Obesity and cell-free DNA "no calls": is there an optimal gestational age at time of sampling?

Cell-free DNA screen failures or "no calls" occur in 1-12% of samples and are frustrating for both clinician and patient. The rate of "no calls" has been shown to have an inverse relationship with gestational age. Recent studies have shown an increased risk for "no calls" among obese women.

We sought to determine the optimal gestational age for cell-free DNA among obese women.

We performed a retrospective cohort study of women who underwent cell-free DNA at a single tertiary care center from 2011 through 2016. Adjusted odds ratios with 95% confidence intervals for a "no call" were determined for each weight class and compared to normal-weight women. The predicted probability of a "no call" with 95% confidence intervals were determined for each week of gestation for normal-weight and obese women and compared.

Among 2385 patients meeting inclusion criteria, 105 (4.4%) had a "no call". Compared to normal-weight women, the adjusted odds ratio of a "no call" increased with increasing weight class from overweight to obesity class III (respectively: adjusted odds ratio, 2.31; 95% confidence interval, 1.21-4.42 to adjusted odds ratio, 8.55; 95% confidence interval, 4.16-17.56). A cut point at 21 weeks was identified for obesity class II/III women at which there is no longer a significant difference in the probability of a "no call" for obese women compared to normal weight women. From 8-16 weeks, there is a 4.5% reduction in the probability of a "no call" for obesity class II/III women (respectively: 14.9%; 95% confidence interval, 8.95-20.78 and 10.4%; 95% confidence interval, 7.20-13.61; P_trend < .01).

The cut point of 21 weeks for optimal sampling of cell-free DNA limits reproductive choices. However, a progressive fall in the probability of a "no call" with advancing gestational age suggests that delaying cell-free DNA for obese women is a reasonable strategy to reduce the probability of a "no call".