Friday, April 19, 2024 4/19/2024

PRENATAL AND POSTNATAL EXPOSURE TO ENVIRONMENTAL MIXTURES: NEURODEVELOPMENT AND DNA METHYLATION BIOMARKERS

Award Number: R01ES031259
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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PROJECT SUMMARY Prenatal and postnatal childhood exposure to metals, essential and non-essential, is ubiquitous via dietary and environmental sources. Heavy metals, including lead and methylmercury, are well characterized as potent neurotoxicants, associated with lower cognition and poor learning abilities. Yet, our understanding of the neurotoxicity and joint impact of many other common prenatal and postnatal metal exposures remains extremely limited. Even less is known about the combined impact of exposure to multiple metals during fetal development or postnatal exposure during early childhood, or the influence of other environmental mixtures such as nutrients, which may have shared sources, on the neurodevelopmental effects of metals. To address this significant gap, our long-term goal is to quantify the neurocognitive impact of ubiquitous prenatal and postnatal environmental mixtures and identify cord blood DNA methylation biomarkers that can reconstruct prenatal environmental exposures and predict future neurocognitive development in children. We will test if objective measures of key prenatal maternal nutrients, such as folate, vitamin B12 and essential metals attenuate or mitigate the neurotoxicity of metal mixtures. To accomplish this goal, we will leverage resources from an established U.S. pre-birth cohort, Project Viva. In this cohort, we have measured concentrations for 14 prenatal maternal metals in the first trimester of pregnancy and blood samples collected in early-childhood (~3 years) ready for metal testing as well as ready to use genome-wide cord blood DNA methylation screens. Children have been followed prospectively and undergone detail testing for neurodevelopment in early (~3 years of age) and mid-childhood (~7 years). We hypothesize that prenatal maternal 1st trimester and postnatal early childhood neurotoxic metal mixtures are associated with poor neurodevelopment in early and mid-childhood (Aim 1), and that prenatal first trimester maternal plasma folate, vitamin B12 and blood concentration of essential metals protect against prenatal metal mixture neurotoxicity (Aim 2). We also hypothesize that DNA methylation marks measured in umbilical cord blood at birth can reconstruct prenatal exposure to metals (Aim 3.a) and that cord blood DNAm marks predict future neurocognitive development in early and mid-childhood (Aim 3.b). By testing longitudinal associations in a large cohort of children with detail cognitive assessments as well as objective biomarkers of metals and nutrients, we will overcome limitations currently faced by existing studies testing few exposures simultaneously. We will use novel statistical methodology to model prenatal and postnatal environmental mixtures and machine learning algorithms to build epigenetic predictors of exposure and neurodevelopment. This research will provide a comprehensive quantification of the cognitive burden of prenatal and postnatal mixtures, the development of biomarkers of exposure and neurodevelopment and the identification of potential prenatal nutritional intervention strategies.


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: 2024 ( Subtotal = $348,517 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Environmental Health	000	6	2/27/2024	NON-COMPETING CONTINUATION	$348,517
														Subtotal = $348,517

Issue Date FY: 2023 ( Subtotal = $378,972 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Environmental Health	002	5	2/23/2023	NON-COMPETING CONTINUATION	$369,918
2023	2022	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Environmental Health	005	4	7/2/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$263,358
2023	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Environmental Health	001	4	10/31/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$227,067
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Environmental Health	004	3	7/2/2023	NON-COMPETING CONTINUATION	-$136,842
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Environmental Health	000	3	10/28/2022	NON-COMPETING CONTINUATION	-$218,013
2023	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Environmental Health	003	2	7/2/2023	NON-COMPETING CONTINUATION	-$126,516
														Subtotal = $378,972

Issue Date FY: 2022 ( Subtotal = $354,855 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Environmental Health	000	3	2/23/2022	NON-COMPETING CONTINUATION	$354,855
														Subtotal = $354,855

Issue Date FY: 2021 ( Subtotal = $425,421 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Environmental Health	000	2	3/22/2021	NON-COMPETING CONTINUATION	$425,421
														Subtotal = $425,421

Issue Date FY: 2020 ( Subtotal = $438,331 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Environmental Health	000	1	6/8/2020	NEW	$438,331
														Subtotal = $438,331

Grand Total All Awards = $1,946,096

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PRENATAL AND POSTNATAL EXPOSURE TO ENVIRONMENTAL MIXTURES: NEURODEVELOPMENT AND DNA METHYLATION BIOMARKERS

Award Number: R01ES031259

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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