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The GROWTH Study, Glycemia Range and Offspring Weight and adiposity in response To Human milk

Award Number: R01HD109260
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The GROWTH Study, Glycemia Range and Offspring Weight and adiposity in response To Human milk - ABSTRACT Maternal metabolism during pregnancy is a key contributor to developmental origins of metabolic disease. Offspring exposed to maternal hyperglycemia and obesity have increased rates of obesity and disordered glucose metabolism. The lactation period is also a critical window for programming. Lactogenesis initiates in the second half of gestation, thus human milk (HM) biosynthesis is susceptible maternal metabolism. Interindividual variation in HM nutrients reveals the influence of maternal metabolism on milk biosynthesis. A knowledge gap exists as to whether HM composition alters developmental pathways of offspring programmed in utero. Maternal metabolic states including gestational diabietes (GDM) and obesity alter HM nutrient profiles, including milk fatty acids (FA). Our studies identified altered HM linoleic acid and dihomo-gamma-linolenic acid (DGLA) in conditions of maternal diabetes, hyperglycemia, and obesity, as well as HM palmitic acid and DGLA associations with infant growth. However, any impact of maternal metabolism across the entire range of glycemia on both HM composition and offspring programming has not been evaluated in context of detailed profiling of in utero exposures. Our goal is to understand how HM susceptibility to maternal metabolism impacts offspring metabolism, identifying interventions to mitigate adverse developmental programming. This proposal’s objective is to determine the impact of maternal glycemia in pregnancy on HM composition and effects of HM nutrients on offspring adiposity. Translational science approaches will determine how maternal glycemia alters mammary gland epithelial cell gene expression and how HM lipids across the range of maternal glycemia regulate infant adipoctyes. Our overarching hypothesis is that maternal glycemia in normal and pathologic ranges impacts HM composition, which in turn influences offspring metabolic programming as reflected by early childhood adiposity. Capitalizing on the detailed metabolic phenotyping of the GO MOMs cohort, we will conduct prospective HM profiling at 1, 2 and 6 months post-partum in a cohort of 450 women to associate maternal glycemia during and after pregnancy, focusing on HM lipids known to regulate offspring adiposity (Aim 1). Mammary epithelial cells shed in expressed HM will be evaluated using transcriptomics (SubAim 1). For reproducibility, HM lipids will be compared to a separate validation cohort enrolling women with GDM. We will measure offspring body composition to discern adiposity at months 1, 2, and 6 and 2 years, accounting for childhood diet (Aim 2). A human infant preadipocyte strain will be exposed to HM lipids collected and grouped by quartiles of maternal glycemia to determine mechanisms altering infant adipocyte development (Aim 3). Completing the aims will define HM composition in a pregnancy cohort with comprehensive metabolic profiling throughout pregnancy and lactation across the range of glycemia and BMI. Offspring growth and translational studies will advance understanding of how lactation exposures modify in utero programming. This will further the field by revealing interventions to reduce risk of adverse offspring metabolic health.


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: 2025 ( Subtotal = $1,872,667 )
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	002	3	4/21/2025	NON-COMPETING CONTINUATION	$187,265
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	3	1/13/2025	NON-COMPETING CONTINUATION	$1,685,402
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	001	3	1/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,872,667

Issue Date FY: 2024 ( Subtotal = $1,886,293 )
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	001	2	5/22/2024	NON-COMPETING CONTINUATION	$171,482
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	2	1/15/2024	NON-COMPETING CONTINUATION	$1,714,811
														Subtotal = $1,886,293

Issue Date FY: 2023 ( Subtotal = $2,007,921 )
2023	2023	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	001	1	4/11/2023	NEW	$0
2023	2023	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	1	3/29/2023	NEW	$2,007,921
														Subtotal = $2,007,921

Grand Total All Awards = $5,766,881

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The GROWTH Study, Glycemia Range and Offspring Weight and adiposity in response To Human milk

Award Number: R01HD109260

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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