Nutrition and inflammation in pregnancy: impacts on early human brain development

Active Project Grant Awarded Last action

Award ID
R01HD106106
Recipient
Awarding agency
Obligated
$9,486,913

Award facts

Completion date 91% complete
Place of performance
Providence, RI 02903, USA

Award details come from USAspending.gov.

Description

Abstract
In low-resource settings, undernutrition and infections during the first 1000 days of life are prevalent, modifiable risk factors that may have lifelong effects on a child's cognitive and psychological development. The rapidly developing fetal brain has increased nutritional and metabolic demands and is highly susceptible to the effects of inflammation. Protein, energy, and iron are key nutrients required for early brain development; yet, among women of reproductive age in sub-saharan africa, 10% are underweight and 20% have iron deficiency anemia. Pregnancy infections are also common in africa, where one in three women have a GEO-helminthic infection, contributing to iron deficiency and inflammation. Hepcidin, a regulator of iron homeostasis, is stimulated by inflammation, yet there is limited research on hepcidin in pregnancy and how to optimize fetal iron bioavailability in the context of inflammation. Understanding the complex relationship between nutrition, inflammation, and neurodevelopment is a major research GAP. The predominant approach to understanding mechanisms of prenatal brain development is derived predominantly from animal and observational studies. Here, we present an unprecedented opportunity to leverage an ongoing, independently funded randomized controlled trial (RCT) to examine casual relationships and rigorously investigate biological pathways by which prenatal nutrition and inflammation influence human fetal brain development in an undernourished and high- risk population in rural ethiopia. In the parent trial, women in early pregnancy are randomized to receive: 1) standard prenatal care, 2) a package of strengthened nutritional support (iron-folate, iodized salt, fortified balanced energy protein (BEP) supplement), 3) a package of infection management (deworming, treatment of urinary tract infections), or 4) both packages. The proposed project will support advanced, multi-modal, infant neurodevelopmental assessments (EEG/VEP, cranial ultrasound, neurologic exam, elicited imitation tasks) at 6 and 24 months of age, and analysis of maternal and newborn cord blood for inflammation biomarkers (C- reactive protein, alpha-1 acid glycoprotein, interleukin (IL)-6), neurotropic factors (IL-6 soluble receptor), iron stores (serum ferritin, soluble transferrin receptor, total body iron), and hepcidin. Our specific aims are to: (1) determine the effects of interventions on offspring neurodevelopment, (2) investigate the effects of interventions on maternal-newborn iron and inflammation biomarkers, and (3) examine the role of maternal- newborn iron status and inflammation on child neurodevelopment. Leveraging an ongoing RCT in ethiopia, we will determine the effects of iron, BEP, and inflammation on advanced measures of childhood neurobehavior and function and will deepen the understanding of biological pathways and intervention targets. We will elucidate the complex dynamics of iron and inflammation in pregnancy and their effects on neural networks, brain structure, and behavior in childhood. Our work will help optimize prenatal intervention strategies to improve early human brain development in high disease burden and vulnerable populations globally.

Transactions

Action Obligated Date
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Amendment $728,566
Original award $728,566
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Subawards

Subrecipient Amount Awarded
Addis Continental Entrepreneurs Plc. The Addis Continental Institute of Public Health (ACIPH) will be responsible for overseeing the scientific and operational implementation of NINO activities… $293,696
Brigham & Womens Hospital Inc. The Laboratory of Genital Tract Biology, led by Subrecipient PI, will process 200 human serum samples to analyze biomarkers of immune homeostasis and iron… $46,306
The Johns Hopkins University The Department of International Health will conduct the following activities in support of the above-mentioned project: 1. Participate together with… $25,542
Brigham & Womens Hospital Inc. The Laboratory of Genital Tract Biology, led by Subrecipient PI, will process 200 human serum samples to analyze biomarkers of immune homeostasis and iron… $38,694
The Children's Hospital Corporation The PI of this subcontract will oversee the implementation of measures designed to examine the neurodevelopmental outcomes of infants of pregnant women… $30,655
Addis Continental Entrepreneurs Plc. Addis Continental Institute of Public Health shall be involved in overseeing the scientific and field implementation of NINO activities at ENAT project health… $135,046
The Johns Hopkins University The Department of International Health, under the direction of Dr. Parul Christian, MSc, MPH, DrPH, will conduct the following activities in support of the… $10,819
The Children's Hospital Corporation The PI of this subcontract (Charles A. Nelson, Ph.D.) will oversee the implementation of measures designed to examine the neurodevelopmental outcomes of infants… $75,800
Addis Continental Entrepreneurs Plc. Addis Continental Institute of Public Health shall be involved in overseeing the scientific and field implementation of NINO activities at ENAT project health… $77,250
The Johns Hopkins University The Department of International Health, under the direction of Dr. Parul Christian, MSc, MPH, DrPH, will conduct the following activities in support of the… $56,787
The Johns Hopkins University $41,616
Addis Continental Entrepreneurs Plc. Addis Continental Institute of Public Health shall be involved in overseeing the scientific and field implementation of NINO activities at ENAT project health… $154,903
New York University This project will leverage an ongoing, independently funded, large-scale randomized controlled trial in Amhara, Ethiopia to address the consequences of… $40,832
The Johns Hopkins University The Department of International Health, under the direction of Dr. Parul Christian, MSc, MPH, DrPH, will conduct the following activities in support of the… $98,081
The Children's Hospital Corporation The PI of this subcontract (Charles A. Nelson, Ph.D.) will oversee the implementation of measures designed to examine the neurodevelopmental outcomes of infants… $81,213
Addis Continental Entrepreneurs Plc. Addis Continental Institute of Public Health shall be involved in overseeing the scientific and field implementation of NINO activities at ENAT project health… $422,254
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Quick answers

Who received award R01HD106106?

R01HD106106 was awarded to Brown University by National Institute of Child Health and Human Development (National Institutes of Health) on July 1, 2022.

How much is award R01HD106106 worth?

$9,486,913 has been obligated on R01HD106106.

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