Background Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. Results We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down’s syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. Conclusions In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.)

Background-Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis.

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We used Doppler echocardiography to quantitate the changes in intracardiac blood flow velocities and right and left ventricular stroke volumes in 80 normal human fetuses from 19 to 40 weeks gestation. Blood flow velocity spectra across the aortic, pulmonary, tricuspid, and mitral valves were digitized to obtain peak velocities (m/sec) and flow velocity integrals. Aortic and pulmonary diameters were measured at valve level from two-dimensional echocardiographic images and cross-sectional area was calculated assuming a circular orifice. Ventricular stroke volume was calculated as the product of the cross-sectional area of a great vessel and the flow velocity integral through that vessel. The pulmonary arterial and aortic diameters increased linearly with gestational age (r = .82, r = .84), and pulmonary arterial diameter consistently exceeded aortic diameter. There was a positive relationship between stroke volume and gestational age: stroke volume increased exponentially from 0.7 ml at 20 weeks to 7.6 ml at 40 weeks for the right ventricle (r = .87) and from 0.7 ml at 20 weeks to 5.2 ml at 40 weeks for the left ventricle (r = .91). Similar results were obtained for right and left ventricular and combined cardiac outputs. In 44% of the fetuses it was possible to quantitate both right and left ventricular stroke volumes. There was a close correlation between right and left ventricular stroke volumes in these fetuses (r = .96) and right ventricular stroke volume exceeded left ventricular stroke volume by 28%. Flow velocity across the tricuspid and mitral valves was consistently greater during atrial systole (A wave) than during rapid ventricular filling (E wave) (0.52 0.07 vs 0.37 + 0.08 m/sec and 0.45 ± 0.07 vs 0.33 ± 0.06 mlsec). The E/A ratios for the mitral and tricuspid valves were similar throughout the period of gestation studied, indicating equivalent diastolic ventricular function. This study demonstrates that right and left ventricular stroke volumes increase by approximately 10-fold from 20 to 40 weeks gestation in the normal human fetus. It also demonstrates, within the limitations of the equipment, that right ventricular stroke volume exceeds that of the left ventricle, thus confirming right ventricular dominance in utero. Circulation 74, No. 6, 1208-1216 TWO-DIMENSIONAL echocardiographic imaging of the fetal heart has permitted accurate definition of intracardiac anatomy and characterization of the growth patterns of the four cardiac chambers throughout the second and third trimesters.'-Echocardiography has also enabled recognition of cardiac rhythm distur-