Non-invasive RNA test could help assess fetal lung maturity

A simple blood test may predict whether a fetus's lungs are sufficiently mature to breathe on their own, according to new research.

Currently, doctors give antenatal steroids to pregnant women at risk of preterm birth to help the baby's lungs develop faster and reduce the risk of respiratory complications. But when given too late or when the fetus's lungs are already mature, the steroids offer little benefit and may pose unnecessary risks to mother and child. An international research team led by the National University of Singapore has developed a new blood test to help guide these decisions.

'The results of this study have the potential to form the basis of a clinical test to optimise and personalise patient selection for antenatal steroid therapy to those women carrying a fetus with immature lungs,' said the authors of the study published in BMC Medicine.

A form of non-invasive prenatal testing, the test looks for fragments of fetal RNA (known as cell-free RNA or cfRNA) in the mother's blood. These RNAs give a snapshot of gene expression in the fetus's lung cells, indicating their level of maturity. The researchers developed a panel screening for 21 specific cfRNAs, which together are 97-100 percent accurate in distinguishing between fetal lung maturity states. Additionally, the test is accurate whether steroids have been given or not.

The researchers first tested the approach in sheep. They ran the cfRNA panel in maternal and fetal sheep blood plasma, comparing those treated with steroids and those allowed to mature naturally. They measured cfRNA in the mother's blood and directly compared it to gene activity in the fetus's lung tissue. The team then confirmed the findings in ten healthy human pregnancies, using maternal blood collected in each trimester of pregnancy.

'We demonstrate that cfRNA in maternal plasma is highly accurate for the prediction of physiological lung maturation in both sheep and human maternal plasma samples,' said the authors. 'Specifically, the expression of cfRNA in human maternal plasma was highly accurate at predicting lung maturation, comparing first to third trimester expression, first compared to second trimester expression and second compared to third trimester expression.'

'Further development of this technology may provide a rapid, minimally invasive, and cost-effective clinical tool to optimise patient selection for initial and repeat courses of antenatal steroids, along with insights into the molecular mechanisms underlying fetal lung development,' they added.

If larger trials confirm its effectiveness, this 'liquid biopsy' could be integrated into prenatal care pathways, especially for pregnancies at high risk of premature delivery.