Allostatic Load & Epigenetic Mechanisms in Lifecourse Trajectories of Premature Infants at Age 30
静态负荷
基本信息
- 批准号:10335154
- 负责人:
- 金额:$ 52.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-06 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:37 weeks gestationAccelerationAdultAffectAgeAge-YearsBiologicalBiometryBirthBirth WeightCaliforniaCardiovascular systemCategoriesChemicalsChildhoodChronicChronic stressCognitiveCollaborationsCoupledCpG dinucleotideDNA MethylationDataDatabasesDevelopmentDiscipline of NursingDiseaseEconomic BurdenEducationEnvironmentEnvironmental Risk FactorEpigenetic ProcessExposure toFamily health statusGenderGoalsHealthHealthcareHeterogeneityHospitalsIndependent LivingIndividualInfantInflammatoryInstitute of Medicine (U.S.)Interdisciplinary StudyInterventionLearningLinear RegressionsLogistic RegressionsLongevityMeasuresMediatingMedicalMedicineMemoryMental HealthMetabolicModelingMolecularMotorNeonatalNeonatal Intensive Care UnitsNeurosecretory SystemsObesityOccupationalOutcomeOutcome StudyParticipantPediatricsPerinatalPhysiologicalPregnancyPremature BirthPremature InfantProceduresProcessPsychoneuroendocrinologyPublic HealthRecommendationReportingResearchRhode IslandRiskSamplingScienceSignal TransductionSignaling MoleculeSocial FunctioningStressSurvivorsSystemTimeUnited StatesUniversitiesWorkallostatic loadbiological adaptation to stresscohortcomparison groupcostemerging adultevidence baseexecutive functionexperiencefollow-uphypothalamic-pituitary-adrenal axisimmune functionindexinginnovationlongitudinal designmaternal separationmethyl groupneonatal morbidityneonatal periodnovelnutritionpeerphysical conditioningpostnatalpredictive modelingprematureprospectiveprotective effectprotective factorspsychobiologyresiliencesocialsocial skillssocietal costssocioeconomicsstressortheoriesyoung adult
项目摘要
Allostatic Load & Epigenetic Mechanisms in Lifecourse Trajectories of Premature Infants at Age 30
Among the most intense experiences of adversity for infants is premature birth. Annually, 1 in 10 (450,000 in
the US, 15 million worldwide) infants are born prematurely. The societal cost of preterm birth in the US is
estimated to be $26 billion/year. An infant's early birth marks the beginning of a long trajectory that broadly
impacts families, health care, education, social systems, and the survivors themselves. Yet, studies of
premature infants at adulthood are few compared to those at younger ages and most focus on the smallest
20% of premature infants. We do know that their transition to adulthood is challenging, and often hampered by
cognitive, physical and mental health, motor and independence difficulties. In this application, we respond to
an Institute of Medicine recommendation for long-term outcome studies into young adulthood for premature
infants. We now propose the 10th wave at 30-33 years of age for a well-characterized preterm sample of 215
infants representing a wide range of neonatal morbidity, birth weight, and all SES strata. We have retained
96% of the sample between ages 17 and 23 years, and 85% since birth. In a prospective, longitudinal design,
the specific aims are to: (1) Determine the lifecourse and cumulative impact of medical risk, socioeconomic
risk, and protection on adult outcomes of physical and psychological health, adaptive function, executive
function, work, and social competence to age 30y; (2) Determine the allostatic load across prematurity groups
and socioeconomic levels, and its impact on outcomes of physical and psychological health, adaptive function,
executive function, work, and social competence to age 30y; and in exploratory aim (3), examine and compare
epigenomewide DNA methylation and estimates of age acceleration (Horvath's epigenetic clock) across full-
term and preterm groups at age 30y. Variability of DNA methylation and the `clock' across preterm groups and
gender will be examined as well as the association with 30y cardiovascular indicators of obesity. We will
explore longitudinal associations between medical risk, SES, and protection with the epigenetic clock. The
project represents collaboration between the University of Rhode Island, Memorial Hospital of Rhode Island,
and the University of California Irvine. The interdisciplinary research team is comprised of experts in nursing,
medicine, developmental pediatrics, stress and psychoneuroendocrinology, nutrition, epigenetics and
biostatistics. The analysis approach includes adjusted models (e.g. linear regression model for continuous,
logistic regression for binary, generalized odds model for categorical outcomes). Linear mixed models (LMM)
and generalized linear mixed models (GLMM) with both fixed and random effects of time included in the
models to examine the differences in trajectories of the outcome variables over time. Appropriate covariates
will be assessed at baseline and all data points if applicable. Given the state of the science, the proposed
project takes a novel lifecourse perspective that accounts for the stress of the neonatal period, the cumulative
developmental context (risk, protection), molecular and epigenetic mechanisms, and individual resilience over
time. The allostatic load index adds a cumulative measure of biological risk since it captures cumulative
physiological effects across major regulatory systems. We will explore epigenomewide DNA methylation as a
mechanism underlying allostatic load processes. Both allostatic load and DNA methylation build on a stress
paradigm theorized at Developmental Origins Theory of Health and Disease. In this project we propose a
synthesis in a lifecourse perspective to determine how prematurity and environmental stress effect preterm-to-
adult health. To our knowledge, this would be the only U.S. study of premature infants to age 30-33y. Thus,
there is limited research-based evidence to inform the timing and content for interventions despite millions of
preterm survivors.
30岁早产儿生命历程轨迹的适应负荷和表观遗传机制
项目成果
期刊论文数量(0)
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Amy L D'Agata其他文献
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{{ truncateString('Amy L D'Agata', 18)}}的其他基金
Allostatic Load & Epigenetic Mechanisms in Lifecourse Trajectories of Premature Infants at Age 30
静态负荷
- 批准号:
10569056 - 财政年份:2019
- 资助金额:
$ 52.25万 - 项目类别:
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