Association between adverse maternal factors and neurodevelopmental outcomes among children in Kenya

ABSTRACT More than half of Kenyan children under 5-years (~4 million Kenyan children) will not reach their developmental potential, a pathway partly determined by modifiable maternal risk factors such as stress, infection, and inadequate nutrition in pregnancy and lactation. Maternal factors such as older age, anemia, poor nutrition, HIV

infection and depression have been associated with adverse effects on child neurodevelopment, although the quality and strength of the evidence varies. Data on the relationship between maternal factors and human milk oligosaccharides (HMOs), one of the most abundant bioactive molecules in human milk, are all from high-income

settings, where the composition of HMOs differs by maternal age, nutritional status, depression, and HIV infection. Limited data exists on the influence of HMOs on child neurodevelopment, including in Sub-Saharan Africa. HMOs and maternal factors may act independenly to influence child neurodevelopment. It is plausible

that the maternal factors may impact HMO profiles, and, in turn, influence child neurodevelopment. The proposed F32 research project leverages data from an ongoing cohort ongoing cohort of Kenyan mother-infant pairs (N=350) (Tunza Mwana R01HD096999; 1P01HD107669-01) followed up for 2-years from birth to evaluate

the association between maternal HIV infection, milk composition, and the infant gut microbiome, and characterize infant growth and neurodevelopment at 24 months of age. In Aim 1, we will determine how adverse maternal factors in pregnancy (older age, depressive symptoms, anemia, HIV infection, and nutritional status)

affect HMO composition at 6 weeks postpartum. In Aim 2, we will determine the association between adverse maternal factors in pregnancy and child neurodevelopmental outcomes at 2-years of age. Finally, in Aim 3, we will assess if HMOs mediate the relationship between adverse maternal factors in pregnancy and child

neurodevelopment at 2-years of age. This project will provide new insights on modifiable maternal factors and child neurodevelopment in Sub-Saharan Africa region, and inform ways to prevent or reverse the neurodevelopmental consequences of adverse maternal environment by highlighting the potential mechanisms

of neurodevelopmental impairment. The research plan will provide the F32 candidate rigorous postdoctoral training including training in 1) child neurodevelopmental assessment and research 3) content area expertise in breastmilk research 3) advanced statistical methods of epidemiologic research 4) strengthen publication record

and communication skills.