Abstinence and Drug Withdrawal: Innovative Translational Methods for Neonates

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SUMMARY/ABSTRACT Fetal drug exposure is a nationwide problem. Nearly five percent of pregnant women nationwide expose their unborn child to drugs in utero (illicit and prescription). Neonatal Abstinence Syndrome (NAS) refers to multi- system disturbances and dysregulated neurobehaviors caused by discontinuation of drug/s to which an infant has developed tolerance and physical dependence. Novel approaches to study and treat NAS are needed because despite current interventions NAS infants often require prolonged hospitalization and pharmacological treatment for central, autonomic, vasomotor and gastrointestinal instabilities, which may contribute also to poor neurobehavioral outcomes. Growing research suggests the importance of sensory stimulation, particularly tactile stimulation for enhancing normal brain development and stability of function. There is evidence that unperceivable noise-like vibrations (stochastic resonance) can provoke stability in destabilized biological systems. The underlying hypothesis of this proposal is that NAS in newborns is characterized by physiological disturbances that reflect drug-withdrawal severity and that pathophysiological instabilities in drug-withdrawing neonates can be stabilized by stochastic, vibro-tactile stimuli. Forty NAS (opiate-exposed) neonates will participate in a rigorous, short-term study at UMass Memorial Healthcare to examine the following two aims: Aim 1. Quantify via intensive measurement the instabilities of physiological signals of drug withdrawal in NAS infants. Changes and relationships among physiological signals, e.g., instability of respiration, heart beat and temperature, and excessive movement, will be quantified using non-linear computational signal analyses (point process and wavelet) to explore whether physiological instabilities can index NAS severity and predict onset/offset of withdrawal symptoms. Such information would help facilitate pharmacological management of abstinence and drug withdrawal in neonates. Aim 2. Examine the efficacy of stochastic, vibro-tactile stimulation for enhancing physiological stability in NAS infants and alleviating the symptoms of drug withdrawal. Subjects will serve as their own control to test the hypothesis that stochastic, vibro-tactile perturbations impinge upon destabilized neural circuits and reduce the progressive spread of NAS irritability from subcortical (brainstem) to cortical structure, marked by excessive changes in respiration, heart rate, temperature and subsequent upsurge in movement. Conditions of stochastic vibration (specially designed mattress with mechanical actuators embedded in foam; 30-60Hz, RMS amplitude 0.1mm) will be compared to control periods to test whether stimulation: 1) Improves cardio-respiratory control by reducing instability of heart beat (e.g., bradycardia, tachycardia) and respiration, including decreasing incidents of apnea, periodic breathing and tachypnea; 2) Inhibits sleep disruption as marked by reduction of excessive body movements; and 3) Relieves withdrawal symptoms indexed by improved NAS clinical assessment scores. Findings from this proposal will elucidate whether stochastic, vibro-tactile stimulation has potential as an adjuvant treatment of NAS for improving cardio-respiratory control and reducing sleep disruption (indexed by excessive movement) in NAS infants. A more rigorous future prospective study may ultimately help elucidate underlying mechanisms involved in NAS, lead to improved therapeutic interventions for reducing severity and duration of drug withdrawal complementary to standard care, and thereby improve morbidity and reduce hospitalization and medical costs among NAS infants.