Cell-free RNA in amniotic fluid used to identify stage of human fetal organ maturity.


With premature birth now a persistent health problem, the need for standardised biomarkers is a necessity.  Amniotic fluid (AF) both contributes to and reflects the status of the fetus, and has been shown to provide a screenshot into the maturation processes of fetal development. At present, AF from different time points in pregnancy is used to provide important information about pregnancy management and delivery planning, such as mid-trimester screening for aneuploidy, diagnostic testing for intra-amniotic infection, or fetal lung maturity testing.

However, with debate on the usefulness of fetal lung maturity testing, and the advent of non-invasive methods of prenatal diagnosis, practice patterns are changing to make amniocentesis, and thereby, analysis of AF, a much rarer occurrence.  This is a problem as AF has important advantages over other maternal sourced specimens. Now, a study from researchers at Cincinnati Children’s Hospital has identified a way to test RNA and specific genetic signatures in amniotic fluid to see whether fetal lungs,  and potentially other organs, are mature enough for a safe and viable delivery. The team state that their findings will allow pediatricians and neonatologists to prepare for the various neonatal morbidities preterm infants may face, and allow the obstetrician to better weigh risks to the baby when making decisions about preterm delivery.  The opensource study is published in the journal BMC Medical Genomics.

Previous studies show that AF contains larger amounts of fetal and pregnancy-related DNA, RNA, and proteins than maternal serum.  While cell-free fetal RNA and DNA in maternal serum can be used for prenatal screening, these analyses have not been extensively studied for the purpose of understanding the heterogeneous process of fetal maturation.  Recent studies have indicated that amniotic fluid supernatant provides a snapshot of developmental processes occurring in the fetus. Most of these studies have focused on the analysis of amniotic fluid supernatant from second trimester fetuses which have indicated a pattern of enrichment in brain-specific genes. In addition, further studies have demonstrated a difference in gene expression patterns between AF obtained in the second trimester compared to that obtained at term.  The current study identifies unique gene expression patterns at different time points in pregnancy that could be utilized as biomarkers for a better understanding of overall fetal maturity and is unique in the use of samples from the late preterm period.

The current study isolated and characterized RNA in amniotic fluid at different pregnancy time points, namely, 18 to 24 weeks; 34 to 36 weeks and 39 to 40 weeks. Results show that genetic analysis at different pregnancy time points give a strong correlation with cell types found in the intrauterine environment. Data findings show that the presence of some RNA and genes expressed at certain time points were associated with characteristics of fetal immaturity, such as respiratory distress.

Results identified 257 genes that were expressed differently in late preterm fetuses (34-36 weeks) compared to full-term fetuses. Through additional analysis, the group linked genes expressed differently in preterm fetuses to underdeveloped lungs, decreased lean body mass and immature feeding patterns.  The lab stress that additional research is needed beyond the current study, in part because of its small study sample involving only 16 women, all of whom participated after giving prior consent.

The team surmise that their findings demonstrate the feasibility of testing amniotic fluid to identify biomarkers for fetal organ maturation to better enable obstetricians to make delivery planning decisions for preterm births. For the future, the researchers state that they are preparing to validate their current results with a larger study. They go on to add that they will then work towards developing a test to assess fetal maturity that can be done in the expectant mother’s blood or urine so that amniocentesis can be avoided.

Source: Cincinnati Children’s Hospital Medical Center

 

RNA’s Secret Life Outside the Cell.  Illustration by the National Institutes of Health.

RNA’s Secret Life Outside the Cell. Illustration by the National Institutes of Health.

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