Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

OBJECTIVE: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. DESIGN: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. SETTING: Rigshospitalet and Hvidovre Hospital, Denmark. SAMPLE: Normotensive pregnant women aged 18-45 years with singleton pregnancies, enrolled in the PEACH study in 2016-2018. METHODS: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. MAIN OUTCOME MEASURES: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28-40. RESULTS: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30-32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. CONCLUSIONS: Our reference ranges allow the use of a bedside ultrasound device to non-invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow-up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Cohort profile: The PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension (PEACH) Study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal morbidity and mortality worldwide, with implications for maternal and neonatal well-being in the short term and for long-term maternal cardiovascular health. Although the mechanisms behind HDP remain incompletely understood, evidence suggests that preeclampsia in particular is a syndrome with more than one distinct subtype. OBJECTIVES: The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction, Hypertension) Study was established to identify new HDP subtyping systems reflecting aetiology and prognosis and to find markers of later cardiovascular disease risk associated with preeclampsia. POPULATION: The PEACH Study recruited pregnant women referred to two Copenhagen-area hospitals with suspected preeclampsia (mean gestational age at enrolment: 36.7 weeks) and a group of frequency-matched pregnant women planning delivery at the same hospitals and healthy when enrolled mid-pregnancy. DESIGN: Prospective, longitudinal pregnancy cohort. METHODS: Participants underwent repeated third-trimester blood sample collection, longitudinal cardiac function assessments using the USCOM-1A during the third trimester and at 1 year postpartum and collection of placental samples immediately after delivery. Medical information was abstracted from medical records and hospital databases. PRELIMINARY RESULTS: During 2016-2018, we recruited 1149 pregnant women, of whom 1101 were followed to delivery. Among 691 women enrolled with suspected preeclampsia, 310 and 172 developed preeclampsia and gestational hypertension respectively. Among 410 women with healthy pregnancies when enrolled mid-pregnancy, 37 later developed hypertensive disorders of pregnancy. Of 1089 women still in the cohort 1 year postpartum, 578 (53.1%) participated in the follow-up assessment. CONCLUSIONS: The PEACH Study's rich data from women with and without HDP will enable us to identify new, clinically useful HDP subtypes to aid in decision-making regarding monitoring and treatment. Continued postpartum follow-up will help us develop algorithms to identify women at risk of persistent postpartum cardiac dysfunction and later cardiovascular disease after pregnancies complicated by HDP.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Third-Trimester Cardiovascular Function and Risk of Hypertensive Disorders of Pregnancy.

BACKGROUND: Whether cardiovascular dysfunction is associated with preeclampsia in women without fetal growth restriction (FGR) is unclear. Our objective was to investigate associations between third-trimester cardiac output (CO) and systemic vascular resistance and risk of hypertensive disorders of pregnancy in women with and without FGR. METHODS AND RESULTS: A case-cohort study in 906 pregnant women in Denmark with repeated third-trimester cardiac function assessments was performed using the Ultrasound Cardiac Output Monitor 1A. Using Cox regression, we compared rates of hypertensive disorders of pregnancy in women with low, normal, and high CO and normal and high systemic vascular resistance, by FGR status and gestational age, and evaluated associations between a third-trimester drop in CO or increase in systemic vascular resistance and preeclampsia risk in women without FGR. The analysis included 249 women with preeclampsia (42 with FGR) and 119 women with gestational hypertension. Low CO was strongly associated with preeclampsia at <37 weeks (women with FGR: hazard ratio [HR], 5.25 [95% CI, 1.26-21.9]; women without FGR: HR, 2.19 [95% CI, 1.07-4.48]). Our results also suggested an association between low CO and preeclampsia at ≥37 weeks among women without FGR (HR, 1.31 [95% CI, 0.84-2.03]), and between a third-trimester drop in CO >75th percentile and preeclampsia in women without FGR (odds ratio, 1.91 [95% CI, 0.84-4.36]). High systemic vascular resistance was strongly associated with increased rates of all forms of hypertensive disorders of pregnancy. CONCLUSIONS: Low CO is associated with preeclampsia risk in women with and without FGR, particularly before 37 weeks. Repeated measurements of third-trimester cardiovascular function might identify women without FGR for monitoring for preeclampsia, but this result needs to be confirmed in other studies.