Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19.

Introduction: There remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19. Methods: Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured. Results: Differences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis. Discussion: Elevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.

Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior.

Introduction: Thromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype. Methods: We treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing. Results: We found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression. Discussion: Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.

Does a video module improve patient adherence to recommended gestational weight gain guidelines?

OBJECTIVES: We aim to assess if implementation of an educational video module can improve patient adherence to recommended weight gain guidelines. Secondarily, we investigated if patients' knowledge about gestational weight gain was improved with use of the video, as well as if there was a difference in maternal and neonatal outcomes, and patient satisfaction. METHODS: This was an IRB-approved, prospective cohort study conducted from February 2019 to October 2019. Patients were recruited from a large academic practice during their first trimester of pregnancy. Patients in the control cohort received routine care. Patients in the video cohort watched a 5-min educational video module about gestational weight gain. Pre-pregnancy weight and baseline demographics were recorded. All patients took a baseline questionnaire assessing gestational weight gain knowledge upon enrollment, and again 4 weeks later. Pre and post score differences were calculated. On admission to the hospital for delivery, all patients' gestational weight gain was calculated, and the overall gestational weight gain differences between the two groups were calculated. Maternal and neonatal delivery outcomes were also collected. T-tests, Mann-Whitney U tests, and Chi-square analyses were used to compare groups, and a p-value of <.05 was deemed statistically significant. RESULTS: During the study period, 155 patients were recruited, with 79 in control cohort and 76 in video cohort, respectively. There was no significant difference in the percentage of patients who gained the appropriate amount of weight between the two groups; 25% (18/74) of patients in the control vs. 25% (17/68) of patients in video cohort (p = .926). There was no difference in the improvement of the pre and post assessment scores when compared between the two cohorts; the average score improvement was 1.72 ± 15.09% for the control, vs. 6.20 ± 12.51% for video cohort (p = .129). There was no difference in maternal or neonatal outcomes between the two groups. Patients were overall satisfied with the video module, with 67.6% (n = 45) reporting the video to be very educational. CONCLUSIONS: Use of a video module did not improve GWG outcomes or knowledge in our study. Future work can focus on use of a recurring intervention throughout pregnancy, either with app-based technology or multiple videos.

Missingness patterns in a comprehensive instrument identifying psychosocial and substance use risk in antenatal care.

BACKGROUND: Psychosocial vulnerabilities (e.g. inadequate social support, financial insecurity, stress) and substance use elevate risks for adverse perinatal outcomes and maternal mental health morbidities. However, various barriers, including paucity of validated, simple and usable comprehensive instruments, impede execution of the recommendations to screen for such vulnerabilities in the first antenatal care visit. The current study presents findings from a newly implemented self-report tool created to overcome screening barriers in outpatient antenatal clinics. METHODS: This was a retrospective chart-review of 904 women who completed the Profile for Maternal & Obstetric Treatment Effectiveness (PROMOTE) during their first antenatal visit between June and December 2019. The PROMOTE includes the 4-item NIDA Quick Screen and 15 additional items that each assess a different psychosocial vulnerability. Statistical analysis included evaluation of missing data, and exploration of missing data patterns using univariate correlations and hierarchical clustering. RESULTS: Three quarters of women (70.0%) had no missing items. In the entire sample, all but four PROMOTE items (opioid use, planned pregnancy, educational level, and financial state) had < 5% missing values, suggesting good acceptability and feasibility. Several respondent-related characteristics such as lower education, less family support, and greater stress were associated with greater likelihood of missing items. Instrument-related characteristics associated with missing values were completing the PROMOTE in Spanish or question positioning at the end of the instrument. CONCLUSIONS AND IMPLICATIONS: Conducting a comprehensive screening of theoretically and clinically meaningful vulnerabilities in an outpatient setting is feasible. Study findings will inform modifications of the PROMOTE and subsequent digitisation.

Psychological measures of patient's decision-making for prenatal genetic testing.

OBJECTIVE: To use a questionnaire to determine the levels of maternal decision-related distress, clarity of the pros and cons, and certainty when considering prenatal genetic diagnostic testing; and to assess the relationship between these constructs and patient characteristics. METHOD: Cross-sectional study. Voluntary, anonymous questionnaires distributed 2017-2019 to women referred for invasive prenatal genetic testing. Excluded: English or Spanish illiterate. Maternal characteristics were collected. Questions evaluated distress, decisional certainty, and decisional clarity on a 5-point Likert scale (range: 0 = low/uncertain/unclear to 4 = high/certain/clear). Analysis: non-parametric Kruskal-Wallis, correlation statistics, and ANOVA. RESULTS: Forty-four female patients completed it. Most were married, white, Catholic, and multiparous. 58% had already made a testing decision. Patients expressed low distress levels (mean 1.18 ± 0.80) and expressed high decisional certainty (mean 3.28 ± 0.76) and clarity (mean 3.30 ± 0.99). Decisional certainty and clarity were positively correlated (r = 0.47, p < .01), whereas distress was negatively correlated with decisional certainty (r = -0.8136, p < .0005) and decisional clarity (r = -0.49, p = .007). No significant differences by religion or parity. Greater distress (p < .05) and less decisional clarity (p = .07) occurred between those still debating testing vs those who had decided. CONCLUSIONS: Higher maternal distress scores were associated with lower decisional certainty and decisional clarity in women considering prenatal genetic testing.

Histological Changes Observed in Placentas Exposed to Medication-Assisted Treatment.

INTRODUCTION: To compare the effects of medication-assisted treatment on the placenta in pregnant women with opioid use disorder and uncomplicated pregnancies. METHODS: This is a case-controlled study of pregnant women utilizing medication-assisted treatment, buprenorphine or methadone, which were matched to healthy uncomplicated controls by gestational age. Placental evaluations and neonatal outcomes were evaluated. Data analysis performed standard statistics and relative risk analysis with a p < 0.05 considered significant. RESULTS: There were 143 women who met the inclusion criteria: 103 utilizing MAT, 41 buprenorphine and 62 methadone, and 40 uncomplicated matched healthy controls. The incidence of delayed villous maturation was 36% in the medication-assisted group compared with 10% in controls (RR 3.6: 95% CI 1.37-9.43; p < 0.01). The placental weight was greater (541 ± 117 g versus 491 ± 117 g; p = 0.02), and the fetoplacental weight ratio was lower (5.70 ± 1.1 versus 7.13 ± 1.4; p < 0.01) in the medication-exposed pregnancies compared with controls. The mean birth weight of the MAT newborns was significantly lower than that of the healthy controls (3018 ± 536 g versus 3380 ± 492 g; p < 0.01). When evaluating the subgroups of the MAT newborns, the birth weight of the methadone-exposed newborns (2886 ± 514 g) was significantly lower than that of the buprenorphine-exposed newborns (3218 ± 512 g; p < 0.01). CONCLUSION: Medication-exposed pregnancies have a greater incidence of delayed villous maturation, a larger placental size, and a decreased fetoplacental weight ratio compared to the healthy controls. Larger long-term follow-up studies to evaluate outcomes with the presence of delayed villous maturation are needed.

Risk of metformin failure in the treatment of women with gestational diabetes.

OBJECTIVES: To estimate the metformin failure rate in women with gestational diabetes. METHODS: The study was designed as a retrospective cohort of women diagnosed with gestational diabetes by the 75 g 2 h oral glucose tolerance test. Women were placed into two groups: metformin success (107 patients not requiring insulin therapy) or metformin failure (15 patients requiring the addition of, or, transition to insulin). Primary outcome: rate of metformin failure. Secondary outcomes: maternal and neonatal factors. RESULTS: The failure rate of metformin was 15% (19/122 women) in the study. The failure group was more likely to have 3 abnormal values on a 2-h 75 g oral glucose tolerance test (37% (n=7/19) vs. 15% (n=15/103), p=0.02). Patients who failed had higher average fasting blood glucose levels on the glucose tolerance test as well as on pretreatment fasting finger stick values. Those who failed metformin were diagnosed with gestational diabetes and started on metformin earlier in gestation. CONCLUSIONS: Overall low rate of metformin failure in treatment of gestational diabetes.

Bayesian Nonparametric Dimensionality Reduction of Categorical Data for Predicting Severity of COVID-19 in Pregnant Women.

The coronavirus disease (COVID-19) has rapidly spread throughout the world and while pregnant women present the same adverse outcome rates, they are underrepresented in clinical research. We collected clinical data of 155 test-positive COVID-19 pregnant women at Stony Brook University Hospital. Many of these collected data are of multivariate categorical type, where the number of possible outcomes grows exponentially as the dimension of data increases. We modeled the data within the unsupervised Bayesian framework and mapped them into a lower dimensional space using latent Gaussian processes. The latent features in the lower dimensional space were further used for predicting if a pregnant woman would be admitted to a hospital due to COVID-19 or would remain with mild symptoms. We compared the prediction accuracy with the dummy/one-hot encoding of categorical data and found that the latent Gaussian process had better accuracy.

Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies.

Objectives To compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder. Methods A cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10-year period. Women were excluded with delivery <37 weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of <0.05 was significant. Results There were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4 days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4 days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay >7 days (OR 3.61; 95% confidence interval 1.32-9.86; p=0.01). Conclusions Medication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

First-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease.

BACKGROUND: While elevated second-trimester maternal serum alpha fetoprotein has been associated with adverse pregnancy outcomes, the utility of first-trimester maternal serum alpha fetoprotein in predicting these outcomes is limited. Some laboratories have been including maternal serum alpha fetoprotein as part of the first-trimester analyte screening for aneuploidy and preeclampsia, offering its potential utility in predicting pregnancy outcomes. OBJECTIVE: Our primary objective was to determine the association between elevated first-trimester maternal serum alpha fetoprotein and preeclampsia as well as ischemic placental disease (a composite of preeclampsia, fetal growth restriction, and/or placental abruption). Secondary outcomes included early-onset preeclampsia requiring delivery at <34 weeks gestation, fetal growth restriction, placental abruption, preterm delivery, fetal demise, and spontaneous abortion. STUDY DESIGN: An institutional review board-approved multisite retrospective cohort study was performed including all patients with first-trimester maternal serum alpha fetoprotein as part of routine first-trimester aneuploidy screening from April 2015 through January 2017. Pregnancies with multiple gestations, known structural or chromosomal abnormalities, known malignancy, and incomplete delivery records were excluded. Delivery records were reviewed for baseline characteristics and adverse pregnancy outcomes. The optimal cutoff point for first-trimester maternal serum alpha fetoprotein to predict these outcomes was assessed, and an elevated maternal serum alpha fetoprotein was considered >2.0 multiple of the median. A Fisher exact test and odds ratios were used to determine the association between elevated first-trimester maternal serum alpha fetoprotein and adverse pregnancy outcomes. Spearman correlation coefficient assessed the relationship between first- and second-trimester maternal serum alpha fetoprotein. RESULTS: Of 1478 patients with first-trimester maternal serum alpha fetoprotein, 1280 had complete records available for review (86.6%). There was no association demonstrated between elevated first-trimester maternal serum alpha fetoprotein (>2.0 multiple of the median) and the primary outcome, overall preeclampsia (5.8% vs 4.6%, odds ratio, 1.29, 95% confidence interval, 0.58-2.91). However, there was an increased incidence of ischemic placental disease, 15.8% vs 7.7% (odds ratio, 2.26, 95% confidence interval, 1.33-3.87) in those with an elevated alpha fetoprotein. Also, elevated first-trimester maternal serum alpha fetoprotein was associated with a higher incidence of fetal growth restriction (7.5% vs 2.3%, odds ratio, 3.40, 95% confidence interval, 1.56-7.42) and preterm birth (18.3% vs 10.3%, odds ratio, 1.95, 95% confidence interval, 1.18-3.21). Also, a positive correlation between first- and second-trimester maternal serum alpha fetoprotein was demonstrated (rho = 0.46, P < .0001). CONCLUSION: Elevated first-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated maternal serum alpha fetoprotein may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine whether the addition of first-trimester maternal serum alpha fetoprotein to existing algorithms can improve the early detection of ischemic placental disease.

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes.

OBJECTIVE: We sought to determine if insulin detemir (IDet) is noninferior to insulin neutral protamine Hagedorn (NPH) for the treatment of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) in pregnancy. STUDY DESIGN: We conducted a randomized, controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014. Exclusion criteria were type 1 diabetes, age <18 years, and insulin allergy. Women who failed to achieve good glycemic control (GC) (mean blood glucose [BG] <100 mg/dL) on diet and/or hypoglycemic agents were randomized to receive either IDet or NPH, with short-acting insulin aspart added as needed. Patients were instructed to test BG 4 times a day (fasting and 2-hour postprandial). Targets of GC were fasting BG <90 mg/dL and postprandial BG <120 mg/dL, and insulin was adjusted as needed to achieve the targets. The primary outcome was overall mean BG during insulin treatment; secondary outcomes included overall mean postprandial and fasting BG, median number of weeks to achieve GC, percent of patients with overall GC, maternal weight gain, perinatal/neonatal outcomes, and number of hypoglycemic events. Power analysis (90% power) determined that 88 patients would need to be randomized, assuming a maximal acceptable difference in overall mean BG of 7 mg/dL (SD ± 10 mg/dL). A per protocol analysis was performed. RESULTS: In all, 105 women were randomized. Eighteen women were excluded leaving 87 participants for analysis (45 NPH, 42 IDet). Maternal characteristics were similar in both groups. The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95% confidence limit of 5.5 mg/dL (less than the maximal acceptable difference of 7 mg/dL; P = .2937). There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded. The time to achieve GC was similar in both groups. There were no differences in perinatal outcomes and maternal weight gain among the groups. There were more hypoglycemic events per patient in the NPH group. CONCLUSION: IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy.

The importance of fasting blood glucose in screening for gestational diabetes.

OBJECTIVE: To determine how well an isolated abnormal fasting blood glucose (FBG) value on the 1-step, 75-g, 2-hour glucose tolerance test (GTT) indicates significant gestational diabetes (GDM). METHODS: Retrospective cohort study, January 2011 to May 2012. Patients diagnosed by the 1-step method were assigned by their abnormal results to the isolated fasting (FBG), isolated 1-hour (1HBG), isolated 2-hour (2HBG), or multiple-value (≥2BG) group. Characteristics and outcomes were compared using ANOVA, Kruskal--Wallis, and Chi-squared tests. RESULTS: 324 patients were included. Compared to other groups, the FBG group (N = 23) had the highest incidence of requiring medical therapy (78.26%), mean body mass index (29.40 ± 6.20 kg/m(2)), and percentage of Black plus Hispanic women (60.87%). CONCLUSIONS: Seven percent of women were diagnosed with GDM by an isolated abnormal fasting BG and have significant disease. This group should not be missed; therefore, fasting BG should be integrated into all GDM screening.

Labor induction in nulliparous women with an unfavorable cervix: double balloon catheter versus dinoprostone.

OBJECTIVE: We sought to compare the efficacy of the double-balloon catheter and dinoprostone for induction of labor among nulliparous women with an unfavorable cervix. STUDY DESIGN: Nulliparous women with a Bishop score <6 were randomized to receive a 10-mg intra-vaginal dinoprostone insert or a double-balloon catheter. Primary outcome was time to delivery. Statistical analyses were performed by intention to treat using the chi-square, Fisher's exact, and Student's t-test, as appropriate. RESULTS: The mean induction-to-delivery time was shorter in the double-balloon group as compared to the dinoprostone group (17.9±5.8 vs. 26.3±9.7 h) as was the time from induction to vaginal delivery (19.13±5 vs. 24.45±8.7 h, respectively). More women in the catheter group were delivered within 24 h compared to the dinoprostone group (87.1% vs. 47.4%). Approximately 50% of women in both groups delivered by cesarean section. CONCLUSION: Induction of labor with the double-balloon catheter in nulliparous women with an unfavorable cervix is associated with a shorter time to delivery compared to dinoprostone.