Temporal Trend of COVID-19 Clinical Severity and the Ethnic/Racial Disparity: A Report from the Maryland Study Group.

OBJECTIVES: This study aimed to evaluate the temporal trend of novel coronavirus disease 2019 (COVID-19) symptoms and severity of clinical outcomes among pregnant women over a calendar year in the State of Maryland and compare clinical outcomes between different ethnic and racial groups. STUDY DESIGN: We conducted a retrospective, multicenter observational study of the temporal trend of COVID-19 clinical presentation during pregnancy in the State of Maryland. We reviewed consecutive charts of adult pregnant females, aged 18 to 55 years, with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between March 1, 2020, and February 28, 2021, and managed within the University of Maryland Medical System and Johns Hopkins Medicine. We excluded cases with insufficient data for assessing the COVID-19 diagnosis, pregnancy status, or clinical outcomes. We evaluated the evolution of COVID-19 symptoms at the time of presentation. Also, we compared COVID-19 infection rate, hospitalization rate, oxygen use, and intensive care unit (ICU) admission rates between different ethnic and racial groups. RESULTS: We included 595 pregnant women with laboratory-confirmed COVID-19 over the study period. The prevalence of respiratory and systemic symptoms decreased over time with incidence rate ratios (IRRs) of 0.91 per month (95% confidence interval [CI]: 0.88-0.95) and 0.87 per month (95% CI: 0.83-0.95), respectively. The prevalence of hospitalization, O2 requirement, and ICU admission decreased over time with IRRs of 0.86 per month (95% CI: 0.82-0.91), 0.91 per month (95% CI: 0.84-0.98), and 0.70 per month (95% CI: 0.57-0.85), respectively. The Hispanic and Black populations had a higher COVID-19 infection rate and hospitalization rate than the non-Hispanic White population (p = 0.004, < 0.001, and < 0.001, respectively). CONCLUSION: Understanding the concepts of viral evolution could potentially help the fight against pandemics like COVID-19. Moreover, this might improve the knowledge of how pandemics affect disadvantaged populations and help close the gap in health care inequities. KEY POINTS: · A trade-off between virulence and transmissibility is determined by the natural selection of viruses.. · Understanding the concepts of viral evolution can help the fight against pandemics like COVID-19.. · Evolution of SARS-CoV-2 over time resulted in decreased virulence and increased infectivity..

Progesterone and Preterm Birth: Using Empirical Research to Explore Structural Racism Within Midwifery-Led Care.

BACKGROUND: Progesterone has been the standard of practice for the prevention of preterm birth for decades. The drug received expedited Food and Drug Administration approval, prior to the robust demonstration of scientific efficacy. METHODS: Prospective research from the American Association of Birth Centers Perinatal Data Registry, 2007-2020. Two-tailed t tests, logistic regression, and propensity score matching were used. RESULTS: Midwifery-led care was underutilized by groups most at risk for preterm birth and was shown to be effective at maintaining low preterm birth rates. The model did not demonstrate reliable access to progesterone. People of color are most at risk of preterm birth, yet were least likely to receiving progesterone treatment. Progesterone was not demonstrated to be effective at decreasing preterm birth when comparing the childbearing people with a history of preterm birth who used the medication and those who did not within this sample. CONCLUSIONS: This study adds to the body of research that demonstrates midwifery-led care and low preterm birth rates. The ineffectiveness of progesterone in the prevention of preterm birth among people at risk was demonstrated.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation-induced oxidative stress in a mouse model.

Melatonin has been shown to reduce oxidative stress and mitigate hypercoagulability. We hypothesized that maternally administered melatonin may reduce placental oxidative stress and hypercoagulability associated with exposure to intrauterine inflammation (IUI) and consequently improve fetoplacental blood flow and fetal sequelae. Mice were randomized to the following groups: control (C), melatonin (M), lipopolysaccharide (LPS; a model of IUI) (L), and LPS with melatonin (ML). The expression of antioxidant mediators in the placenta was significantly decreased, while that of pro-inflammatory mediators was significantly increased in L compared to C and ML. The systolic/diastolic ratio, resistance index, and pulsatility index in uterine artery (UtA) and umbilical artery (UA) were significantly increased in L compared with other groups when analyzed by Doppler ultrasonography. The expression of antioxidant mediators in the placenta was significantly decreased, while that of pro-inflammatory mediators was significantly increased in L compared to C and ML. Vascular endothelial damage and thrombi formation, as evidenced by fibrin deposits, were similarly increased in L compared to other groups. Maternal pretreatment with melatonin appears to modulate maternal placental malperfusion, fetal cardiovascular compromise, and fetal neuroinflammation induced by IUI through its antioxidant properties.

Increasing effective postpartum care in an obstetric clinic using ACOG's postpartum toolkit.

BACKGROUND: Approximately 69% of maternal mortality occurs in the postpartum period. Contributing factors include the absence of preparation of pregnant women for the postpartum period during the antenatal period, postpartum follow-up care not being scheduled until 6 weeks after childbirth, and the lack of further care coordination. AIM: The aim of this project was to increase the frequency of effective postpartum care visits to 80% in 8 weeks at an urban obstetric clinic. METHODS: A quality improvement project was conducted through four Plan-Do-Study-Act cycles over 8 weeks. INTERVENTIONS: Postpartum Readiness & Awareness Tools (PRATs) were reviewed with patients during their late third trimester, to review postpartum warning signs that warrant further evaluation. A population health registry was created to manage early follow-up for newly postpartum patients, to ensure their recovery was progressing normally. A note template was created and implemented to guide the completion of comprehensive postpartum visits. RESULTS: Over 8 weeks, 188 patients received 1 of the 3 standardized interventions. Effective postpartum visits increased to 88%. The PRATs increased patient postpartum warning sign knowledge, with a project mean risk factor knowledge score of 6 (Goal = 5). The population health registry drove right care by ensuring early postpartum patients were recovering as expected, as seen by a project mean right-care score of 16 (Goal = 12). The note template increased the effectiveness of postpartum visits, with a mean effective postpartum care score of 10 (Goal = 10). CONCLUSIONS: The PRATs, population health registry, and note template collectively increased the quality and effectiveness of postpartum care.

Analysis of Clinical Outcomes of Pregnant Patients Treated With Nirmatrelvir and Ritonavir for Acute SARS-CoV-2 Infection.

Importance: Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available. Objective: To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients. Design, Setting, and Participants: This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022. Exposures: Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures: Clinical characteristics and outcomes were ascertained through manual record review. Results: Forty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities. Conclusions and Relevance: In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.

Findings From Severe Maternal Morbidity Surveillance and Review in Maryland.

Importance: In the US, more than 50 000 women experience severe maternal morbidity (SMM) each year, and the SMM rate more than doubled during the past 25 years. In response, professional organizations called for birthing facilities to routinely identify and review SMM events and identify prevention opportunities. Objective: To examine SMM levels, primary causes, and factors associated with the preventability of SMM using Maryland's SMM surveillance and review program. Design, Setting, and Participants: This cross-sectional study included pregnant and postpartum patients at 42 days or less after delivery who were hospitalized at 1 of 6 birthing hospitals in Maryland between August 1, 2020, and November 30, 2021. Hospital-based SMM surveillance was conducted through a detailed review of medical records. Exposures: Hospitalization during pregnancy or within 42 days post partum. Main Outcomes and Measures: The main outcomes were admission to an intensive care unit, having at least 4 U of red blood cells transfused, and/or having COVID-19 infection requiring inpatient hospital care. Results: A total of 192 SMM events were identified and reviewed. Patients with SMM had a mean [SD] age of 31 [6.49] years; 9 [4.7%] were Asian, 27 [14.1%] were Hispanic, 83 [43.2%] were non-Hispanic Black, and 68 [35.4%] were non-Hispanic White. Obstetric hemorrhage was the leading primary cause of SMM (83 [43.2%]), followed by COVID-19 infection (57 [29.7%]) and hypertensive disorders of pregnancy (17 [8.9%]). The SMM rate was highest among Hispanic patients (154.9 per 10 000 deliveries), primarily driven by COVID-19 infection. The rate of SMM among non-Hispanic Black patients was nearly 50% higher than for non-Hispanic White patients (119.9 vs 65.7 per 10 000 deliveries). The SMM outcome assessed could have been prevented in 61 events (31.8%). Clinician-level factors and interventions in the antepartum period were most frequently cited as potentially altering the SMM outcome. Practices that were performed well most often pertained to hospitals' readiness and adequate response to managing pregnancy complications. Recommendations for care improvement focused mainly on timely recognition and rapid response to such. Conclusions and Relevance: The findings of this cross-sectional study, which used hospital-based SMM surveillance and review beyond the mere exploration of administrative data, offers opportunities for identifying valuable quality improvement strategies to reduce SMM. Immediate strategies to reduce SMM in Maryland should target its most common causes and address factors associated with preventability identified at individual hospitals.

Dysregulated immunity in SARS-CoV-2 infected pregnant women.

IMPORTANCE: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. OBJECTIVE: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DESIGN: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SETTING: Johns Hopkins Hospital (JHH). PARTICIPANTS: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. RESULTS: SARS-COV-2 positive pregnant women expressed more IL1ß , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

Maternal Supplementation of Low Dose Fluoride Alleviates Adverse Perinatal Outcomes Following Exposure to Intrauterine Inflammation.

Maternal periodontal disease has been linked to adverse pregnancy sequelae, including preterm birth (PTB); yet, root planing and scaling in pregnancy has not been associated with improved perinatal outcomes. Fluoride, a cariostatic agent, has been added to drinking water and dental products to prevent caries and improve dental health. The objective of this study was to explore the effects of fluoride supplementation using a mouse model of preterm birth and perinatal sequalae. Pregnant mice were fed low dose fluoride (LF-) or high dose fluoride (HF-) and given intrauterine injections of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). We found that LPS + LF- significantly increased livebirths, pup survival, and litter size compared to LPS alone. Moreover, offspring from the LPS + LF- group exhibited significantly improved neuromotor performance and more neurons compared to those from the LPS group. Additionally, LF- treatment on human umbilical vein endothelial cells (HUVECs) increased cell viability and decreased oxidative stress after treatment with LPS. Collectively, our data demonstrates that maternal LF- supplementation during pregnancy postpones the onset of PTB, acts to increase the liveborn rate and survival time of newborns, and reduces perinatal brain injury in cases of intrauterine inflammation.