Can amniotic fluid predict time of delivery?
Analyzing gene expression of a pregnant woman's amniotic fluid could give doctors an important tool for deciding when it is safe to deliver premature babies.
Researchers at Cincinnati Children's Hospital Medical Center report they have identified a way to test RNA and specific genetic molecules in amniotic fluid to see whether fetal lungs — and potentially other organs — are mature enough for a safe and viable delivery.
The paper is published online in the journal BMC Medical Genomics.
"This study demonstrates 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," said Beena Kamath-Rayne, MD, MPH, a lead author and researcher in the Perinatal Institute at Cincinnati Children's. "This will allow pediatricians and neonatologists to prepare for the various neonatal morbidities these preterm infants may face, and allow obstetricians to better weigh risks to the baby when making decisions about preterm delivery."
In the study, researchers isolated and characterized RNA in amniotic fluid at different weekly intervals: 18 to 24, 34 to 36 and 39 to 40 weeks. They found some of the RNA and genes expressed during these periods were associated with fetal immaturity, such as characteristics of respiratory distress.
Researchers identified 257 genes expressed differently at 34-36 weeks compared to genes expressed by a full-term fetus. Through more analysis, the genes expressed were linked to underdeveloped lungs, decreased body fat and patterns indicating an immature feeding ability.
The authors emphasize additional research is needed, partly due to the small study study involving only 16 women, all of whom gave prior consent. But the study takes aim at the persistent public health problem of premature birth. In these particular cases, children scheduled for elective birth before 39 weeks.
In 2008, the American Congress of Obstetricians and Gynecologists recommended testing fetal lung maturity for all elective deliveries prior to 39 weeks, but this recommendation has been withdrawn. Subsequent research shows that focusing only on fetal lung maturity is not sufficient to determine a baby's readiness for postnatal life, according to the authors.
The research team is preparing to confirm their current results with a larger study. Their aim is to develope a test to assess fetal maturity based on an expectant mother's blood or urine to avoid amniocentesis.
Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation.
We isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions.
Sample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity.
The AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing.
Keywords: Amniotic fluid; Fetal lung maturity; Transcriptome; Prenatal diagnosis
The research team at Cincinnati Children's included senior authors Nathan Salomonis, PhD, (Division of Biomedical Informatics), Yan Xu, PhD, (Division of Bioinformatics and Perinatal Institute), and other co-investigators in neonatology, pulmonary biology, bio-informatics, and maternal-fetal medicine.
Funding support for the study came from the National Institutes of Health (K12HL119986, HL110964, HL122642, HL105433, U01HL099997), the March of Dimes Premature Research Center Ohio Collaborative and the Cincinnati Children's Hospital Medical Center Perinatal Institute Pilot and Feasibility Grant.
About Cincinnati Children's:
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S.News and World Report's 2015 Best Children's Hospitals. It is also ranked in the top 10 for all 10 pediatric specialties, including a #1 ranking in pulmonology and #2 in cancer and in nephrology. Cincinnati Children's, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati's College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at http://www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter
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