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Influence of Pregnancy and Early Life Metabolome and Lipidome on Child Growth and Neurodevelopment

Award Number: R01HD123845
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: 09/11/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Influence of Pregnancy and Early Life Metabolome and Lipidome on Child Growth and Neurodevelopment - PROJECT SUMMARY More than one million children HIV exposed but uninfected (CHEU) are born annually, with the majority in sub- Saharan Africa. CHEU are at an increased risk of poor linear growth and neurodevelopment, infectious morbidity, and mortality compared to their HIV unexposed uninfected (CHU) peers. Breastfeeding reduces but does not eliminate poor health outcomes in HEU infants, despite improving maternal health with optimized antiretroviral treatment (ART). The biological mechanisms for vulnerabilities in breastfed CHEU remain unclear. It is plausible that systemic metabolic dysfunction and inflammation associated with maternal HIV infection may affect infant growth and neurodevelopment. Few studies have investigated the microbiome, plasma metabolome and inflammation longitudinally in the context of the WHO recommended first-line of dolutegravir (DTG) in combination with lamivudine and tenofovir. We propose to utilize banked biospecimens from the Tunza Mwana Kenyan birth cohort (NICHD R01HD096999) including women living with and without HIV and their infants. Utilizing banked maternal third trimester and infant 6 month, 12 month, and 24 month plasma and stool samples from a subset of 200 cohort participants (100 living with HIV and 100 without HIV) and infant growth and neurodevelopment to age 36 months, we will expand this unique cohort performing targeted metabolomics and lipidomics, stool metagenomics and metabolomics, and inflammatory assays to characterize relationships between the gut microbiome-plasma metabolome- inflammation in pregnancy and early infancy with infant growth and neurodevelopment to 24 months. Specific Aims are to 1) identify longitudinal associations between maternal third trimester plasma metabolites and lipids and infant plasma metabolites and lipids at 6, 12, 24 months, and child growth and neurodevelopmental outcomes at 24 and 36 months, 2) evaluate the gut microbiome composition and microbial metabolites in the third trimester of pregnancy and early infancy and examine how maternal profiles influence the development of the infant gut microbiome and gut and plasma metabolome to 24 months of age, and 3) identify relationships between the plasma metabolome, systemic inflammation (CRP, IFN-γ,IL-1β, IL-6, TNF-α) and monocyte activation (sCD14) in mother-infant dyads during the third trimester of pregnancy and early childhood, and evaluate how pregnancy and infant inflammation and immune activation influences child growth and neurodevelopmental outcomes to 36 months of age. Study Impact: This work will identify key pathways by which HIV exposure may alter the gut microbiome and plasma metabolome and influence infant health. We will generate new data on metabolomic, lipidomic, gut microbiome, and inflammatory profiles associated with infant growth and neurodevelopment that will inform potential targets for intervention in future studies.


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 = $2,264,208 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	000	1	9/11/2026	NEW	$2,264,208
														Subtotal = $2,264,208

Grand Total All Awards = $2,264,208

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Influence of Pregnancy and Early Life Metabolome and Lipidome on Child Growth and Neurodevelopment

Award Number: R01HD123845

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: 09/11/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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