Prenatal exposure to nicotine through maternal smoking leads to alterations in fetal responses related to arousal and cardiorespiratory control far beyond the period of exposure. The drug pets fetuses at increased risk for growth restriction, prematurity, perinatal complications and after birth, for the Sudden Infant Death Syndrome, behavioral and learning disabilities, and attention deficit disorders; while the adolescent female offspring may be at increased risk for becoming smokers themselves. By hypoxia and direct effects of nicotine on fetal neurodevelopment have been implicated as mechanisms for this array of consequences. Our overall hypothesis is that excessive and untimely stimulation of fetal nicotinic receptors by nicotine induces wide ranging structural and functional changes in the developing nervous system leading to alterations in central regulatory mechanisms controlling autonomic and behavioral functions. While fetal regulatory mechanisms adapt to chronic nicotine exposure to maintain a relatively "normal" physiology, hypoxic stress will reveal deficiencies in physiologic competence. These structural functional alterations, established in utero produce a "vulnerable" newborn who will have a life long risk for stress related pathologies. To test these hypotheses, we will compare key markers of neurophysiologic function (coordinated fetal states, response to hypoxia and baroreceptor gain) in nicotine exposed fetuses with controls and relate their functional impairments to structural differences in brainstem and forebrain arousal and cardiorespiratory centers. Studies are carried out in a unique chronically instrumented baboon model. The homologies in neurodevelopment between the human and baboon fetus make knowledge gained from this research relevant to identifying high risk fetuses and infants.
NIH ExPorter
NIH ExPorter