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.

Assessment of a hearing protection device on infant sleep in the neonatal intensive care unit.

Premature infants often require prolonged hospitalisation in the neonatal intensive care unit (NICU) where they are exposed to adverse noise that may disrupt sleep and further compromise recovery and developmental outcomes. This single-session trial assessed the effects of a novel circumaural hearing protection device (DREAMIES®; NEATCAP Medical LLC) on sleep in 10 premature infants (mean 34.1 weeks GA) in a Level III NICU. Using polysomnography (PSG), the infant's sleep was compared between three interfeed periods throughout which DREAMIES® was ON or OFF. Each infant received the same condition order, OFF1-ON-OFF2. The PSG 30 s epochs were scored by a rater masked to the condition as Quiet Sleep, Active Sleep, Indeterminate Sleep, and Wake. There was a 14.1% increase in sleep from OFF1 to ON (p = 0.05) and an 18.4% decrease in sleep from ON to OFF2 (p = 0.02); an analogous inverse effect was observed for wake (χ2  = 5.03, p = 0.08). There was a main effect of DREAMIES on active sleep (χ2  = 7.4, p = 0.025) due to more active sleep for ON1 (46%) compared with OFF2 (32%; p = 0.074). No significant effect was observed for quiet sleep or indeterminate sleep. On average, the sound level was 51 dBA (range 36-113 dBA) and did not differ significantly among the three periods. The strongest relationship between the minute-by-minute maximum sound level and movement actigraphy was observed for the OFF1 condition (ρ0.301, p < 0.001). These findings suggest that DREAMIES® may augment sleep in premature infants by reducing acute episodes of adverse noise in the NICU.

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.

Actigraphy: Metrics reveal it is not a valid tool for determining sleep in neonates.

Study of emerging sleep-wake patterns in neonates is important for promptly identifying and treating abnormal sleep behaviours to ensure healthy infant development and neurobehavioral outcomes. Current methods to assess sleep are costly, labour intensive, and particularly difficult to implement in fragile, hospitalised infants requiring intensive medical care. The aim of the present study was to assess the validity of actigraphy as a tool for detecting sleep in preterm infants, using polysomnography (PSG) as the "gold standard". A total of 10 neonates (mean [SD] 35.8 [1.2] weeks post-menstrual age; five female) hospitalised since birth for prematurity each participated in one 8-10 hr session during which PSG and actigraphy were recorded simultaneously. Inter-feed minute-by-minute PSG Sleep-Wake scores were compared to concurrent actigraph epochs categorised as either "Sleep" or "Wake" using three separate movement-per-minute thresholds (≤20, ≤40, ≤80). Tool validity was assessed using five metrics. A key finding was that for each of the movement thresholds there was high agreement rate, sensitivity, and predictive value of sleep (85.2%-97.2%), whereas specificity and predictive value of wake remained low (12%-46%). Receiver operating characteristic curve analysis also revealed low discriminatory power of actigraphy for estimating sleep (area under the curve = 0.636; Youden's Index J = 0.2173). Lack of sufficient minutes of autonomous wake periods among infants was identified as a key limitation in actigraphy. Findings from the present study suggest actigraphy cannot be validated for Sleep/Wake discrimination in preterm infants and that proper validation requires sufficient data from periods of both Sleep and Wake.