# Multi-Omics Analysis of Pain/Stress Impact on Neurodevelopment in Preterm Infants

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $541,577

## Abstract

PROJECT SUMMARY
 Despite substantial gains in survival of preterm infants, concerns remain regarding the
significant neurological morbidity and long-term adverse outcomes related to insults on the
immature immune and brain-gut-microbiota systems affected by painful/stressful early life
experience during the neonatal intensive care (NICU) stay. Our preliminary K23 results show
that cumulative pain/stress events are significantly associated with higher abundance of gut
Enterobacteria (Phylum: Proteobacteria), a characteristic pattern of dysbiosis, which may
contribute to neurodevelopmental deficits during the NICU stay. In light of these results, the
primary hypothesis driving this research is that cumulative pain/stress experienced in
early life combined with gut dysbiosis and specific genetic susceptibilities increase the
risk of neurodevelopmental morbidity in preterm infants during infancy and early
childhood.
 A prospective longitudinal design will be used to examine: 1) the impact of cumulative
pain/stress events in the NICU along with gut microbiome development on infant
neurodevelopmental outcomes over the short- (NICU stay) and long-term (follow-up); 2)
interaction effects of host genetics, gut microbiome, and early life pain/stress events on infant
neurodevelopmental outcomes, while controlling for sex, feeding and other environmental
factors over time; and 3) the impact of different levels of pain/stress experiences on the gut
microbiome and neurodevelopment outcomes as well as other growth parameters using twin-
pairs. The proposed 4-year project will recruit and follow 200 preterm infants (160 infants in the
final analysis considering the attrition) during NICU hospitalization and until 18-24 months
corrected age (CA). Primary measures in the NICU include daily pain/stress events (NICU
Infant Stressor Scale), gut microbiome patterns and function (stool sample: twice/week; 16S
rRNA gene and metagenomic sequencing), host genetics (whole exome sequencing to identify
genetic variants that effect neuro-gut-immune signaling), autonomic responses (weekly; heart
rate variability) and neurodevelopmental outcomes (at 36 weeks CA; NICU Network
Neurobehavioral Scale). At follow-up visits, gut microbiome, neurodevelopmental outcomes,
including pain sensitivity will be measured at 4, 8-12, and 18-24 months CA.

## Key facts

- **NIH application ID:** 9981824
- **Project number:** 5R01NR016928-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Xiaomei Sophia Cong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $541,577
- **Award type:** 5
- **Project period:** 2017-09-14 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981824

## Citation

> US National Institutes of Health, RePORTER application 9981824, Multi-Omics Analysis of Pain/Stress Impact on Neurodevelopment in Preterm Infants (5R01NR016928-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9981824. Licensed CC0.

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