Preparing for Disease X: Ensuring Vaccine Equity for Pregnant Women in Future Pandemics.

Disease X represents a yet unknown human pathogen which has potential to cause a serious international epidemic or pandemic. The COVID-19 pandemic has illustrated that despite being at increased risk of severe disease compared with the general population, pregnant women were left behind in the development and implementation of vaccination, resulting in conflicting communications and changing guidance about vaccine receipt in pregnancy. Based on the COVID-19 experience, the COVAX Maternal Immunization Working Group have identified three key factors and five broad focus topics for consideration when proactively planning for a disease X pandemic, including 10 criteria for evaluating pandemic vaccines for potential use in pregnant women. Prior to any disease X pandemic, collaboration and coordination are needed to close the pregnancy data gap which is currently a barrier to gender equity in health innovation, which will aid in allowing timely access to life-saving interventions including vaccines for pregnant women and their infants.

IMPaCT: A Pilot Randomized Trial of an Intervention to Reduce Preterm Birth Among Non-Hispanic Black Patients at High Risk.

Introduction: Preterm birth is a major cause of neonatal morbidity and mortality rate. Non-Hispanic black patients disproportionately experience preterm birth and nonadherence to evidence-based preventive measures. Interventions tailored to non-Hispanic black birthing individuals (NHBBIs) that address barriers to preterm birth preventions are urgently needed. Methods: Together with a community-engaged multidisciplinary stakeholder group, we developed an intervention to improve adherence to preterm birth preventions among black pregnant patients with prior preterm birth. The intervention included the following: (1) preterm birth prevention education, (2) an employment navigation toolkit, and (3) encouragement text messages. We piloted the intervention by recruiting self-identified non-Hispanic black patients at or before 20 weeks of gestation with a prior preterm birth and randomizing them to the intervention or an active control. The primary outcomes were feasibility and acceptability. Our secondary outcomes were preliminary efficacy based on birth outcomes, patient experience, and pregnancy-specific anxiety (PSA). Descriptive statistics, analysis of verbatim survey responses, Wilcoxon signed rank, and Fisher's exact were used to describe and compare quantitative and qualitative data. Results: We identified 53 individuals who met the inclusion criteria, 35 were reachable remotely and 30 were enrolled and randomized. More than 80% (n=26) were retained throughout the study, and 100% of participants identified at least one intervention component as helpful. In this small pilot, there were no detectable differences in adherence to preterm birth preventive recommendations. No difference in preterm births, other pregnancy, or patient experience outcomes was detected between the intervention and active control participants. Discussion: The intervention is feasible and acceptable. Larger, appropriately powered studies are needed to assess whether the intervention will decrease PSA and reduce preterm birth. This trial was registered with ClinicalTrials.gov (NCT04933812).

OB/GYN Providers' Knowledge of Racial and Ethnic Reproductive Health Disparities.

OBJECTIVE: This study explores OB/GYN providers' knowledge about published health and healthcare disparities in women's reproductive health. METHOD: We collected demographic and health disparities knowledge information from OB/GYN providers who were members of ACOG District IV using an online survey (n = 483). We examined differences across groups using statistical tests and regression analyses in a structural equation modeling approach. RESULTS: Receiving disparities education was positively associated with higher self-reported disparities knowledge and disparities quiz performance (p < 0.05). African American/Black providers had higher quiz scores than their white counterparts, and providers varied in their levels of disparities knowledge across practice settings (p < 0.05). CONCLUSIONS: Differences in levels of knowledge of racial/ethnic disparities in health and healthcare outcomes among OB/GYN providers varied across race/ethnicity, practice context, and whether providers had received formal disparities education. Future research should explore these differences at a population level and develop interventions to improve health disparities education among OB/GYN providers.

Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Administration of corticosteroids to women at high risk for delivery in the late preterm period (34-36 weeks' gestation) improves short-term neonatal outcomes. The cost implications of this intervention are not known. Objective: To compare the cost-effectiveness of treatment with antenatal corticosteroids with no treatment for women at risk for late preterm delivery. Design, Setting, and Participants: This secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter randomized clinical trial of antenatal corticosteroids vs placebo in women at risk for late preterm delivery conducted from October 30, 2010, to February 27, 2015. took a third-party payer perspective. Maternal costs were based on Medicaid rates and included those of betamethasone, as well as the outpatient visits or inpatient stay required to administer betamethasone. All direct medical costs for newborn care were included. For infants admitted to the neonatal intensive care unit, comprehensive daily costs were stratified by the acuity of respiratory illness. For infants admitted to the regular newborn nursery, nationally representative cost estimates from the literature were used. Effectiveness was measured as the proportion of infants without the primary outcome of the study: a composite of treatment in the first 72 hours of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, supplemental oxygen with a fraction of inspired oxygen of 30% or more for 4 hours or more, and extracorporeal membrane oxygenation or mechanical ventilation. This secondary analysis was initially started in June 2016 and revision of the analysis began in May 2017. Exposures: Betamethasone treatment. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Costs were determined for 1426 mother-infant pairs in the betamethasone group (mean [SD] maternal age, 28.6 [6.3] years; 827 [58.0%] white) and 1395 mother-infant pairs in the placebo group (mean [SD] maternal age, 27.9 [6.2] years; 794 [56.9%] white). Treatment with betamethasone was associated with a total mean (SD) woman-infant-pair cost of $4681 ($5798), which was significantly less than the mean (SD) amount of $5379 ($8422) for women and infants in the placebo group (difference, $698; 95% CI, $186-$1257; P = .02). The Antenatal Late Preterm Steroids trial determined that betamethasone use is effective: respiratory morbidity decreased by 2.9% (95% CI, -0.5% to -5.4%). Thus, the cost-effectiveness ratio was -$23 986 per case of respiratory morbidity averted. Inspection of the bootstrap replications confirmed that treatment was the dominant strategy in 5000 samples (98.8%). Sensitivity analyses showed that these results held under most assumptions. Conclusions and Relevance: The findings suggest that antenatal betamethasone treatment is associated with a statistically significant decrease in health care costs and with improved outcomes; thus, this treatment may be an economically desirable strategy.

Induction of Labor versus Scheduled Cesarean in Morbidly Obese Women: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the costs, complication rates, and harm-benefit tradeoffs of induction of labor (IOL) compared to scheduled cesarean delivery (CD) in women with class III obesity. STUDY DESIGN: We conducted a cost analysis of IOL versus scheduled CD in nulliparous morbidly obese women. Primary outcomes were surgical site infection (SSI), chorioamnionitis, venous thromboembolism, blood transfusion, and readmission. Model outcomes were mean cost of each strategy, cost per complication avoided, and complication tradeoffs. We assessed the costs, complication rates, and harm-benefit tradeoffs of IOL compared with scheduled CD in women with class III obesity. RESULTS: A total of 110 patients underwent scheduled CD and 114 underwent IOL, of whom 61 (54%) delivered via cesarean. The group delivering vaginally experienced fewer complications. SSI occurred in 0% in the vaginal delivery group, 13% following scheduled cesarean, and 16% following induction then cesarean. In the decision model, the mean cost of induction was $13,349 compared with $14,575 for scheduled CD. Scheduled CD costs $9,699 per case of chorioamnionitis avoided, resulted in 18 cases of chorioamnionitis avoided per additional SSI and 3 cases of chorioamnionitis avoided per additional hospital readmission. In sensitivity analysis, IOL is cost saving compared with scheduled CD unless the cesarean rate following induction exceeds 70%. CONCLUSION: In morbidly obese women, induction of labor remains cost-saving until the rate of cesarean following induction exceeds 70%.

Geographic and Racial Disparities in Infant Hearing Loss.

OBJECTIVE: Approximately 1 to 2 of every 1000 American newborns has hearing loss identified by newborn screening. This study was designed to determine if infant hearing loss is more common in socioeconomically disadvantaged communities. STUDY DESIGN: In this retrospective study, we analyzed electronic medical record data using geostatistical models. SETTING: Infants were residents of Durham County, North Carolina, born in 2 hospitals of the Duke University Health System. This county includes the city of Durham and surrounding suburban and rural communities. SUBJECTS AND METHODS: Subjects were hearing-screened newborns, born between 2005 and 2016, whose residential address was in Durham County, North Carolina. This was a retrospective study using medical record data. We used Bayesian regression models with smoothing of coordinate date to identify both spatial and nonspatial predictors of infant hearing loss. RESULTS: We identified 19,348 infants from Durham County, of whom 675 had failed initial hearing screening and 191 had hearing loss confirmed on follow-up. Hearing loss was significantly associated with minority race (odds ratio [OR], 2.45; 95% confidence interval, 1.97-3.06), as well as lower gestational age and maternal sexually transmitted infections. We identified significant geographic heterogeneity, with a higher probability of hearing loss in poorer urban neighborhoods (local OR range, 0.59-1.39). Neighborhood disadvantage was a significant predictor of hearing loss, as was high local seroprevalence of cytomegalovirus (CMV) among pregnant women. CONCLUSIONS: Urban, low-income neighborhoods have a high prevalence of infant hearing loss compared with more affluent surrounding communities, particularly among minorities. This distribution may be attributable to congenital CMV infection.

The Effects of a Couples-Based Health Behavior Intervention During Pregnancy on Latino Couples' Dyadic Satisfaction Postpartum.

Many couples tend to report steadily decreasing relationship quality following the birth of a child. However, little is known about the postpartum period for Latino couples, a rapidly growing ethnic group who are notably underserved by mental and physical health caregivers in the United States. Thus, this study investigated whether a brief couples' intervention focused on helping couples support each other while increasing healthy behaviors might improve dyadic functioning postpartum. This study presents secondary analyses of data regarding couple functioning from a larger randomized controlled trial with 348 Latino couples to promote smoking cessation. Portions of the intervention taught the couple communication and problem-solving skills to increase healthy behavior. Couples participated in four face-to-face assessments across 1 year starting at the end of the first trimester. Latent growth curve analyses revealed that the treatment group reported an increase in relationship satisfaction and constructive communication after the intervention, which diminished by 1-year follow-up, returning couples to their baseline levels of satisfaction. Results suggest that incorporating a brief couple intervention as part of a larger health intervention for Latinos may prevent postpartum decreases in relationship satisfaction.

The Excess Burden of Cytomegalovirus in African American Communities: A Geospatial Analysis.

Background. Cytomegalovirus (CMV) is a common cause of birth defects and hearing loss in infants and opportunistic infections in the immunocompromised. Previous studies have found higher CMV seroprevalence rates among minorities and among persons with lower socioeconomic status. No studies have investigated the geographic distribution of CMV and its relationship to age, race, and poverty in the community. Methods. We identified patients from 6 North Carolina counties who were tested in the Duke University Health System for CMV immunoglobulin G. We performed spatial statistical analyses to analyze the distributions of seropositive and seronegative individuals. Results. Of 1884 subjects, 90% were either white or African American. Cytomegalovirus seropositivity was significantly more common among African Americans (73% vs 42%; odds ratio, 3.31; 95% confidence interval, 2.7-4.1), and this disparity persisted across the life span. We identified clusters of high and low CMV odds, both of which were largely explained by race. Clusters of high CMV odds were found in communities with high proportions of African Americans. Conclusions. Cytomegalovirus seropositivity is geographically clustered, and its distribution is strongly determined by a community's racial composition. African American communities have high prevalence rates of CMV infection, and there may be a disparate burden of CMV-associated morbidity in these communities.

Research on vaccines during pregnancy: protocol design and assessment of safety.

The Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health organized a series of conferences, entitled "Enrolling Pregnant Women in Clinical Trials of Vaccines and Therapeutics", to discuss study design and the assessment of safety in clinical trials conducted in pregnant women. A panel of experts was charged with developing guiding principles for the design of clinical trials and the assessment of safety of vaccines during pregnancy. Definitions and a grading system to evaluate local and systemic reactogenicity, adverse events, and other events associated with pregnancy and delivery were developed. The purpose of this report is to provide investigators interested in vaccine research in pregnancy with a basic set of tools to design and implement maternal immunization studies which may be conducted more efficiently using consistent definitions and grading of adverse events to allow the comparison of safety reports from different trials. These guidelines and safety assessment tools may be modified to meet the needs of each particular protocol based on evidence collected as investigators use them in clinical trials in different settings and share their findings and expertise.

Spiritual needs of couples facing pregnancy termination because of fetal anomalies.

The spiritual needs of couples (9 mothers and 5 fathers) who were planning to terminate wanted second trimester pregnancies because of serious fetal anomalies were surveyed. Their greatest needs were for a "guidance from a higher power" and for "someone to pray for them." Unlike other reported groups of patients, they did not want or expect their healthcare team to discuss their faith, or to pray with them. Most would prefer support from their own pastors, but their religious community was involved to only a small extent. They would welcome support from hospital chaplains, who could play a substantive and unique pastoral role in this clinical context.

A Bayesian growth mixture model to examine maternal hypertension and birth outcomes.

Maternal hypertension is a major contributor to adverse pregnancy outcomes, including preterm birth (PTB) and low birth weight (LBW). Although several studies have explored the relationship between maternal hypertension and fetal health, few have examined how the longitudinal trajectory of blood pressure, considered over the course of pregnancy, affects birth outcomes. In this paper, we propose a Bayesian growth mixture model to jointly examine the associations between longitudinal blood pressure measurements, PTB, and LBW. The model partitions women into distinct classes characterized by a mean arterial pressure (MAP) curve and joint probabilities of PTB and LBW. Each class contains a unique mixed effects model for MAP with class-specific regression coefficients and random effect covariances. To account for the strong correlation between PTB and LBW, we introduce a bivariate probit model within each class to capture residual within-class dependence between PTB and LBW. The model permits the association between PTB and LBW to vary by class, so that for some classes, PTB and LBW may be positively correlated, whereas for others, they may be uncorrelated or negatively correlated. We also allow maternal covariates to influence the class probabilities via a multinomial logit model. For posterior computation, we propose an efficient MCMC algorithm that combines full-conditional Gibbs and Metropolis steps. We apply our model to a sample of 1027 women enrolled in the Healthy Pregnancy, Healthy Baby Study, a prospective cohort study of host, social, and environmental contributors to disparities in pregnancy outcomes.

Influence of timing of seasonal influenza vaccination on effectiveness and cost-effectiveness in pregnancy.

The purpose of this review was to estimate the impact of timing of seasonal influenza vaccination during pregnancy on health and economic outcomes. Cost-effectiveness analysis with a dynamic model of the US population of pregnant women and infants who were <6 months incorporated seasonal variation in influenza incidence. Compared with no vaccination, seasonal influenza vaccination in pregnancy costs $70,089 per quality-adjusted life year. Most of the benefit for infants was limited to those whose mothers were vaccinated within the first 4 weeks of vaccine availability. Once all women who were pregnant at the time of vaccine availability were vaccinated, vaccination of newly pregnant women had benefits for mothers but not infants. Delay of vaccination beyond November reduced both effectiveness and cost-effectiveness. The greatest population benefit from seasonal influenza vaccination in pregnancy was realized if pregnant women were vaccinated as soon as possible after trivalent inactivated influenza vaccine became available. Efforts to increase vaccine rates should be concentrated early in the influenza season.

Kids and adults now! Defeat Obesity (KAN-DO): rationale, design and baseline characteristics.

BACKGROUND: Prevention of childhood obesity is a public health priority. Parents influence a child's weight by modeling healthy behaviors, controlling food availability and activity opportunities, and appropriate feeding practices. Thus interventions should target education and behavioral change in the parent, and positive, mutually reinforcing behaviors within the family. METHODS: This paper presents the design, rationale and baseline characteristics of Kids and Adults Now! - Defeat Obesity (KAN-DO), a randomized controlled behavioral intervention trial targeting weight maintenance in children of healthy weight, and weight reduction in overweight children. 400 children aged 2-5 and their overweight or obese mothers in the Triangle and Triad regions of North Carolina are randomized equally to control or the KAN-DO intervention, consisting of mailed family kits encouraging healthy lifestyle change. Eight (monthly) kits are supported by motivational counseling calls and a single group session. Mothers are targeted during a hypothesized "teachable moment" for health behavior change (the birth of a new baby), and intervention content addresses: parenting skills ((e.g., emotional regulation, authoritative parenting), healthy eating, and physical activity. RESULTS: The 400 mother-child dyads randomized to trial are 75% white and 22% black; 19% have a household income of $30,000 or below. At baseline, 15% of children are overweight (85th-95th percentile for body mass index) and 9% are obese (≥ 95th percentile). CONCLUSION: This intervention addresses childhood obesity prevention by using a family-based, synergistic approach, targeting at-risk children and their mothers during key transitional periods, and enhancing maternal self-regulation and responsive parenting as a foundation for health behavior change.

Disparities in maternal hypertension and pregnancy outcomes: evidence from North Carolina, 1994-2003.

OBJECTIVES: To better understand disparities in pregnancy outcomes, we analyzed data from North Carolina to determine how the pattern of maternal hypertensive disorders differs among non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic women across the range of maternal ages. In addition, we explored whether rates of poor birth outcomes, including low birthweight (LBW) and preterm birth (PTB), among hypertensive women differed by race. METHODS: We restricted our analyses to births occurring between 1994 and 2003, constructing six five-year maternal age categories: 15-19 years, 20-24 years, 25-29 years, 30-34 years, 35-39 years, and 40-44 years. We used logistic regression to determine the relative contribution of race and age to incidence of maternal hypertension. All analyses controlled for the standard covariates of maternal education, marital status, and tobacco use. To assess the impact of maternal hypertension on birth outcomes, we limited the dataset to women with any hypertensive disorder and used linear regression to determine how particular race-age combinations affected outcomes. We also used logistic regression to find out how particular race-age combinations affected the likelihood of LBW and PTB. RESULTS: The risk of hypertension differed by race, with NHB women exhibiting the highest risk and Hispanic women the lowest risk. Further, rates of hypertension increased with age. Among hypertensive women, pregnancy outcomes differed by race and age, with NHB women having the poorest outcomes (i.e., LBW and PTB) and age exhibiting a dose-response relationship in PTB and very PTB. CONCLUSIONS: Patterns of maternal hypertension and subsequent outcomes are important contributors to persistent disparities in pregnancy outcomes.

Effect of breastfeeding on weight retention from one pregnancy to the next: results from the North Carolina WIC program.

OBJECTIVES: Pregnancy-related weight retention can contribute to obesity, and breastfeeding may facilitate postpartum weight loss. We investigated the effect of breastfeeding on long-term postpartum weight retention. METHODS: Using data from the North Carolina Special Supplemental Nutrition Program for Women, Infants, and Children (WIC; 1996-2004), weight retention was assessed in women aged 18 years or older who had more than one pregnancy available for analysis (n=32,920). Using multivariable linear regression, the relationship between duration of breastfeeding after the first pregnancy and change in pre-pregnancy weight from the first pregnancy to the second pregnancy was estimated, controlling for demographic and weight-related covariates. RESULTS: Mean time between pregnancies was 2.8 years (standard deviation (SD) 1.5), and mean weight retention from the first to the second pregnancy was 4.9kg (SD 8.7). In covariate-adjusted analyses, breastfeeding for 20 weeks or more resulted in 0.39kg (standard error (SE) 0.18) less weight retention at the beginning of the second pregnancy relative to no breastfeeding (p=0.025). CONCLUSION: In this large, racially diverse sample of low-income women, long-term weight retention was lower among those who breastfed for at least 20 weeks.

Predictors of adverse events among pregnant smokers exposed in a nicotine replacement therapy trial.

OBJECTIVE: The purpose of this study was to determine the contribution of randomization to nicotine replacement therapy (NRT), sociodemographic and psychosocial factors, and pregnancy and medical history to serious perinatal adverse events among pregnant smokers. STUDY DESIGN: We performed a retrospective review of all medical records for participants in the Baby Steps Trial. Data that were abstracted from 157 records were combined with baseline characteristics for logistic regression modeling of serious adverse events and adjusted for covariates. RESULTS: Serious adverse events occurred in 17% (9/52 pregnancies) and 31% (33/105 pregnancies) of participants in the control and NRT arms, respectively. Black race, adverse pregnancy history, and use of analgesic medication during pregnancy were significant predictors (P = .02, .04, and .01, respectively). Remaining covariates, which included randomization to NRT, were not statistically significant. CONCLUSION: Although race, poor pregnancy history, and use of analgesics were associated with serious adverse events, randomization to NRT during pregnancy was not a significant factor. Further research is needed to examine the safety of analgesic medications during pregnancy.