A major international study led by researchers at the Nuffield Dept of Women's & Reproductive Health, University of Oxford and in collaboration with the University of Leeds has identified how early disruptions in fetal brain growth are linked to poorer child development outcomes and uncovered the biological mechanisms underlying these effects.
By integrating clinical, placental, metabolic, and epigenetic data, we have identified biological pathways that could help explain why some children experience poorer developmental outcomes – Professor José Villar, University of Oxford.
The study, published in The Lancet Obstetrics, Gynaecology & Women’s Health, followed nearly 3,600 pregnancies from early gestation through to children’s second birthday.
Researchers found that specific patterns of fetal brain growth, emerging before 20–25 weeks’ gestation, are strongly associated with differences in growth, vision, and neurodevelopment at age two. They then discover that early maternal disruption of fats required for normal fetal brain growth is associated with reduced gene activation needed to produce these fats in the newborn.
Key Findings
- Fetuses whose brain growth started slowing down early in pregnancy (early faltering growth or EFG) had the poorest outcomes, including lower cognitive, motor, language, and vision scores at age two. EFG was associated with reduced blood supply to the placenta, indicating impaired oxygen and nutrient delivery during pregnancy.
- Distinct maternal metabolic signatures in early pregnancy (<16 weeks) were identified, including a change in types of fat within the blood linked to adverse fetal growth patterns. Evidence for altered epigenetic regulation of the biological mechanisms required to make these neurologically related fats was observed in cord blood.
- Genetic factors only displayed a limited association with slower brain growth of the fetus, indicating that environmental and metabolic influences affecting the interaction between the mother and the baby and related to switching genes on and off during pregnancy are key drivers.
It is hugely surprising to find this pattern of neurologically related fats in the mothers’ blood early in pregnancy which can indicate that the children may have developmental delays at 2 years old. This could mean better ways of detecting and intervening in reduced brain growth rates in the babies to limit the effects of developmental delay in children.– Professor Lee Roberts, University of Leeds
Figures
Red dots activity in the EFG (right hand figure) mostly related to lipids (fat) associated with neurological development ,matched by fetal samples at birth of the same family of fats (not in the figures) are related to fetal brain volume (line red, left side figure)
Understanding early fetal brain development
Fetal brain growth is a critical determinant of lifelong health. This study is the first to combine detailed fetal imaging with molecular analyses across pregnancy and early childhood and relating these to child neurological development at age 2.
The findings show that early alterations in placental function and fetal metabolism are central to impaired brain development.
The findings highlight the potential for early identification of at-risk pregnancies, possibly as early as the first trimester, using maternal biomarkers. Such advances could enable targeted interventions during a critical window of fetal development.
Contributions and Collaborators
The study involved significant work from Professor Lee Roberts (The University of Leeds) and departmental colleagues: Professor José Villar, Professor Aris Papageorghiou and Professor Stephen Kennedy. This research was funded by the Bill & Melinda Gates Foundation.
Full publication
Learn more about the INTERGROWTH-21ST project and the department's other Global Health research projects.