Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19)

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race–ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2–11%) incidence of venous thromboembolism among those with severe–critical illness compared with 0.2% in mild–moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe–critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30–1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18–2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42–5.14) compared with asymptomatic patients. Mild–moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. CONCLUSION: Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe–critical COVID-19, but not those with mild–moderate COVID-19, were at increased risk of perinatal complications

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Association between time of delivery and composite adverse outcomes in pregnancies complicated by hypertensive disorders

Introduction: A potential manner to lower the morbidity with the hypertensive disoreders of pregancy is to explore the time of day of delivery. Objective: To compare composite neonatal adverse outcomes among term women with hypertensive disorders. Methods: This population-based cohort study used the U.S. vital statistics dataset from 2013 to 2017. Time of delivery was categorized into three shifts. The primary outcome was composite neonatal adverse outcome.. Results: Compared to neonates delivered at the first shift, the risk of composite neonatal adverse outcome was higher at the third shift (aRR = 1.19, 95% CI = 1.13–1.25). Conclusion: the risk of composite neonatal adverse outcome is higher if the delivery occurs at the third (23:00–7:00) shift

Evidence-Based Cesarean Delivery for the Nonobstetrician

Cesarean delivery (CD) is one of the most common major surgeries performed in the United States and worldwide. Surgical techniques evaluated in well-designed randomized controlled trials (RCTs) that demonstrate maternal benefit should be incorporated into practice. The objective of this review is to provide a summary of surgical techniques of the procedure and review the evidence basis for them for the nonobstetrician. The following techniques with the strongest evidence should be commonly performed, when feasible: (1) prophylactic antibiotics with a single dose of ampicillin or first-generation cephalosporin prior to skin incision; (2) postpartum hemorrhage prevention with oxytocin infusion of 10 to 40 IU in 1 L crystalloid over 4 to 8 hours; (3) low transverse skin incision; (4) blunt or sharp subcutaneous and fascial expansion; (5) blunt, cephalad–caudad uterine incision expansion; (6) spontaneous placental removal; (7) blunt-tip needle usage during closure; (8) subcutaneous suture closure (running or interrupted) if thickness is ≥2 cm; and (9) skin closure with suture. Although the number of RCTs designed to optimize maternal and neonatal outcomes of this common procedure is encouraging, further work is needed to minimize surgical morbidity. Optimal methods for postpartum hemorrhage prevention, adhesion prevention, and venous thromboembolism prophylaxis remain ongoing areas of active research, with outcomes that could markedly improve maternal morbidity and mortality. If evidence of a surgical technique appears preferred over another, clinicians should be comfortable adopting the evidence-based technique when performing and teaching CD

Evidence-Based Cesarean Delivery for the Nonobstetrician

Cesarean delivery (CD) is one of the most common major surgeries performed in the United States and worldwide. Surgical techniques evaluated in well-designed randomized controlled trials (RCTs) that demonstrate maternal benefit should be incorporated into practice. The objective of this review is to provide a summary of surgical techniques of the procedure and review the evidence basis for them for the nonobstetrician. The following techniques with the strongest evidence should be commonly performed, when feasible: (1) prophylactic antibiotics with a single dose of ampicillin or first-generation cephalosporin prior to skin incision; (2) postpartum hemorrhage prevention with oxytocin infusion of 10 to 40 IU in 1 L crystalloid over 4 to 8 hours; (3) low transverse skin incision; (4) blunt or sharp subcutaneous and fascial expansion; (5) blunt, cephalad–caudad uterine incision expansion; (6) spontaneous placental removal; (7) blunt-tip needle usage during closure; (8) subcutaneous suture closure (running or interrupted) if thickness is ≥2 cm; and (9) skin closure with suture. Although the number of RCTs designed to optimize maternal and neonatal outcomes of this common procedure is encouraging, further work is needed to minimize surgical morbidity. Optimal methods for postpartum hemorrhage prevention, adhesion prevention, and venous thromboembolism prophylaxis remain ongoing areas of active research, with outcomes that could markedly improve maternal morbidity and mortality. If evidence of a surgical technique appears preferred over another, clinicians should be comfortable adopting the evidence-based technique when performing and teaching CD