Obesity and no call results: optimal timing of cell-free DNA testing and redraw.

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.