# Nutrition and Inflammation in Pregnancy: Impacts on Early Human Brain Development

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $728,566

## Abstract

PROJECT SUMMARY
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 th...

## Key facts

- **NIH application ID:** 10443147
- **Project number:** 1R01HD106106-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Anne Shee CC Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $728,566
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443147

## Citation

> US National Institutes of Health, RePORTER application 10443147, Nutrition and Inflammation in Pregnancy: Impacts on Early Human Brain Development (1R01HD106106-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10443147. Licensed CC0.

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