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

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, yet effective interventions addressing prevailing mechanisms are still to be validated. Iron, protein and energy are critical nutrients that support the rapidly developing fetal brain, however, 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 resulting in blood loss, iron deficiency and inflammation. The interaction between iron and inflammation in pregnancy is particularly complex. NICHD has identified the complex relationship between nutrition, inflammation, and neurodevelopment as a major research gap. A barrier to progress is that mechanistic understanding of prenatal brain development is based on animal or observational studies. We present a unique opportunity to leverage an ongoing randomized controlled trial (RCT) to examine the consequences of pregnancy nutrition and inflammation on child neurodevelopment.

The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) RCT enrolled pregnant women in Amhara, Ethiopia to study independent and overlapping effects of prenatal nutrition and infection interventions on birth outcomes. Women were randomized to receive: 1) standard prenatal care, 2) enhanced nutrition package (ENP) (counseling, iron-folic acid [IFA], iodized salt, and balanced energy protein [BEP] supplementation), 3) enhanced infection management package (EIMP) (anti-helminthics, urinary tract infection treatment), or 4) ENP+EIMP. The current follow-up study (Longitudinal Infant Development and Growth; LIDG) will investigate biological pathways by which ENAT interventions, specifically iron, protein-energy, and inflammation, influence child neurodevelopment.

Our overarching hypotheses are that improving prenatal nutrition will improve brain structural and network development, reducing inflammation will improve white matter maturation, and the combination will have synergistic effects on child neuro-cognitive outcomes. This study will follow up to 500 ENAT children to assess neurodevelopment through 24 months of age, including neurobehavior and neural networks.

Inclusion criteria

• Mothers who have participated in ENAT study who consent to participate in the infant follow up study
• Intention to stay in the study catchment area
• Healthy infants without severe clinical signs or symptoms including headache, vomiting, or dizziness

Exclusion criteria

• Major congenital anomalies
• Infants with severe morbidity or developmental disorder
• Neonatal encephalopathy
• Plan to move out of study catchment area