Maternal inflammation in relation to offspring epigenetic aging and neurodevelopment

Active Project Grant Awarded Last action

Award ID
R01HD111550
Recipient
Awarding agency
Obligated
$4,729,966

Award facts

Completion date 85% complete
Place of performance
Newark, NJ 07107, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Maternal inflammation during pregnancy, as defined by elevated levels of circulating pro-inflammatory cytokines, can have adverse effects on offspring neurodevelopment. However, mechanisms remain elusive. Accelerated biological aging has been proposed as an underlying mechanism by which prenatal exposures influence future health. This process can be evaluated through epigenetic clocks, which estimate epigenetic age based on DNA methylation levels, and are widely used as clinically relevant biomarkers that measure epigenetic age acceleration. To date, pediatric epigenetic studies have been limited by: (1) use of adult-specific or all-age clocks; and (2) scant longitudinal epigenetic data due to challenges of pediatric blood collection. Here, we use a newly developed pediatric-specific clock [the pediatric buccal epigenetic (pedbe) clock] that can be evaluated using non-invasive buccal swabs, facilitating repeat measures across childhood. Our long-term goal is to identify easy- to-measure biomarkers in infants and young children that reflect exposure to maternal inflammation during pregnancy and predict subsequent risk for morbidity in offspring. This innovative and cost-effective longitudinal study will leverage the infrastructure, biorepository, and extant data of a rigorously phenotyped cohort of healthy pregnant women and their offspring followed from the first trimester through age 4 (R01HD083369, UH3OD023349). The understanding pregnancy signals and infant development (upside-echo) cohort includes comprehensive assessments of inflammation across pregnancy, repeated measures of neurodevelopment across childhood, detailed psychological, sociodemographic, clinical, and life history data, and a rich repository of biospecimens collected from 2015 - 2024 (age 3-4 visits in progress). Our central hypothesis is that maternal inflammation during pregnancy accelerates the offspring's epigenetic age, adversely influencing neurodevelopment. Our interdisciplinary research team is comprised of experts in maternal and child health, epigenomics, immunology, cognitive science, perinatal epidemiology, and biostatistics. In aim 1, we will establish trajectories of longitudinal changes in offspring epigenetic age from birth through 4 years of age and identify factors associated with offspring epigenetic age acceleration. In aim 2, we will study associations between maternal inflammation during pregnancy and offspring epigenetic age acceleration. In aim 3, we will examine associations between offspring epigenetic age and neurocognition through age 4, and explore if epigenetic age mediates the association between maternal inflammation during pregnancy and neurocognitive outcomes. The research proposed in this R01 is significant because IT will generate new insights into the link between maternal inflammation during pregnancy and genomic biomarkers of accelerated aging, with a focus on how accelerated epigenetic age can impact offspring neurocognition. This formative work will advance our understanding of how epigenetic age trajectories change across a critical developmental period and identify opportunities for maternal/offspring interventions to improve neurocognitive outcomes across the entire lifespan.

Transactions

Action Obligated Date
Amendment $621,943
Amendment $623,100
Amendment $666,126
Amendment $666,126
Amendment $717,557
Amendment $717,557
Amendment -$717,557
Amendment -$717,557
Amendment -$717,557
Amendment $717,557
Amendment $717,557
Amendment $717,557
Original award $717,557
Show all 13

Subawards

Subrecipient Amount Awarded
Yale University [R01] Maternal inflammation in relation to offspring epigenetic aging and neurodevelopment $84,548
University Of Rochester $87,482
Yale Univ $92,776
University Of Rochester $84,934
Yale Univ $260,667
University Of Rochester $105,964

Quick answers

Who received award R01HD111550?

R01HD111550 was awarded to Rutgers The State University Of New Jersey by National Institute of Child Health and Human Development (National Institutes of Health) on June 1, 2023.

How much is award R01HD111550 worth?

$4,729,966 has been obligated on R01HD111550.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login