Avoiding Unnecessary Disparities in Care: Evaluating Noninvasive Prenatal Screening Performance via Whole Genome Sequencing Across Classes of Obesity

Purpose/Aim Examine how well noninvasive prenatal screening (NIPS) performs in women across body mass index (BMI) classes. Hypothesis NIPS via whole genome sequencing better serves all women, regardless of BMI, compared with traditional maternal serum screening. Significance/Background Noninvasive Prenatal Screening (NIPS), increasingly offered as a first‐line aneuploidy screen, has superior performance compared with maternal serum screening (MSS). Fetal fraction (FF) is one of the many factors that influence the performance of NIPS. Low FF is associated with early gestational age, a compromised placenta (eg, from triploidy and certain aneuploidies), and high BMI. By far, the most common driver of low FF is high BMI. The most recent American College of Medical Genetics and Genomics statement recommends “offering aneuploidy screening other than NIPS in cases of significant obesity.” However, patients with high BMI constitute approximately25% of US pregnancies, creating a significant disparity in care based on weight. Methods 58,639 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. Findings Due to downward shifts in the FF distribution, NIPS sensitivity drops as BMI increases: non‐obese analytical sensitivity for T21 is 99.5%, whereas for class III it is 94.1%. Nevertheless, even patients with class III BMI have expected T21 sensitivity in excess of that obtainable via standard MSS (92.9%). Sensitivity for T13 and T18 was also higher across the BMI spectrum for WGS‐based NIPS relative to MSS. Discussion WGS‐based NIPS with high performance at low FF is a high‐quality aneuploidy screening option for all women, regardless of BMI. Providers can therefore offer the same high level of care to all patients, regardless of body habitus.