Maeve K Hopkins1, Nathanael Koelper2, Samantha Caldwell3, Lorraine Dugoff4. 1. Women's Health Institute, Division of Maternal and Fetal Medicine, Cleveland Clinic, Cleveland, OH. Electronic address: hopkinm7@ccf.org. 2. Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3. Laboratory Corporation of America Holdings, Sequenom Center for Molecular Medicine, LLC, San Diego, California, USA. 4. Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Divisions of Reproductive Genetics and Maternal Fetal Medicine, Philadelphia, PA.
Abstract
BACKGROUND: Fetal fraction of cell free DNA decreases with increasing maternal weight. Consequently, cell-free DNA screening for fetal aneuploidy has higher screen failures or "no call" rates in women with obesity due to a low fetal fraction. The optimal timing of testing based on maternal weight is unknown. OBJECTIVE: To identify the optimal timing of initial cell-free DNA testing based on maternal weight and to identify the optimal timing of repeat cell-free DNA testing in cases with an initial screen failure. STUDY DESIGN: Retrospective cohort study of women undergoing cell-free DNA for fetal aneuploidy screening between 9-18 weeks through a single laboratory over one year from 2018-2019. Fetal fraction change per week was calculated and generalized linear models were used to calculate relative risk and 95% confidence interval of a no call result at given maternal weights and gestational ages. RESULTS: The vast majority (99.22%) of samples received a test result. The risk of a no call result due to a low fetal fraction was higher with increasing maternal weight. At 9-12 weeks, the rate of a no call result due to a low fetal fraction in women who weighed < 150 lbs was 0.14%, compared to 17.39% in women weighing > 400 lbs. Fetal fraction increased with increasing gestational age, although the incremental increase in fetal fraction over time is inversely proportional to maternal weight. At 13-18 weeks' gestation, 6.45% of women > 400 lbs received a no call result due to a low fetal fraction. In women in the highest weight category, > 400 lbs, fetal fraction increased 0.5% with each week of gestation. CONCLUSION: Although the risk of a no call result increases with maternal weight, cell-free DNA screening should be offered to all women at 9-12 weeks' gestation, allowing the option to have chorionic villus sampling following a positive test result. Pre-test counseling for women with obesity should include the increased chance for a test failure. The majority of women weighing less than 400 pounds will receive a test result and over 80% of women with a weight > 400 pounds will receive a test result at 9-12 weeks' gestation. Data regarding the expected increase in cell-free DNA fetal fraction per week may help guide the timing of a redraw to optimize test success.
BACKGROUND: Fetal fraction of cell free DNA decreases with increasing maternal weight. Consequently, cell-free DNA screening for fetal aneuploidy has higher screen failures or "no call" rates in women with obesity due to a low fetal fraction. The optimal timing of testing based on maternal weight is unknown. OBJECTIVE: To identify the optimal timing of initial cell-free DNA testing based on maternal weight and to identify the optimal timing of repeat cell-free DNA testing in cases with an initial screen failure. STUDY DESIGN: Retrospective cohort study of women undergoing cell-free DNA for fetal aneuploidy screening between 9-18 weeks through a single laboratory over one year from 2018-2019. Fetal fraction change per week was calculated and generalized linear models were used to calculate relative risk and 95% confidence interval of a no call result at given maternal weights and gestational ages. RESULTS: The vast majority (99.22%) of samples received a test result. The risk of a no call result due to a low fetal fraction was higher with increasing maternal weight. At 9-12 weeks, the rate of a no call result due to a low fetal fraction in women who weighed < 150 lbs was 0.14%, compared to 17.39% in women weighing > 400 lbs. Fetal fraction increased with increasing gestational age, although the incremental increase in fetal fraction over time is inversely proportional to maternal weight. At 13-18 weeks' gestation, 6.45% of women > 400 lbs received a no call result due to a low fetal fraction. In women in the highest weight category, > 400 lbs, fetal fraction increased 0.5% with each week of gestation. CONCLUSION: Although the risk of a no call result increases with maternal weight, cell-free DNA screening should be offered to all women at 9-12 weeks' gestation, allowing the option to have chorionic villus sampling following a positive test result. Pre-test counseling for women with obesity should include the increased chance for a test failure. The majority of women weighing less than 400 pounds will receive a test result and over 80% of women with a weight > 400 pounds will receive a test result at 9-12 weeks' gestation. Data regarding the expected increase in cell-free DNA fetal fraction per week may help guide the timing of a redraw to optimize test success.