Wataganara Tuangsit, Peter Inga, Messerlian Geralyn M, Borgatta Lynn, Bianchi Diana W
Division of Genetics, Department of Pediatrics, Institute of Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Obstet Gynecol. 2004 Sep;104(3):545-50. doi: 10.1097/01.AOG.0000137352.93110.15.
Clinical applications of the analysis of cell-free fetal DNA in maternal plasma and serum are expanding. However, use of fetal DNA during prenatal screening requires knowledge of variables that might affect its levels in the maternal circulation. We conducted this study to estimate the effect of selected demographic factors on fetal DNA levels in the first and second trimesters of pregnancy.
We developed a database that included fetal DNA levels and clinical information, such as maternal age, ethnicity, weight, and smoking history. We measured fetal DNA levels in maternal plasma and serum using real-time quantitative polymerase chain reaction amplification of a Y chromosome specific sequence. The fetal DNA data from fresh first trimester plasma and previously frozen second trimester serum samples were analyzed separately. Fetal DNA levels were adjusted according to gestational age and storage time and then analyzed in association with the demographic factors.
In the first trimester group, no significant association between maternal age, weight, ethnic background, or smoking and plasma fetal DNA levels was observed. In the second trimester group, a significant inverse correlation between maternal weight and serum fetal DNA level was demonstrated (r = -0.26, P =.007). This was especially prominent when the mothers weighed more than 170 lb (P =.001). Maternal age, ethnicity, and smoking were not significantly associated with the second trimester serum fetal DNA levels.
Fetal DNA levels are affected by maternal weight in the second trimester. A correction for this effect may be needed in larger-scale studies or for future clinical applications that measure cell-free fetal nucleic acids in maternal circulation.
母体血浆和血清中游离胎儿DNA分析的临床应用正在不断扩展。然而,在产前筛查中使用胎儿DNA需要了解可能影响其在母体循环中水平的变量。我们开展这项研究以评估选定的人口统计学因素对妊娠早、中期胎儿DNA水平的影响。
我们建立了一个数据库,其中包括胎儿DNA水平以及临床信息,如母亲年龄、种族、体重和吸烟史。我们使用Y染色体特异性序列的实时定量聚合酶链反应扩增法测量母体血浆和血清中的胎儿DNA水平。分别分析来自新鲜孕早期血浆和先前冷冻的孕中期血清样本的胎儿DNA数据。根据孕周和储存时间对胎儿DNA水平进行校正,然后与人口统计学因素进行关联分析。
在孕早期组中,未观察到母亲年龄、体重、种族背景或吸烟与血浆胎儿DNA水平之间存在显著关联。在孕中期组中,母亲体重与血清胎儿DNA水平之间存在显著负相关(r = -0.26,P = 0.007)。当母亲体重超过170磅时,这种相关性尤为明显(P = 0.001)。母亲年龄、种族和吸烟与孕中期血清胎儿DNA水平无显著关联。
孕中期胎儿DNA水平受母亲体重影响。在大规模研究或未来测量母体循环中游离胎儿核酸的临床应用中,可能需要对此影响进行校正。