Evaluating the Association between Assisted Conception and the Severity of Preeclampsia

Objective. To investigate the association between assisted conceptions and preeclampsia (PEC), including assessment of severity of disease. Methods. In a prospective case control study, cases were selected from women with preeclampsia and controls from women without preeclampsia. Exposure was defined as assisted conception with intrauterine insemination or in vitro fertilization (IUI or IVF). We assessed the association between exposure and outcome, using Chi square or Fisher's exact tests. Stratified analyses and multivariable logistic regression were used to control for confounders. Results. Preeclampsia was associated with assisted conception after controlling for age and race (AOR 2.2, [1.03–4.72]). All women with preeclampsia who had assisted conceptions demonstrated severe disease and were more likely to have abnormal lab values: AST >45 (AOR = 6.01 [1.63–22.21] P = 0.007), creatinine ≥1 (AOR 2.92 [0.82–10.4], P = 0.09) or platelets <100 (AOR 5.74 [1.00–32.76] P = 0.049), after adjusting for race, age, and multiple gestations. Conclusion. Assisted conceptions are associated with a more severe preeclamptic phenotype

Morbidity and mortality associated with mode of delivery for breech periviable deliveries

OBJECTIVE: The purpose of this study was to estimate the odds of morbidity and death that are associated with cesarean delivery, compared with vaginal delivery, for breech fetuses who are delivered from 23-24 6/7 weeks' gestational age. STUDY DESIGN: We conducted a retrospective cohort study of state-level maternal and infant hospital discharge data that were linked to vital statistics for breech deliveries that occurred from 23-24 6/7 weeks' gestation in California, Missouri, and Pennsylvania from 2000-2009 (N = 1854). Analyses were stratified by gestational age (23-23 6/7 vs 24-24 6/7 weeks' gestation). RESULTS: Cesarean delivery was performed for 46% (335 fetuses) and 77% (856 fetuses) of 23- and 24-week breech fetuses. In multivariable analyses, overall survival was greater for cesarean-born neonates (adjusted odds ratio [AOR], 3.98; 95% confidence interval [CI], 2.24-7.06; AOR, 2.91; 95% CI, 1.76-4.81, respectively). When delivered for nonemergent indications, cesarean-born survivors were more than twice as likely to experience major morbidity (intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, asphyxia composite; AOR, 2.83; 95% CI, 1.37-5.84; AOR, 2.07; 95% CI, 1.11-3.86 at 23 and 24 weeks' gestation, respectively). Among intubated neonates, despite a short-term survival advantage, there was no difference in survival to >6-month corrected age (AOR, 1.77; 95% CI, 0.83-3.74; AOR, 1.50; 95% CI, 0.81-2.76, respectively). There was no difference in survival for intubated 23-week neonates who were delivered by cesarean for nonemergent indications or cesarean-born neonates who weighed <500 g. CONCLUSION: Cesarean delivery increased overall survival and major morbidity for breech periviable neonates. However, among intubated neonates, despite a short-term survival advantage, there was no difference in 6-month survival. Also, cesarean delivery did not increase survival for neonates who weighed <500 g. Patients and providers should discuss explicitly the trade-offs related to neonatal death and morbidity, maternal morbidity, and implications for future pregnancies

Antistress and antimicrobial studies of biphenyl chalcone derivatives

This work reports the synthesis, characterization of new (2E)-1-(biphenyl-4-yl)-3-aryl)-prop-2-en-1-one derivatives (C1-C10). The chalcone derivatives were evaluated for in vitro antibacterial, antifungal, antioxidant activities. The compounds exhibited moderate to good antimicrobial activity at MIC 10-40 μg/mL. The compounds were docked at the active site of the methionyl-tRNA synthetase (metRS) (PDB ID: 1A8H) to predict their putative interactions. The compounds further screened for antioxidant property, amid C5, C7 and C8 exhibited good DPPH radical scavenging activity. Compound C5 was selected for antistress studies against gamma radiation induced oxidative stress markers in E .coli K 12. The C5 pretreatment and irradiated bacteria sample showed modulatory action of stress enzymes SOD and CAT to near basal level and significant demulating effect on the level of TBARS.Keywords: Biphenyl chalcone derivatives, radioprotection, antioxidant activity, antimicrobial activity, molecular dockin

Lifetime Racism and Blood Pressure Changes During Pregnancy: Implications for Fetal Growth

Objective: Research suggests that exposure to racism partially explains why African American women are 2 to 3 times more likely to deliver low birth weight and preterm infants. However, the physiological pathways by which racism exerts these effects are unclear. This study examined how lifetime exposure to racism, in combination with maternal blood pressure changes during pregnancy, was associated with fetal growth. Methods: African American pregnant women (n = 39) reported exposure to childhood and adulthood racism in several life domains (e.g., at school, at work), which were experienced directly or indirectly, meaning vicariously experienced when someone close to them was treated unfairly. A research nurse measured maternal blood pressure at 18 to 20 and 30 to 32 weeks gestation. Standardized questionnaires and trained interviewers assessed maternal demographics. Neonatal length of gestation and birth weight data were collected from medical charts. Results: Childhood racism interacted with diastolic blood pressure to predict birth weight. Specifically, women with two or more domains of indirect exposure to racism in childhood and increases in diastolic blood pressure between 18 and 32 weeks had lower gestational age adjusted birth weight than the other women. A similar pattern was found for direct exposure to racism in childhood. Conclusions: Increases in diastolic blood pressure between the second and third trimesters predicted lower birth weight, but only when racism exposure in childhood (direct or indirect) was relatively high. Understanding pregnant African American women’s lifetime direct and indirect experiences with racism in combination with prenatal blood pressure may improve identification of highest risk subgroups within this population

Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study

<p>Abstract</p> <p>Background</p> <p>Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the <it>endoplasmic reticulum aminopeptidase 2 (ERAP2) </it>gene were recently reported to be associated with increased risk for preeclampsia in two different populations. <it>ERAP2 </it>is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, <it>ERAP2 </it>expression is altered in first trimester placentas of women destined to develop preeclampsia.</p> <p>Methods</p> <p>A case-control design was used to test for associations between two SNPs in <it>ERAP2</it>, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal).</p> <p>Results</p> <p>We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (<it>P </it>= 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population.</p> <p>Conclusions</p> <p>We report an association between fetal <it>ERAP2 </it>and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, <it>ERAP2 </it>has now been associated with preeclampsia in three populations. This provides strong evidence that <it>ERAP2 </it>plays a role in the development of preeclampsia.</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570