Low fetal fraction in obese women at first trimester cell‐free DNA based prenatal screening is not accompanied by differences in total cell‐free DNA. (14th August 2021)

• Record Type: Journal Article
• Authors: Shree, Raj; Kolarova, Teodora R.; MacKinnon, Hayley J.; Hedge, Jaclynne M.; Vinopal, Elena; Ma, Kimberly K.; Lockwood, Christina M.; Chandrasekaran, Suchitra
• Is Part Of: Prenatal diagnosis. Volume 41:Number 10(2021)
• Page Start: 1277
• Page End: 1286
• Publication Date: 2021-08-14
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.6023
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: Reasons for first trimester noninvasive prenatal screening (NIPS) test failure in obese women remain elusive. As dilution from maternal sources may be explanatory, we determined the relationship between obesity, fetal fraction (FF), and total cell‐free DNA (cfDNA) using our NIPS platform. Methods: We assessed differences in first trimester (≤14 weeks) FF, indeterminate rate, and total cfDNA between obese ( n = 518) and normal‐weight women ( n = 237) after exclusion of confounders (anticoagulation, autoimmunity, aneuploidy) and controlling for covariates. Results: Fetal fraction was lower, and the indeterminate rate higher, in obese compared to controls (9.2% ± 4.4 vs. 12.5% ± 4.5, p < 0.001 and 8.4 vs. 1.7%, p < 0.001, respectively), but total cfDNA was not different (92.0 vs. 82.1 pg/µl, p = 0.10). For each week, the FF remained lower in obese women (all p < 0.01) but did not increase across the first trimester for either group. Obesity increased the likelihood of indeterminate result (OR 6.1, 95% CI 2.5, 14.8; p < 0.001) and maternal body mass index correlated with FF ( β −0.27, 95% CI −0.3, −0.22; p < 0.001), but not with total cfDNA ( β 0.49, 95% CI −0.55, 1.53; p = 0.3). Conclusions: First trimester obese women have persistently low FF and higher indeterminate rates, without differences in total cfDNA, suggesting placental‐specific mechanisms versus dilution from maternal sources as a potential etiology. Key points: What's already known about this topic? Maternal obesity influences cell‐free DNA (cfDNA)‐based noninvasive prenatal screening test performance Dilution from maternal sources of cfDNA may explain this phenomenon; however, data restricted to the first trimester is lacking What does this study add? Fetal fraction (FF) remains low throughout the first trimester in obese women First trimester total cfDNA does not differ between obese and normal‐weight women, suggesting additional or alternative mechanisms to dilution from maternal cfDNA sources as an explanation for the low FF