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Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.

The current national COVID-19 mortality rate for Black Americans is 2.1 times higher than that of Whites. In this commentary, we provide historical context on how structural racism undergirds multi-sector policies which contribute to racial health inequities such as those highlighted by the COVID-19 pandemic. We offer a concrete, actionable path forward to address structural racism and advance health equity for Black Americans through anti-racism, implicit bias, and cultural competency training; capacity building; community-based participatory research (CBPR) initiatives; validated metrics for longitudinal monitoring of efforts to address health disparities and the evaluation of those interventions; and advocacy for and empowerment of vulnerable communities. This necessitates a multi-pronged, coordinated approach led by clinicians; public health professionals; researchers; social scientists; policy-makers at all governmental levels; and local community leaders and stakeholders across the education, legal, social service, and economic sectors to proactively and systematically advance health equity for Black Americans across the USA.

Introduction Fundal pressure during the second stage of labor is widely practiced but understudied. Violent fundal pressure can cause maternal and fetal injuries. Many providers believe the maneuver is effective. Administrative efforts to ban fundal pressure are unsuccessful and only drive the procedure to an underground practice. Material and Methods In this single‐center, open‐label, randomized trial, nulliparous women with term singleton cephalic pregnancy under epidural analgesia were assigned to receive gentle manual fundal pressure (GMFP) or routine labor care. The GMFP was designed not to exceed a maximum of 120 mmHg. Women were randomized after 30 min of pushing in the second stage of labor. The primary outcome was the time from randomization to delivery. Secondary outcomes were mode of delivery, episiotomy, perineal laceration, cord blood pH, and other maternal and fetal outcomes. Results Between July 2023 and January 2024, 164 women were randomized to GMFP (n = 82) or to routine care (n = 82). The time from randomization to vaginal delivery did not show statistical significance between the fundal pressure group and the control group (mean [SD], 46.3 [33.3] vs. 55.9 [45.8] min; p = 0.13). Significantly fewer women in the fundal pressure group had operative vaginal deliveries (4 of 82 [4.9%]) than women in the control group (13 of 82 [15.9%]; relative risk [RR] 0.308, 95% confidence interval [CI] 0.105–0.904; p = 0.021). Similarly, mediolateral episiotomy was performed in fewer women in the fundal pressure group (6 of 82 [7.32%]) than in the control group (16 of 82 [19.51%], RR 0.375, 95% CI 0.154–0.910; p = 0.022). Other maternal and fetal outcomes were similar in the two groups. Conclusions GMFP resulted in a nonsignificant reduction in the second stage of labor and a significant reduction in operative vaginal delivery and episiotomy without an increase in adverse outcomes. Fundal pressure during the second stage of labor deserves further investigation. Gentle manual fundal pressure results in a nonsignificant reduction in the second stage of labor and significant reduction in operative vaginal delivery and episiotomy without an increase in adverse outcomes.

Background The prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk. Methods ETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child’s 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years. Discussion This is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention. Trial registration number ClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1 .

Background Overweight, obesity, and associated comorbidities are a pressing global issue among children of all ages, particularly among low-income populations. Rapid weight gain (RWG) in the first 6 months of infancy contributes to childhood obesity. Suboptimal sleep-wake patterns and gut microbiota (GM) have also been associated with childhood obesity, but little is known about their influences on early infant RWG. Sleep may alter the GM and infant metabolism, and ultimately impact obesity; however, data on the interaction between sleep-wake patterns and GM development on infant growth are scarce. In this study, we aim to investigate associations of infant sleep-wake patterns and GM development with RWG at 6 months and weight gain at 12 months. We also aim to evaluate whether temporal interactions exist between infant sleep-wake patterns and GM, and if these relations influence RWG. Methods The Snuggle Bug/ Acurrucadito study is an observational, longitudinal study investigating whether 24-h, actigraphy-assessed, sleep-wake patterns and GM development are associated with RWG among infants in their first year. Based on the Ecological Model of Growth, we propose a novel conceptual framework to incorporate sleep-wake patterns and the GM as metabolic contributors for RWG in the context of maternal-infant interactions, and familial and socio-physical environments. In total, 192 mother-infant pairs will be recruited, and sleep-wake patterns and GM development assessed at 3 and 8 weeks, and 3, 6, 9, and 12 months postpartum. Covariates including maternal and child characteristics, family and environmental factors, feeding practices and dietary intake of infants and mothers, and stool-derived metabolome and exfoliome data will be assessed. The study will apply machine learning techniques combined with logistic time-varying effect models to capture infant growth and aid in elucidating the dynamic associations between study variables and RWG. Discussion Repeated, valid, and objective assessment at clinically and developmentally meaningful intervals will provide robust measures of longitudinal sleep, GM, and growth. Project findings will provide evidence for future interventions to prevent RWG in infancy and subsequent obesity. The work also may spur the development of evidence-based guidelines to address modifiable factors that influence sleep-wake and GM development and prevent childhood obesity.

There is well-documented evidence on how interpregnancy interval (IPI) is associated with adverse perinatal outcomes and how short and long IPIs are associated with increased risk for preterm birth, low birth weight, and intra-uterine growth restriction. However, the extremes of IPI on infant mortality are less well documented. The current study builds on the existing evidence on IPI to examine if extremes of IPI are associated with infant mortality, and also examines if IPI is associated with both neonatal and post-neonatal mortality after adjusting for several known confounders. Matched birth and death certificate data for Arizona resident infants was drawn for 2003–2007 cohorts. The analysis was restricted to singleton births among resident mothers with a previous live birth (n = 1,466) and a randomly selected cohort of surviving infants during the same time-frame was used as a comparison group (n = 2,000). Logistic regression models were utilized to assess the odds for infant mortality at monthly interpregnancy intervals (<6, 6–11, 12–17, 18–23, 24–59, ≥60), while adjusting for established predictors of infant mortality (i.e., preterm birth, low birth weight, and small for gestational age), and other potential confounders. Unadjusted analysis showed greater clustering at extreme IPIs of <6 months and ≥60 months for infants that died (32 %) compared to infants that survived (24.7 %). Shorter IPI (i.e., <6 months, 6–11 months, and 12–17 months) compared to ‘ideal’ IPI (i.e., 18–23 months), were associated with infant mortality even after adjusting for confounders. Short intervals were significantly associated with neonatal, but not post-neonatal deaths. IPI above 23 months were not associated with infant mortality in our analyses. Shorter IPIs (18 months or less) significantly increases the risk for neonatal infant mortality even after controlling for known confounders, and our study adds to the existing evidence on adverse perinatal outcomes. Counseling women of reproductive age on the benefits of spacing pregnancies to at least 18 months addresses one preventable risk for early infant mortality.

The clinical management of pregnancy and spontaneous preterm birth (sPTB) relies on estimates of gestational age (GA). Our objective was to evaluate the effect of GA dating uncertainty on the observed performance of a validated proteomic biomarker risk predictor, and then to test the generalizability of that effect in a broader range of GA at blood draw. In a secondary analysis of a prospective clinical trial (PAPR; NCT01371019), we compared two GA dating categories: both ultrasound and dating by last menstrual period (LMP) (all subjects) and excluding dating by LMP (excluding LMP). The risk predictor’s performance was observed at the validated risk predictor threshold both in weeks 191/7–206/7 and extended to weeks 180/7–206/7. Strict blinding and independent statistical analyses were employed. The validated biomarker risk predictor showed greater observed sensitivity of 88% at 75% specificity (increases of 17% and 1%) in more reliably dated (excluding-LMP) subjects, relative to all subjects. Excluding dating by LMP significantly improved the sensitivity in weeks 191/7–206/7. In the broader blood draw window, the previously validated risk predictor threshold significantly stratified higher and lower risk of sPTB, and the risk predictor again showed significantly greater observed sensitivity in excluding-LMP subjects. These findings have implications for testing the performance of models aimed at predicting PTB.

With the increasing Latino population in the United States, it is critical to examine the influence of the process of acculturation on health care practices and utilization. The purpose of this study was to evaluate the relationship between acculturation level and post-partum visit (PPV) compliance among Latinas participating in a larger psycho-educational intervention aimed at encouraging women to engage in positive healthcare practices. Acculturation was measured with the Bicultural Involvement Questionnaire which assigned participants to five categories: Assimilated, Separated, Moderate, Bicultural and Alienation. Logistic Regression analyses were conducted to predict post-partum visit attendance. Odds ratios and relative risk of not attending the post-partum visit are presented. Results suggest women in the Separation and Assimilation groups were less likely than bicultural group members to attend the PPV. The only other variable that was significant in this analysis is the group condition, indicating that the intervention group was more likely to attend the PPV than the control group. Women identifying as bicultural seem to participate more actively in their own healthcare as they draw on the cultural assets that have a positive influence on informal health practices, such as healthy eating and refraining from drug use. Bicultural group members can also use formal skills related to language and knowledge of the dominant culture to help effectively navigate the healthcare system. Implications for research, intervention and practice are discussed to improve healthcare practices and increase utilization among Latinas.

Abstract Purpose This chapter examines birth outcomes of patients enrolled in Familias Sanas (Healthy Families), an educational intervention designed to reduce health disadvantages of low-income, immigrant Latina mothers by providing social support during and after pregnancy. Methodology/approach Using a randomized control-group design, the project recruited 440 pregnant Latina women, 88% of whom were first generation. Birth outcomes were collected through medical charts and analyzed using regression analysis to evaluate if there were any differences between patients enrolled in Familias Sanas compared to those patients who followed a typical prenatal course. Findings Control and intervention groups were found to be similar with regard to demographic characteristics. In addition, we did not observe a decrease in rate of a number of common pregnancy-related complications. Likewise, rates of operative delivery were similar between the two groups as were fetal weight at delivery and use of regional anesthesia at delivery. Research limitations/implications The lack of improvements in birth outcomes for this study was perhaps because this social support intervention was not significant enough to override long-standing stressors such as socioeconomic status, poor nutrition, genetics, and other environmental stressors. Originality/value of chapter This study was set in an inner-city, urban hospital with a large percentage of patients being of Hispanic descent. The study itself is a randomized controlled clinical trial, and data were collected directly from electronic medical records by physicians.

Introduction In early childhood, irregular sleep schedules that may promote circadian rhythm misalignment predict greater weight gain. However, circadian rest-activity (CRA) rhythmicity in infancy in relation to growth is understudied. The aim of the present study was to investigate the association between newborn circadian rest-activity rhythmicity and change in weight-for-age from birth to three months. Methods Data were captured as a secondary data analysis from the Snuggle Bug / Acurrucadito Study (see Support). English or Spanish speaking mothers (n=41, age M±SD=33.1±4.6y, 31.7% Hispanic/Latina) and their full-term (≥37wk) infants of normal weight (2.5-4kg; 58.5% female; 25.6% WIC enrolled) were recruited from Phoenix, Arizona. CRA rhythmicity was measured at eight weeks with ankle-worn Micro Motionloggers (Ambulatory Monitoring Inc.) for five 24hr periods at one-minute epochs. CRA metrics assessed included 24hr autocorrelation, mesor, magnitude, acrophase, goodness-of-fit R2, interdaily stability, intradaily variability, and relative amplitude. Birthweight was mother-reported and 3mon infant weight was measured with a Seca scale. Weight-for-age Z-scores (WAZ) by infant sex were computed based upon World Health Organization growth charts and the change difference between timepoints was the primary outcome. Regression models adjusting for birth WAZ examined the relationships between CRA metrics at eight weeks with change in WAZ from birth to 3mo. Results At eight weeks, mean±SD CRA metrics were as follows: 24hr autocorrelation of 0.25±0.03, mesor of 115.6±14.7, amplitude of 68.1±18.3, goodness-of-fit R2 of 0.42±0.10, acrophase of 14:12±1:42, interdaily stability of 0.57±0.12, intradaily variability of 0.93±0.19, and relative amplitude of 0.61±0.11. Mean birth WAZ and change in WAZ from birth to 3mon were 0.39±0.73 and -0.57±0.77, respectively. After adjusting for birth WAZ, in separate models, greater mesor (R2 Change=0.10, β=-0.32, p=0.03), amplitude (R2 Change=0.11, β=-0.34, p=0.03), and goodness-of-fit R2 (R2 Change=0.10, β=-0.32, p=0.04) were significantly associated with less change in WAZ from birth to 3mon. Conclusion Among relatively healthy, full-term infants born of normal weight, greater 24hr circadian rest-activity rhythmicity achieved by 8 weeks was associated with slower rate of weight gain across the newborn stage. Promoting behaviors and environmental cues from parents that strengthen early circadian rhythmicity in their infants may promote healthy weight trajectories. Support (if any) NIH/NHLBI R01HL147931