Inverse Correlation Between Maternal Weight and Second Trimester Circulating Cell-Free Fetal DNA Levels

Wataganara, Tuangsit; Peter, Inga; Lambert-Messerlian, Geralyn; Borgatta, Lynn; Bianchi, Diana W.

doi:10.1097/01.aog.0000137352.93110.15

Cited by 46 publications

(41 citation statements)

References 14 publications

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“…Several studies have detected significant effects of storage, as a binary or continuous variable, on circulating cfDNA levels in plasma and serum. 14,15 Moreover, a suggestive gradient of −0.66 GE/mL per month of storage has been reported. 9 However, this study shows that the effects of storage on DNA are complex and might not be properly controlled for by assuming a linear association with length of storage.…”

Section: Discussionmentioning

confidence: 95%

Cell-free DNA Fragmentation Patterns in Amniotic Fluid Identify Genetic Abnormalities and Changes due to Storage

Peter

Tighiouart²,

Lapaire³

et al. 2008

Diagnostic Molecular Pathology

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Circulating cell-free DNA (cfDNA) has become a promising biomarker in prenatal diagnosis. However, despite extensive studies in different body fluids, cfDNA predictive value is uncertain owing to the confounding factors that can affect its levels, such as gestational age, maternal weight, smoking status, and medications. Residual fresh and archived amniotic fluid (AF) supernatants were obtained from gravid women (mean gestational age 17 wk) carrying euploid (N = 36) and aneuploid (N = 29) fetuses, to characterize cfDNA-fragmentation patterns with regard to aneuploidy and storage time (−80°C). AF cfDNA was characterized by the real-time quantitative polymerase chain reaction amplification of glyceraldehyde-3-phosphate dehydrogenase, gel electrophoresis, and pattern recognition of the DNA fragmentation. The distributions of cfDNA fragment lengths were compared using 6 measures that defined the locations and slopes for the first and last peaks, after elimination of the confounding variables. This method allowed for the unique classification of euploid and aneuploid cfDNA samples in AF, which had been matched for storage time. In addition, we showed that archived euploid AF samples gradually lose long cfDNA fragments: this loss accurately distinguishes them from the fresh samples. We present preliminary data using cfDNA-fragmentation patterns, to uniquely distinguish between AF samples of pregnant women with regard to aneuploidy and storage time, independent of gestational age and initial DNA amount. In addition to potential applications in prenatal diagnosis, these data suggest that archived AF samples consist of large amounts of short cfDNA fragments, which are undetectable using standard real-time polymerase chain reaction amplification.

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Section: Discussionmentioning

confidence: 95%

Cell-free DNA Fragmentation Patterns in Amniotic Fluid Identify Genetic Abnormalities and Changes due to Storage

Peter

Tighiouart²,

Lapaire³

et al. 2008

Diagnostic Molecular Pathology

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“…Furthermore, maternal cffDNA levels increase by 21% per week in the first trimester. 14 Maternal concentrations of cffDNA then rise rapidly during the last few weeks of normal pregnancies, 14,15 and again there appears to be an association with placental apoptosis. 16 The incidence of cells displaying condensed chromatin at term is double that during the first trimester, and trophoblastic nuclei are principally involved.…”

Section: Discussionmentioning

confidence: 98%

Trophoblastic Oxidative Stress and the Release of Cell-Free Feto-Placental DNA

Tjoa

Cindrová‐Davies

Spasić-Bošković

et al. 2006

The American Journal of Pathology

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198

149

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Considerable quantities of cell-free fetal DNA circulate in the maternal blood during human pregnancy, but the origin of the DNA remains uncertain. Circumstantial evidence suggests the placenta is the principal source, so we tested the hypothesis that release occurs from the syncytiotrophoblast after the induction of apoptotic changes. Villous explants from normal placentas delivered by elective caesarean section were cultured under normoxic conditions (10% oxygen) for up to 20 hours or exposed to hypoxia (0.5% oxygen) for 1 hour followed by reoxygenation. The concentration of ␤-globin cell-free DNA in the supernatant, measured using realtime polymerase chain reaction methodology, was significantly increased at 20 hours after hypoxia-reoxygenation. Release was associated with increased apoptosis, confirmed by increased activation of caspase-3 on Western blotting, and immunolocalized to the syncytiotrophoblast; necrosis was also evidenced by release of lactate dehydrogenase. Both release of cell-free DNA and apoptosis could be significantly reduced by the addition of antioxidant vitamins C and E to the culture medium. This study provides the first evidence of a mechanistic and quantitative link between placental apoptosis/necrosis and release of cell-free DNA, hence confirming that maternal serum/plasma concentrations of cell-free DNA may act as a biomarker of trophoblast well-being during pregnancy.

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“…This was in contrast to the preliminary results of Wataganara et al, which showed a significant inverse correlation between cff DNA and maternal weight, after adjustment for gestational age. 24 In this retrospective study, maternal weight was expressed in pounds (lb). Alternatively, in our prospective study, we used the BMI as an international standard for obesity measurement, adjusting bodyweight for height (weight [kg]/height squared [m 2 ]), instead of maternal weight alone.…”

Section: Discussionmentioning

confidence: 99%

Significant Correlation Between Maternal Body Mass Index at Delivery and in the Second Trimester, and Second Trimester Circulating Total Cell-free DNA Levels

et al. 2009

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Inverse Correlation Between Maternal Weight and Second Trimester Circulating Cell-Free Fetal DNA Levels

Abstract: 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.

Cited by 46 publications

References 14 publications

Cell-free DNA Fragmentation Patterns in Amniotic Fluid Identify Genetic Abnormalities and Changes due to Storage

Cell-free DNA Fragmentation Patterns in Amniotic Fluid Identify Genetic Abnormalities and Changes due to Storage

Trophoblastic Oxidative Stress and the Release of Cell-Free Feto-Placental DNA

Significant Correlation Between Maternal Body Mass Index at Delivery and in the Second Trimester, and Second Trimester Circulating Total Cell-free DNA Levels

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