Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk.

BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

Prediction of metabolic syndrome following a first pregnancy.

BACKGROUND: The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. OBJECTIVE: This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. STUDY DESIGN: This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. RESULTS: A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). CONCLUSION: We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

NuMoM2b Study Insights: Primary Exposures, Outcomes, and Directions for Future Research.

OBJECTIVE: To summarize the publications to date from a large obstetric cohort of nulliparous individuals. STUDY DESIGN: We summarized all of the publications from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). We descriptively summarized the most common outcomes and exposures reported in current publications. RESULTS: Fifty-six publications to date are discussed. The most common primary exposures reported are participant baseline characteristics such as body mass index (24%), sociodemographic characteristics (22%), and sleep factors (16%). These exposures were most commonly measured in the first trimester (77%). The most commonly reported primary outcomes were related to adverse pregnancy outcomes (APOs, 51.6%), with 25% using a composite of multiple APOs as the primary outcome. At least 8,000 participants were used in the analyses of over half of the publications. CONCLUSION: The nuMoM2b study has generated a diverse array of publications and conclusions on factors associated with APOs. The publicly available data set from the nuMoM2b study continues to hold potential for considerable advances, new insights, and future research opportunities to optimize pregnancy and pregnancy-related health. KEY POINTS: · The nuMoM2b pregnancy cohort has generated 56 publications thus far.. · The main findings of these publications are summarized and categorized in this work.. · The data and specimens from this cohort are available and can answer many clinical questions..

Associations of the Neighborhood Built Environment with Gestational Weight Gain.

OBJECTIVE: This study aimed to determine whether specific factors of the built environment related to physical activity and diet are associated with inadequate and excessive gestational weight gain (GWG). STUDY DESIGN: This analysis is based on data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be, a prospective cohort of nulliparous women who were followed from the beginning of their pregnancies through delivery. At each study visit, home addresses were recorded and geocoded. Locations were linked to several built-environment characteristics such as the census tract National Walkability Score (the 2010 Walkability Index) and the number of gyms, parks, and grocery stores within a 3-km radius of residential address. The primary outcome of GWG (calculated as the difference between prepregnancy weight and weight at delivery) was categorized as inadequate, appropriate, or excessive based on weight gained per week of gestation. Multinomial regression (generalized logit) models evaluated the relationship between each factor in the built environment and excessive or inadequate GWG. RESULTS: Of the 8,182 women in the analytic sample, 5,819 (71.1%) had excessive GWG, 1,426 (17.4%) had appropriate GWG, and 937 (11.5%) had inadequate GWG. For the majority of variables examined, built environments more conducive to physical activity and healthful food availability were associated with a lower odds of excessive or inadequate GWG category. For example, a higher number of gyms or parks within 3 km of a participant's residential address was associated with lower odds of having excessive (gyms: adjusted odds ratio [aOR] = 0.93 [0.89-0.96], parks: 0.94 [0.90-0.98]) or inadequate GWG (gyms: 0.91 [0.86-0.96]; parks: 0.91 [0.86-0.97]). Similarly, a higher number of grocery stores was associated with lower odds of having excessive GWG (0.94 [0.91-0.97]). CONCLUSION: Among a diverse population of nulliparous women, multiple aspects of the built environment are associated with excessive and inadequate GWG. KEY POINTS: · There are little data on the association between the built environment and pregnancy outcomes.. · Multiple aspects of the built environment are associated with excessive and inadequate GWG.. · These results suggest the role that neighborhood investment may play in improving pregnancy outcomes..

Serum Cotinine and Adverse Cardiovascular Outcomes: A Cross-sectional Secondary Analysis of the nuMoM2b Heart Health Study.

OBJECTIVE: We aimed to (1) compare serum cotinine with self-report for ascertaining smoking status among reproductive-aged women; (2) estimate the relative odds of adverse cardiovascular (CV) outcomes among women by smoking status; (3) assess whether the association between adverse pregnancy outcomes (APOs) and CV outcomes varies by smoking status. STUDY DESIGN: We conducted a cross-sectional study of the nuMoM2b Heart Health Study. Women attended a study visit 2 to 7 years after their first pregnancy. The exposure was smoking status, determined by self-report and by serum cotinine. Outcomes included incident chronic hypertension (HTN), metabolic syndrome (MetS), and dyslipidemia. Multivariable logistic regression estimated odds ratios (ORs) for each outcome by smoking status. RESULTS: Of 4,392 women with serum cotinine measured, 3,610 were categorized as nonsmokers, 62 as secondhand smoke exposure, and 720 as smokers. Of 3,144 women who denied tobacco smoke exposure, serum cotinine was consistent with secondhand smoke exposure in 48 (1.5%) and current smoking in 131 (4.2%) After adjustment for APOs, smoking defined by serum cotinine was associated with MetS (adjusted OR [aOR] = 1.52, 95% confidence interval [CI]: 1.21, 1.91) and dyslipidemia (aOR = 1.28, 95% CI: 1.01, 1.62). When stratified by nicotine exposure, nonsmokers with an APO in their index pregnancy had higher odds of stage 1 (aOR = 1.64, 95% CI: 1.32, 2.03) and stage 2 HTN (aOR = 2.92, 95% CI: 2.17, 3.93), MetS (aOR = 1.76, 95% CI: 1.42, 2.18), and dyslipidemia (aOR = 1.55, 95% CI: 1.25, 1.91) relative to women with no APO. Results were similar when smoking exposure was defined by self-report. CONCLUSION: Whether determined by serum cotinine or self-report, smoking is associated with subsequent CV outcomes in reproductive-aged women. APOs are also independently associated with CV outcomes in women. KEY POINTS: · Cotinine was detected in 5.7% of reported nonsmokers.. · Smoking and APOs were independently associated with CV health.. · Smoking was associated with MetS and dyslipidemia..

Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery.

Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal stress years after pregnancy. The 10-item Perceived Stress Scale (PSS) (0-40 range) was completed in the first and third trimesters, and 2-7 years after delivery among a subsample (n = 4161) of nulliparous women enrolled at eight US medical centers between 2010 and 2013 in a prospective, observational cohort study. Demographics, medical history, and presence of APOs (gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preeclampsia (PE), and medically indicated or spontaneous preterm birth (miPTB, sPTB)) were obtained. The associations of prenatal PSS and the presence of APOs with PSS scores years after delivery were estimated using multivariable linear regression. Mean PSS scores were 12.5 (95% CI 12.3, 12.7) and 11.3 (95% CI 11.1, 11.5) in the first and third trimesters respectively and 14.9 (95% CI 14.7, 15.1) 2-7 years later, an average increase of 2.4 points (95% CI 2.2, 2.6) from the start of pregnancy. Regressing PSS scores after delivery on first-trimester PSS and PSS increase through pregnancy showed positive associations, with coefficients (95% CI) of 2.8 (2.7, 3.0) and 1.5 (1.3, 1.7) per 5-point change, respectively. Adding APO indicator variables separately showed higher PSS scores for women with HDP (0.7 [0.1, 1.3]), PE (1.3 [0.6, 2.1]), and miPTB (1.3 [0.2, 2.4]), but not those with GDM or sPTB. In this geographically and demographically diverse sample, prenatal stress and some APOs were positively associated with stress levels 2-7 years after pregnancy.ClinicalTrials.gov Registration number NCT02231398.

The Gulf War Era Cohort and Biorepository: A Longitudinal Research Resource of Veterans of the 1990-1991 Gulf War Era.

The US Department of Veterans Affairs (VA) Gulf War Era Cohort and Biorepository (GWECB) is a nationally representative longitudinal cohort of US veterans who served during the 1990-1991 Gulf War era. The GWECB combines survey data, such as demographic, health behavior, and environmental exposure data; medical records; and a linked biorepository of blood specimens that can support a broad range of future research regarding health concerns unique to veterans of this era. To build this resource, the VA Cooperative Studies Program initiated a pilot study (2014-2016) to establish the GWECB and evaluate the processes required to build and maintain the resource. Participants (n = 1,275) consented to future sharing of their data and biospecimens for research purposes. Here we describe the pilot study, including recruitment and enrollment procedures, data collection and management, quality control, and challenges experienced. The GWECB data available to investigators under approved sharing mechanisms and the procedures for accessing them are extensively detailed. The study's consenting documents and a website link for the research survey are provided. Our hope is that new research drawing on the GWECB data and biospecimens will result in effective treatments and improved approaches to address the health concerns of Gulf War-era veterans.

Implementation of new clinical programs in the VHA healthcare system: the importance of early collaboration between clinical leadership and research.

Collaboration between policy, research, and clinical partners is crucial to achieving proven quality care. The Veterans Health Administration has expended great efforts towards fostering such collaborations. Through this, we have learned that an ideal collaboration involves partnership from the very beginning of a new clinical program, so that the program is designed in a way that ensures quality, validity, and puts into place the infrastructure necessary for a reliable evaluation. This paper will give an example of one such project, the Lung Cancer Screening Demonstration Project (LCSDP). We will outline the ways that clinical, policy, and research partners collaborated in design, planning, and implementation in order to create a sustainable model that could be rigorously evaluated for efficacy and fidelity. We will describe the use of the Donabedian quality matrix to determine the necessary characteristics of a quality program and the importance of the linkage with engineering, information technology, and clinical paradigms to connect the development of an on-the-ground clinical program with the evaluation goal of a learning healthcare organization. While the LCSDP is the example given here, these partnerships and suggestions are salient to any healthcare organization seeking to implement new scientifically proven care in a useful and reliable way.

Relapse patterns after transoral laser microsurgery and postoperative irradiation for squamous cell carcinomas of the tonsil and tongue base.

OBJECTIVES: We evaluated relapse patterns after transoral laser microsurgery (TLM) in squamous cell carcinoma (SCC) of the tonsil and tongue base and evaluated the indications for adjuvant irradiation. METHODS: Between December 1, 1996, and December 31, 2005, 79 patients with previously untreated SCC of the tonsil or tongue base underwent TLM with or without neck dissection. Thirty-eight patients (48%) underwent postoperative irradiation (median, 62 Gy) to the primary site and the neck. Analysis of relapse patterns was performed on the basis of adverse risk factors and the presence or absence of adjuvant irradiation. RESULTS: The median follow-up for living patients was 47 months (range, 10 to 107 months), and patients were monitored for at least 2 years or until recurrence or death. Local, regional, and distant treatment failures numbered 4, 6, and 4 for surgery alone (n = 41) and 0, 2, and 6 for adjuvant irradiation (n = 38), respectively. Patients with high-risk features (extracapsular extension or at least 2 adverse factors) had locoregional control rates at 2 or more years of 66% and 94% for TLM alone and TLM plus adjuvant irradiation, respectively. CONCLUSIONS: Adjuvant irradiation after TLM resection of oropharyngeal SCC with intermediate- or high-risk features improves locoregional control compared with TLM alone.

Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia. Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP. Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates. Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models. Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC). Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs. Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

An assessment of survey measures used across key epidemiologic studies of United States Gulf War I Era veterans.

Over the past two decades, 12 large epidemiologic studies and 2 registries have focused on U.S. veterans of the 1990-1991 Gulf War Era. We conducted a review of these studies' research tools to identify existing gaps and overlaps of efforts to date, and to advance development of the next generation of Gulf War Era survey tools. Overall, we found that many of the studies used similar instruments. Questions regarding exposures were more similar across studies than other domains, while neurocognitive and psychological tools were the most variable. Many studies focused on self-reported survey results, with a range of validation practices. However, physical exams, biomedical assessments, and specimen storage were not common. This review suggests that while research may be able to pool data from past surveys, future surveys need to consider how their design can yield data comparable with previous surveys. Additionally, data that incorporate recent technologies in specimen and genetic analyses would greatly enhance such survey data. When combined with existing data on deployment-related exposures and post-deployment health conditions, longitudinal follow-up of existing studies within this collaborative framework could represent an important step toward improving the health of veterans.

Adverse Pregnancy Outcomes and Future Metabolic Syndrome.

Background: Metabolic syndrome (MetS) is associated with a history of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB), but it is unclear whether this association is due to the pregnancy complication(s) or prepregnancy/early pregnancy confounders. The study examines the association of GDM, HDP, and PTB with MetS 2-7 years later, independent of early pregnancy factors. Materials and Methods: Large, diverse cohort of nulliparous pregnant people with singleton gestations enrolled during their first trimester and who attended a follow-up study visit 2-7 years after delivery. The longitudinal cohort was recruited from eight medical centers across the United States. Using standardized protocols, anthropometry, biospecimens, and surveys were collected at study visits and pregnancy outcomes were abstracted from medical records. We estimated the relative risk of prevalent MetS at the follow-up study visit for participants with GDM, HDP, or PTB (vs. no complications), adjusting for early pregnancy age, body mass index, self-reported race/ethnicity, insurance type, and smoking status. Results: Of 4,402 participants, 738 (16.8%) had MetS at follow-up: 13.1% (441/3,365) among those with no complications, and 27.9% (290/1,002) among those with complications. MetS occurred in 39.0% of GDM (73/187, adjusted relative risk [aRR] = 1.75; 95% confidence interval [CI] 1.42-2.16); 29.2% of HDP (176/603, aRR = 1.49; 95% CI 1.27-1.75); and 29.7% of PTB (113/380, aRR = 1.78; 95% CI 1.49-2.12). Those who had both HDP and PTB (n = 113) had an aRR = 1.95 (95% CI 1.50-2.54). Conclusions: People whose pregnancies were complicated by GDM, HDP, or PTB are at a higher risk of MetS within 2-7 years after delivery, independent of early pregnancy risk factors. The highest MetS risk follows pregnancies complicated by both HDP and PTB.

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.

Genetic Associations with Dynamic Placental Proteins Identify Causal Biomarkers for Hypertension in Pregnancy.

Preeclampsia (PE), a gestational hypertensive disorder, ranks as the second leading cause of maternal mortality worldwide. While PE is considered a multifactorial disease, placental insufficiency is believed to drive its progression. To noninvasively study placental physiology related to adverse pregnancy outcomes (APOs) and predict these outcomes before symptom onset, we measured nine placental protein levels in first- and second-trimester serum samples from 2,352 nulliparous pregnant women in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers- to-Be (nuMoM2b) study. The proteins analyzed include VEGF, PlGF, ENG, sFlt-1, ADAM-12, PAPP-A, fßHCG, INHA, and AFP. Currently, little is known about the genetic variants contributing to the heritability of these proteins during pregnancy, and no studies have explored the causal relationships between early pregnancy proteins and gestational hypertensive disorders. Our study has three objectives. First, we conducted genome-wide association study (GWAS) of nine placental proteins in maternal serum during the first and second trimesters and the difference between time points to understand how genetics may influence placental proteins in early pregnancy. Second, we examined whether early pregnancy placental proteins are causal factors for PE and gestational hypertension (gHTN). Lastly, we investigated the causal relationship between PE/gHTN and long-term HTN. In conclusion, our study discovered significant genetic associations with placental proteins ADAM-12, VEGF, and sFlt-1, offering insights into their regulation during pregnancy. Mendelian randomization (MR) analyses demonstrated evidence of causal relationships between placental proteins, particularly ADAM-12, and gHTN, potentially informing prevention and treatment strategies. Our findings suggest that placental proteins like ADAM-12 could serve as biomarkers for postpartum HTN risk.

Characteristics of primary care office visits to nurse practitioners, physician assistants and physicians in United States Veterans Health Administration facilities, 2005 to 2010: a retrospective cross-sectional analysis.

BACKGROUND: Primary care, an essential determinant of health system equity, efficiency, and effectiveness, is threatened by inadequate supply and distribution of the provider workforce. The Veterans Health Administration (VHA) has been a frontrunner in the use of nurse practitioners (NPs) and physician assistants (PAs). Evaluation of the roles and impact of NPs and PAs in the VHA is critical to ensuring optimal care for veterans and may inform best practices for use of PAs and NPs in other settings around the world. The purpose of this study was to characterize the use of NPs and PAs in VHA primary care and to examine whether their patients and patient care activities were, on average, less medically complex than those of physicians. METHODS: This is a retrospective cross-sectional analysis of administrative data from VHA primary care encounters between 2005 and 2010. Patient and patient encounter characteristics were compared across provider types (PA, NP, and physician). RESULTS: NPs and PAs attend about 30% of all VHA primary care encounters. NPs, PAs, and physicians fill similar roles in VHA primary care, but patients of PAs and NPs are slightly less complex than those of physicians, and PAs attend a higher proportion of visits for the purpose of determining eligibility for benefits. CONCLUSIONS: This study demonstrates that a highly successful nationwide primary care system relies on NPs and PAs to provide over one quarter of primary care visits, and that these visits are similar to those of physicians with regard to patient and encounter characteristics. These findings can inform health workforce solutions to physician shortages in the USA and around the world. Future research should compare the quality and costs associated with various combinations of providers and allocations of patient care work, and should elucidate the approaches that maximize quality and efficiency.

Association of N-Terminal Pro-Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension.

IMPORTANCE: Hypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy. OBJECTIVE: To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021. EXPOSURES: NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. MAIN OUTCOMES AND MEASURES: Hypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit. RESULTS: A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy. CONCLUSIONS AND RELEVANCE: In this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.

A common language for Gulf War Illness (GWI) research studies: GWI common data elements.

AIMS: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. MAIN METHODS: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. KEY FINDINGS: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. SIGNIFICANCE: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.

Trainee participation is associated with increased small adenoma detection.

BACKGROUND: Previous studies examining the effect of fellow participation on adenoma detection rate in colonoscopy have yielded conflicting results, and factors such as adenoma size and location have not been rigorously evaluated. OBJECTIVE: To examine whether fellow participation during screening, surveillance, or diagnostic colonoscopy affects overall, size-specific, or location-specific adenoma or polyp detection rate. METHODS: This was a retrospective study of 2430 colonoscopies performed in our ambulatory surgical center between September 2006 and December 2007, comparing adenoma and polyp detection rates of colonoscopies performed by fellows with supervising staff endoscopists (n = 318) with colonoscopies performed by staff endoscopists without fellow participation (n = 2112). Study participants included patients who underwent screening, surveillance, or diagnostic colonoscopies in our GI suite. Logistic regression analysis was used to evaluate the association of fellow participation with adenoma and polyp detection. RESULTS: There was evidence of a higher rate of small (<5 mm) adenoma detection in colonoscopies with a fellow present (25% vs 17%, P = .001). This remained significant after multiple-testing adjustment (P ≤ .003 considered significant). Findings were similar, although not significant for small polyps (36% vs 29%, P = .007). There was a trend toward increased adenoma detection in colonoscopies with a fellow present compared with those without (30% vs 26%, P = .11). Multivariable adjustment for potentially confounding variables did not alter these associations. LIMITATIONS: The study had a retrospective design, and information regarding bowel preparation was not available for 37% of patients. CONCLUSION: Fellow involvement was associated with increased detection rates of small adenomas, providing evidence that the presence of a fellow during colonoscopy plays a role in enhancing the effectiveness of the examination.

Vitamin D deficiency and insufficiency is common during pregnancy.

The objective was to determine the incidence of vitamin D deficiency, insufficiency, and sufficiency in African-American, Hispanic, and Caucasian pregnant women. Blood samples were taken from 154 African-American, 194 Hispanic, and 146 Caucasian women at <14 weeks of gestation; 25 hydroxyvitamin D levels (25(OH)D) levels were measured by radioimmunoassay. The mean 25(OH)D levels in African-American, Hispanic, and Caucasian pregnant women were 15.5 ± 7.2 (standard deviation), 24.1 ± 8.7, 29.0 ± 8.5 ng/mL, respectively. Ninety-seven percent of African-Americans, 81% of Hispanics, and 67% of Caucasians were deficient (25(OH)D levels <20 ng/mL or <50 nmol/L) or insufficient (25(OH)D levels ≥ 20 ng/mL or <32 ng/mL or ≥ 50 nmol/L or <80 nmol/L). Of these pregnant women, 82% had vitamin D levels <32 ng/mL (<80 ng/mL). In logistic regression models, race was the most important risk factor for vitamin D deficiency or insufficiency. African-American women and Hispanic women were more likely to have vitamin D insufficiency and deficiency than Caucasian women. Furthermore, primigravid women were more at risk for vitamin D insufficiency. This study demonstrates widespread vitamin D deficiency and insufficiency in pregnant females living at a southern latitude. African-Americans are at greatest risk.

Validity of the posterior tibial edema sign in posterior tibial tendon dysfunction.

BACKGROUND: Posterior tibial tendon dysfunction (PTTD) is a common malady leading to acquired flatfoot, which frequently causes foot and ankle pain and swelling. We hypothesized that patients with PTTD and pitting edema along the course of the posterior tibial tendon (PTT) would have evidence of fluid within the tendon sheath on MRI. We introduce and validate a novel, yet simple physical examination finding, the posterior tibial edema (PTE) sign, to help distinguish PTTD from other causes of foot and ankle pain and swelling. PATIENTS AND METHODS: To determine an association between the PTE sign and changes to the PTT evident on MRI, we reviewed the medical records of patients with PTTD who underwent magnetic resonance imaging (MRI). RESULTS: Of 186 patients identified with PTTD, 49 underwent MRI, and 42 (86%) demonstrated imaging characteristics consistent with tendonitis, tendinosis, or tenosynovitis. Presence or absence of increased posterior malleolar pitting edema agreed with presence or absence of these MRI findings in 43 patients (88%), making the clinical examination finding significantly predictive of MRI results (p= 0.01). The sensitivity of the test for PTE was 86%, with specificity of 100%. CONCLUSION: The PTE sign refers to pitting edema along the course of the PTT, not associated with acute trauma and not accompanied by other areas of edema. Physical examination signs that are highly sensitive and specific to the condition may help lower the cost of diagnosis by eliminating the need for expensive tests that are not always necessary.