Research overview
Fetal hypoxia occurs when oxygen delivery to the fetus is compromised. This oxygen deficiency may lead to brain injury, resulting in impaired fetal development as well as increasing the risk of perinatal and infant mortality.
The timely diagnosis and management of fetal hypoxia, a leading cause of neonatal mortality and disease, remains an important unresolved challenge in perinatal medicine.
Current antenatal monitoring methods, such as cardiotocography, are subjective, lack sensitivity, and frequently result in delayed or unnecessary interventions.
Assessments of intrauterine fetal status prior to delivery cannot distinguish easily between newborns exposed to brief hypoxic episodes with minimal risk and those with severe, extended compromise who may benefit from aggressive brain-sparing interventions.
Improving the detection and management of fetal hypoxia requires a comprehensive understanding of gestation-specific physiological and molecular responses to acute hypoxic events. However, progress in this field has been hindered by the lack of standardized, real-time controllable model systems for hypoxic conditions.
This study employed artificial placenta therapy to model acute fetal hypoxia in the preterm fetal sheep at two gestational ages.
This study aimed to use measurements of fetal physiology, plasma protein and cell-free RNA (cfRNA) parameters, correlated with histological and blood chemistry data, to develop biomarkers for acute fetal hypoxia.
Research conclusions
We have developed a highly standardized and real-time modifiable model of acute fetal hypoxia using artificial placenta technology in mid- and early-gestation ovine fetuses, identifying fetal heart rate and external iliac artery pulsatility index as potential antenatal markers of hypoxia.
Our findings reveal significant, gestation-specific differences in physiological, plasma protein, and plasma transcriptomic responses to progressive fetal hypoxia, as well as histological evidence of brain injury in a preterm fetal sheep model.
Ultrasound, plasma protein, and plasma cfRNA biomarker analyses may serve as a novel means of accurately assessing fetal oxygenation status antenatally, as well as assigning brain and organ-sparing interventions at delivery.
Simultaneously, this platform may have the potential to develop both antenatal and post-natal tests for various degrees of fetal hypoxic insult and to trial the efficacy of targeted brain and organ-sparing postnatal interventions.
These insights may lay a foundation for improving early detection and monitoring of acute fetal hypoxia, supporting the development of targeted interventions.
Project researchers
Dr Haruo Usuda
Ms Erin Fee
Dr Sean Carter
Ms Hannah Watson
Professor Matt Kemp
Partners
Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia
Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Nipro Corporation, Osaka, Japan
School of Veterinary and Life Sciences, Murdoch University, WA, Australia
Funders
Channel 7 Telethon Trust
The Stan Perron Charitable Foundation
The Bendat Family Foundation
Nipro Corporation, Osaka, Japan.
Project timeline
Project complete 2025
