OBJECTIVE: Clinical applications of the analysis of cellfree fetal DNA in ma te rnal plasma and serum are expanding. However, use of fetal DNA during prenatal s creening requires knowledge of variables that might affe...OBJECTIVE: Clinical applications of the analysis of cellfree fetal DNA in ma te rnal plasma and serum are expanding. However, use of fetal DNA during prenatal s creening requires knowledge of variables that might affect its levels in the mat ernal circulation. We conducted this study to estimate the effect of selected de mographic factors on fetal DNA levels in the first and second trimesters of preg nancy. METHODS: We developed a database that included fetal DNA levels and clini cal information, such as maternal age, ethnicity, weight, and smoking history. W e measured fetal DNA levels in maternal plasma and serum using real-time quanti tative polymerase chain reaction amplification of a Y chromosome specific sequen ce. The fetal DNA data from fresh first trimester plasma and previously frozen s econd trimester serum samples were analyzed separately. Fetal DNA levels were ad justed according to gestational age and storage time and then analyzed in associ ation with the demographic factors. RESULTS: In the first trimester group, no si gnificant association between maternal age, weight, ethnic background, or smokin g and plasma fetal DNA lev els was observed. In the second trimester group, a significant inverse correla tion 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. CONCLUSION: Fetal D NA 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 ap plications that measure cell-free fetal nucleic acids in maternal circulation.展开更多
Objective: Measurement of cell- free fetal (cff) DNA in maternal plasma may have clinical application in prenatal screening for fetal Down syndrome and preeclampsia. Little is known regarding the tissue of origin of t...Objective: Measurement of cell- free fetal (cff) DNA in maternal plasma may have clinical application in prenatal screening for fetal Down syndrome and preeclampsia. Little is known regarding the tissue of origin of these fetal-derived sequences. We tested the hypothesis that if the placenta is the major contributor of cff DNA, then an increased placental volume should be associated with higher maternal plasma cff DNA levels. Study design: We enrolled 143 pregnant women who underwent first trimester placental volume measurement using 3- dimensional ultrasonography. Cff DNA in maternal plasma on the day of the scan was quantified by real-time polymerase chain reaction (PCR) amplification of a Y- chromosome sequence. The association between measured placental volume and maternal plasma cff DNA levels was analyzed along with relevant clinical variables. Results: The median (25th, 75th percentiles) maternal plasma cff DNA level was 16.9 genome equivalents (GE)/mL (10.8, 28.7). Raw values were adjusted for gestational age and maternal body mass index. Results: The median (25th, 75th percentiles) placental volume was 53.2 mL (43.0, 64.7), and median placental quotient (ratio of placental volume to fetal crown-rump length) was 1 mm2 (0.8, 1.1). Based on multivariate linear regression analyses, neither of the above placental measurements showed a significant association with maternal plasma cff DNA levels (P = .43 and .43, respectively). A modest association was found between plasma cff DNA levels and gravidity (P = .03). Conclusion: Our data did not show a significant association between either the placental volume or placental quotient, and maternal plasma cff DNA levels. We speculate that it is the extent of placental apoptosis that primarily affects the amount of cff DNA released into the maternal circulation.展开更多
文摘OBJECTIVE: Clinical applications of the analysis of cellfree fetal DNA in ma te rnal plasma and serum are expanding. However, use of fetal DNA during prenatal s creening requires knowledge of variables that might affect its levels in the mat ernal circulation. We conducted this study to estimate the effect of selected de mographic factors on fetal DNA levels in the first and second trimesters of preg nancy. METHODS: We developed a database that included fetal DNA levels and clini cal information, such as maternal age, ethnicity, weight, and smoking history. W e measured fetal DNA levels in maternal plasma and serum using real-time quanti tative polymerase chain reaction amplification of a Y chromosome specific sequen ce. The fetal DNA data from fresh first trimester plasma and previously frozen s econd trimester serum samples were analyzed separately. Fetal DNA levels were ad justed according to gestational age and storage time and then analyzed in associ ation with the demographic factors. RESULTS: In the first trimester group, no si gnificant association between maternal age, weight, ethnic background, or smokin g and plasma fetal DNA lev els was observed. In the second trimester group, a significant inverse correla tion 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. CONCLUSION: Fetal D NA 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 ap plications that measure cell-free fetal nucleic acids in maternal circulation.
文摘Objective: Measurement of cell- free fetal (cff) DNA in maternal plasma may have clinical application in prenatal screening for fetal Down syndrome and preeclampsia. Little is known regarding the tissue of origin of these fetal-derived sequences. We tested the hypothesis that if the placenta is the major contributor of cff DNA, then an increased placental volume should be associated with higher maternal plasma cff DNA levels. Study design: We enrolled 143 pregnant women who underwent first trimester placental volume measurement using 3- dimensional ultrasonography. Cff DNA in maternal plasma on the day of the scan was quantified by real-time polymerase chain reaction (PCR) amplification of a Y- chromosome sequence. The association between measured placental volume and maternal plasma cff DNA levels was analyzed along with relevant clinical variables. Results: The median (25th, 75th percentiles) maternal plasma cff DNA level was 16.9 genome equivalents (GE)/mL (10.8, 28.7). Raw values were adjusted for gestational age and maternal body mass index. Results: The median (25th, 75th percentiles) placental volume was 53.2 mL (43.0, 64.7), and median placental quotient (ratio of placental volume to fetal crown-rump length) was 1 mm2 (0.8, 1.1). Based on multivariate linear regression analyses, neither of the above placental measurements showed a significant association with maternal plasma cff DNA levels (P = .43 and .43, respectively). A modest association was found between plasma cff DNA levels and gravidity (P = .03). Conclusion: Our data did not show a significant association between either the placental volume or placental quotient, and maternal plasma cff DNA levels. We speculate that it is the extent of placental apoptosis that primarily affects the amount of cff DNA released into the maternal circulation.
