Research overview
Intrauterine infection is a significant contributor to preterm birth, particularly among high-risk infants born at or before 28 weeks’ gestation. Beyond its role in preterm birth, intrauterine inflammation independently increases the risk of fetal injury, including severe complications such as fetal brain injury.
This research project has led to groundbreaking discoveries on how the fetal body responds to intrauterine infection. One of the most significant findings was that fetal skin has the capacity to act as a pro-inflammatory organ through Toll-like receptor 2 and 4 (TLR2/4) activation. This work, recognized by F1000 as potentially paradigm-shifting, has deepened our understanding of the mechanisms leading to preterm birth.
Further studies revealed that infections caused by Ureaplasma spp. and Candida spp. – both linked to preterm birth – trigger a robust inflammatory response in fetal skin. Expanding on these findings, the research demonstrated that fetal skin and lung tissues play key roles in driving systemic inflammatory responses in the fetus. Notably, acute fetal systemic inflammation in the context of amniotic infection originates from the skin and lung, rather than from circulating immune cells.
The research extended beyond foundational discoveries to translational applications. In a non-human primate model, findings confirmed the role of fetal skin and lungs in intrauterine inflammation. This work also led to the development of a novel antigen capture approach that inhibits TLR2/4 activation by repurposing the antibiotic polymyxin B.
These novel insights into the aetiology of intrauterine inflammation and the fetal inflammatory response syndrome are important as it is now well understood that anti-inflammatory interventions must be targeted to fetal surfaces exposed to the amniotic fluid.
Key insights
One of the key insights from this research is that effective anti-inflammatory treatments must be specifically designed to target fetal surfaces exposed to the amniotic fluid.
Building on this knowledge, the laboratory has developed several targeted interventions aimed at mitigating the harmful effects of intrauterine infection.
This research continues to inform new strategies to prevent and manage intrauterine infections, with the goal of reducing preterm birth rates and improving neonatal health outcomes.
Project researchers
Professor Matt Kemp
Yuki Takahashi MD
Erin Fee
Tsukasa Takahasi MD
Project timeline
2010 – current
