Critical Period Research Articles

Early-Life Sodium Restriction Programs Autonomic Dysfunction and Salt- Sensitivity in Male C57BL/6J Mice.

Preterm birth increases the risk of cardiometabolic disease in adulthood. Infants born during the second trimester of pregnancy, a critical period of hypothalamic development, are at risk of sodium (Na) depletion due to renal immaturity and large urine Na losses. We previously demonstrated in male mice that Na restriction during the equivalent mouse hypothalamic development period (PD21-PD42) programs long-term changes in energy balance via increased thermogenic sympathetic nervous activity. We therefore hypothesized that early-life Na restriction programs changes in cardiovascular control via altered autonomic activity. C57BL/6J male mice were supplied a low (0.04%) Na or supplemented (0.30%) Na diet from PD21-PD42, before return to standard (0.15%) Na diet. Hemodynamic and autonomic functions were assessed by radiotelemetry and acute administration of autonomic antagonists before and after all animals were switched to a high Na diet (HSD; 1% Na) at 12 weeks of age. Mice were additionally treated with the angiotensin II type 1 receptor (AT1R) antagonist, losartan, for two weeks. On standard diet, early-life Na restriction resulted in small but significantly different hemodynamic responses to autonomic blockers without effect on systolic blood pressure (SBP) or heart rate (HR). HSD increased SBP in 0.04% but not 0.30% Na mice, accompanied by increased cardiac sympathetic activity. Losartan had a greater BP lowering effect in early life Na-restricted mice. Our findings suggest Na restriction during a critical hypothalamic developmental period programs long-term changes in autonomic control of cardiovascular functions and may offer insight into the increased risk of cardiovascular disease in former preterm infants.

Endocannabinoid dysregulation and PTSD in urban adolescents: Associations with anandamide concentrations and FAAH genotype.

The endocannabinoid system, which regulates fear- and anxiety-related behaviors, is dysregulated in adults with posttraumatic stress disorder (PTSD), as indicated by higher circulating anandamide (AEA) concentrations. The C385A (rs324420) polymorphism in the fatty acid amide hydrolase (FAAH) gene, which catabolizes AEA, is linked to higher AEA concentrations and greater PTSD symptoms in adults. Given that adolescence is a critical period during which trauma and psychiatric disorders emerge, understanding this relationship in youth is essential. This study examines PTSD symptoms, AEA concentrations, and FAAH genotype in a diverse adolescent sample. This study included 102 Detroit-area adolescents (M ± SD = 13.33 ± 2.21 years, 54.9% female) and their parents/guardians. The sample consisted of 40.2% White Non-Hispanic, 34.3% Black Non-Hispanic, 6.9% White Hispanic, 4.9% Asian/Pacific Islander, and 12.7% Biracial adolescents. Trauma exposure and PTSD symptoms were assessed using the UCLA PTSD Reaction Index for DSM-5. Plasma concentrations of AEA were measured by liquid chromatography-tandem mass spectrometry, and FAAH genotype was determined from saliva samples and high-throughput screening. The majority (90%) of adolescents reported trauma exposure, and 20% met PTSD criteria. Higher AEA concentrations were associated with more severe PTSD symptoms (p = 0.009), especially hyperarousal. The FAAH A-allele (present in 52.5% of participants) was associated with higher AEA concentrations (2.11 ± 0.69 pmol/ml, p = 0.013) and greater PTSD severity (22.65 ± 15.931, p = 0.027), particularly those with the reexperiencing cluster, compared to the CC genotype (1.79 ± 0.66 pmol/ml and 15.87 ±+ 13.043, respectively). Elevated AEA concentrations and the FAAH A-allele were associated with greater PTSD symptom severity in urban adolescents. These findings suggest endocannabinoid dysregulation may play a role in adolescent PTSD, highlighting the need for further research and targeted interventions.

Maternal Characteristics and Iron Intake as a Factors of Iron Deficiency Anemia among Pregnant Women

Pregnancy is a critical period for fetal growth and development, nutritional issues can significantly affect both maternal and fetal health. This phase is marked by increased nutritional needs to support fetal development and maintain maternal well-being. This study investigates the prevalence and risk factors of iron deficiency anemia among pregnant women in Parung Panjang District Health Center, Indonesia. A cross-sectional study was conducted on 92 pregnant women, examining various maternal characteristics and nutrient adequacy levels. The prevalence of anemia was found to be 36%. Parity emerged as a significant factor, with primipara mothers showing a higher anemia rate (46%) compared to multipara mothers (23.8%). Iron intake adequacy was also significantly associated with anemia status (p = 0.050). Women with insufficient iron intake had a higher rate of anemia (45.7%) compared to those with sufficient intake (26.1%). Other factors such as maternal age, education, and vitamin C intake did not show significant associations with anemia. These findings highlight the importance of targeted interventions for primipara mothers and emphasize the crucial role of adequate iron intake during pregnancy. The study underscores the need for comprehensive anemia prevention strategies in prenatal care.

A prospective multicenter birth cohort in China: pregnancy health atlas.

The China Prospective Multi-Center Birth Cohort Study was launched in 2022. In collaboration with medical centers in 12 cities, it aims to establish a high-quality, multidimensional cohort comprising 20,000 natural pregnancy and assisted reproductive families. As of June 26, 2024, 12,911 pregnant women have participated in this study, and 161,122 biological samples have been collected. These samples cover four critical periods (early pregnancy, mid-pregnancy, late pregnancy, and postpartum) and comprise 10 different types such as serum, plasma, and urine. The study has collected comprehensive information from early pregnancy to newborns. The participants have an average age of 29.76years, an average height of 160.46cm, an average pre-pregnancy BMI of 23.11, and an average BMI of 27.25 before delivery. The cohort includes individuals from 26 ethnic groups, with 25 minority groups comprising 5.03% of the population. Guizhou Province exhibits the highest percentage of ethnic minorities at 24.96% and Guangdong Province owns the highest proportion (12.22%)of women with two or more children. The prevalence of thalassemia in Guangdong Province is seven times higher than in other provinces. Among pregnant women over 35years old, the prevalence of gestational diabetes mellitus is twice that of women under 35. Additionally, the prevalence of preeclampsia in women with assisted reproductive pregnancies is more than twice that of those with natural pregnancies. The study extensively collected diverse data and biological samples, making this cohort an ideal candidate for DOHaD field and multi-omics research.

Associations of Neighborhood Food and Physical Activity Environments in Young Adulthood With Cardiovascular Health in Midlife: The CARDIA Study.

Adults who maintain ideal cardiovascular health (CVH) profiles up to midlife have lower risk of several chronic diseases and better quality of life. Some evidence suggests that individual-level exposures earlier in life shape midlife CVH, but the impact of neighborhood-level exposures over the life course remains understudied. Participants were 3017 Black and White men and women aged 18 to 30 years at baseline (1985-1986), recruited from Birmingham, Alabama; Minneapolis, Minnesota; Chicago, Illinois; and Oakland, California, as part of the CARDIA (Coronary Artery Risk Development in Young Adults) study. Measures of the neighborhood food and physical activity environment were linked to participant addresses collected at baseline. CVH was measured on the basis of the American Heart Association's Life's Simple 7 criteria in young adulthood and 30 years later (2015-2016) when participants were midlife (aged 48-60 years). Associations of young adult neighborhood food environment and physical activity resources with midlife CVH (moderate versus high and low versus high) were examined using multinomial logistic regression. Models were adjusted for young adult sociodemographic factors. Participants who lived farther away from a major park in young adulthood were more likely to have low versus high CVH scores (odds ratio, 1.54 [95% CI, 1.22-1.96]) and more likely to have moderate versus high CVH scores (odds ratio, 1.39 [95% CI, 1.12-1.73]) in midlife. No other neighborhood measures were significantly associated with CVH. Young adulthood may be a sensitive period in which having convenient access to physical activity-promoting resources may help them establish healthy habits that can carry into midlife.

The impact of the early environment on oxytocin receptor epigenetics and potential therapeutic implications.

Oxytocin research is rapidly evolving and increasingly reveals that epigenetic modifications to the oxytocin receptor gene (OXTR) are functional, plastic, and reliable components of oxytocinergic system function. This review outlines how OXTR epigenetics are shaped by the early life environment, impact social-developmental outcomes, and have strong potential to serve as therapeutic targets. We first establish the malleability of OXTR epigenetics in infancy in both animal models and humans through research demonstrating the impact of the early life environment on OXTR DNA methylation (OXTRm) and subsequent social behavior. Next, we detail how OXTRm serves as a predictive mechanism for neurodevelopmental outcomes in animal models of social behavior such as the prairie vole, and summarize the role of OXTRm in psychiatric disorders, emotional processing, and attachment behavior in humans. We discuss the potential of further OXTRm research to improve oxytocin therapeutics by highlighting how a deeper knowledge of OXTRm could improve the therapeutic potential of exogenous oxytocin, how OXTRm may impact additional cellular mechanisms with therapeutic potential including control of the perinatal GABA switch, and how early life therapies may target the tuning of endogenous OXTRm. Finally, we review limitations of previous oxytocin research and make recommendations for future research. IMPACT: Previous research into oxytocin therapeutics has been hampered by methodological difficulties that may be improved by assay of the oxytocin receptor gene (OXTR) and its methylation (OXTRm) Key sites of OXTRm modification link early life exposures to developmental and behavioral outcomes OXTRm appears to have a critical period of development in early life Epigenetic modification of the oxytocin receptor gene could serve as a powerful target for therapeutic interventions.

A New Geological Map of the Marginal Basins of Eastern Papua New Guinea: Implications for Crustal Accretion and Mineral Endowment at Arc–Continent Collisions

Abstract Accretion of island arc terranes is a fundamental process of crustal growth and the formation of new continents. Convergent margin tectonics, both compressional and extensional, in accretionary orogens also control the origin and distribution of their contained mineral resources, including many of the world’s important Cu and Au deposits. However, the details of crustal growth and accretion are often lost because of deformation and selective preservation during subduction. The Melanesian Borderland, which includes the offshore regions of eastern Papua New Guinea and the Solomon Islands, contains several active and relict arc and backarc systems that have formed in response to more than 50 Ma of subduction and complex plate tectonic adjustments. The composite terrane is a region of some of the fastest growing crust on Earth and also spectacular mineral endowment, including three of the top ten porphyry Cu and epithermal Au deposits in the world. However, more than 80% of the belt is submerged, and so little is known about its geological evolution and makeup. Here, we present the first detailed geological map of the region in one map sheet, including the marginal deep ocean basins. The map identifies and groups the key lithostratigraphic formations and correlates associated tectonic events across the belt. The final compilation is presented at 1:1,000,000 scale, which is sufficient to allow quantitative analysis of crustal growth and accretion during ocean–continent collision throughout the region. The map shows the diversity of assemblages in accreting terranes that may eventually become part of a growing continent and highlights their complex formation and structural relationships. Because so much of that history has occurred offshore, the new map presents the first complete picture of the geology of the region in the critical period leading up to its eventual incorporation in the Australian continent.

Digital media in early childhood: risk factors for online harm and psychosocial correlates

IntroductionEarly and middle childhood are times of rapid development, and critical periods for laying the foundations of life-long trajectories of socioemotional well-being. High levels of screen media use are of growing concern to parents, health professionals, and researchers, given the increasing body of research demonstrating detrimental impacts of excessive screen use in young children. One particular consequence is the risk that children encounter online content or experiences that are upsetting or distressing, including exposure to inappropriate or adult content, cyberbullying, and interactions with strangers that they don't know.MethodsThis research examined experiences of online harm reported in a sample of 8-year-old children, with a focus on identifying risk factors and psychosocial correlates of online harm. Data for this study were collected from children and their mothers as part of the prospective longitudinal Growing Up in New Zealand (GUiNZ) study (n = 4,920 children with data at age 8). Children were assessed at 4.5-years-old and 8-years-old.ResultsThe findings of this research indicate that approximately a quarter of New Zealand children have experienced online harm (that is, have encountered online content that worried, upset, or bothered them) by the age of 8. Our analysis indicates that children with behavioral difficulties are at greater risk of online harm, as are children with more personal devices. Experiences of online harm were found to be negatively associated with child self-worth and positively associated with depressive symptoms.DiscussionFindings highlighting the critical importance of considering online harm as a contributing factor to child and youth well-being and mental health in our media-saturated world. Our results also point to practical solutions for parents, such as limiting the number of personal media devices that children have in early and middle childhood.

Upper Limb Therapy for Infants and Young Children with Unilateral Cerebral Palsy: A Clinical Framework

Early detection and rehabilitation interventions are essential to optimise motor function in infants and young children with unilateral cerebral palsy. In this paper we report a clinical framework aimed at enhancing upper limb therapy for infants and young children with unilateral cerebral palsy during a sensitive period of brain development. We describe two major therapeutic approaches based on motor learning principles and evidence: constraint-induced movement therapy and bimanual therapy. These two therapies have demonstrated efficacy in older children and emerging evidence is available for their application to infants younger than 2 years of age. To provide clinicians with guidance as to when to implement these therapies, we discuss the key consideration when undertaking upper limb therapy programs. In addition, we describe the factors to consider when choosing which approach may be suitable for an individual child and family. Detailed strategies for implementing these therapies in infants and young children of different ability levels are given.

Imaging Photoplethysmography (iPPG) in Head and Neck Reconstructive Surgery: A Novel Technique for Noninvasive Flap Perfusion Monitoring.

Evaluate imaging photoplethysmography (iPPG) as a novel noninvasive technique to assess flap perfusion in head and neck free flap reconstructive (FFR) surgeries. Intraoperative iPPG was performed in 17 patients undergoing FFR surgery. Imaging consisted of a 30-s video from which perfusion maps were extracted, providing detailed information about blood flow and pulsatility in the flap microvasculature. During each procedure, iPPG acquisitions were acquired representing distinct perfusion conditions of the flap (fully perfused/ischemic/reperfused). When possible, postoperative measurements were performed to assess flap recovery during the critical time period (3 days) and long-term follow-up (30 days). Perfusion maps, displaying iPPG amplitude and delay times, correlated strongly (p < 0.001) with the perfusion status of the tissue. One case of postoperative thrombosis, leading to flap failure, was identified with iPPG. After surgical revision in this case, flap perfusion was restored and confirmed by iPPG. Postoperative follow-up imaging allowed for objective visualization of flap recovery short term (3 days) and up to 30 days after the surgical procedure. This study shows that iPPG is suitable for objective and noninvasive assessment of flap perfusion in head and neck FFR surgery. In addition, postoperative monitoring shows potential for assessing flap perfusion in patients with increased risk of postoperative complications.

Prenatal chemical exposures and the methylome: current evidence and opportunities for environmental epigenetics.

Exposure to pollutants and chemicals during critical developmental periods in early life can impact health and disease risk across the life course. Research in environmental epigenetics has provided increasing evidence that prenatal exposures affect epigenetic markers, particularly DNA methylation. In this article, we discuss the role of DNA methylation in early life programming and review evidence linking the intrauterine environment to epigenetic modifications, with a focus on exposure to tobacco smoke, metals, and endocrine-disrupting chemicals. We also discuss challenges and novel approaches in environmental epigenetic research and explore the potential of epigenetic biomarkers in studies of pediatric populations as indicators of exposure and disease risk. Overall, we aim to highlight how advancements in environmental epigenetics may transform our understanding of early-life exposures and inform new approaches for supporting long-term health.

Spatiotemporal analysis of Zika virus transmission dynamics incorporating human mobility and seasonal variations using modified homotopy perturbation method

AbstractThis study employed a mathematical model to evaluate how seasonal variations, vector dispersal, and mobility of people affect the spread of the Zika virus. The model's positive solutions, invariant zones, and solution existence and uniqueness were validated through proved theorems. The equilibria points were identified, and the basic reproduction number was calculated. The model was semi-analytically solved using a modified homotopy perturbation approach, and an applied convergence test proved that the solution converges. The simulation results indicated that under optimal breeding conditions, the density of healthy mosquitoes peaked in the fourth month. Two months later, increased mosquito dispersal and human carriers facilitated by favorable weather led to a rise in mosquito infectiousness, peaking between the fourth and eighth months due to significant seasonal effects, resulting in high Zika transmission. To effectively control mosquito populations and reduce Zika transmission, it is recommended that public health interventions focus on the critical periods spanning the third to eighth months.

The next generation of physician-researchers: undergraduate medical students' and residents' attitudes, challenges, and approaches towards addressing them.

Undergraduate medical education and residency training are critical periods for conducting research. Medical diagnoses and therapies are direct results of successful research efforts that have advanced several scientific fields. This review highlights the importance of incorporating scientific research training into the curricula of undergraduate medical education and residency programs. We utilized key databases such as PubMed, Web of Science, and Google Scholar to conduct a narrative review of English-language articles published between 2002 and 2024. Ultimately, we selected 49 studies that examined the attitudes of undergraduate medical students and residents toward research, the common challenges they encounter while participating in research activities, and the strategies that support and encourage their involvement, all in alignment with our study objectives and keywords. In addition, we identified several relevant themes, including the value of research experience in shaping well-rounded medical professionals; the integrity of research practices in residency selection, which addresses concerns such as the arms race and misrepresentation, as well as the balance between quality and quantity; striking a balance between research and clinical training while promoting equity and inclusion; and effective programs and mentorship strategies to enhance research engagement. Translating the positive attitudes of undergraduate medical students and residents into improved knowledge and practice necessitates the development of structured mentoring programs and advanced training systems. Institutions must provide the necessary tools, guidance, and support to overcome research barriers. This will help establish an environment in undergraduate medical education and residency training that values research, facilitates access to it, and integrates it into the curriculum. To address the critical shortage of physician-researchers and improve evidence-based medical practice, it is crucial for medical schools to focus on research education and create avenues for student involvement. By tackling research challenges and implementing supportive strategies, these efforts empower the next generation of physician-researchers to embrace research, contribute to medical progress, and uphold the highest standards of patient care.

Physical Fitness and Self-Perception in Adolescents: A Public Health Perspective

Adolescence is a critical period for physical and psychological development. The relationship between physical fitness and self-perception, particularly in the context of adolescents, has garnered significant attention due to its implications for long-term health outcomes. This article explores the intersection of physical fitness and self-perception in adolescents, emphasizing the role of physical activity in shaping self- esteem, body image, and mental health. From a public health perspective, promoting physical fitness in this age group can contribute not only to improved physical health but also to better psychological well-being. The article discusses interventions, policy initiatives, and practical recommendations to support adolescents in developing positive physical fitness habits and fostering healthy self-perception.

Impact of the COVID-19 pandemic on children and adolescents with autism spectrum disorder and their caregivers

Objective: To analyze the impact of the COVID-19 pandemic and social distancing on children and adolescents with autism spectrum disorder (ASD) and their caregivers. Methods: Observational, descriptive, and cross-sectional study conducted with parents/caregivers of children with ASD through an online questionnaire with 39 questions. Data were collected from October 2020 to January 2021, referring to the critical period of the pandemic in Ceará, from March to June 2020. Results: Of the 122 research participants (children/adolescents aged 2 to 18 years, average of 6.7 years), 87.7% interrupted multidisciplinary treatments during isolation. Most caregivers (86.8%) had more difficulties managing the children's free time. Behavioral problems became more intense for 61.5% and more frequent for 59.8% of participants. Difficulties in managing meals were reported by 39.3% of participants, and 97.1% stated that problems in managing autonomy were amplified. Behavioral regressions and worsening symptoms occurred in 81.1% of cases. Children and adolescents with pre-pandemic behavioral problems showed a significantly greater increase in the intensity (OR = 3.87, p = 0.05) and frequency (OR = 3.42, p = 0.05) of behavioral problems. In contrast, being an only child proved to be a protective factor against the negative impacts of isolation, with a significant reduction in the intensification (OR = 0.16, p &lt; 0.05) and frequency (OR = 0.08, p &lt; 0.01) of behavioral problems. Conclusion: The COVID-19 pandemic and social distancing negatively altered behavior, eating, and self-care patterns in children and adolescents with ASD, making this period more challenging for their caregivers.

Cannabis, Endocannabinoids and Brain Development: From Embryogenesis to Adolescence

The endocannabinoid signalling system (ECS) plays a critical role from the very beginning of embryogenesis. Accordingly, the ECS is engaged early on in nervous system development, starting from neurulation, supported by the identification of ECS components—both receptors and enzymes controlling endocannabinoid metabolism—at these early stages. In particular, regarding the brain, the ECS is involved in the tightly regulated sequence of events that comprise brain development, from neurogenesis to neuronal migration, morphological guidance for neuronal connectivity, and synaptic circuitry refinement. The importance of this broad role of the ECS across various brain development processes is further underscored by the growing understanding of the consequences of cannabis exposure at different developmental stages. Despite the considerable knowledge we have on the role of the ECS in brain development, significant gaps in our understanding remain, particularly regarding the long-term impact and underlying mechanisms of cannabis exposure at different developmental stages. This review provides an overview of the current state of knowledge on the role of the ECS throughout brain development, from embryogenesis to adulthood, and discusses the impact of cannabis exposure, especially during adolescence—a critical period of circuitry maturation and refinement coinciding with an increased risk of cannabis use.

Early-Life Stress Influences the Transcriptional Activation of Alpha-2A Adrenergic Receptor and Associated Protein Kinase A Signaling Molecules in the Frontal Cortex of Rats.

Early life is a highly sensitive period associated with profound changes in brain structure and function. Adverse experiences of early-life stress (ELS) are prominent risk factors for the precipitation of major depressive disorder (MDD). In recent years, dysfunction of the central noradrenergic (NA) system and subsequent deficits in norepinephrine (NE) signaling have gained increasing attention in the pathophysiology of MDD. However, the role of the α-2A adrenergic receptor and its downstream second messenger signaling system has not been investigated in connection to early-life stress-induced depression, limiting valuable insights into neurobiological mechanisms underlying this disorder. In this study, we used maternal separation (MS) as a rodent model of ELS to investigate whether ELS-induced depressive behavior is related to the α-2A adrenergic receptor and its associated second messenger signaling cascade. To do so, we studied expression levels of the α-2A adrenergic receptor (Adra2a), G alpha proteins (stimulatory subunit-Gαs [Gnas] and inhibitory subunit-Gαi [Gnai1 and Gnai2]), and downstream protein kinase A (PKA) catalytic [Prkarcα and Prkarcβ] and regulatory subunits [Prkar1α, Prkar1β, Prkar2α, and Prkar2β]) in the frontal cortex (FC) of MS rats. We found reduced sucrose preference in MS animals, along with reduced transcript levels of Adra2a, Gnai2, Prkar1β, and Prkarcβ. These findings suggest that ELS exposure may contribute to depression symptomatology via alterations in the expression of key genes involved in the NA system, highlighting potential mechanisms underlying ELS-induced depressive behavior.

Abstract 4117594: Fetal Synthetic Glucocorticoid (sGC) Exposure Results in Later Life Cardiac Dysfunction and Ventricular Remodeling in Male Baboon Offspring

The “theory of developmental origins of health and disease” posits that stress in critical developmental periods will program life-course health and may affect cardiovascular (CV) health. Mothers at risk for premature delivery receive synthetic glucocorticoids (sGC) to enhance fetal lung maturation and manage fetal respiratory distress, but sGC exposure is linked to long-term CV dysfunction in offspring. Four groups of male baboons were studied: sGC exposed in utero at middle age (sGC-MA, 13.8±0.2Y), older sGC exposed in utero (sGC-O, 17.1±0.4Y), middle age unexposed (CTR-MA, 13.5±0.6Y), and older, unexposed baboons (CTR-O, 17.4±0.4Y). Gated, breath-hold, cine cardiac magnetic resonance imaging was performed at 3 Tesla (Siemens TIM Trio) to assess left ventricular (LV) function and myocardial strain, analyzed using cvi42® software. Mitochondrial electron transport chain (ETC) complex activity was analyzed using LV tissue from sGC-O and CTR-O euthanized baboons. Protein quantification was used to measure mitochondrial function and RNA-seq assessed differential gene expression and gene ontology (GO) enrichment. Unpaired t-tests were used. Data are reported as mean ± SD. Stroke volume and ejection fraction were similar in the elderly groups (4 sGC-O, 8 CTR-O). However, higher end-systolic and end-diastolic sphericity indexes (SI) and shorter LV axis lengths indicated remodeling. Also, global longitudinal and radial strains were reduced (both p&lt;0.04) in sGC-O vs. CTR-O. Reduced LV cardiac output (p=0.005) was found in 5 sGC-MA animals vs 4 sGC-O animals, but not in 5 CTR-MA vs 8 CTR-O. In sGC-MA vs sGC-O, but not CTR-MA vs CTR-O, significant increases in SI (p=0.001), radial strain (p=0.02), and longitudinal (p=0.03) strain were found, but LV axis length (p=0.03) was reduced. LV mitochondrial analysis in 4 sGC-O vs 4 CTR-O myocardial samples revealed 33.5% less ETC activity (p=0.002) and 19.8% less complex I expression (p=0.048) in sGC. LV RNA-seq identified 63 upregulated and 20 downregulated genes in the sGC-O samples. GO pathway enrichment included changes in heart contraction, wounding responses, and leukocyte regulation pathways. These findings indicate that fetal sGC exposure developmentally programs offspring with LV remodeling and long-term cardiac and gene expression changes in male baboons, the closest available experimental nonhuman primate species to man. Future studies on females will probe sexual dimorphism in developmental programming.

Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD). Methods: CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education. Results: There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) ( Figure ). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8. Conclusions: Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.

Abstract 4141472: Birthweight is Associated with Left Ventricular Mass Index in Childhood

Introduction/Background: Increased left ventricular mass (LVM) is a risk factor for adult CV disease and is associated with cardiac development in utero. Associations of birthweight with LVM have been demonstrated in young children and adolescence, however, the association between birth weight and LVM in mid-childhood is not well described. Research Questions/Hypothesis: Utilizing an existing longitudinal data set of healthy children, we aimed to determine the association of birthweight to increased LVM at 6-8 years of age. Methods/Approach: A longitudinal cohort of 372 term-born children was enrolled at age 3 and followed until age 6-8 years. Anthropometrics, echocardiography, and maternal recall of birth weight were collected. LVM from echocardiography was indexed to height 2.7 . Multiple linear regression analysis was performed to assess the association of birthweight with LVM index at 6-8 years of age, adjusting for race, sex, body mass index (BMI) z-score, and systolic blood pressure (SBP) percentile collected at the time of echocardiography. Results: 303 children were included in the analysis (21.5% Black and 88.5% White, mean age 7.4 ± 0.3 years at the time of echocardiography, mean birthweight 3.4 ± 0.6 kg, mean SBP percentile 42.7 ± 21.6 percentile). Greater birthweight significantly contributed to greater LVM index (1.2 ± 0.6, p = 0.03), along with Black race (1.9 ± 0.8, p = 0.02) and greater current BMI z-score (2.1 ± 0.3, p &lt; 0.01). Sex and SBP percentile were included in the model but were not significantly related to LVM index (p = 0.23 and 0.51 respectively) in this analysis. Conclusions: Greater birthweight is significantly associated with greater left ventricular mass in childhood, independent of BMI z-score at the time of echocardiography. This suggests a critical period in fetal cardiac development that affects cardiac structure in mid-childhood.