A Multi-Site Study to Develop and Validate First Trimester, Circulating Microparticle Biomarkers for Tiered Risk Stratification of Spontaneous Preterm Birth in Nulliparas.

BACKGROUND: Despite much research, advances in early prediction of spontaneous preterm birth (sPTB) has been slow. The evolving field of circulating microparticle (CMP) biology may identify novel blood-based, and clinically useful, biomarkers. OBJECTIVE: To test the ability of a previously identified, 7-marker set of CMP-derived proteins from the first trimester of pregnancy, in the form of an in vitro diagnostic multivariate index assay (IVDMIA), to stratify pregnant patients according to their risk for sPTB. STUDY DESIGN: We employed a previously validated set of CMP protein biomarkers, utilizing mass spectrometry assays and a nested case-control design in a subset of participants from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). We evaluated these biomarkers in the form of an IVDMIA to predict risk for sPTB at different gestational ages. Plasma samples collected at 9- to 13-weeks' gestation were analyzed. The IVDMIA assigned subjects to one of three sPTB risk categories: low risk (LR), moderate risk (MR), or high risk (HR). Independent validation on a set-aside set confirmed the IVDMIA's performance in risk stratification. RESULTS: Samples from 400 participants from the nuMoM2b cohort were used for the study; of these, 160 delivered <37 weeks and 240 delivered at term. Through Monte Carlo simulation in which the validation results were adjusted based on actual weekly sPTB incidence rates in the nuMoM2b cohort, the IVDMIA stratifications demonstrated statistically significant differences among the risk groups in time-to-event (birth) analysis (p < 0.0001). The incidence-rate adjusted cumulative risks of sPTB at ≤ 32 weeks' gestation were 0.4%, 1.6%, and 7.5%, respectively for the LR, MR, and HR groups, respectively. Compared to the LR group, the corresponding risk ratios (RR) of the IVDMIA assigned MR and HR group were 4.25 (95% CI 2.2 to 7.9) and 19.92 (95% CI 10.4 to 37.4), respectively. CONCLUSION: A first trimester CMP protein biomarker panel can be used to stratify risk for sPTB at different gestational ages. Such a multi-tiered stratification tool could be used to assess risk early in pregnancy to enable timely clinical management and interventions, and, ultimately, to enable the development of tailored care pathways for sPTB prevention.

COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast.

SARS-CoV-2 infection and the resulting coronavirus disease (COVID-19) complicate pregnancies as the result of placental dysfunction which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests maternal response to infection is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs) are altered by COVID-19 during pregnancy and contribute to placental dysfunction. To examine this, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their functional effect on trophoblast cells in vitro. We found the timing of infection is a major determinant of the effect of COVID-19 on circulating EVs. Additionally, we found differentially expressed EV mRNA cargo in COVID-19 groups compared to Controls that regulates the differential gene expression induced by COVID-19 in the placenta. In vitro exposure of trophoblasts to EVs isolated from patients with an active infection, but not EVs isolated from Controls, reduced key trophoblast functions including hormone production and invasion. This demonstrates circulating EVs from subjects with an active infection disrupt vital trophoblast function. This study determined that COVID-19 has a long-lasting effect on circulating EVs and circulating EVs are likely to participate in the placental dysfunction induced by COVID-19.

Are Racial Disparities in Cesarean Due to Differences in Labor Induction Management?

OBJECTIVE: While there are known racial disparities in cesarean delivery (CD) rates, the exact etiologies for these disparities are multifaceted. We aimed to determine if differences in induction of labor (IOL) management contribute to these disparities. STUDY DESIGN: This retrospective cohort study evaluated all nulliparous patients with an unfavorable cervix and intact membranes who underwent IOL of a term, singleton gestation at a single institution from October 1, 2018, to September 30, 2020. IOL management was at clinician discretion. Patients were classified as Black, Indigenous, and People of Color (BIPOC) or White based on self-report. Overall rates of CD were compared for BIPOC versus White race. Chart review then evaluated various IOL management strategies as possible contributors to differences in CD by race. RESULTS: Of 1,261 eligible patients, 915 (72.6%) identified as BIPOC and 346 (27.4%) as White. BIPOC patients were more likely to be younger (26 years interquartile range (IQR) [22-30] vs. 32 years IQR [30-35], p < 0.001) and publicly insured (59.1 vs. 9.9%, p < 0.001). Indication for IOL and modified Bishop score also differed by race (p < 0.001; p = 0.006). There was 40% increased risk of CD for BIPOC patients, even when controlling for confounders (30.7 vs. 21.7%, p = 0.001; adjusted relative risk (aRR) 1.41, 95% confidence interval (CI) [1.06-1.86]). Despite this difference in CD, there were no identifiable differences in IOL management prior to decision for CD by race. Specifically, there were no differences in choice of cervical ripening agent, cervical dilation at or time to amniotomy, use and maximum dose of oxytocin, or dilation at CD. However, BIPOC patients were more likely to undergo CD for fetal indications and failed IOL. CONCLUSION: BIPOC nulliparas are 40% more likely to undergo CD during IOL than White patients within our institution. These data suggest that the disparity is not explained by differences in IOL management prior to cesarean, indicating that biases outside of induction management may be important to target to reduce CD disparities. KEY POINTS: · The etiologies for racial disparities in cesarean are likely multifaceted.. · In this work, there were no differences by race in measures of labor induction management.. · Biases outside of induction management during labor may be targeted to reduce CD disparities..

Breastfeeding Initiation, Duration, and Associated Factors Among People With Hepatitis C Virus Infection.

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection. METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and multivariable analyses were performed. RESULTS: Overall, 579 individuals (75.0% of participants in the parent study) were included. Of those, 362 (62.5%) initiated breastfeeding or provided breast milk to their infants, with a median duration of breastfeeding of 1.4 months (interquartile range 0.5-6.0). People with HCV viremia , defined as a detectable viral load at any point during pregnancy, were less likely to initiate breastfeeding than those who had an undetectable viral load (59.4 vs 71.9%, adjusted odds ratio [aOR] 0.61, 95% CI, 0.41-0.92). People with private insurance were more likely to initiate breastfeeding compared with those with public insurance or no insurance (80.0 vs 60.1%; aOR 2.43, 95% CI, 1.31-4.50). CONCLUSION: Although HCV seropositivity is not a contraindication to breastfeeding regardless of viral load, rates of breastfeeding initiation were lower among people with HCV viremia than among those with an undetectable viral load. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01959321 .

Community-level social determinants of health and pregestational and gestational diabetes.

BACKGROUND: Individual adverse social determinants of health are associated with increased risk of diabetes in pregnancy, but the relative influence of neighborhood or community-level social determinants of health is unknown. OBJECTIVE: This study aimed to determine whether living in neighborhoods with greater socioeconomic disadvantage, food deserts, or less walkability was associated with having pregestational diabetes and developing gestational diabetes. STUDY DESIGN: We conducted a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. Home addresses in the first trimester were geocoded at the census tract level. The exposures (modeled separately) were the following 3 neighborhood-level measures of adverse social determinants of health: (1) socioeconomic disadvantage, defined by the Area Deprivation Index and measured in tertiles from the lowest tertile (ie, least disadvantage [T1]) to the highest (ie, most disadvantage [T3]); (2) food desert, defined by the United States Department of Agriculture Food Access Research Atlas (yes/no by low income and low access criteria); and (3) less walkability, defined by the Environmental Protection Agency National Walkability Index (most walkable score [15.26-20.0] vs less walkable score [<15.26]). Multinomial logistic regression was used to model the odds of gestational diabetes or pregestational diabetes relative to no diabetes as the reference, adjusted for age at delivery, chronic hypertension, Medicaid insurance status, and low household income (<130% of the US poverty level). RESULTS: Among the 9155 assessed individuals, the mean Area Deprivation Index score was 39.0 (interquartile range, 19.0-71.0), 37.0% lived in a food desert, and 41.0% lived in a less walkable neighborhood. The frequency of pregestational and gestational diabetes diagnosis was 1.5% and 4.2%, respectively. Individuals living in a community in the highest tertile of socioeconomic disadvantage had increased odds of entering pregnancy with pregestational diabetes compared with those in the lowest tertile (T3 vs T1: 2.6% vs 0.8%; adjusted odds ratio, 2.52; 95% confidence interval, 1.41-4.48). Individuals living in a food desert (4.8% vs 4.0%; adjusted odds ratio, 1.37; 95% confidence interval, 1.06-1.77) and in a less walkable neighborhood (4.4% vs 3.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.04-1.71) had increased odds of gestational diabetes. There was no significant association between living in a food desert or a less walkable neighborhood and pregestational diabetes, or between socioeconomic disadvantage and gestational diabetes. CONCLUSION: Nulliparous individuals living in a neighborhood with higher socioeconomic disadvantage were at increased odds of entering pregnancy with pregestational diabetes, and those living in a food desert or a less walkable neighborhood were at increased odds of developing gestational diabetes, after controlling for known covariates.

Desirability of outcome ranking for obstetrical trials: illustration and application to the ARRIVE trial.

BACKGROUND: In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently. OBJECTIVE: This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal-perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). STUDY DESIGN: This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. RESULTS: All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51-54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51-53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. CONCLUSION: Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care.

Validation of Three Models for Prediction of Blood Transfusion during Cesarean Delivery Admission.

OBJECTIVE: Prediction of blood transfusion during delivery admission allows for clinical preparedness and risk mitigation. Although prediction models have been developed and adopted into practice, their external validation is limited. We aimed to evaluate the performance of three blood transfusion prediction models in a U.S. cohort of individuals undergoing cesarean delivery. STUDY DESIGN: This was a secondary analysis of a multicenter randomized trial of tranexamic acid for prevention of hemorrhage at time of cesarean delivery. Three models were considered: a categorical risk tool (California Maternal Quality Care Collaborative [CMQCC]) and two regression models (Ahmadzia et al and Albright et al). The primary outcome was intrapartum or postpartum red blood cell transfusion. The CMQCC algorithm was applied to the cohort with frequency of risk category (low, medium, high) and associated transfusion rates reported. For the regression models, the area under the receiver-operating curve (AUC) was calculated and a calibration curve plotted to evaluate each model's capacity to predict receipt of transfusion. The regression model outputs were statistically compared. RESULTS: Of 10,785 analyzed individuals, 3.9% received a red blood cell transfusion during delivery admission. The CMQCC risk tool categorized 1,970 (18.3%) individuals as low risk, 5,259 (48.8%) as medium risk, and 3,556 (33.0%) as high risk with corresponding transfusion rates of 2.1% (95% confidence interval [CI]: 1.5-2.9%), 2.2% (95% CI: 1.8-2.6%), and 7.5% (95% CI: 6.6-8.4%), respectively. The AUC for prediction of blood transfusion using the Ahmadzia and Albright models was 0.78 (95% CI: 0.76-0.81) and 0.79 (95% CI: 0.77-0.82), respectively (p = 0.38 for difference). Calibration curves demonstrated overall agreement between the predicted probability and observed likelihood of blood transfusion. CONCLUSION: Three models were externally validated for prediction of blood transfusion during cesarean delivery admission in this U.S. COHORT: Overall, performance was moderate; model selection should be based on ease of application until a specific model with superior predictive ability is developed. KEY POINTS: · A total of 3.9% of individuals received a blood transfusion during cesarean delivery admission.. · Three models used in clinical practice are externally valid for blood transfusion prediction.. · Institutional model selection should be based on ease of application until further research identifies the optimal approach..

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

Comparing population-based fetal growth standards in a US cohort.

BACKGROUND: No fetal growth standard is currently endorsed for universal use in the United States. Newer standards improve upon the methodologic limitations of older studies; however, before adopting into practice, it is important to know how recent standards perform at identifying fetal undergrowth or overgrowth and at predicting subsequent neonatal morbidity or mortality in US populations. OBJECTIVE: To compare classification of estimated fetal weight that is <5th or 10th percentile or >90th percentile by 6 population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. STUDY DESIGN: We used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be cohort, which recruited nulliparous women in the first trimester at 8 US clinical centers (2010-2014). Estimated fetal weight was obtained from ultrasounds at 16 to 21 and 22 to 29 weeks of gestation (N=9534 women). We calculated rates of fetal growth restriction (estimated fetal weight <5th and 10th percentiles; fetal growth restriction<5 and fetal growth restriction<10) and estimated fetal weight >90th percentile (estimated fetal weight>90) from 3 large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization-sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific and unified, and the historic Hadlock reference. To determine whether differential classification of fetal growth restriction or estimated fetal weight >90 among standards was clinically meaningful, we then compared area under the curve and sensitivity of each standard to predict small for gestational age or large for gestational age at birth, composite perinatal morbidity and mortality alone, and small for gestational age or large for gestational age with composite perinatal morbidity and mortality. RESULTS: The standards classified different proportions of fetal growth restriction and estimated fetal weight>90 for ultrasounds at 16 to 21 (visit 2) and 22 to 29 (visit 3) weeks of gestation. At visit 2, the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific, World Health Organization sex-specific and World Health Organization-combined identified similar rates of fetal growth restriction<10 (8.4%-8.5%) with the other 2 having lower rates, whereas Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific identified the highest rate of fetal growth restriction<5 (5.0%) compared with the other references. At visit 3, World Health Organization sex-specific classified 9.2% of fetuses as fetal growth restriction<10, whereas the other 5 classified a lower proportion as follows: World Health Organization-combined (8.4%), Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific (7.7%), INTERGROWTH (6.2%), Hadlock (6.1%), and Eunice Kennedy Shriver National Institute of Child Health and Human Development unified (5.1%). INTERGROWTH classified the highest (21.3%) as estimated fetal weight>90 whereas Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset fetal growth restriction, World Health Organization had the highest area under the curve of 0.53 (95% confidence interval, 0.51-0.53) for fetal growth restriction<10 at 22 to 29 weeks of gestation, but the areas under the curve were similar among standards (0.52). Sensitivity was generally low across standards (22.7%-29.1%). When predicting small for gestational age birthweight with composite neonatal morbidity or mortality, for fetal growth restriction<10 at 22 to 29 weeks of gestation, World Health Organization sex-specific had the highest area under the curve (0.64; 95% confidence interval, 0.60-0.67) and INTERGROWTH had the lowest (area under the curve=0.58; 95% confidence interval 0.55-0.62), though all standards had low sensitivity (7.0%-9.6%). CONCLUSION: Despite classifying different proportions of fetuses as fetal growth restriction or estimated fetal weight>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as fetal growth restriction or estimated fetal weight>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for fetal growth restriction or cesarean delivery for suspected large for gestational age. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying the risk of morbidity or mortality.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

A Simple Intervention to Improve Equity in Obstetric Research.

Introduction: To evaluate if a simple intervention, including formation of a Research Equity Committee and a dashboard detailing study approach and enrollment statistics by race, could improve equitable inclusion in obstetric research. Methods: Our intervention had four components: (1) research personnel submitted dashboards every 3 months to the Research Equity Committee; (2) approach and enrollment by race were compared with expected racial breakdown; (3) study teams with rates of approach and/or enrollment of black birthing people below goal met with the committee for root cause analysis (RCA) and action planning; (4) all dashboards, RCAs, and action plans were presented at 3-month intervals. We prospectively evaluated the impact of this intervention on the inclusion of self-reported black birthing people in actively enrolling obstetrical studies at an academic university from July 2021 to June 2022. Results: Seven qualifying prospective studies submitted 23 equity dashboards, which encompassed 692 patients. Six RCAs and action planning were held. Themes of developed action plans included: (1) standardizing how, when, and which patients to approach to eliminate approach bias, (2) standardized scripts for patient recruitment, and (3) study expansion to more diverse clinics. All four studies that underwent an RCA demonstrated improvements after the intervention; however, only one study demonstrated a statistically significant increase in approach (p=0.002) and enrollment (p=0.02) of black birthing people across the study period. Discussion and Health Equity Implications: A simple intervention can improve approach and enrollment of black birthing people in obstetric research.

Neighborhood Socioeconomic Disadvantage and Abnormal Birth Weight.

OBJECTIVE: To examine whether exposure to community or neighborhood socioeconomic disadvantage as measured by the ADI (Area Deprivation Index) is associated with risk of abnormal birth weight among nulliparous individuals with singleton gestations. METHODS: This was a secondary analysis from the prospective cohort NuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be). Participant addresses at cohort enrollment between 6 and 13 weeks of gestation were geocoded at the Census tract level and linked to the 2015 ADI. The ADI, which incorporates the domains of income, education, employment, and housing quality into a composite national ranking of neighborhood socioeconomic disadvantage, was categorized by quartiles (quartile 1, least disadvantaged, reference; quartile 4, most disadvantaged). Outcomes were large for gestational age (LGA; birth weight at or above the 90th percentile) and small for gestational age (SGA; birth weight below the 10th percentile) compared with appropriate for gestational age (AGA; birth weight 10th-90th percentile) as determined with the 2017 U.S. natality reference data, standardized for fetal sex. Multinomial logistic regression models were adjusted for potential confounding variables. RESULTS: Of 8,983 assessed deliveries in the analytic population, 12.7% (n=1,143) were SGA, 8.2% (n=738) were LGA, and 79.1% (n=7,102) were AGA. Pregnant individuals living in the highest ADI quartile (quartile 4, 17.8%) had an increased odds of delivering an SGA neonate compared with those in the lowest referent quartile (quartile 1, 12.4%) (adjusted odds ratio [aOR] 1.32, 95% CI 1.09-1.55). Pregnant individuals living in higher ADI quartiles (quartile 2, 10.3%; quartile 3, 10.7%; quartile 4, 9.2%) had an increased odds of delivering an LGA neonate compared with those in the lowest referent quartile (quartile 1, 8.2%) (aOR: quartile 2, 1.40, 95% CI 1.19-1.61; quartile 3, 1.35, 95% CI 1.09-1.61; quartile 4, 1.47, 95% CI 1.20-1.74). CONCLUSION: Neonates of nulliparous pregnant individuals living in U.S. neighborhoods with higher area deprivation were more likely to have abnormal birth weights at both extremes.

Sodium intake and the development of hypertensive disorders of pregnancy.

BACKGROUND: In nonpregnant populations, sodium intake has been associated with the development of chronic hypertension, and sodium restriction has been identified as a strategy to reduce blood pressure. Data regarding the relationship between sodium intake and the development of hypertensive disorders of pregnancy are limited and conflicting. OBJECTIVE: This study aimed to assess the association between daily periconceptional sodium intake and the risk of hypertensive disorders of pregnancy. STUDY DESIGN: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study. Individuals with nonanomalous, singleton pregnancies who completed food frequency questionnaires with recorded sodium intake in the 3 months before pregnancy were included in the analysis. Individuals whose pregnancies did not progress beyond 20 weeks of gestation were excluded from the analysis. Sodium intake was categorized as low (<2 g per day), medium (2 to <3 g per day), or high (≥3 g per day), based on thresholds used in the nonpregnant population. The primary outcome was the development of a new-onset hypertensive disorder of pregnancy, including gestational hypertension; preeclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; superimposed preeclampsia; or eclampsia. Bivariable analyses were performed using Kruskal-Wallis and chi-square tests. Poisson regression was used to estimate adjusted incidence risk ratios with 95% confidence intervals after controlling for potentially confounding factors. RESULTS: Among 7458 individuals included in this analysis, 2336 (31%) reported low sodium intake, 2792 (37%) reported medium sodium intake, and 2330 (31%) reported high sodium intake. Individuals with high sodium intake were more likely to have chronic hypertension, to use tobacco, and to be living with obesity. The risk of developing a hypertensive disorder of pregnancy was similar among groups (medium vs low adjusted incidence risk ratio: 1.10 [95% confidence interval, 0.94-1.28]; high vs low adjusted incidence risk ratio: 1.17 [95% confidence interval, 1.00-1.37]). There was no difference in neonatal outcomes by sodium intake, including preterm birth, small-for-gestational-age neonate, and admission to the neonatal intensive care unit. CONCLUSION: Sodium intake was not associated with the risk of developing a hypertensive disorder of pregnancy. This lack of association contrasts with that between sodium intake and hypertension in the nonpregnant state and may reflect differences in the pathophysiology underlying pregnancy- vs non-pregnancy-related hypertensive disorders.

Risk Factors for Perinatal Transmission of Hepatitis C Virus.

OBJECTIVE: To estimate the rate of perinatal transmission of hepatitis C virus (HCV) infection, to identify risk factors for perinatal transmission of HCV infection, and to determine the viremic threshold for perinatal transmission. METHODS: This was a prospective, multicenter, observational study of pregnant individuals at less than 24 weeks of gestation screened for HCV infection from 2012 to 2018 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Individuals found to be HCV antibody-positive were followed throughout pregnancy. Children were followed for evidence of perinatal transmission at 2-6 months (HCV RNA testing) and at 18-24 months (HCV RNA and antibody testing) of life. The primary outcome was perinatal transmission, defined as positive test results at either follow-up time point. RESULTS: A total of 109,379 individuals were screened for HCV infection. Of the 1,224 participants who screened positive, 772 (63.1%) enrolled and 432 of those 772 (56.0%) had data available to assess primary outcome. The overall rate of perinatal transmission was 6.0% (26/432, 95% CI 4.0-8.7%). All children with HCV infection were born to individuals with demonstrable viremia. In viremic participants (n=314), the perinatal transmission rate was 8.0% (95% CI 5.2-11.5%). Risk factors for perinatal transmission included HCV RNA greater than 106 international units/mL (adjusted odds ratio [aOR] 8.22, 95% CI 3.16-21.4) and vaginal bleeding reported at any time before delivery (aOR 3.26, 95% CI 1.32-8.03). A viremic threshold for perinatal transmission could not be established. CONCLUSION: Perinatal transmission of HCV infection was limited to viremic individuals. High viral loads and antepartum bleeding were associated with perinatal transmission.

An innovative sequential mixed-methods approach to evaluating clinician acceptability during implementation of a standardized labor induction protocol.

BACKGROUND: Implementation outcomes, including acceptability, are of critical importance in both implementation research and practice. The gold standard measure of acceptability, Acceptability of Intervention Measure (AIM), skews positively with a limited range. In an ongoing hybrid effectiveness-implementation trial, we aimed to evaluate clinician acceptability of induction standardization. Here, we describe an innovative mixed-methods approach to maximize the interpretability of the AIM using a case study in maternal health. METHODS: In this explanatory sequential mixed methods study, we distributed the validated, 4-question AIM (total 4-20) to labor and delivery clinicians 6 months post-implementation at 2 sites (Site 1: 3/2021; Site 2: 6/2021). Respondents were grouped by total score into tertiles. The top ("High" Acceptability) and bottom ("Low" Acceptability) tertiles were invited to participate in a 30-minute semi-structured qualitative interview from 6/2021 to 10/2021 until thematic saturation was reached in each acceptability group. Participants were purposively sampled by role and site. Interviews were coded using an integrated approach, incorporating a priori attributes (Consolidated Framework for Implementation Research constructs) into a modified content analysis approach. RESULTS: 104 clinicians completed the initial survey; 24 were interviewed (12 "High" and 12 "Low" Acceptability). Median total AIM scores were 20/20 IQR[20-20] in the High and 12.5/20 IQR[11-14] in the Low Acceptability groups. In both groups, clinicians were enthusiastic about efforts to standardize labor induction, believing it reduces inter-clinician variability and improves equitable, evidence-based care. In the Low Acceptability group, clinicians stated the need for flexibility and consideration for patient uniqueness. Rarely, clinicians felt labor induction could not or should not be standardized, citing discomfort with medicalization of labor, and concerns with "bulldozing" the patient with interventions. Suggested strategies for overcoming negative sentiment included comprehensive clinician education, as well as involving patients as active participants in the protocol prenatally. CONCLUSIONS: This study utilized AIM in an innovative sequential mixed-methods approach to characterize clinician acceptability, which may be generalizable across implementation endeavors. By performing this work during a hybrid trial, implementation strategies to improve acceptability emerged (clinician education focusing on respect for flexibility; involving patients as active participants prenatally) for year 2, which will inform future multi-site work.