Risk of pre-eclampsia in patients with a maternal genetic predisposition to common medical conditions: a case-control study.

OBJECTIVE: To assess whether women with a genetic predisposition to medical conditions known to increase pre-eclampsia risk have an increased risk of pre-eclampsia in pregnancy. DESIGN: Case-control study. SETTING AND POPULATION: Pre-eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene-centric array. METHODS: Significant single-nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre-eclampsia. Odds of pre-eclampsia were compared across quartiles of the genetic instrument and evaluated for significance. MAIN OUTCOME MEASURES: Genetic predisposition to medical conditions and relationship with pre-eclampsia. RESULTS: An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre-eclampsia (DBP, overall OR 1.11, 95% CI 1.01-1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00-1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82-0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early-onset pre-eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08-1.56, P = 0.005). For other traits, there was no evidence of an association. CONCLUSIONS: These results suggest that the underlying genetic architecture of pre-eclampsia may be shared with other disorders, specifically hypertension and obesity. TWEETABLE ABSTRACT: A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre-eclampsia.

Hemodynamic changes in patients with SARS-CoV-2 infection presenting for cesarean delivery under spinal anesthesia: a retrospective case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with adverse maternal and neonatal outcomes. Early studies suggested that COVID-19 was associated with a higher incidence of hypotension following neuraxial anesthesia in parturients. We explored the hemodynamic response to spinal anesthesia for cesarean delivery in pregnant severe respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) positive patients, using a retrospective case-control design. METHODS: We searched our electronic medical records for patients who received spinal anesthesia for cesarean delivery, and were SARS-CoV-2 positive or recovered at delivery, and used historical and SARS-CoV-2 negative controls from two tertiary care hospitals. We compared the demographic, clinical, and hemodynamic variables between patients who were SARS-CoV-2 positive at delivery, those who were positive during pregnancy and recovered before delivery, and controls. Analyses were stratified by normotensive versus hypertensive status of the patients at delivery. RESULTS: We identified 22 SARS-CoV-2 positive, 73 SARS-CoV-2 recovered, and 1517 controls. The SARS-CoV-2 positive, and recovered pregnant patients, had on average 5.6 and 2.2 mmHg, respectively, higher post-spinal mean arterial pressures (MAPs) than control patients, adjusting for covariates. Additionally, the lowest post-spinal MAP was negatively correlated with the number of daysbetween the onset of COVID-19 symptoms and delivery in patients with hypertension (correlation -0.55, 95% CI -0.81 to -0.09). CONCLUSIONS: Patients with SARS-CoV-2 infection during pregnancy exhibit less spinal hypotension than non-infected patients. While the clinical significance of this finding is unknown, it points to important cardiovascular effects of the virus.

Serum uric acid as a novel marker for uterine atony and post-spinal vasopressor use during cesarean delivery.

INTRODUCTION: Serum uric acid is a marker for oxidative stress in preeclampsia. Because oxidative stress can result in diminished uterine contractility and impaired vascular relaxation, we hypothesized that an elevated serum uric acid level in women undergoing neuraxial anesthesia for cesarean delivery would be associated with greater uterine atony, as measured by supplemental uterotonic agent use and blood loss, and less hypotension, as measured by total vasopressor use. METHODS: All records of patients (n=2527) undergoing cesarean delivery in 2009 were reviewed. Serum uric acid was measured within 24h of delivery in 509 patients; data from 345 patients with singleton pregnancies undergoing neuraxial anesthesia were analyzed. Demographic data, medical and obstetric history, anesthetic management and peripartum course were evaluated. ANOVA, Chi-square, and multivariate logistic and linear regression analyses were performed. RESULTS: Increased serum uric acid correlated positively with preeclampsia and the need for supplemental uterotonic agents (odds ratio 1.53, 95%CI 1.2-2.0, P=0.002), but not blood loss. The presence of preeclampsia also correlated with greater supplemental uterotonic agent use (P=0.01). The correlation between serum uric acid and post-spinal vasopressor use (i.e., none, moderate, and high) was of borderline significance (P=0.05). In patients without diabetes, serum uric acid levels correlated inversely with post-spinal vasopressor use (P=0.04). CONCLUSIONS: Elevated serum uric acid in parturients undergoing cesarean delivery with neuraxial anesthesia correlated with increased use of supplemental uterotonic agents and decreased use of post-spinal vasopressors. Further validation of this study is required to determine if serum uric acid in parturients can serve as a reliable predictor for higher and lower occurrences of uterine atony and spinal-induced hypotension, respectively.