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Objective To determine the effects of gestational age and maternal weight on percent fetal cell-free DNA (cfDNA) in maternal plasma and the change in fetal cfDNA amounts within the same patient over time. MethodsThe cfDNA was extracted from maternal plasma from 22 384 singleton pregnancies of at least 10 weeks gestation undergoing the Harmony TM Prenatal Test. The Harmony Prenatal Test determined fetal percentage via directed analysis of cfDNA.Results At 10 weeks 0 days to 10 weeks 6 days gestation, the median percent fetal cfDNA was 10.2%. Between 10 and 21 weeks gestation, percent fetal increased 0.1% per week (p < 0.0001), and 2% of pregnancies were below 4% fetal cfDNA. Beyond 21 weeks gestation, fetal cfDNA increased 1% per week (p < 0.0001). Fetal cfDNA percentage was proportional to gestational age and inversely proportional to maternal weight (p = 0.0016). Of 135 samples that were redrawn because of insufficient fetal cfDNA of the initial sample, 76 (56%) had greater than 4% fetal cfDNA in the sample from the second draw.Conclusion Fetal cfDNA increases with gestation, decreases with increasing maternal weight, and generally improves upon a blood redraw when the first attempt has insufficient fetal cfDNA.

ObjectiveTo develop a novel prenatal assay based on selective analysis of cell-free DNA in maternal blood for evaluation of fetal Trisomy 21 (T21) and Trisomy 18 (T18).MethodsTwo hundred ninety-eight pregnancies, including 39 T21 and seven T18 confirmed fetal aneuploidies, were analyzed using a novel, highly multiplexed assay, termed digital analysis of selected regions (DANSR™). Cell-free DNA from maternal blood samples was analyzed using DANSR assays for loci on chromosomes 21 and 18. Products from 96 separate patients were pooled and sequenced together. A standard Z-test of chromosomal proportions was used to distinguish aneuploid samples from average-risk pregnancy samples. DANSR aneuploidy discrimination was evaluated at various sequence depths.ResultsAt the lowest sequencing depth, corresponding to 204 000 sequencing counts per sample, average-risk cases where distinguished from T21 and T18 cases, with Z statistics for all cases exceeding 3.6. Increasing the sequencing depth to 410 000 counts per sample substantially improved separation of aneuploid and average-risk cases. A further increase to 620 000 counts per sample resulted in only marginal improvement. This depth of sequencing represents less than 5% of that required by massively parallel shotgun sequencing approaches.ConclusionDigital analysis of selected regions enables highly accurate, cost efficient, and scalable noninvasive fetal aneuploidy assessment. © 2012 John Wiley & Sons, Ltd.

ObjectiveEvaluate the clinical and economic consequences of fetal trisomy 21 (T21) screening with non-invasive prenatal testing (NIPT) in high-risk pregnant women.MethodsUsing a decision-analytic model, we estimated the number of T21 cases detected, the number of invasive procedures performed, corresponding euploid fetal losses and total costs for three screening strategies: first trimester combined screening (FTS), integrated screening (INT) or NIPT, whereby NIPT was performed in high-risk patients (women 35 years or older or women with a positive conventional screening test). Modeling was based on a 4 million pregnant women cohort in the US.ResultsNIPT, at a base case price of $795, was more clinically effective and less costly (dominant) over both FTS and INT. NIPT detected 4823 T21 cases based on 5330 invasive procedures. FTS detected 3364 T21 cases based on 108 364 procedures and INT detected 3760 cases based on 108 760 procedures. NIPT detected 28% and 43% more T21 cases compared to INT and FTS, respectively, while reducing invasive procedures by >95% and reducing euploid fetal losses by >99%. Total costs were $3786M with FTS, $3919M with INT and $3403M with NIPT.ConclusionsNIPT leads to improved T21 detection and reduction in euploid fetal loss at lower total healthcare expenditures.

Objective: To examine the possible relationship between maternal and fetal characteristics and pregnancy outcomes on fetal and maternal cell-free (cf) DNA in maternal plasma at 11-13 weeks' gestation. Methods: cfDNA was extracted from maternal plasma of 1,949 singleton pregnancies and chromosome-selective sequencing was used to determine the proportion of cfDNA and total cfDNA counts which was of fetal and maternal origin. Multivariate regression analysis was used to determine whether specific maternal and fetal characteristics and pregnancy complications, such as preeclampsia (PE), early spontaneous preterm birth (SPB) and delivery of small for gestational age (SGA) neonates, were significant predictors of fetal and maternal cfDNA in maternal plasma. Results: The fetal and maternal cfDNA plasma concentration increased with serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin level, was higher in women of Afro-Caribbean and East-Asian racial origin than in Caucasians, and lower in smokers, but it was not significantly altered in pregnancies complicated by PE, SPB or SGA. The fetal cfDNA level was inversely related to maternal weight and uterine artery pulsatility index, and maternal cfDNA increased with maternal weight. Conclusions: The fetal and maternal cfDNA level in maternal plasma is affected by maternal and fetal characteristics, but it is not altered in pregnancy complications.

Objective To assess the performance of chromosomeselective sequencing of maternal plasma cell-free DNA (cfDNA)

By monolayer coverage of highly acidic semiconductors, such as MoO 3 and WO 3 on the surface of TiO 2 nanoparticles (Degussa P25), the stability of colloidal suspensions in aqueous solution can be greatly improved. The average diameter of agglomerated MoO 3 /TiO 2 and WO 3 /TiO 2 particles in aqueous suspension is only 85-110 nm, respectively, which is about one-fifth to one-fourth of that of pure TiO 2 suspension. The optically transparent photocatalytic films have been prepared with deposition of these colloidal suspensions. The colloidal particles in aqueous solution and the prepared transparent photocatalytic films were characterized with TEM, SEM, AFM, and other spectroscopic techniques. It has also been found that the photocatalytic activity of WO 3 /TiO 2 film is 2.8-3 times that of pure TiO 2 film in decomposing gas-phase 2-propanol, while MoO 3 /TiO 2 film is less effective.