Noninvasive single-cell-based prenatal genetic testing: A proof of concept clinical study.

OBJECTIVE: To clinically assess a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood. METHODS: Blood was obtained from 401 (243 + 158) individuals (8-22 weeks) and shipped overnight. Red cells were lysed, and nucleated cells stained for cytokeratin (CK) and CD45 and enriched for positive CK staining. Automated scanning was used to identify and pick single CK+ /CD45- trophoblasts which were subjected to next-generation sequencing. RESULTS: Blood was obtained from 243 pregnancies scheduled for CVS or amniocentesis. Luna results were normal for 160 singletons while 15 cases were abnormal (14 aneuploidy and one monozygotic twin with Williams syndrome deletion). The deletion was confirmed in both fetuses. Placental mosaicism occurred in 7 of 236 (3.0%) Luna cases and in 3 of 188 (1.6%) CVS cases (total 4.6%). No scorable trophoblasts were recovered in 32 of 236 usable samples. Additionally, 158 low-risk pregnancies not undergoing CVS/amniocentesis showed normal results in 133 cases. Seven had aneuploidy results, and there were three likely pathogenic deletions/duplications, including one15q11-q13 deletion. CONCLUSION: Although the sample size is modest and statistically accurate measures of test performance are not possible, the Luna test detected aneuploidy and deletions/duplications based on concordance with CVS/amniocentesis.

Examining provider practice-level disparities in delivery outcomes among patients with a history of Cesarean Delivery.

BACKGROUND: Choosing whether to pursue a trial of labor after cesarean (TOLAC) or scheduled repeat cesarean delivery (SRCD) requires prenatal assessment of risks and benefits. Providers and patients play a central role in this process. However, the influence of provider-associated characteristics on delivery methods remains unclear. We hypothesized that different provider practice groups have different obstetric outcomes in patients with one prior cesarean delivery (CD). METHODS: This was a retrospective cohort study of deliveries between April 29, 2015 - April 29, 2020. Subjects were divided into three cohorts: SRCD, successful VBAC, and unsuccessful VBAC (patients who chose TOLAC but had a CD). Disparities were reviewed between five different obstetric provider practice groups, determined from a breakdown of different providers delivering at the study site during the study period. Proportional differences were examined using Chi-squared tests and logistic regression models. RESULTS: 1,439 deliveries were included in the study. There were significant proportional disparities between patients in the different groups. Specifically, patients from Group D were significantly more likely to undergo successful VBAC, while patients seeing a provider from Group A were more likely to deliver by SRCD. In our multivariate analysis of successful versus unsuccessful VBAC, patients from Group D had greater odds ratios of successful VBAC compared to Group A. Patients delivered by Group E had a significantly lower odds ratio of successful VBAC. CONCLUSION: This study suggests an association between provider practice groups and delivery outcomes among patients with one prior CD. These data contribute to a growing body of literature around patient choice in pregnancy and the interplay of patients and providers. These findings help to guide future investigations to improve outcomes among patients with a history of CD.

Preoperative Application of Chlorhexidine to Reduce Infection with Cesarean Delivery after Labor (PRACTICAL): A Randomized Clinical Trial.

OBJECTIVE: To evaluate whether use of both preoperative 2% chlorhexidine gluconate abdominal cloth and 4% chlorhexidine gluconate vaginal scrub is effective in reducing surgical site infections (SSIs) in patients undergoing cesarean delivery after labor. STUDY DESIGN: This is a single-center, randomized clinical trial in which patients were randomized 1:1 to receive 2% chlorhexidine gluconate cloth applied to the abdomen in addition to the application of 4% chlorhexidine gluconate vaginal scrub versus standard of care. The primary outcome was rate of SSIs, including endometritis, by 6 weeks postdelivery. The secondary outcomes were other wound complications (erythema at the operative site, skin separation, drainage, fever, hematoma, seroma) by 6 weeks postdelivery, hospital readmission for wound complications, and day of discharge after cesarean delivery. RESULTS: A total of 319 patients between September 2018 and February 2021 met eligibility criteria: 160 were randomized to the chlorhexidine gluconate abdominal cloth and vaginal scrub group and 159 were randomized to the standard of care group. The groups did not have significant differences in maternal demographic characteristics. Of the 302 (95%) individuals included in primary analysis, there was no statistically significant difference in SSI and endometritis rate by 6 weeks postdelivery (6.6% in chlorhexidine vs. 5.3% standard of care, p = 0.65). Secondary outcomes were also similar among the two groups. CONCLUSION: The combination of preoperative 2% chlorhexidine gluconate abdominal cloth and 4% chlorhexidine gluconate vaginal scrub does not appear to reduce the risk of SSI with cesarean delivery after trial of labor when compared with standard of care. KEY POINTS: · Preoperative chlorhexidine abdominal cloth/vaginal scrub does not decrease SSI in cesarean after labor.. · Preoperative chlorhexidine abdominal cloth/vaginal scrub does not decrease other wound complications in cesarean after labor.. · There was no difference in discharge day, 2-week or 6-week SSI rates..

Examining inequities in rates of undiagnosed HIV and rectal STIs in a large nationwide cohort study of sexual minority men.

OBJECTIVE: Sexual minority men (SMM) of colour are disproportionately impacted by HIV and bacterial STIs (bSTIs). To better understand within-group heterogeneity and differential risk factors by race and ethnicity, we sought to examine rates of undiagnosed HIV and rectal bSTI at the intersection of racial and ethnic identity with other sociodemographic factors. METHODS: We examined data from 8105 SMM conducting home-based self-testing at enrolment in a nationwide cohort study collected from November 2017 to August 2018. We conducted analyses stratified by racial and ethnic groups to examine within-group (ie, subgroup) unadjusted rates of HIV and rectal bSTI infection across a range of characteristics. RESULTS: Rates of undiagnosed HIV were highest among Black (4.3%, n=39) and Latino (2.4%, n=38) SMM, with lower rates among those identified as multiracial (1.6%, n=15), white (1.3%, n=56) and other races (1.3%, n=6). Across the stratified analyses of HIV infection, 15 significant associations emerged showing that age, region, insurance type, sexual positioning and incarceration history had differential impacts across racial and ethnic groups. In particular, private and public insurance were protective against HIV for white but not Black and Latino SMM, and incarceration was associated with substantially higher rates of HIV infection for Black and Latino SMM relative to white SMM. We found significant co-occurrence of HIV and bSTI rates for participants who identified as Latino (OR=7.5, 95% CI 2.12 to 26.54), white (OR=3.19, 95% CI 1.14 to 8.98) and multiracial (OR=5.5, 95% CI 1.08 to 27.90), but not those who identified as Black (OR=0.82, 95% CI 0.10 to 6.56) or other races (OR=3.56 95% CI 0.31 to 40.80). CONCLUSIONS: Stratified analyses showed differential rates of HIV infection at the intersection of racial and ethnic groups with other characteristics, particularly insurance status and incarceration history, pointing to structural inequities rather than individual behaviours underlying disproportionately high rates of HIV for Black and Latino SMM.

Leveraging Technology to Blend Large-Scale Epidemiologic Surveillance With Social and Behavioral Science Methods: Successes, Challenges, and Lessons Learned Implementing the UNITE Longitudinal Cohort Study of HIV Risk Factors Among Sexual Minority Men in the United States.

The use of digital technologies to conduct large-scale research with limited interaction (i.e., no in-person contact) and objective endpoints (i.e., biological testing) has significant potential for the field of epidemiology, but limited research to date has been published on the successes and challenges of such approaches. We analyzed data from a cohort study of sexual minority men across the United States, collected using digital strategies during a 10-month period from 2017 to 2018. Overall, 113,874 individuals were screened, of whom 26,000 were invited to the study, 10,691 joined the study, and 7,957 completed all enrollment steps, including return of a human immunodeficiency virus-negative sample. We examined group differences in completion of the steps towards enrollment to inform future research and found significant differences according to several factors, including age and race. This study adds to prior work to provide further proof-of-concept for this limited-interaction, technology-mediated methodology, highlighting some of its strengths and challenges, including rapid access to more diverse populations but also potential for bias due to differential enrollment. This method has strong promise, and future implementation research is needed to better understand the roles of burden, privacy, access, and compensation, to enhance representativeness and generalizability of the data generated.

The Effect of Implicit Bias on the OB/GYN Residency Application Process.

Background Medical students from racially minoritized backgrounds receive negative evaluations more frequently, possibly from implicit bias. Objective To determine if a preference for White applicants over Asian and Black applicants exists among resident and attending reviewers of obstetrics and gynecology (OB/GYN) residency applications. Methods In 2021, we sampled academic OB/GYN physicians from 6 academic institutions to randomly receive questionnaire form A or B, each containing 4 contrived Electronic Residency Application Service profiles stratified by United States Medical Licensing Examination scores; institutions attended; and strength of recommendation letters into top-, mid-, and low-tiers. Form A applicants were White top-tier, White mid-tier without resilience, Asian mid-tier with resilience, and White low-tier. Form B applicants were Black top-tier, Asian mid-tier without resilience, White mid-tier with resilience, and White low-tier applicants. Both questionnaires' profiles were identical except for applicants' names and races. The primary outcome was participants' rankings of applicants from most to least desirable. Baseline characteristics of participants were compared with chi-square tests. Rankings were compared using generalized estimating equations to calculate the odds ratio (significance P<.05). Results One hundred and ninety-one were invited to participate; 109 participants started the questionnaire, and 103 ranked applicants (response rate 54%). Fifty-three participants completed form A, and 56 completed form B. No significant differences were found in participants' demographics. Participants frequently ranked White applicants significantly more highly than Black applicants (-3.3, 95% CI -3.5, -3.1) and Asian applicants (-3.3, 95% CI -3.5, -3.1). Conclusions Despite identical qualifications, a stronger preference for White applicants over Black or Asian applicants was found.

Implementation of an Enhanced Prenatal Checklist to Increase Rates of Counseling of Prenatal Fetal Aneuploidy Testing.

Aim This study aims to assess the effect of implementing an enhanced prenatal genetic checklist to guide the provider's discussion on both screening and diagnostic options for fetal aneuploidy testing at the initial prenatal visit. Methods A retrospective quality improvement (QI) project was performed at a single, large, urban academic medical center. The implementation of this project was prospective; however, data was examined retrospectively after the QI initiative was implemented for three months. Patients were included if they were less than 24 weeks gestational age with a live intrauterine gestation at their initial obstetric (OB) visit. Patients less than 18 years old at the initial OB visit were excluded. The results were analyzed using the statistical software R. Chi-squared tests were used to examine proportional differences between the pre- and post-intervention groups with respect to demographic and clinical characteristics and documented genetic counseling discussions. Results A total of 416 patients were included in the final cohort. As measured by documentation, the rate of discussion of diagnostic prenatal genetic testing increased significantly from the pre-intervention proportion of 54% to the post-intervention proportion of 72% (p < 0.001). In the subgroup analysis of patients with advanced maternal age, the rate of discussion of diagnostic prenatal genetic testing increased significantly from the pre-intervention proportion of 53% to the post-intervention proportion of 83% (p = 0.003), and the rate of genetics counseling referrals made at the initial prenatal visit increased significantly from 4% pre-intervention to 38% post-intervention (p < 0.001). Conclusions The use of an enhanced prenatal genetic checklist led to increased discussion of diagnostic fetal aneuploidy testing and increased rates of referral to genetics counseling.

Social disparities in delivery choice among patients with history of cesarean.

OBJECTIVE: Given the call to reduce rates of non-medically indicated cesarean deliveries (CDs) by encouraging trials of labor after cesarean (TOLAC), this study looks at social characteristics of patients choosing a TOLAC versus a scheduled repeat cesarean delivery (SRCD) to determine disparities regarding delivery method choice. METHODS: This was a retrospective cohort study of patients with a history of one CD between April 29, 2015-April 29, 2020. Patients were divided based on type of delivery chosen at admission. Chi-squared tests examined proportional differences between groups and logistic regression models examined odd ratios of choosing TOLAC versus SRCD according to socially dependent categories including race/ethnicity, health insurance, pre-pregnancy body mass index, and Social Vulnerability Index (SVI). RESULTS: 1,983 patients were included. Multivariable logistic regression models revealed that patients with a high SVI (reference: low/medium SVI) (AOR 2.0, CI: 1.5, 2.5), self-identified as Black/ African American (AOR: 2.4, CI: 1.6, 3.6) or Hispanic/Latina (AOR: 2.0, CI: 1.4, 2.8) (reference: White), had public insurance (reference: private insurance) (AOR: 3.7, CI: 2.8, 5.0), and who had an obese BMI (reference: non-obese BMI) were more likely to opt for a TOLAC rather than SRCD. CONCLUSION: These findings demonstrate differences in delivery method preferences. Specifically, more disadvantaged patients are more likely to choose TOLAC, suggesting that social and economic factors may play a role in delivery preferences. These findings have implications for improving individualized counselling and engaging in shared decision-making around mode of delivery.

Is There Utility in Transvaginal Cervical Length Surveillance After Cerclage Placement for the Prediction of Spontaneous Preterm Birth?

INTRODUCTION: Transvaginal cervical length (TVCL) surveillance post-transvaginal cerclage placement is not universally performed, despite the correlated risk of short TVCL with spontaneous preterm birth (sPTB). This study evaluated if patients with a TVCL <2.5 cm after cerclage placement had higher odds of sPTB than those with a TVCL ≥2.5 cm after cerclage placement. METHODS: This retrospective cohort study included patients with a singleton, non-anomalous gestation with a transvaginal cerclage who had TVCL surveillance post-cerclage placement. The primary outcome was the odds of sPTB among patients with TVCL <2.5 cm vs TVCL ≥2.5 cm after cerclage placement. Transvaginal cerclage placement indications included history indicated, physical exam indicated, and ultrasound indicated. Outcomes were assessed using univariate and multivariate analysis while adjusting for progesterone use, TVCL before cerclage placement, and cerclage indication. RESULTS: The analysis included 210 patients, and the sPTB rate was 46.7%. Those with sPTB underwent cerclage placement at later gestational ages, had higher rates of exam-indicated cerclage, and were more likely to be prescribed vaginal progesterone. Patients with a TVCL of <2.5 cm after cerclage placement did not have significantly increased odds of sPTB (OR: 2.8, 95% CI: 0.9-8.7, p=0.07); however, patients with a TVCL <2.0 cm had significantly increased odds of sPTB (OR: 6.3, 95% CI: 2.2-18.8, p<0.001). CONCLUSION: In patients with transvaginal cerclage, there does not appear to be increased odds of sPTB with TVCL <2.5 cm after cerclage placement; however, there does appear to be an increased odds of sPTB in patients with a TVCL of <2.0 cm after cerclage placement.

Examining the predictive value of fetal fraction on hypertensive disorders of pregnancy.

BACKGROUND: Cell-free fetal DNA (cffDNA) screening is routinely performed in pregnancy. Abnormal fetal fraction has been associated with adverse pregnancy outcomes, including hypertensive disorders of pregnancy, which are associated with severe maternal and neonatal morbidity and mortality. OBJECTIVE: This study examined whether abnormal fetal fraction, defined in this study as fetal fraction either <6 or >15 on the basis of restricted-cubic-spline-plot within our study population, was associated with HDP in a retrospective sample, as well as whether fetal fraction improves the prediction of hypertensive disorders of pregnancy (HDP). We hypothesized that abnormal fetal fraction would be associated with HDP and that adding fetal fraction to a model would significantly improve its strength to predict HDP. STUDY DESIGN: This was a retrospective cohort study of 729 patients delivering singleton, non-anomalous pregnancies with conclusive cffDNA screening. The primary outcome was HDP. Logistic regression models tested associations between fetal fraction and HDP. We evaluated the impact of including fetal fraction on the prediction of hypertensive disorders of pregnancy (HDP) by comparing the area under the receiver operating characteristic (ROC) curve (AUC) between predictive models with and without fetal fraction. RESULTS: Among the study sample, there was an HDP rate of 11.5 %. Abnormal fetal fraction was defined as <6 % percentile and >15 %, HDP incidence was significantly higher in patients with fetal fraction <6 % compared to patients with fetal fraction in normal range (fetal fraction 6-15 %) (19.5 % vs 10.7 %, p = 0.006 on post hoc comparison). Model 1 had one predictor (fetal fraction) with an AUC of 0.59, Model 2 had three predictors (BMI, nulliparity, history of HDP) with an AUC of 0.71, and Model 3 had four predictors (BMI, nulliparity, history of HDP, and fetal fraction) with an AUC of 0.73. Models 2 and 3 were not significantly different (p = 0.18). CONCLUSIONS: More patients who developed HDP had low fetal fraction and fewer patients who developed HDP had high fetal fraction compared to those patients who did not develop HDP. Based on results from multivariable regression models, we cannot conclude that fetal fraction improves HDP prediction. However, developing standardized values for abnormal fetal fraction may be clinically useful.

Adjusting models to better predict obstetric anal sphincter injury (OASIS) in forceps-assisted vaginal deliveries: A retrospective cross-sectional trial.

OBJECTIVE: Obesity and maternal age are increasing among pregnant patients. The understood effect of body mass index (BMI), advanced maternal age (AMA), and second stage of labor on obstetric anal sphincter injury (OASIS) at delivery is varied. The objective of this study was to assess whether incorporating BMI, second stage of labor length, and AMA into a model for predicting OASIS among forceps-assisted vaginal deliveries (FAVD) had a higher predictivity value compared to models without these additions. METHOD: This was an IRB-approved retrospective cohort study of singleton gestations who underwent a FAVD between 2017 and 2021. The primary outcome was prediction of OASIS via established models versus models including the addition of new predictive factors. RESULTS: A total of 979 patients met inclusionary criteria and were included in the final analysis. 20.4% of patients had an OASIS laceration, 11.3% of neonates had NICU admissions, 23.7% had a composite all neonatal outcome, and 8% had a composite subgaleal/cephalohematoma outcome. Comparisons of known factors that predict OASIS (nulliparity, race, episiotomy status) to known factors with additional predictors (BMI, AMA, and length of second stage in labor) were explored. After comparing each model's AUC to one another (a total of 3 comparisons made), there was no statistically significant difference between the models (all P > 0.62). CONCLUSION: Including BMI, AMA, and second stage of labor length does not improve the predictivity of OASIS in patients with successful FAVD. These factors should not impact a provider's decision to perform a FAVD when solely considering increased odds of OASIS.

Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

BACKGROUND: Placenta accreta spectrum is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in the outcomes of patients with placenta accreta spectrum. OBJECTIVE: This study aimed to investigate health inequities in maternal and neonatal outcomes of pregnancies with placenta accreta spectrum. STUDY DESIGN: This multicentered retrospective cohort study included patients with a histopathological diagnosis of placenta accreta spectrum at 4 regional perinatal centers between January 1, 2013, and June 30, 2022. Maternal race and ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. The primary outcome was a composite adverse maternal outcome: transfusion of ≥4 units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury, or mortality. The secondary outcomes were a composite adverse neonatal outcome (Apgar score of <7 at 1 minute, morbidity, or mortality), gestational age at placenta accreta spectrum diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race and ethnicity with maternal and neonatal outcomes. RESULTS: A total of 408 pregnancies with placenta accreta spectrum were included. In 218 patients (53.0%), the diagnosis of placenta accreta spectrum was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, body mass index, income, and parity, there was no difference in composite adverse maternal outcomes among the racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team, and cesarean hysterectomy were similar among groups. CONCLUSION: In our multicentered placenta accreta spectrum cohort, race and ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis, or planned multidisciplinary care. This study hypothesized that a comparable incidence of individual risk factors for perinatal morbidity and geographic proximity reduces potential inequities that may exist in a larger population.