Imaging the Developing Fetal Brain: Novel Markers of Risk for Maternal Smoking

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DESCRIPTION (provided by applicant): This application is responsive to PAR-12-066; Imaging-Science Track Award for Research Transition; I/START). The proposed study will facilitate the addition of neural mechanisms to the PI's program of maternal smoking/offspring behavior research. Maternal smoking during pregnancy is associated with morbidity and mortality in infants and behavioral deficits (attention deficits, substance use, disruptive behaviors) in older children. Despite pervasive sanctions against smoking during pregnancy, 13-30% of infants are born exposed. Given continued high exposure rates and links to costly offspring outcomes, innovative approaches are needed to identify and protect high risk offspring and help pregnant smokers quit. Identification of pre-birth markers of offspring risk offers potential for developing novel therapeutic targets and early intervention efforts to mitigate adverse outcomes. Our group previously utilized 2D ultrasound to reveal effects of maternal smoking on fetal behavioral deficits. However, although structural brain deficits have been proposed as a key candidate mechanism underlying links between maternal smoking and offspring neurobehavioral deficits, no studies have included neural markers of fetal risk from maternal smoking. The proposed I/START will allow the PI to expand and increase the impact of her program of maternal smoking research by including novel neural markers of fetal risk. The advent of 3D ultrasound offers higher resolution fetal images and allows volumetric characterization of specific fetal structures in clinical studies. The proposed I/START study will determine, for the first time, the feasibility of applying 3D ultrasound technology to identify neural markers of risk from maternal smoking in the developing fetus. The I/START study will capitalize on infrastructure and participants from the PI's ongoing study of maternal smoking and infant behavior (R01 DA031188). Pregnant smokers and controls from the ongoing study will complete three fetal ultrasound assessments involving 3D volumetric assessment of fetal neural (fronto-cerebellar regions) and neuroendocrine (adrenal gland) structures. Acceptability and adherence to ultrasound protocols and reliability of volumetric assessments will be assessed. Our goals are: 1) to demonstrate feasibility of our novel ultrasound methodology for volumetric assessment of fetal neural and neuroendocrine structures, and 2) to conduct a preliminary characterization of effects of maternal smoking on fetal neural and neuroendocrine structures over pregnancy in preparation for a larger R01 study. If successful, results from this pilot study offer future potential for: a) promoting discovery of mechanisms of maternal smoking in real-time during pregnancy, b) improving clinical care for pregnant smokers, c) identifying novel therapeutic targets to protect exposed fetuses, and d) developing new foci for cessation efforts with pregnant smokers.