Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia

Abstract

BackgroundApnea of Prematurity (AOP) is common, affecting the majority of infants born at <34 weeks gestational age. Apnea and periodic breathing are accompanied by intermittent hypoxia (IH). Animal and human studies demonstrate that IH exposure contributes to multiple pathologies, including retinopathy of prematurity (ROP), injury to sympathetic ganglia regulating cardiovascular action, impaired pancreatic islet cell and bone development, cerebellar injury, and neurodevelopmental disabilities. Current standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and methylxanthine therapy; these interventions are inadequate, and not optimal for early development.ObjectiveThe objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements trigger reflexive facilitation of breathing.MethodsPremature infants (23–34 wks gestational age), with clinical evidence of AOP/IH episodes were enrolled 1 week after birth. Caffeine treatment was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in 6 hour ON/OFF sequences for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected.ResultsFewer respiratory pauses occurred during vibration periods, relative to baseline (p<0.005). Significantly fewer SpO2 declines occurred with vibration (p<0.05), relative to control periods. Significantly fewer bradycardic events occurred during vibration periods, relative to no vibration periods (p<0.05).ConclusionsIn premature neonates, limb proprioceptive stimulation, simulating limb movement, reduces breathing pauses and IH episodes, and lowers the number of bradycardic events that accompany aberrant breathing episodes. This low-cost neuromodulatory procedure has the potential to provide a non-invasive intervention to reduce apnea, bradycardia and intermittent hypoxia in premature neonates.Trial RegistrationClinicalTrials.gov NCT02641249

Effect of Tactile Stimulation on Termination and Prevention of Apnea of Prematurity: A Systematic Review

“…The mean/median GA varied between studies from 28 to 32.1 weeks. Three studies reported the GA at the start of the study, ranging from 32 to 35 weeks ( 14 , 25 , 26 ) and five studies reported the (mean/median) age when the study started, ranging from 4.3 to 35 days after birth ( 27 – 31 ). The mean/median birth weight also differed between studies from 1,080 to 1,760 g. Three studies reported a mean weight of 1,264–2,013 g at the start of the study ( 14 , 26 , 29 ).…”

“…The mean/median birth weight also differed between studies from 1,080 to 1,760 g. Three studies reported a mean weight of 1,264–2,013 g at the start of the study ( 14 , 26 , 29 ). In a number of studies (some of) the infants were supported by means of: administered caffeine ( 14 , 25 , 26 ), theophylline ( 28 , 30 , 32 , 33 ) or antibiotics ( 29 ), supplemental oxygen ( 14 , 25 , 26 ), and continuous positive airway pressure or assisted ventilation ( 27 , 32 , 33 ).…”

“…The following study designs were used in the included preventative research: two randomized controlled trials ( 33 , 34 ), three counterbalanced quasi-experimental studies ( 27 – 29 ), and six crossover studies of which four were randomized ( 14 , 25 , 26 , 30 ) and two were quasi-experimental ( 31 , 32 ). In most of these studies, the data of equal lasting periods with and without stimulation were compared.…”

“…Cardiorespiratory monitoring and HR and respiratory pneumograms were used to detect apnea. All other studies used mechanical ways of continuous stimulation composed of the following: a cuff placed under the upper thorax pulsating 16 ± 4 times/min ( 27 ), a 128 Hz vibrating disk attached to the foot ( 25 ), two vibrating mattress using exerting a filtered white noise signal of 30–60 Hz with a displacement of 0.01–0.02 ( 14 ), respectively, 0.09 mm ( 26 ), four water mattresses with varying mean frequencies ranging from 8 to 16 oscillations/min and amplitudes of 1–2.4 mm ( 28 – 30 , 34 ), one oscillating air mattress with a frequency of 14–16 oscillations/min ( 33 ) and one oscillating and vibrating mattress with a frequency of 5–20 oscillations/min and 8–10 Hz ( 32 ). The composition of signals that were recorded varied a lot between the studies.…”

Apnea of Prematurity: An Update

“…43,44 • Several other nonpharmacological approaches have been tested, albeit with mixed results. These include physical stimulation, 45,46 olfactory stimulation, 47 and sound stimulation using maternal sounds. 48 Other interventions such as increased low dose inspired CO 2 49 and red blood cell transfusions 50,51 have been suggested for AOP, though current evidence does not support their routine use.…”