A new UCLA study is harnessing the power of molecular changes during pregnancy in a way that could help to more accurately predict such complications as gestational diabetes and preeclampsia before symptoms arise. In modifying a blood test used to detect DNA-level changes that could point to fetal abnormalities, this research is the first to tie potential pregnancy complications to the presence of cell-free nucleic acids — free-standing genetic material — shed from the placenta into the mother’s blood.
To Sherin U. Devaskar, MD, physician-in-chief at UCLA Mattel Children’s Hospital, this blood test is the first step in addressing at-risk pregnancies. “Most often in medicine, we’re fixing a problem after it occurs,” Dr. Devaskar says. “If we are able to detect some of these pregnancy disorders before they happen, and if we can prevent them, that will be phenomenal.”
To isolate cell-free nucleic acids shed from the placenta into the blood, the interdisciplinary team used state-of-the-art imaging, mathematical algorithms and modeling. Between February 2017 and January 2019, the researchers periodically tested the blood of a group of expectant mothers through the duration of their pregnancies. Giorgia Del Vecchio, PhD, a post-doctoral researcher in the UCLA Department of Pediatrics, analyzed the cell-free DNA from samples of maternal plasma taken during the first, second and third trimesters of pregnancy, and also at delivery. “We found that in patients who developed gestational diabetes later in pregnancy, the percentage of DNA coming from the placenta in the first trimester was higher compared to the patients with pregnancies that didn’t have complications,” Dr. Del Vecchio says.
The disorder typically is diagnosed with a glucose-tolerance test at 24-to-28 weeks, but with the blood test developed by UCLA researchers, it is detectable during the first trimester, between 10 and 12 weeks. The research team also was able to develop a model to predict preeclampsia with up to 86% accuracy by isolating and sequencing cell-free RNA to identify whether certain preeclampsia-indicating genes were at play.
New information paired with early detection will lead to better outcomes for mothers and their babies, Dr. Devaskar says. Mothers will be forewarned and, therefore, better able to work with their doctors on making the necessary diet, medical and behavioral changes to stave off pregnancy-related complications. “Knowledge is power,” she says. “And patients have the right to knowledge and to be powerful in their own care.”
— Jocelyn Apodaca Schlossberg
“Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes,” Epigenetics, October 13, 2020