Fetal Hypoxia Determined by mRNAs Abundance in Maternal Blood

A decrease in oxygen supply to a developing fetus can result in serious complications, permanent disability, and stillbirth. Current methods of determining fetal hypoxia are not sufficiently sensitive or accurate.

Prof. Stephen Tong and colleagues from the Mercy hospital (Heidelberg, Australia) and Melbourne University (Melbourne, Australia) have developed a method to determine fetal hypoxia by examining a maternal blood sample.

During the past 10 years, it was discovered that mRNAs of placental origin leak into the maternal circulation where they can be sampled and quantified. Prof. Tong's team hypothesized that when the fetus is hypoxic, it will upregulate and release hypoxia-induced mRNAs into maternal blood and that the relative abundance of these mRNAs would correlate with the degree of hypoxia. If correct, then measuring hypoxia-induced mRNAs could form the basis of a noninvasive clinical blood test of fetal hypoxia.

The team studied acute hypoxia by serially sampling blood from women undergoing labor. They also investigated chronic hypoxia, recruiting women with pregnancies complicated by severe preterm fetal growth restriction. They found hypoxia-induced mRNAs abundance in maternal blood taken close to delivery did correlate with the hypoxic status of the fetus during its last moments in utero (determined by measuring fetal blood pH, or lactate levels from the placenta at birth).Thus, the data provided proof of principle evidence that measuring hypoxia-induced mRNAs abundance in maternal blood could be used to determine the degree of fetal hypoxia in utero.

The study was published in Biomedical Central on December 9, 2013. The authors believe there may be a variety of clinical situations where the test to determine fetal hypoxia levels could be useful. However, they consider the greatest impact could be in monitoring fetuses that are growth restricted at very preterm gestations.

With preterm fetal growth restriction, the risks of stillbirth are high and clinicians face the tricky situation of having to time delivery. The clinician is required to balance the probability of stillbirth, or permanent disability (caused by leaving the baby too long in an environment of severe chronic hypoxia) if the pregnancy is left to continue versus the risk of causing “iatrogenic” prematurity if the preterm fetus is delivered unnecessarily early (severe prematurity has, itself, serious complications including cerebral palsy).

A test that is able to more precisely estimate fetal blood pH in utero could be used to help the clinician make more informed decisions regarding delivery, improving outcomes.

The investigators have implemented a large observational multicenter study (seven referral centers in Australia and New Zealand) to verify their findings and develop a test with clinical care in mind. Called the FOX study, i.e., Fetal Oxygenation study, the team hopes to recruit 180 participants with severe preterm growth restriction. The aim is to confirm the inverse correlation between hypoxic–induced mRNAs abundance and fetal blood pH determined at delivery, but with greatly expanded numbers.

Related Links:
Mercy Hospital
Melbourne University