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 we will begin to acquire in 2005-2006 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 birth that in turn may facilitate future clinical strategies for successful postnatal care.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL060061-03
Application #
7215881
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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