Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial.

Importance: Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancies at a high risk of trisomy 21 to decrease the number of required invasive fetal karyotyping procedures and their associated miscarriages. The effect of this strategy has not been evaluated. Objective: To compare the rates of miscarriage following invasive procedures only in the case of positive cfDNA test results vs immediate invasive testing procedures (amniocentesis or chorionic villus sampling) in women with pregnancies at high risk of trisomy 21 as identified by first-trimester combined screening. Design, Setting, and Participants: Randomized clinical trial conducted from April 8, 2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first-trimester screening. Interventions: Patients were randomized to receive either cfDNA testing followed by invasive testing procedures only when cfDNA tests results were positive (n = 1034) or to receive immediate invasive testing procedures (n = 1017). The cfDNA testing was performed using an in-house validated method based on next-generation sequencing. Main Outcomes and Measures: The primary outcome was number of miscarriages before 24 weeks' gestation. Secondary outcomes included cfDNA testing detection rate for trisomy 21. The primary outcome underwent 1-sided testing; secondary outcomes underwent 2-sided testing. Results: Among 2051 women who were randomized and analyzed (mean age, 36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial. The miscarriage rate was not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk difference of -0.03% (1-sided 95% CI, -0.68% to ∞; P = .47). The cfDNA detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%). Conclusions and Relevance: Among women with pregnancies at high risk of trisomy 21, offering cfDNA screening, followed by invasive testing if cfDNA test results were positive, compared with invasive testing procedures alone, did not result in a significant reduction in miscarriage before 24 weeks. The study may have been underpowered to detect clinically important differences in miscarriage rates. Trial Registration: ClinicalTrials.gov Identifier: NCT02127515.

Association between amniotic fluid evaluation and fetal biometry: a prospective French "Flash" study.

We aimed to study the association between three different methods of assessing the amount of amniotic fluid (subjective method (SM), deepest vertical pocket (DVP) and amniotic fluid index (AFI)) and estimated fetal weight (EFW) (in percentile or Z-score) after adjustment on maternal-fetal parameters. We performed a nationwide cross-sectional study through the French network of obstetric sonographers using the "flash" study method and including low-risk singleton pregnancies from 18-40 weeks. Crude and adjusted odds ratio were computed after stratification upon 2nd and 3rd trimester of pregnancy. 1667 ultrasound scans performed by 65 operators were included. Only Z-score of EFW was significantly associated with SM in both trimesters. For DVP and AFI, Z-score of EFW and male fetal gender was significantly associated with them in 2nd trimester. In the 3rd trimester, both Z-score of EFW and large (LGA) or small for gestational age (SGA) fetus were significantly associated with AFI. and DVP. Overweight woman and class I obesity women were also significantly associated with DVP modification. In conclusion, all three methods of amniotic fluid evaluation are significantly associated to estimated fetal weight. DVP and AFI appeared equivalent except that maternal-fetal factors seemed to have a higher impact in DVP than AFI.

Gas bubbles in simulation and experiment.

An experimental setup for the examination of single bubbles, rising in a liquid, is presented. Its main part is a rotating chamber, in which the bubble is spatially stabilized by a balance of buoyancy, drag, and lift forces. This allows for long observation periods in time. Experimental results are presented for air bubbles in silicone oil. The experimental results are validated by a comparison with numerical simulations. A modified, mass-conserving level-set method is used for the representation of the free interface, while an immersed-boundary formulation is engaged for the conservation equations. The agreement between experiment and simulation, and to available correlations from literature, is found to be perfect. It is shown that the influence of the liquid shear due to the rotation is negligible. Also, for the presented liquid system, no influence by Marangoni stresses could be found, which makes the system of air and silicone oil a good choice for validation purposes.