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The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.

Prospective, multiyear epidemiologic studies have proven to be highly effective in discovering preventable risk factors for chronic disease. Investigations such as the Framingham Heart Study have produced blueprints for disease prevention and saved millions of lives and billions of dollars. To discover preventable environmental risk factors for disease in children, the US Congress directed the National Institute of Child Health and Human Development, through the Children's Health Act of 2000, to conduct the National Children's Study. The National Children's Study is hypothesis-driven and will seek information on environmental risks and individual susceptibility factors for asthma, birth defects, dyslexia, attention-deficit/hyperactivity disorder, autism, schizophrenia, and obesity, as well as for adverse birth outcomes. It will be conducted in a nationally representative, prospective cohort of 100 000 US-born children. Children will be followed from conception to 21 years of age. Environmental exposures (chemical, physical, biological, and psychosocial) will be assessed repeatedly during pregnancy and throughout childhood in children's homes, schools, and communities. Chemical assays will be performed by the Centers for Disease Control and Prevention, and banks of biological and environmental samples will be established for future analyses. Genetic material will be collected on each mother and child and banked to permit study of gene-environment interactions. Recruitment is scheduled to begin in 2007 at 7 Vanguard Sites and will extend to 105 sites across the United States. The National Children's Study will generate multiple satellite studies that explore methodologic issues, etiologic questions, and potential interventions. It will provide training for the next generation of researchers and practitioners in environmental pediatrics and will link to planned and ongoing prospective birth cohort studies in other nations. Data from the National Children's Study will guide development of a comprehensive blueprint for disease prevention in children. Key Words National Children's Study, epidemiology, asthma, attention-deficit/hyperactivity disorder, autism, schizophrenia, obesity Abbreviations CVD--cardiovascular disease NICHD--National Institute of Child Health and Human Development CDC--Centers for Disease Control and Prevention NCS-- National Children's Study HPV-- high production volume NCPP--National Collaborative Perinatal Project CHDS--Child Health Development Study NIH--National Institutes of Health, ENVIRONMENTAL EXPOSURES IN early life can influence development, impair health, and increase risk of disease and dysfunction. (1-3) Chemical, physical, and psychosocial factors have all been shown to exert great [...]

The application of ultrasound in assessing the fetal cardiovascular system often requires the accurate estimation of maximum blood flow velocity waveforms using Doppler measurements. The modified geometric method estimates the maximum Doppler frequency as the frequency at which the vertical distance between the integrated spectrum and the reference line that connects the origin to the maximum value of the integrated spectrum is the largest. This paper presents a mathematical formulation for a class of maximum blood flow velocity estimation algorithms that includes the modified geometric method. The analysis provides a rationale for the continued use of the modified geometric method for estimating the maximum frequency envelopes of Doppler signals. This paper also contains experimental results demonstrating the superiority of the modified geometric method over a commonly used threshold crossing method. Index Terms--Integrated spectrum, maximum flow velocity, modified geometric method.

This paper presents a new measure of heart rate variability (HRV) that can be estimated using Doppler ultrasound techniques and is robust to variations in the angle of incidence of the ultrasound beam and the measurement noise. This measure employs the multiple signal characterization (MUSIC) algorithm which is a high-resolution method for estimating the frequencies of sinusoidal signals embedded in white noise from short-duration measurements. We show that the product of the square-root of the estimated signal-to-noise ratio (SNR) and the mean-square error of the frequency estimates is independent of the noise level in the signal. Since varying angles of incidence effectively changes the input SNR, this measure of HRV is robust to the input noise as well as the angle of incidence. This paper includes the results of analyzing synthetic and real Doppler ultrasound data that demonstrates the usefulness of the new measure in HRV analysis. Index Terms--Angle of incidence, heart rate variability, multiple signal characterization.

The hypothesis that early vascularization of the embryonic heart is improved after bolus injections of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) into the vitelline vein before the start of myocardial vasculogenesis was investigated. Findings showed that enhancement of bFGF or VEGF before myocardial vascularization increases vascular growth, the effects of these growth factors on vascular volume and numerical density are temporarily dependent, and bFGF affects ventricular modeling aside from its effects on the coronary vasculature.

A theoretical model is presented for the primitive right ventricle of the stage 21 chick embryo. At this stage of development, the wall of the heart is trabecular with direct intramyocardial blood flow. The model is a pressurized fluid-filled cylinder composed of a porous inner layer of isotropic myocardium and a relatively thin compact outer layer of transversely isotropic myocardium. The analysis is based on nonlinear poroelasticity theory, modified to include residual strain and muscle activation. Correlating theoretical and experimental pressure-volume loops and epicardial strains gives first-approximation constitutive relations for stage 21 embryonic myocardium. The results from the model suggest three primary conclusions: (1) Some muscle fibers likely are aligned in the compact layer, with a fiber angle approximately +10 deg from the circumferential direction. (2) Blood is drawn into the wall of the ventricle during diastolic filling and isovolumic contraction and is squeezed out of the wall during systolic ejection, giving a primitive intramyocardial circulation before the coronary arteries form. As the heart rate increases, the transmural blood-flow velocity increases, but the volume of blood exchanged with the lumen per beat decreases. (3) Residual strain affects transmural stress distributions, producing nearly uniform stresses in the porous layer, where the peak end-systolic stress occurs. These results improve our understanding of the relation between form and function in the developing heart and provide directions for biological experiments to study cardiac morphogenesis.