Background Very preterm infants are at risk for poor oral feeding endurance, early cessation of eating, poor fluid management with aspiration risk, behavioral distress, and unstable heart rate and oxygenation during feeding. Objective To determine the preliminary effectiveness of a Co-Regulated Approach (CoReg) to oral feeding for very preterm infants at risk for lung disease. Method A randomized, within-subjects, cross-over design was used with 20 very preterm infants requiring oxygen at the start of oral feeding. Infants were bottle fed by the Usual Care approach and by the CoReg approach on 2 consecutive days for an average of four feedings each. Intervention components included co-regulation of suck, swallow, and breathe rhythms using enhanced auditory assessment, infant-guided feeding onsets, and infant positioning in a semielevated, side-lying position. Infant physiology metrics (heart rate, SaO2) were collected continuously prior to and during the feeding. Behavioral and auditory indicators of regulation were coded continuously from videotape during the feeding. Results Seventy feedings were analyzed (38 Usual Care, 32 CoReg) using repeated measures modeling. CoReg feedings were characterized by more frequent preparation of the infant for the feeding, were more commonly initiated in response to infant readiness cues, had more rest periods and breath regulation events, and had fewer sucking stimulation events. CoReg feedings had less SaO2 variability, decline, and time spent in a desaturated state; less heart rate fluctuation and decline; less behavioral disorganization; better fluid management; and less observed effort to breathe. Discussion Support is provided for a co-regulated approach to feeding vulnerable infants. Enhanced auditory assessment of infant feeding rhythms increases the responsiveness of the feeder and improves infant behavioral and physiologic responses.

Exposure to nickel sulfate (NiSO(4)) leads to impaired olfaction and anosmia through an unknown mechanism. We tested the hypothesis that ATP is released following NiSO4-induced injury and that ATP promotes regenerative cell proliferation in the olfactory epithelium (OE). Male Swiss Webster mice were intranasally instilled with NiSO(4) or saline followed by ATP, purinergic receptor antagonists, or saline. We assessed the olfactory epithelium for NiSO(4)-induced changes using histology and immunohistochemistry 1-7 days postinstillation and compared results to olfactory bulb ablation-induced toxicity. Intranasal instillation of NiSO(4) produced a dose- and time-dependent reduction in the thickness of turbinate OE. These reductions were due to sustentacular cell loss, measured by terminal dUTP nick-end labeling (TUNEL) staining at 1-day postinstillation and caspase-3-dependent apoptosis of olfactory sensory neurons at 3 days postinstillation. A significant increase in cell proliferation was observed at 5 and 7 days postinstillation of NiSO(4) evidenced by BrdU incorporation. Treatment with purinergic receptor antagonists significantly reduced NiSO(4)-induced cell proliferation and posttreatment with ATP significantly increased cell proliferation. Furthermore, posttreatment with ATP had no effect on sustentacular cell viability but significantly reduced caspase-3-dependent neuronal apoptosis. In a bulbectomy-induced model of apoptosis, exogenous ATP produced a significant increase in cell proliferation that was not affected by purinergic receptor antagonists, suggesting that ATP is not released during bulbectomy-induced apoptosis. ATP is released following NiSO(4)-induced apoptosis and has neuroproliferative and neuroprotective functions. These data provide therapeutic strategies to alleviate or cure the loss of olfactory function associated with exposure to nickel compounds.