Explore New Ways to Measure Brain Development and Gestational Age (Round 14)

Roadblock:

There has been striking progress in preventing deaths of children <5 years of age. Challenges remain, however, to ensure the healthy development of these children beginning in fetal life. An intense period of brain development takes place during the fetal and early childhood period. Significant adversity early in life – encompassing biological as well as social factors – can produce physiological disruptions to the developing brain circuits, leading to effects that persist into adulthood. These effects include a substantially higher risk of cognitive, sensorimotor, and psychosocial impairment, with preterm and small-for-gestational-age infants at particularly high risk. 



To help guide and monitor interventions seeking to promote healthy brain development in the early years, we need suitable measures of fetal and infant brain function and development – and the ability to determine gestational age prenatally and at delivery when traditional measures, such as ultrasound or last menstrual period, are unavailable. Many current measures of brain function and development have major drawbacks: they are not readily and objectively comparable across different populations; they are not suitable for fetal life and for newborns, or are applicable only for a narrow age range; and it is not clear which are good predictors of adult productivity and success. This is a particularly good time to address these drawbacks, given the science and technologies emerging from increased investment in brain research, including the BRAIN Initiative, the NIH Blueprint for Neuroscience Research, and the solutions to foster healthy brain development being explored through Grand Challenges Canada’s Saving Brains initiative.

What We Are Looking For:

This call for proposals seeks new approaches in two complementary areas: 

1. We seek innovative ideas for measuring brain function and development, with a focus on tests that are simple, reliable, non-invasive, objective, universally applicable, and include those appropriate for fetal life, newborns, and early infancy. Such tests would be used to guide and monitor existing and new health interventions, and potentially could be used to establish standard curves of brain function-for-age, enabling early detection of deviation from healthy development.
2. We seek new approaches for accurately measuring gestational age, focusing on simple, reliable, non-invasive, universally applicable tests that can be applied either to pregnant women or to the newborn or infant.

We seek proposals that: 

• Build on the rapidly growing knowledge of early development – and in particular brain development – as well as advances in measurement tools, such as imaging technologies;
• Are "off the beaten track," daring in premise, and clearly differentiated from approaches currently being developed or employed; and
• Have a testable hypothesis, include an associated plan for how the idea would be tested or validated, and yield interpretable and unambiguous data in Phase I so as to increase the chance of consideration for Phase II funding.

A few of the many options we will consider include:

Brain function and development 

• Tests of fetal brain function and development
• Tests that – either individually or in sequence – establish a trajectory of healthy brain development from conception to early infancy
• Tests that build on brain research on other diseases or conditions, including autism, Alzheimer’s disease, and age-related decline, but now focus on the fetus and newborn
• Tests that better predict capacities thought to contribute to adult productivity, such as executive function (e.g., attention, self-control, problem solving, and working memory), social-emotional intelligence, or behavioral traits like grit and creativity
• Tests that help correlate elements of early growth and brain development
• Brain function tests in animal models, especially primate models, as long as plans include demonstration of why they will be relevant in humans
• Tests that can be reliably implemented in low-resource settings, will work across diverse cultures and geographies, and require limited training to administer
• Tests that make use of creative new technologies or laboratory investigations, but are applicable to remote field settings

Gestational age 

• Tests that use new biomarkers or technologies or innovative modifications of existing approaches to measure gestational age at birth – and that provide substantial improvements over existing methodologies; are safe, robust, and cost-effective; can be applied effectively across any population; and correlate well with current technologies, such as ultrasound
• Tests that could be administered beginning very early in pregnancy that might be more accurate than last menstrual period or ultrasound
• Tests that use new biomarkers or technologies to retrospectively determine gestational age in an infant or even in older children or adults
• Tests for gestational age that build on individual or combinatorial metabolic, microbial, image-based, or epigenetic signatures

We will not consider funding for: 

Brain function and development 

• Modifications of existing tests that provide only incremental benefits
• Tests that are applicable to only one or a few specific populations or geographies
• Tests based on existing proxy measures that poorly predict human health and productivity later in life
• Tests based on anatomical or physiological measures that are not clearly linked to cognitive, sensorimotor, or socioemotional capacities
• Animal models without clear and direct relevance to humans
• In vitro studies

Gestational age 

• Incremental changes in known gestational age assessment methods, such as hormone testing, ultrasound or infant and mother physical and neurodevelopmental exams
• Animal models without clear and direct relevance to humans
• In vitro studies