Measuring the amount of hypoxia-induced mRNA in maternal blood is clinically correlated with the degree of fetal hypoxia in utero, according to a study published Dec. 9 in BMC Medicine. Using such a biochemical or molecular marker could be a new, direct strategy to monitor fetal hypoxia in utero, and researchers say the novel noninvasive maternal blood test represents a great advance in quantitatively measuring fetal danger from hypoxia both during labor or resulting from severe, chronic fetal growth restriction. Current tests (cardiotocograph, ultrasound, Doppler waveform velocimetry analysis) can indirectly identify hypoxic fetuses but not the severity of fetal acidemia (fetal blood pH/lactate concentrations), which can have detrimental birth outcomes including stillborn and severe perinatal injury and disability. Serial samples of maternal blood were collected prior to induction and commencement of uterine contractions, at commencement of the second stage of labor including full dilatation, and at delivery. The researchers correlated hypoxia-induced mRNA in the samples with the degree of fetal umbilical artery blood samples and placental biopsies collected immediately after delivery. Two cohorts were evaluated—one group with acute fetal hypoxia caused by induction of labor (n=30) and one group with chronic fetal hypoxia due to severe, preterm growth restriction (n=20 […]
Measuring the amount of hypoxia-induced mRNA in maternal blood is clinically correlated with the degree of fetal hypoxia in utero, according to a study published Dec. 9 in BMC Medicine. Using such a biochemical or molecular marker could be a new, direct strategy to monitor fetal hypoxia in utero, and researchers say the novel noninvasive maternal blood test represents a great advance in quantitatively measuring fetal danger from hypoxia both during labor or resulting from severe, chronic fetal growth restriction.
Current tests (cardiotocograph, ultrasound, Doppler waveform velocimetry analysis) can indirectly identify hypoxic fetuses but not the severity of fetal acidemia (fetal blood pH/lactate concentrations), which can have detrimental birth outcomes including stillborn and severe perinatal injury and disability.
Serial samples of maternal blood were collected prior to induction and commencement of uterine contractions, at commencement of the second stage of labor including full dilatation, and at delivery. The researchers correlated hypoxia-induced mRNA in the samples with the degree of fetal umbilical artery blood samples and placental biopsies collected immediately after delivery. Two cohorts were evaluated—one group with acute fetal hypoxia caused by induction of labor (n=30) and one group with chronic fetal hypoxia due to severe, preterm growth restriction (n=20 cases plus 30 controls), with fetuses delivered by cesarean section. Microarray and real-time reverse-transcription polymerase chain reaction (PCR) were used to quantify mRNAs.
The researchers found that hypoxia-induced mRNAs in maternal blood rose across labor with a “precipitous increase” during the second stage of induced labor. In the second cohort, hypoxia-induced mRNAs were elevated in the blood of women carrying severely growth-restricted preterm fetuses. The hypoxia gene score (sum of the relative expression of four hypoxia-induced genes, Hif1α, Hif2α, LdhA, and Adm) was strongly correlated with fetal acidemia at birth in both cohorts, as well as with the severity of ultrasound Doppler velocimetry abnormalities in fetal vessels.
“Ours may be the first ‘theoretical’ noninvasive test for women in labor that can determine the degree of in utero fetal acidemia,” write the authors, led by Clare Whitehead, M.B.Ch.B., from the University of Melbourne in Australia. “The speed of current PCR technologies means such a test is not feasible as a clinical tool to make decisions during labor but improvements in nucleic acid detection technologies might make such a test possible in the future.”
However, the test may have more immediate potential in the case of chronic hypoxia from severe fetal growth restriction, although larger validation would still be necessary for that indication.
“It is conceivable that day-to-day clinical decisions regarding timing of a fetal growth restriction fetus can await the results of a PCR result performed using machines available today. Therefore, our test may have a role in situations where current tests of fetal well-being are equivocal and the clinician is left unsure whether the fetus should be delivered,” writes Whitehead. Other future iterations of the test may include expansion with identification of other hypoxia-induced genes and development of a clinical test that expresses mRNA abundance by copy number versus relative expression.
Takeaway: A future test that can quantify the severity of fetal hypoxia has the potential to improve fetal and birth outcomes.
