Laura Jelliffe-Pawlowski of the University of California, San Francisco in the U.S. is developing an algorithm to measure gestational age from metabolic markers taken during routine newborn screening. Measuring accurate gestational age is important for assessing infant health such as brain development, but it is challenging in developing countries without specialized equipment and expertise. In Phase I, they developed a statistical model using data on 51 metabolic markers from around 730,000 newborns in the U.S. that predicted gestational age at birth within around an average of one week margin of error. In Phase II, they will further adapt and test their algorithm for use in Malawi and Uganda by using existing data from 500 pregnancies in Malawi and 1000 in Uganda, and also determine its value for identifying newborns at risk of neonatal death or complications.

John Spencer of the University of East Anglia in the United Kingdom along with Sean Deoni of the University of Colorado in the U.S. are assessing the trajectory of brain development during the first two years of age using a range of imaging, physiological and behavioral assessment tools to understand how development is affected by environmental factors such as nutrition, stress, and parent-child interaction. In their Phase I project, Spencer and colleagues (while at the University of Iowa in the U.S.) used a neuroimaging technology – functional near-infrared spectroscopy (fNIRS) – to localize brain activity during a preferential looking task as a representation of visual working memory in children between four months and four years of age. They used this data to create a developmental trajectory for this visual working memory task and the underlying functional brain network. Sean Deoni and colleagues in their Phase I project (while at Brown University in the U.S.) used MRI to characterize developmental trajectories of myelination in healthy infants and young children to understand the relationship between myelination and cognitive ability. In Phase II, these two research groups will partner together along with an organization in the state of Uttar Pradesh in India, and use the same methods to assess functional brain development over the first two years of age in two cohorts from different socioeconomic-educational settings starting at six and nine months of age. They will also analyze the effects of various factors such as sleep and nutrition on brain development. In addition, they will develop and test a new tablet-based application for larger-scale studies by untrained assessors in the field, and identify tailored approaches for parents to help them promote healthy cognitive development in their children.

Kumanan Wilson of Ottawa Hospital Research Institute in Canada is developing an algorithm to estimate gestational age using specific metabolic analytes found in blood spots collected routinely from newborns in many countries. Knowing the precise age of infants is important for evaluating development particularly of brain function. It is currently measured by ultrasound, which requires expertise and expensive equipment, and is not available in many countries. In Phase I, they used data from around one million ethnically-diverse Canadian newborns to demonstrate that specific metabolites along with sex and birth weight shortly after birth could be used to predict gestational age within one to two weeks. In Phase II, they will further adapt and test their algorithm using existing newborn data from varied international settings, and evaluate the performance of the resultant global algorithm on samples from Bangladesh and Zambia.

Phillip Tarr of Washington University in the U.S. is developing a method to evaluate gut permeability by measuring levels of ingested fluorescent molecules non-invasively through the skin. Gut permeability is increased in infants with environmental enteropathy, which is associated with impaired growth and development, and is prevalent in developing countries. Current tests are problematic due to the required collection and handling of body fluids from young children, and can produce varying results. In contrast, this new method would allow direct measurement in the field, and be suitable for resource-poor settings. In Phase I, they showed that orally ingested pyrazine-based fluorophores could be measured through the skin and could detect gut injury in a rat model of enteropathy. In Phase II, they will optimize the fluorophores to improve solubility, and evaluate them in a preliminary trial in human volunteers.