The aerodigestive system is comprised of a complex of integrated anatomic structures that support both ingestive and respiratory physiologies throughout the human lifespan. The developmental origins of this system---in both its form and function, begin in utero where prenatal morphologies and associated processes form the foundations for extrauterine survival at birth. When this prenatal development is disrupted, alterations to normal physiologic functioning may serve as antecedents of later neonatal respiratory distress, dysphagia, or upper gastrointestinal dysfunction. Further, premature birth before upper airway processes are fully established may exacerbate many of these conditions. In turn, this may prompt a cascade of respiratory-related dysfunctions throughout postnatal life. It is therefore important to understand how the respiratory system develops, how mechanisms regulate normal emerging physiologic processes, and the events that predicate fetal and neonatal compromise. To do this work in the living human fetus, we apply a novel noninvasive ultrasound imaging and analysis method to measure the role of altered amniotic fluid exchange in developing prenatal respiratory and ingestive mechanisms. The key components of this protocol are to:? 1. Extend the use of prenatal ultrasound sonography to detect and measure the developing upper aerodigestive region. ? 2. Prospectively characterize differences in ingestive versus respiratory fluid flow-related dynamics across maturation in normal fetuses and those with conditions that may influence airway development. Using spectral Doppler-derived fluid flow analyses, we will map across the spectrum of gestation the fluid dynamics of upper airway development and the factors that influence functional integrity of upper airway amniotic fluid exchange.? 3. Identify how deviations in amniotic fluid regulation within the upper aerodigestive system may be associated with fetal and neonatal morbidity and mortality and, the predictive utility of these indices in conditions such as oligohydramnios or polyhydramnios.? ? This study (approved by NIH IRB on August 5, 2003; MOU approved May 24, 2004) is a collaborative effort with National Naval Medical Center Bethesda, Childrens and Womens Health. Data colllection began in June, 2004 with 122 subjects recruited in the 2004-2005 fiscal year. The project uses a novel standardized 4-axis sonographic examination to quantify growth and respiratory-related fluid flow mechanics in the upper airway of the living human fetus. Our team has added the semi-automatic analysis of respiratory patterns using computer programs developed in-house and the addition of 3D analyses of organ growth. In addition, we have begun to look at analyis of emerging motor patterns and differences across gestation and gender. We are studying lung maturity in high-risk infants and developing several teaching models for medical students. The use of this noninvasive ultrasound technique as part of the clinical prenatal examination will not only discriminate function at four upper airway sites (perinasal, oral, pharyngeal, and tracheal), but provide estimates of amniotic fluid flow volumes, inspiratory-expiratory fluid flow velocities and durations, and Doppler waveform patterns associated with fetal breathing and ingestive processes. This provides a method to explore how deviations in amniotic fluid regulation may be associated with morbidity and mortality and, the predictive utility of these indices in understanding conditions such as oligohydramnios or polyhydramnios. The database will include healthy fetuses 16.0 to 39.6 weeks gestational age and test cases with polyhydramnios/oligohydramnios. By elucidating how developing structures integrate with emerging upper respiratory behaviors, this work will document the maturational events underlying normal function at To reach these objectives, a series of projects has been implemented in three phases spanning clinical research of prenatal populations to the development and application of new scientific technologies. The first phase included development of software and technical applications, refinement of analytical tools, and feasibility testing. The second phase has focused on the incorporation of advanced technology 3D volumetric measures of developing organ systems and feasibility trials of 4D kinematic movement analyses. The third phase of the initiative has encompassed small pilot studies to identify the construct validity of these technologies in identifying high-risk prenatal populations, the creation of computer-aided diagnostic programs to assist in pattern detection, automated analyses, and diagnostic precision. In addition, the predictive strengths of these techniques against current clinical standards of fetal lung maturity were tested. Our future work will expand to include partnerships with leaders in the medical imaging industry to develop state-of-the-art sonographic technologies for measurement of critical physiologic systems throughout the fetus, establishment of novel software techniques for four-dimensional quantification of fetal movements, interventional studies of steroids and prenatal lung function, and the further development of computer-aided analyses of populations at risk for premature birth and postnatal disability. birth that in turn may facilitate future clinical strategies for successful postnatal care.? ? Past accomplishments and/or major findings:? ? In-house (MATLAB) software programs were developed to automatically quantify spectral waveform kinematics and volume flow estimates.? ? These programs were piloted in healthy populations where significant differences in respiratory patterns as a function of development were documented. Kinematic data derived from the waveform samples (n = 1000 samples, 44 fetuses; 16-38 week?s gestation) demonstrated significant positive linear trends in evolution of respiratory patterns with advancing maturity. ? ? Unique differences in development within genders were then identified in a cohort of 85 healthy fetuses (15-38 week?s gestational age). Despite greater physical growth, males demonstrated fewer advanced patterns of movement and a gender-specific trajectory of motor skill development. We continue to track possible biological differences due to gender in all clinical studies. ? ? Tests were then trialed to identify the feasibility of the technique to identify pathology. Clear trends in variable patterns were discriminated in a pilot of healthy (n = 9) and at-risk (n = 10) fetal populations. In a second pilot (n = 10), we discovered respiratory structures/functions appear affected by intrauterine growth restriction and may be a source of neonatal respiratory distress.? ? A computer-aided analysis package was developed to automate analyses and provide instantaneous clinical indicators of diagnosis. The program correctly discriminated waveform patterns of normal groups (n = 44) at > 98% accuracy (2% misclassification error). In high-risk subjects, the program accurately identified (100%) premature, growth-restricted fetuses that at birth exhibited respiratory dysfunction.? ? In comparisons with current clinical techniques to evaluate lung maturity, the computer-aided analysis package correctly predicted neonatal respiratory status in 5/6 cases (83% predictive accuracy) compared to biochemical measures of fetal lung mature (3/6 cases, 50% predictive accuracy) and lecithin to sphingomyelin ratios (2/4 cases, 50% predictive accuracy). We continue to evaluate the feasibility of the technique to identify factors of respiratory distress, a common detriment of premature birth resulting from immature lung development.? ? We continue to develop fuzzy neural network programs based on classification schema to predict normal development.
| Miller, Jeri L; Kang, Seon M (2007) Preliminary ultrasound observation of lingual movement patterns during nutritive versus non-nutritive sucking in a premature infant. Dysphagia 22:150-60 |
| Miller, J L; Macedonia, C; Sonies, B C (2006) Sex differences in prenatal oral-motor function and development. Dev Med Child Neurol 48:465-70 |
| Macedonia, Christian; Miller, Jeri L; Sonies, Barbara C (2002) Power Doppler imaging of the fetal upper aerodigestive tract using a 4-point standardized evaluation: preliminary report. J Ultrasound Med 21:869-78 |
