A multifactorial relationship exists between total circulating cell-free DNA levels and maternal BMI.

摘要: Maternal obesity affects 1 in 5 pregnant women the United States1. is associated with increased circulating total, but not fetal, cf DNA2. This may be a result of production or decreased clearance DNA obese women. It more likely that this due to total cfDNA, because would also lead an increase cell-free fetal cfDNA. In prior study performed on women, we showed active remodeling adipose tissue via adipocyte necrosis and/or apoptosis stromal vascular fraction results release cfDNA maternal origin into circulation3. The focus was mechanisms underlying closely examined correlation between weight and levels. This approved by Institutional Review Boards at Tufts Medical Center Metrohealth Center. samples are from same cohort reported previously3, analysis different. Briefly, sixteen (mean=39.2; pre-gravid BMI range 31–51) 14 lean (mean 21.8; 17–24) carrying male fetuses 10 female (negative controls) were recruited term (37–40 weeks) elective cesarean section. Written informed consent obtained obtaining samples. Women multiple gestations, placenta previa invasive placentation, labor, infection, anomalies aneuploidy, intrauterine growth restriction, preeclampsia excluded. Maternal peripheral venous blood collected MetroHealth admission labor delivery, placement intravenous line for hydration. All subjects had instructions nothing eat drink 6–8 hours draw. EDTA tube plasma separated centrifugation kept frozen −20°C being shipped further analysis. extracted 400 uL using QIAamp Blood Mini Kit (Qiagen, Valencia, CA) according body fluid protocol. eluted 50 μL elution buffer. Real time quantitative PCR amplification as previously described4 amplify glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Y chromosome sequence DYS14 markers DNA, respectively. analyzed triplicate. Analysis blinded, processed handled all so there no risk contaminating DNA. Conversion raw data genome equivalents per mL methods Lo et al.5 The levels compared t test. addition, volume both adjusted volume6 test, experiments our laboratory suggested function weight7. Finally, regression BMI. Analysis 1.7% unit (kg/m2). Following adjustment volume, 3.2% (Table 1). When categorized groups, however, decrease Figure Neither these changes statistically significant. However, lack significance small sample size. Further studies warranted characterize relationship BMI. Figure 1 Graph showing mass index [BMI]. coefficient population -0.061 (p=0.41) 0.23 (p=0.20). Table 1 Change index In study, found levels. reflects dilutional effect seen increasing volume. Conversely, reflect necrosis3 significant enough overcome occurs women. Our similar previous Lapaire al.2, which second trimester There several differences however. Firstly, gestational ages present drawn term, contrast 20 21 weeks. Secondly, al. weight. We method described Lemmens al.6 The Wataganara al.7 suggest correction factor needed when analyses performed. standard practice correct performing serum screening Down syndrome. Diagnostic laboratories typically derive their own curves analytes factors, including instrument sensitivity measurement analytes, well distribution among centers8. literature, indicates consensus best adjust markers, nucleic acids, cases extreme obesity. selected al.6 formula it correlated BMI, although used quantification non-pregnant surgical patients. In summary, show here future, values need adequate interpretation clinical tests involve assessment fraction9. presence suggests analyte biomarker systemic problems during gestation impact health.