinary approach is required to optimize the maternal health outcomes in this complex population.

Maternal and neonatal outcomes in women with disorders of lipid metabolism.

OBJECTIVES: The effects of lipid metabolism disorders (LMD) on pregnancy outcomes is not well known. The purpose of this study is to evaluate the impact of LMD on maternal and fetal outcomes. METHODS: Using the Healthcare Cost and Utilization Project - National Inpatient Sample from the United States, we carried out a retrospective cohort study of all births between 1999 and 2015 to determine the risks of complications in pregnant women known to have LMDs. All pregnant patients diagnosed with LMDs between 1999 and 2015 were identified using the International Classification of Disease-9 coding, which included all patients with pure hypercholesterolemia, pure hyperglyceridemia, mixed hyperlipidemia, hyperchylomicronemia, and other lipid metabolism disorders. Adjusted effects of LMDs on maternal and newborn outcomes were estimated using unconditional logistic regression analysis. RESULTS: A total of 13,792,544 births were included, 9,666 of which had an underlying diagnosis of LMDs for an overall prevalence of 7.0 per 10,000 births. Women with LMDs were more likely to have pregnancies complicated by diabetes, hypertension, and premature births, and to experience myocardial infarctions, venous thromboembolisms, postpartum hemorrhage, and maternal death. Their infants were at increased risk of congenital anomalies, fetal growth restriction, and fetal demise. CONCLUSIONS: Women with LMDs are at significantly higher risk of adverse maternal and newborn outcomes. Prenatal counselling should take into consideration these risks and antenatal care in specialized centres should be considered.

Identifying cardiovascular severe maternal morbidity in epidemiologic studies.

BACKGROUND: Cardiovascular severe maternal morbidity (CSMM) is rising and has become the leading cause of maternal mortality. Research using administrative data sets may allow for better understanding of this critical group of diseases. OBJECTIVE: To validate a composite variable of CSMM for use in epidemiologic studies. METHODS: We analysed delivery hospitalisations at an obstetric teaching hospital from 2007 to 2017. We utilised a subset of indicators developed by the Centers for Disease Control and Prevention based on ICD codes to form the composite variable for CSMM. Two expert clinicians manually reviewed all qualifying events using a standardised tool to determine whether these represented true CSMM events. Additionally, we estimated the number of CSMM cases among delivery hospitalisations without qualifying ICD codes by manually reviewing all hospitalisations with severe preeclampsia, a population at high risk of CSMM, and a random sample of 1000 hospitalisations without severe preeclampsia. We estimated validity of the composite variable. RESULTS: Among 91 355 admissions for delivery, we captured 113 potential CSMM cases using qualifying ICD codes. Of these, 65 (57.5%) were true CSMM cases. Indicators for acute myocardial infarction, cardiac arrest, and cardioversion had the highest true-positive rates (100% for all). We found an additional 70 CSMM cases in the 2102 admissions with severe preeclampsia and a single CSMM case in the random sample. Assuming a rate of 1 CSMM case per 1000 deliveries in the remaining cohort, the composite variable had a positive predictive value of 57.5% (95% CI 47,9, 66.8), a negative predictive value of 99.8% (95% CI 99.8, 99.9), a sensitivity of 29.0% (95% CI 23.2, 35.4), and a specificity of 100% (95% CI 99.9, 100.0). CONCLUSION: A novel composite variable for CSMM had reasonable PPV but limited sensitivity. This composite variable may enable epidemiologic studies geared towards reducing maternal morbidity and mortality.

A critical review of the pathophysiology of thrombotic complications and clinical practice recommendations for thromboprophylaxis in pregnant patients with COVID-19.

Those who are infected with Severe Acute Respiratory Syndrome-related CoronaVirus-2 are theoretically at increased risk of venous thromboembolism during self-isolation if they have reduced mobility or are dehydrated. Should patients develop coronavirus disease (COVID-19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly. These thromboembolic events are the result of at least two distinct mechanisms - microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital-associated venous thromboembolism. Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID-19. To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID-19. Nevertheless, several organizations have vigilantly issued pregnancy-specific guidelines for thromboprophylaxis in COVID-19. Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high-quality evidence available to inform clinical practice. Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID-19. However, its utility in non-pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis. Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID-19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities. There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID-19. Likewise, there is no evidence to comment on the role of low-dose aspirin in thromboprophylaxis or of anti-cytokine and antiviral agents in preventing immunothrombosis. These unanswered questions are being studied within the context of clinical trials.

Diagnosing Pulmonary Embolism in Pregnancy: Synthesis of Current Guidelines and New Evidence.

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).

Capacity Building and Innovation in Caring for Non-communicable Diseases in Maternal Global Health: The Example of Haiti.

Non-communicable diseases (NCDs) are important contributors to maternal morbidity and mortality worldwide. Yet, data on their prevalence and related outcomes in low-income countries are currently lacking. Additionally, screening and treatment protocols adapted for resource-limited settings are urgently required. This collaborative research initiative on the screening and management of hypertensive disorders of pregnancy and gestational diabetes was conducted in Saint-Nicolas Hospital in Saint-Marc, Haiti. The report discusses methods used to overcome several local challenges to implementation of care for NCDs. It also describes how collaborative research initiatives are efficient strategies to innovate and build research capacity for NCD care delivery during pregnancy in low-income countries.