Efficacy of a Vibrating Crib Mattress to Reduce Pharmacologic Treatment in Opioid-Exposed Newborns: A Randomized Clinical Trial.

Importance: Pharmacologic agents are often used to treat newborns with prenatal opioid exposure (POE) despite known adverse effects on neurodevelopment. Alternative nonpharmacological interventions are needed. Objective: To examine efficacy of a vibrating crib mattress for treating newborns with POE. Design, Setting, and Participants: In this dual-site randomized clinical trial, 208 term newborns with POE, enrolled from March 9, 2017, to March 10, 2020, were studied at their bedside throughout hospitalization. Interventions: Half the cohort received treatment as usual (TAU) and half received standard care plus low-level stochastic (random) vibrotactile stimulation (SVS) using a uniquely constructed crib mattress with a 3-hour on-off cycle. Study initiated in the newborn unit where newborns were randomized to TAU or SVS within 48 hours of birth. All infants whose symptoms met clinical criteria for pharmacologic treatment received morphine in the neonatal intensive care unit per standard care. Main Outcomes and Measures: The a priori primary outcomes analyzed were pharmacotherapy (administration of morphine treatment [AMT], first-line medication at both study sites [number of infants treated], and cumulative morphine dose) and hospital length of stay. Intention-to-treat analysis was conducted. Results: Analyses were performed on 181 newborns who completed hospitalization at the study sites (mean [SD] gestational age, 39.0 [1.2] weeks; mean [SD] birth weight, 3076 (489) g; 100 [55.2%] were female). Of the 181 analyzed infants, 121 (66.9%) were discharged without medication and 60 (33.1%) were transferred to the NICU for morphine treatment (31 [51.7%] TAU and 29 [48.3%] SVS). Treatment rate was not significantly different in the 2 groups: 35.6% (31 of 87 infants who received TAU) and 30.9% (29 of 94 infants who received SVS) (P = .60). Adjusting for site, sex, birth weight, opioid exposure, and feed type, infant duration on the vibrating mattress in the newborn unit was associated with reduction in AMT (adjusted odds ratio, 0.88 hours per day; 95% CI, 0.81-0.93 hours per day). This translated to a 50% relative reduction in AMT for infants who received SVS on average 6 hours per day. Among 32 infants transferred to the neonatal intensive care unit for morphine treatment who completed treatment within 3 weeks, those assigned to SVS finished treatment nearly twice as fast (hazard ratio, 1.96; 95% CI, 1.01-3.81), resulting in 3.18 fewer treatment days (95% CI, -0.47 to -0.04 days) and receiving a mean 1.76 mg/kg less morphine (95% CI, -3.02 to -0.50 mg/kg) than the TAU cohort. No effects of condition were observed among infants treated for more than 3 weeks (n = 28). Conclusions and Relevance: The findings of this clinical trial suggest that SVS may serve as a complementary nonpharmacologic intervention for newborns with POE. Reducing pharmacotherapy with SVS has implications for reduced hospitalization stays and costs, and possibly improved infant outcomes given the known adverse effects of morphine on neurodevelopment. Trial Registration: ClinicalTrials.gov Identifier: NCT02801331.

Physiologic dysregulation in newborns with prenatal opioid exposure: Cardiac, respiratory and movement activity.

BACKGROUND: Newborns with prenatal opioid exposure (POE) are commonly diagnosed with neonatal abstinence/opioid-withdrawal syndromes due to characteristic symptoms and overt behaviors. However, little is known about the underlying physiology of opioid-exposed newborns. OBJECTIVE: Cardiac, respiratory and movement activity were measured to identify physiologic dysregulation and quantify pathophysiologic instabilities of the central and autonomic nervous systems in POE newborns. METHODS: In this pilot study, 30 hospitalized POE newborns (>35 wks gestational age) participated in one of two study phases wherein physiologic activity was measured for an 8-10 h session. In Phase 1, 17 infants received usual treatment to provide a general assessment of physiologic activity. In Phase 2, 13 infants participated in an interventional study (NCT02768844) using a prototype mattress that delivered stochastic vibratory stimulation (SVS). Changes in physiologic activity were compared for device on (N) and off (F) for three interfeed periods (FNF or NFN). RESULTS: Phase 1 showed that although infants' heart rate was on average within normal newborn range (mean 137 bpm, SD 7), infants were tachycardic 16% of the study period and tachypneic (mean 74 breaths/min, SD 13) 62% of the period. Infants moved 33% of the period; 17% were durations >30 s. In Phase 2, heart rate, respiratory rate, movement duration and frequency were each reduced for SVS N compared to SVS F in the FNF protocol (P < 0.05). CONCLUSION: Findings support that physiologic measures can identify dysregulation not captured with current withdrawal scoring assessments. Larger studies are warranted to assess if mattress SVS helps regulate pathophysiologic instabilities in infants with POE.

Study design and rationale for a randomized controlled trial to assess effectiveness of stochastic vibrotactile mattress stimulation versus standard non-oscillating crib mattress for treating hospitalized opioid-exposed newborns.

The incidence of Neonatal Abstinence Syndrome (NAS) continues to rise and there remains a critical need to develop non-pharmacological interventions for managing opioid withdrawal in newborns. Objective physiologic markers of opioid withdrawal in the newborn remain elusive. Optimal treatment strategies for improving short-term clinical outcomes and promoting healthy neurobehavioral development have yet to be defined. This dual-site randomized controlled trial (NCT02801331) is designed to evaluate the therapeutic efficacy of stochastic vibrotactile stimulation (SVS) for reducing withdrawal symptoms, pharmacological treatment, and length of hospitalization, and for improving developmental outcomes in opioid-exposed neonates. Hospitalized newborns (n = 230) receiving standard clinical care for prenatal opioid exposure will be randomly assigned within 48-hours of birth to a crib with either: 1) Intervention (SVS) mattress: specially-constructed SVS crib mattress that delivers gentle vibrations (30-60 Hz, ~12 µm RMS surface displacement) at 3-hr intervals; or 2) Control mattress (treatment as usual; TAU): non-oscillating hospital-crib mattress. Infants will be studied throughout their hospitalization and post discharge to 14-months of age. The study will compare clinical measures (i.e., withdrawal scores, cumulative dose and duration of medications, velocity of weight gain) and characteristic progression of physiologic activity (i.e., limb movement, cardio-respiratory, temperature, blood-oxygenation) throughout hospitalization between opioid-exposed infants who receive SVS and those who receive TAU. Developmental outcomes (i.e., physical, social, emotional and cognitive) within the first year of life will be evaluated between the two study groups. Findings from this randomized controlled trial will determine whether SVS reduces in-hospital severity of NAS, improves physiologic function, and promotes healthy development.