In Utero: MEASUREMENT AND MODELLING DURING GESTATIONAL DEVELOPMENT

Funding Agency:
Wellcome Leap

Every 16 seconds one baby is stillborn. That amounts to more than two million stillborn babies globally every year.i Stillbirths have long-lasting personal and psychological consequences for parents, as well as substantial costs for wider society.

Early recognition of emerging complications in utero, coupled with timely and safe delivery, is estimated to have the potential to reduce the number of stillborn babies by half. Yet progress to reduce stillbirth remains stubbornly slow. In sub-Saharan Africa headway in reducing stillbirth rates has been outpaced by growth in the total number of births, so stillbirth numbers are actually rising.i In the USA stillbirth rates have been static for more than a decade, which amounts to a total of 12,000 stillborn babies each year. Every child’s death is heartbreaking, and this number of stillbirths is ten times higher than the annual number of deaths from childhood cancer.v

Worldwide, great strides are being made in reducing the number of baby deaths that occur after birth, but reductions in baby deaths that occur before birth, (stillbirths) are lagging behind.i Globally, in the year 2000 there was 1 stillbirth for every 3 newborn deaths in the first month of life. By 2019, in nearly 50 countries that ratio was more than 1 to 1. For some babies, remaining in utero is higher risk than being born, largely because in utero, life-threatening complications can develop and progress undetected. Our goal is to be able to measure, model and predict gestational development, with a primary focus to reduce stillbirth rates by half. To achieve this we need non-invasive, scalable ways to assess gestational development in utero.

Stillbirth is the endpoint of a number of different processes that involve the mother, baby, or the placenta – or a combination of the three.v The placenta is the life support system of the developing baby. In humans, the placenta couples the separate maternal and developing baby’s circulations to allow transfer of oxygen and nutrients from mother to baby. This placental transfer function is influenced not only by placental size and structure but also by the integrity of the maternal circulation through the uterine vasculature; and adequate circulation through the umbilical cord for the baby. The placenta is also itself metabolically active and secretes bioactive substances and hormones that influence the maternal response to accommodate pregnancy, whilst acting as a barrier to substances, such as viruses and certain drugs, that may damage the developing baby.

The lack of methods to assess gestational development in utero limits our ability to predict the risk of stillbirth. Today 25-50% of stillbirths are unexplained – meaning that no conditions that affect the mother, baby, or placenta that could contribute to the baby’s death are identified. Even in cases where possible contributory conditions are found, it is extremely rare to have sufficient resolution on the sequence, timing and exact mechanisms leading to stillbirth.iv Such inadequate basic understanding restricts opportunities to advance preventative treatments. By developing new measures and models of gestational development, we also will identify new opportunities to prevent stillbirths.

To date, characterisation of gestational development has relied on intermittent, indirect measures. For example, ultrasound assessment of the baby’s growth and/or Doppler assessment of blood flow in the umbilical cord, are often performed weeks to months apart. These tests have poor predictive performance for the risk of stillbirth. Being able to measure and integrate maternal, baby and placental signals, daily or even more frequently, is central to characterising gestational development and is likely key to preventing stillbirth.

Our goal is to create the scalable capacity to measure, model and predict gestational development, with sufficient accuracy to reduce stillbirth rates by half, without increasing provider-initiated delivery.

We are soliciting abstracts and proposals for work over 3 years (with a potential additional one-year option) in one or more of the following thrust areas. Proposers should clearly relate work in these thrust areas to the program goal.

Deadline for Abstracts: June 30, 2022

Duke University is a member of the Wellcome Leap Health Breakthrough Network. Duke Faculty interested in this opportunity should contact Jennifer.Gallina@duke.edu and Stephen.Murray@duke.edu for additional information before applying.

Agency Website

Areas of Interest

  • Thrust Area 1: Identification and testing of new measures and biomarkers 
  • Thrust Area 2: Pilot novel approaches to data collection  
  • Thrust Area 3: Development, integration and validation of predictive models of gestational development 
  • Thrust Area 4: Methods for scalable screening, prevention and intervention  

Funding Type

Grant

Eligibility

Faculty

Category

Medical
Medical - Basic Science
Medical - Clinical Science
Medical - Translational

External Deadline

June 30, 2022