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Prenatal Maternal Stress, Exposure to Environmental Chemicals, and Cognitive Development: Potential Roles for Inflammation and the Developing Gut Microbiome

Award Number: R01HD107019
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/22/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Prenatal Maternal Stress, Exposure to Environmental Chemicals, and Cognitive Development: Potential Roles for Inflammation and the Developing Gut Microbiome - PROJECT SUMMARY Prenatal exposure to maternal psychosocial stress and environmental contaminants is associated with reduced cognitive performance in children. However, efforts to support cognitive development in exposed children are hindered by limited understanding of the mechanisms underlying these epidemiological associations. Our project will address this gap by focusing on 2 potential mechanistic pathways (inflammation and the gut microbiome), which are potentially modifiable. Our central hypothesis is that these pathways alter neurodevelopmental processes (including neurogenesis, neural migration, neurite outgrowth, myelination, and the assembly of functional brain networks) and act as important mediators between psychosocial stress/environmental contaminant exposure and cognitive development. We will test this hypothesis via 3 specific aims: (1) Determine whether psychosocial stress, including from the COVID-19 pandemic, influences cognitive development via altered inflammatory profiles and patterns of gut microbiome development. (2) Determine whether exposure to environmental contaminants (heavy metals & polychlorinated biphenyls) influences cognitive development via altered inflammatory profiles and the microbiome. (3) Identify neural circuits involved in these mechanistic pathways via state-of-the-art multimodal neuroimaging of 4-6 year-old children. The proposed study will capitalize on an existing, probability-based statewide pregnancy cohort that includes 1,100 women and their offspring. Measures of prenatal maternal stress and chemical exposures will be available via the parent study. We also have access to maternal serum and urine, placentas, newborn blood spots, interviews with mothers on health and development at 3, 9, and 24 months and a 3-month fecal sample. We will recruit 150 children into this ancillary study, adding longitudinal fecal sampling and neurocognitive testing (Differential Ability Scales-II) and neuroimaging at 4-6 years of age. Recruitment will focus on families in urban areas (City of Detroit) and suburban areas with lower levels of environmental contaminant exposure for comparison. We will analyze inflammatory markers in maternal serum and newborn blood spots, perform shotgun metagenomics sequencing on approximately 1000 fecal samples, and analyze epinephrine and norepinephrine in 900 maternal urine samples, collected at three points in pregnancy, as an objective measure of stress. Imaging will include structural MRI, diffusion tensor imaging (DTI), and resting state fMRI scans. We will generate measures of subcortical structure volumes, global and regional cortical thickness and surface area, white matter microstructure, and functional brain connectivity to address our aims. This multi-disciplinary proposal will have a positive impact because it will substantially advance our understanding of the biological mechanisms by which psychosocial stressors and environmental chemicals influence cognitive development and lay the groundwork for developing interventions to mitigate the impact of these exposures by targeting inflammatory pathways and/or the microbiome.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $644,271 )
2026	2026	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 360	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	4	4/3/2026	NON-COMPETING CONTINUATION	$644,271
														Subtotal = $644,271

Issue Date FY: 2025 ( Subtotal = $644,271 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	001	3	2/13/2025	NON-COMPETING CONTINUATION	$579,845
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	003	3	5/28/2025	NON-COMPETING CONTINUATION	$0
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	002	3	5/22/2025	NON-COMPETING CONTINUATION	$64,426
2025	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	2	1/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $644,271

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	2	5/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $658,405 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	2	5/10/2023	NON-COMPETING CONTINUATION	$658,405
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	001	2	5/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $658,405

Issue Date FY: 2022 ( Subtotal = $706,925 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	1	8/22/2022	NEW	$706,925
														Subtotal = $706,925

Grand Total All Awards = $2,653,872

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Prenatal Maternal Stress, Exposure to Environmental Chemicals, and Cognitive Development: Potential Roles for Inflammation and the Developing Gut Microbiome

Award Number: R01HD107019

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/22/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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