OP01.02: NIPS for high‐BMI patients: evaluating the impact of deep whole‐genome sequencing on sensitivity and residual risk

Abstract

Fetal fraction (FF) is one of the many factors that influence the performance of non-invasive prenatal screening (NIPS). Low FF is associated with early gestational age, a compromised placenta (eg. from triploidy and certain aneuploidies), and high body mass index (BMI). By far, the most common of these is high BMI: patients with high BMI (>29.9) constitute ∼25% of US pregnancies and ∼20% of UK pregnancies. The most recent American College of Genetics and Genomics statement recommends “offering aneuploidy screening other than NIPS in cases of significant obesity.” We sought to examine whether high-BMI patients benefit from NIPS versus standard maternal serum screening for the purpose of common aneuploidy screening. 51,737 patients who received NIPS were stratified into standard BMI classes. For each BMI group, the aggregate analytical sensitivity was calculated by summing, over the range of FF values, the product of (1) the sensitivity for a given FF and depth based on a model of whole-genome sequencing (WGS) NIPS and (2) the BMI-specific probability of observing a patient at that FF. Scaled sensitivities were incorporated into residual-risk calculations to assess impact on patient results reporting. Due to downward shifts in the FF distribution, NIPS sensitivity drops as BMI increases: non-obese analytical sensitivity for Trisomy 21 (T21) is 99.8%, whereas for class III obesity (BMI >40) it is 95.4%. Nevertheless, even those patients with class III BMI have expected T21 sensitivity in excess of that obtainable via standard maternal serum screening (92.9%). NIPS is a reasonable option for high-BMI patients when using methods that improve the performance at low FF (eg. high-depth WGS), allowing providers to offer the same high level of care to all of their patients, regardless of body habitus. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.