Duration of Simultaneous Exposure to High-Risk and Lower-Risk Nephrotoxic Antimicrobials in the Neonatal Intensive Care Unit (NICU) and Future Adolescent Kidney Health.

OBJECTIVE: To determine whether greater duration of simultaneous exposure to antimicrobials with high nephrotoxicity risk combined with lower-risk antimicrobials (simultaneous exposure) in the neonatal intensive care unit (NICU) is associated with worse later kidney health in adolescents born preterm with very low birth weight (VLBW). STUDY DESIGN: Prospective cohort study of participants born preterm with VLBW (<1500 g) as singletons between January 1, 1992, and June 30, 1996. We defined simultaneous exposure as a high-risk antimicrobial, such as vancomycin, administered with a lower-risk antimicrobial on the same date in the NICU. Outcomes were serum creatinine, estimated glomerular filtration rate (eGFR), and first-morning urine albumin-creatinine ratio (ACR) at age 14 years. We fit multivariable linear regression models with days of simultaneous exposure and days of nonsimultaneous exposure as main effects, adjusting for gestational age, birth weight, and birth weight z-score. RESULTS: Of the 147 out of 177 participants who had exposure data, 97% received simultaneous antimicrobials for mean duration 7.2 days (SD 5.6). No participant had eGFR <90 ml/min/1.73 m2. The mean ACR was 15.2 mg/g (SD 38.7) and 7% had albuminuria (ACR >30 mg/g). Each day of simultaneous exposure was associated only with a 1.04-mg/g higher ACR (95% CI 1.01 to 1.06). CONCLUSIONS: Despite frequent simultaneous exposure to high-risk combined with lower-risk nephrotoxic antimicrobials in the NICU, there were no clinically relevant associations with worse kidney health identified in adolescence. Although future studies are needed, these findings may provide reassurance in a population thought to be at increased risk of chronic kidney disease.

The intergenerational metabolic-cardiovascular life course: maternal body mass index (BMI), offspring BMI, and blood pressure of adolescents born extremely preterm.

BACKGROUND: The aim of this study was to evaluate associations between pre-pregnancy maternal obesity and adolescent blood pressures (BPs) among children born extremely preterm. METHODS: This longitudinal observational cohort study included participants in the multicenter Extremely Low Gestational Age Newborn (ELGAN) study, born before 28 weeks of gestation, recruited at birth between 2002 and 2004, and followed prospectively through late adolescence. Between 2015 and 2022, three oscillometric BPs were obtained from participants (mean age 17.8 years). We used linear regression modeling to evaluate the association between maternal self-reported pre-pregnancy body mass index (BMI) and offspring adolescent systolic BP (SBP). In secondary analyses, we evaluated the association between maternal pre-pregnancy and offspring preadolescent (10-year-old) BMI and between offspring preadolescent BMI and adolescent SBP. RESULTS: The 100 (24%) participants born to a mother with a history of pre-pregnancy obesity (BMI ≥ 30) had a greater mean SBP of 120.5 (± 14.3) mmHg compared to the 324 (76%) of adolescents born to mothers without pre-pregnancy obesity (SBP 115.6 (± 12.0) mmHg). Pre-pregnancy obesity was associated with higher offspring BMI (aß 10.8, 95% CI 2.3, 19.2), and higher offspring BMI was associated with higher adolescent SBP (aß 0.12, 95% CI 0.09,0.16). CONCLUSIONS: For ELGANs, higher maternal pre-pregnancy BMI was associated with higher adolescent SBP. Findings from secondary analyses suggest potential mediation through preadolescent BMI. Future research directions include multi-level interventions to reduce maternal pre-pregnancy obesity, followed by offspring obesity prevention interventions as a way of reducing intergenerational cardiovascular disease in high-risk infants born extremely preterm.

Sexually dimorphic methylation patterns characterize the placenta and blood from extremely preterm newborns.

BACKGROUND: Health outcomes among children born prematurely are known to be sexually dimorphic, with male infants often more affected, yet the mechanism behind this observation is not clear. CpG methylation levels in the placenta and blood also differ by sex and are associated with adverse health outcomes. We contrasted CpG methylation levels in the placenta and neonatal blood (n = 358) from the Extremely Low Gestational Age Newborn (ELGAN) cohort based on the EPIC array, which assays over 850,000 CpG sites across the epigenome. Sex-specific epigenome-wide association analyses were conducted for the placenta and neonatal blood samples independently, and the results were compared to determine tissue-specific differences between the methylation patterns in males and females. All models were adjusted for cell type heterogeneity. Enrichment pathway analysis was performed to identify the biological functions of genes related to the sexually dimorphic CpG sites. RESULTS: Approximately 11,500 CpG sites were differentially methylated in relation to sex. Of these, 5949 were placenta-specific and 5361 were blood-specific, with only 233 CpG sites overlapping in both tissues. For placenta-specific CpG sites, 90% were hypermethylated in males. For blood-specific CpG sites, 95% were hypermethylated in females. In the placenta, keratinocyte differentiation biological pathways were enriched among the differentially methylated genes. No enrichment pathways were observed for blood. CONCLUSIONS: Distinct methylation patterns were observed between male and female children born extremely premature, and keratinocyte differentiation pathways were enriched in the placenta. These findings provide new insights into the epigenetic mechanisms underlying sexually dimorphic health outcomes among extremely premature infants.

Growth During Infancy After Extremely Preterm Birth: Associations with Later Neurodevelopmental and Health Outcomes.

OBJECTIVE: To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm. STUDY DESIGN: Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2 years and evaluated neurocognitive, psychiatric, and health outcomes at age 10 years and 15 years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2 years and outcomes at 10 and 15 years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change. RESULTS: High gains in weight and weight/length were associated with greater odds of obesity at 10 years, but not at 15 years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15 years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10 years. CONCLUSIONS: During the 2 years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10 years, but not at 15 years. Infants with high growth gains in the 2 years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length.

Influence of race on the effect of premature birth on salivary cortisol response to stress in adolescents.

BACKGROUND: Adolescents born preterm have altered hypothalamic-pituitary-adrenal axis function with a blunted cortisol stress response, however, the influences of intrauterine growth restriction and race are unclear. METHODS: We measured salivary cortisol before and 20 min after a maximal-exercise stress test and calculated the cortisol stress response. We used linear regression to compare cortisol stress responses between preterm and term groups, adjusting for birth weight z-score and maternal hypertension, and examined effect modification by race and sex. RESULTS: We evaluated 171 adolescents born preterm with very low birth weight and 50 born term. Adolescents born preterm had reduced cortisol stress response compared to term (0.03 vs. 0.08 µg/dL, p = 0.04). This difference was race dependent: non-Black adolescents born preterm had significantly reduced cortisol stress response compared to those born at term (adjusted ß: -0.74; 95% CI -1.34, -0.15), while there was no difference in Black adolescents (0.53; -0.16, 1.22). Sex did not modify the relationship. CONCLUSIONS: Adolescents born preterm exhibit a reduced salivary cortisol response to exercise stress, suggesting long-term alterations in the hypothalamic-pituitary-adrenal axis. This relationship was evident in non-Black but not in Black adolescents, suggesting that race may modify the influence of preterm birth on stress alterations of the hypothalamic-pituitary-adrenal axis.

Using Ripple Effects Mapping to Evaluate a Community-Based Health Program: Perspectives of Program Implementers.

Traditional evaluation tools are oftentimes ill-suited for use in community settings where intervention outcomes of interest may occur at multiple levels and are influenced by interacting factors. Ripple effects mapping (REM) is a participatory technique engaging stakeholders to visually map project/program efforts and results to collect impact data. Using appreciative inquiry, the method helps participants and evaluators understand context for changes resulting from program experiences and is particularly well suited for community-based, participatory programs where impacts often occur beyond the individual level. This article describes the REM method and how it was applied to explore impact and refine program theory of the Extension Wellness Ambassador Program (EWAP), a community-based health-focused master volunteer program, from the perspective of program implementers (n = 10). Insights emerging from the REM session indicate EWAP promotes health behavior change, contributes to community development due to increased leadership capacity, and sustains and grows implementing organizations. The program theory shaping evaluation was refined to better capture impact beyond individual levels. Application of the REM method to a community health program demonstrates feasibility; health promotion practitioners should consider REM to understand program context and capture outcomes that typically evade measurement using traditional techniques.

Antenatal Steroid Exposure, Aerobic Fitness, and Physical Activity in Adolescents Born Preterm with Very Low Birth Weight.

OBJECTIVE: To determine whether antenatal corticosteroid exposure is associated with aerobic fitness or physical activity participation in adolescents born preterm with very low birth weight (VLBW). STUDY DESIGN: Observational cohort study of 14-year-old adolescents (n = 173) born with VLBW between 1992 and 1996 at a regional perinatal center with 91 exposed to antenatal corticosteroids. Aerobic fitness was determined from peak oxygen uptake (V˙O2peak) obtained via maximal exercise testing on a cycle ergometer. Physical activity levels for the past year and past 2 months were estimated from a questionnaire. Between-group comparisons for continuous variables were evaluated using independent t tests or Mann-Whitney U tests. Generalized linear models were used to compare differences in fitness and physical activity between those exposed to antenatal corticosteroids and not exposed to antenatal corticosteroids, with race and sex in models. RESULTS: Regression analysis revealed an antenatal corticosteroids × sex × race interaction for V˙O2peak (P ≤ .001). Nonblack male adolescents exposed to antenatal corticosteroids had significantly greater V˙O2peak than nonblack male adolescents not exposed to antenatal corticosteroids expressed relative to body mass (mean difference [95% CI]; 8.5 [2.1-15.0] mL·kg-1·min-1) and lean body mass (9.0 [1.1-16.9] mL·kglean body mass-1·min-1). No antenatal corticosteroid group differences in V˙O2peak were evident in black male adolescents, or black and nonblack female adolescents. Male adolescents exposed to antenatal corticosteroids reported participating in significantly more total physical activity (medians: 14.6 vs 8.5) and vigorous physical activity (3.0 vs 0.95) per week for the past 2 months than male adolescents not exposed to antenatal corticosteroids. CONCLUSIONS: Exposure to antenatal corticosteroids was associated with greater physical activity participation and aerobic fitness in adolescents with VLBW, particularly in nonblack male adolescents, which may confer health benefits in this at-risk population.

Obesity is Associated with Higher Blood Pressure and Higher Levels of Angiotensin II but Lower Angiotensin-(1-7) in Adolescents Born Preterm.

OBJECTIVES: To evaluate if obesity is associated with increased angiotensin II (Ang II) and decreased angiotensin-(1-7) or Ang-(1-7) in the circulation and urine among adolescents born prematurely. STUDY DESIGN: In a cross-sectional analysis of 175 14-year-olds born preterm with very low birth weight, we quantified plasma and urinary Ang II and Ang-(1-7) and compared their levels between subjects with overweight/obesity (body mass index ≥85th percentile, n = 61) and those with body mass index <85th percentile (n = 114) using generalized linear models, adjusted for race and antenatal corticosteroid exposure. RESULTS: Overweight/obesity was associated with higher systolic blood pressure and a greater proportion with high blood pressure. After adjustment for confounders, overweight/obesity was associated with an elevated ratio of plasma Ang II to Ang-(1-7) (ß: 0.57, 95% CI 0.23-0.91) and higher Ang II (ß: 0.21 pmol/L, 95% CI 0.03-0.39) but lower Ang-(1-7) (ß: -0.37 pmol/L, 95% CI -0.7 to -0.04). Overweight/obesity was associated with a higher ratio of urinary Ang II to Ang-(1-7) (ß: 0.21, 95% CI -0.02 to 0.44), an effect that approached statistical significance. CONCLUSIONS: Among preterm-born adolescents, overweight/obesity was associated with increased Ang II but reduced Ang-(1-7) in the circulation and the kidney as well as higher blood pressure. Obesity may compound the increased risk of hypertension and cardiovascular disease in individuals born prematurely by further augmenting the prematurity-associated imbalance in the renin-angiotensin system.

Fetal programming and the angiotensin-(1-7) axis: a review of the experimental and clinical data.

Hypertension is the primary risk factor for cardiovascular disease that constitutes a serious worldwide health concern and a significant healthcare burden. As the majority of hypertension has an unknown etiology, considerable research efforts in both experimental models and human cohorts has focused on the premise that alterations in the fetal and perinatal environment are key factors in the development of hypertension in children and adults. The exact mechanisms of how fetal programming events increase the risk of hypertension and cardiovascular disease are not fully elaborated; however, the focus on alterations in the biochemical components and functional aspects of the renin-angiotensin (Ang) system (RAS) has predominated, particularly activation of the Ang-converting enzyme (ACE)-Ang II-Ang type 1 receptor (AT1R) axis. The emerging view of alternative pathways within the RAS that may functionally antagonize the Ang II axis raise the possibility that programming events also target the non-classical components of the RAS as an additional mechanism contributing to the development and progression of hypertension. In the current review, we evaluate the potential role of the ACE2-Ang-(1-7)-Mas receptor (MasR) axis of the RAS in fetal programming events and cardiovascular and renal dysfunction. Specifically, the review examines the impact of fetal programming on the Ang-(1-7) axis within the circulation, kidney, and brain such that the loss of Ang-(1-7) expression or tone, contributes to the chronic dysregulation of blood pressure (BP) and cardiometabolic disease in the offspring, as well as the influence of sex on potential programming of this pathway.

Renal function and blood pressure are altered in adolescents born preterm.

BACKGROUND: Preterm birth increases the risk of hypertension and kidney disease. However, it is unclear when changes in blood pressure (BP) and renal function become apparent and what role obesity and sex play. We hypothesized adolescents born preterm have higher BP and worse kidney function compared to term in an obesity- and sex-dependent manner. METHODS: Cross-sectional analysis of 14-year-olds born preterm with very low birth weight (n = 96) compared to term (n = 43). We used generalized linear models to estimate the associations among preterm birth and BP, estimated glomerular filtration rate (eGFR), and ln (x) urinary albumin-to-creatinine ratio (ACR), stratified by overweight/obesity (OWO, body mass index (BMI) ≥ 85th percentile) and sex. RESULTS: Compared to term, preterm-born adolescents had higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) (adjusted ß (aß) 3.5 mmHg, 95% CI - 0.1 to 7.2 and 3.6 mmHg, 95% CI 0.1 to 7.0), lower eGFR (ß - 8.2 mL/min/1.73 m2, 95% CI - 15.9 to - 0.4), and higher ACR (aß 0.34, 95% CI - 0.04 to 0.72). OWO modified the preterm-term difference in DBP (BMI < 85th percentile aß 5.0 mmHg, 95% CI 0.7 to 9.2 vs. OWO 0.2 mmHg, 95% CI - 5.3 to 5.6) and ACR (OWO aß 0.72, 95% CI 0.15 to 1.29 vs. BMI < 85th percentile 0.17, 95% CI - 0.31 to 0.65). Sex modified the preterm-term ACR difference (female aß 0.52, 95% CI 0.001 to 1.04 vs. male 0.18, 95% CI - 0.36 to 0.72). CONCLUSIONS: Prematurity was associated with higher BP and reduced renal function that were detectable in adolescence. OWO and sex may modify the strength of these relationships.

Antenatal steroid exposure and heart rate variability in adolescents born with very low birth weight.

BACKGROUND: Reduced heart rate variability (HRV) suggests autonomic imbalance in the control of heart rate and is associated with unfavorable cardiometabolic outcomes. We examined whether antenatal corticosteroid (ANCS) exposure had long-term programming effects on HRV in adolescents born with very low birth weight (VLBW). METHODS: Follow-up study of a cohort of VLBW 14-y olds born between 1992 and 1996 with 50% exposed to ANCS. HRV in both the time and frequency domains using Nevrokard Software was determined from a 5-min electrocardiogram tracing. RESULTS: HRV data from 89 (35 male, 53 non-black) exposed (ANCS+) and 77 (28 male, 29 non-black) unexposed (ANCS-) adolescents were analyzed. HRV did not differ between ANCS+ and ANCS- black participants. However, in non-black participants, a significant interaction between ANCS and sex was observed, with ANCS- females having significantly greater HRV than ANCS+ females and males, and ANCS- males for both time and frequency domain variables. CONCLUSION: Among non-black adolescents born with VLBW, ANCS exposure is associated with reduced HRV with apparent sex-specificity. Reduced HRV has been associated with development of adverse cardiometabolic outcomes, thus supporting the need to monitor these outcomes in VLBW adolescents as they mature.

Antenatal corticosteroids and cardiometabolic outcomes in adolescents born with very low birth weight.

BackgroundExposure to antenatal corticosteroids (ANCS) is associated with adverse cardiometabolic outcomes in animal models; however, long-term outcomes in clinical studies are not well characterized. We hypothesized that exposure to ANCS would be associated with markers of increased cardiometabolic risk in adolescents born with very low birth weight (VLBW).MethodsIn an observational cohort of 186 14-year-old adolescents born with VLBW, we measured resting blood pressure (BP), BP response to cold, ambulatory BP, and anthropometrics; performed dual-energy X-ray absorptiometry; and analyzed blood samples for uric acid, cholesterol, glycated hemoglobin, and high-sensitivity C-reactive protein. Multivariate analyses were used to evaluate associations with ANCS, adjusting for race, sex, and maternal hypertensive pregnancy.ResultsThere were no ANCS group differences in BP measures or blood biomarkers. Compared with adolescents unexposed to ANCS, those exposed to ANCS were taller (exposed-unexposed mean difference 3.1 cm (95% confidence interval (CI) 0.7, 5.5)) and had decreased waist-to-height ratio (exposed-unexposed mean difference -0.03 (95% CI -0.058, -0.002)). Males exposed to ANCS had lower total cholesterol (exposed-unexposed mean difference -0.54 mmol/l (95%CI -0.83, -0.06)).ConclusionAmong adolescents born with VLBW, ANCS exposure was not associated with markers of increased cardiometabolic risk.

Antenatal corticosteroids and the renin-angiotensin-aldosterone system in adolescents born preterm.

BACKGROUND: Antenatal corticosteroid (ANCS) treatment hastens fetal lung maturity and improves survival of premature infants, but the long-term effects of ANCS are not well-described. Animal models suggest that ANCS increases the risk of cardiovascular disease through programmed changes in the renin-angiotensin (Ang)-aldosterone system (RAAS). We hypothesized that ANCS exposure alters the RAAS in adolescents born prematurely. METHODS: A cohort of 173 adolescents born prematurely was evaluated, of whom 92 were exposed to ANCS. We measured plasma and urine Ang II and Ang-(1-7) and calculated Ang II/Ang-(1-7) ratios. We used general linear regression models to estimate the difference in the RAAS between the ANCS-exposed and unexposed groups, adjusting for confounding variables. RESULTS: In unadjusted analyses, and after adjustment for sex, race, and maternal hypertension, ANCS exposure was associated with increased urinary Ang II/Ang-(1-7) (estimate 0.27 (95% CI 0.03, 0.5), P = 0.03), increased plasma Ang-(1-7) (0.66 (0.26, 1.07), P = 0.002), and decreased plasma Ang II/Ang-(1-7) (-0.48 (-0.91, -0.06), P = 0.03). CONCLUSION: These alterations indicate an imbalance in the urinary RAAS, promoting the actions of Ang II at the expense of Ang-(1-7), which over time may increase the risk of renal inflammation and fibrosis and ultimately hypertension and renal disease.

Preterm Birth Is Associated with Higher Uric Acid Levels in Adolescents.

OBJECTIVE: To compare serum uric acid levels in adolescents born prematurely and adolescents born at term and to assess the correlation between serum uric acid and blood pressure (BP) in those born prematurely. STUDY DESIGN: In this observational cohort study, 124 adolescents born prematurely and 44 adolescents born at term were studied at 14 years of age. Multivariate analyses were used to describe the relationship of premature birth to serum uric acid while adjusting for confounding variables. Pearson correlation was used to describe the relationship between uric acid and systolic BP among those born prematurely. RESULTS: Adjusting for race, sex, maternal hypertension, and fetal growth, we found that preterm adolescents had greater serum uric acid levels than adolescents born at term (adjusted mean difference 0.46, 95% CI 0.10-0.81 mg/dL; 27.4, 6-48.2 µmol/L; P = .012). Among those born prematurely, uric acid was positively correlated with systolic BP (Pearson correlation coefficient: 0.29, 0.12-0.44; P = .0013). CONCLUSIONS: Serum uric acid levels are greater in adolescents born prematurely than in those born at term, and this difference could contribute to greater BP among individuals born prematurely.

The role of preterm birth in stress-induced sodium excretion in young adults.

BACKGROUND: Early-life programming due to prematurity and very low birth weight (VLBW, <1500 g) is believed to contribute to development of hypertension, but the mechanisms remain unclear. Experimental data suggest that altered pressure natriuresis (increased renal perfusion pressure promoting sodium excretion) may be a contributing mechanism. We hypothesize that young adults born preterm will have a blunted pressure natriuresis response to mental stress compared with those born term. METHODS: In this prospective cohort study of 190 individuals aged 18-23 years, 156 born preterm with VLBW and 34 controls born term with birth weight at least 2500 g, we measured urine sodium/creatinine before and after a mental stress test and continuous blood pressure before and during the stress test. Participants were stratified into groups by the trajectory at which mean arterial pressure (MAP) increased following the test. The group with the lowest MAP trajectory was the reference group. We used generalized linear models to assess poststress urine sodium/creatinine relative to the change in MAP trajectory and assessed the difference between groups by preterm birth status. RESULTS: Participants' mean age was 19.8 years and 57% were women. Change in urine sodium/creatinine per unit increase in MAP when comparing middle trajectory group against the reference group was greater in those born preterm [ß 5.4%, 95% confidence interval (95% CI) -11.4 to 5.3] than those born term (ß 38.5%, 95% CI -0.04 to 92.0), interaction term P = 0.002. CONCLUSION: We observed that, as blood pressure increased following mental stress, young adults born preterm exhibited decreased sodium excretion relative to term-born individuals.

Risk of Obesity and Unhealthy Central Adiposity in Adolescents Born Preterm With Very Low Birthweight Compared to Term-Born Peers.

Background: Early-life factors such as preterm birth or very low birthweight (VLBW) are associated with increased cardiovascular disease risk. However, it remains unknown whether this is due to an increased risk of obesity (unhealthy central adiposity) because studies have predominantly defined obesity based on BMI, an imprecise adiposity measure. Objective: Investigate if adolescents born preterm with VLBW have a higher risk of unhealthy central adiposity compared to term-born peers. Study Design: Cross-sectional analysis of data from a prospective cohort study of 177 individuals born preterm with VLBW (<1500 g) and 51 term-born peers (birthweight ≥2500 g). Individuals with congenital anomalies, genetic syndromes, or major health conditions were excluded. Height, weight, waist circumference, skin fold thickness, and dual energy X-ray absorptiometry body composition were measured at age 14 years. We calculated BMI percentiles and defined overweight/obesity as BMI ≥85th percentile for age and sex. We estimated the preterm-term differences in overweight/obesity prevalence and adiposity distribution with multivariable generalized linear models. Results: There was no difference in small for gestational age status or overweight/obesity prevalence. Compared to term, youth born preterm with VLBW had lower BMI z-score [ß -0.38, 95% confidence limits (CL) -0.75 to -0.02] but no differences in adiposity apart from subscapular-to-triceps ratio (STR; ß 0.18, 95% CL 0.08 to 0.28). Conclusions: Adolescents born preterm with VLBW had smaller body size than their term-born peers and had no differences in central adiposity except greater STR.

Adiposity in adolescent offspring born prematurely to mothers with preeclampsia.

OBJECTIVE: To evaluate the relationship between maternal preeclampsia resulting in premature delivery and adiposity in the offspring during adolescence. STUDY DESIGN: The 172 study participants were 14 years old and had very low birth weight. We compared height, weight, body mass index (BMI), percent fat, waist circumference, and triceps and subscapular skin fold thicknesses between those born prematurely secondary to preeclampsia (n = 51; 22 male) and those born prematurely after normotensive pregnancies (n = 121; 55 male). Multiple linear regression analysis was used to adjust for potential confounders (maternal BMI, antenatal steroid exposure, and race) and to evaluate potential explanatory variables (fetal, infancy, and childhood weight gain, and caloric intake, level of fitness, and physical activity at 14 years). RESULTS: When adjusted for potential prenatal confounders (antenatal steroid exposure and race), adolescent male offspring of preeclamptic pregnancies had higher BMI (4.0 kg/m(2) [1.5, 6.6]) (mean difference [95% CI]), waist circumference (11.8 cm [3.8, 19.7]), triceps (4.6 mm [0.6, 8.6]) and subscapular skinfold thicknesses (6.2 mm [1.5, 10.9]), and percent body fat (4.1% [-0.1, 8.3]). Adjusting for infancy and childhood weight gain attenuated these group differences. There were no group differences among females. CONCLUSION: Male adolescent offspring born prematurely of women with preeclampsia have higher measures of adiposity than those born prematurely of normotensive pregnancies.

U.S. Cooperative Extension's response to substance misuse: A scoping review.

Background: The U.S. has experienced exponential growth in overdose fatalities over the past four decades and more than 22 million people are currently living with a substance use disorder (SUD). While great strides have been made in advancing the science of SUD prevention and treatment, proven programs and interventions are not commonly disseminated at scale in impacted communities. The U.S. Cooperative Extension System (Extension) has been recognized as a valued partner in addressing SUD in communities. Federal funding supporting Extension's response to the opioid epidemic reached $35 million in 2021 primarily through two grant programs: the United States Department of Agriculture's (USDA) Rural Health and Safety Education program; and the Substance Abuse and Mental Health Services Administration (SAMHSA) Rural Opioid Technical Assistance (ROTA) grants. The primary objective of this scoping review was to identify the range of Extension activities aimed at mediating substance misuse. Methods: Authors utilized the PRISMA-SCR model to complete this scoping review. Due to the nature of Extension work and the expectation that few activities would be cited in the peer-reviewed literature, the scoping review included a search of peer-reviewed databases, Extension websites for each state and U.S. territory, and the utilization of a web search engine. Upon initial analysis of records returned, authors noted a discrepancy between results returned and the number of states receiving ROTA grants. Thus, authors supplemented the PRISMA-SCR review protocol with a systematic procedure for investigating ROTA funded activities not readily apparent in the peer-reviewed or grey literature. Results: A total of 87 records met inclusion criteria. Findings included seven peer-reviewed articles and 80 results from the grey literature. An additional 11 ROTA grantees responded to requests for information regarding state level activities. Conclusions: Nationwide, Extension has scaled multiple efforts to address SUD operating through a loose confederation of organizations connected to the land-grant system. Most activities are funded by federal grants and focus on state-sponsored training and resource sharing. The volume of effort is significant, however, implementation at the community-level has been slow. Significant opportunities exist for local adoption of evidence-based practices aimed at mitigating SUD.

Association of antenatal corticosteroids with kidney function in adolescents born preterm with very low birth weight.

OBJECTIVE: Investigate if antenatal corticosteroids (ANCS) are associated with worse kidney function in adolescence and if greater adiposity magnifies this association. STUDY DESIGN: Prospective cohort of 162 14-year-olds born preterm with very low birth weight (<1500 g). Outcomes were estimated glomerular filtration rate (eGFR) and first-morning urine albumin-to-creatinine ratio (UACR). We used adjusted generalized linear models, stratified by waist-to-height ratio (WHR) ≥ 0.5. RESULTS: Fifty-five percent had ANCS exposure and 31.3% had WHR ≥ 0.5. In adjusted analyses of the entire cohort, ANCS was not significantly associated with eGFR or UACR. However, the ANCS-eGFR association was greater in those with WHR ≥ 0.5 (ß -16.8 ml/min/1.73 m2, 95% CL -31.5 to -2.1) vs. WHR < 0.5: (ß 13.9 ml/min/1.73 m2, 95% CL -0.4 to 28.1), interaction term p = 0.02. CONCLUSION: ANCS exposure was not associated with worse kidney function in adolescence, though ANCS may be associated with lower eGFR if children develop obesity by adolescence.

Cooperative Extension professionals' knowledge and attitudes toward the opioid epidemic: Implications for capacity development and outreach.

Introduction: Worsening of the opioid epidemic amplifies calls for involvement of the nationwide Cooperative Extension System (Extension) in addressing this crisis. Understanding knowledge and attitudes among Extension professionals who directly interact with communities is critical given identified needs for increased capacity and substantial federal investments supporting Extension's opioid response. This study explored opioid knowledge and attitudes among Extension professionals in one state to identify attitudes and perceptions that may influence community-level efforts. Methods: An online survey including 25 Likert scale questions about attitudes and beliefs related to substance use was administered to Extension professionals. Questions were categorized into five concept areas: treatment and community support, legal and punitive approaches, substance use as an illness, external causes of substance use, and personal causes of substance use. Descriptive statistics and response frequencies for all variables were calculated. One-way ANOVAs were used to calculate geographic differences between the state's three Extension regions. Results: Survey responses (n = 236) indicated respondents recognized the complexity of the opioid crisis and had favorable attitudes toward treatment and community support approaches. Support for legal and punitive approaches was mixed, as were attitudes toward external and personal causes of substance use. Most indicated needing better resources and more knowledge to engage in work locally. Conclusion: Increased capacity is needed in Extension to adequately support families and communities dealing with substance use disorder. Findings suggest areas of focus and provide insight for others seeking to develop capacity in opioid response by engaging Extension professionals or other community outreach workers in substance use prevention efforts.