The Role of Sleep in the Modulation of Gastroesophageal Reflux and Symptoms in NICU Neonates

Background: Newborns sleep about 80% of the time. Gastroesophageal reflux disease is prevalent in about 10% of neonatal intensive care unit infants. Concurrent polysomnography and pH-impedance studies clarify the relationship of gastroesophageal reflux with sleep.

Aims: To characterize spatiotemporal and chemical characteristics of impedance-positive gastroesophageal reflux and define symptom associations in sleep and wake states in symptomatic neonates. We hypothesized that frequency of impedance-positive gastroesophageal reflux events and their association with cardiorespiratory symptoms is greater during sleep.

Methods: Eighteen neonates underwent concurrent polysomnography with a pH-impedance study. Impedance-positive gastroesophageal reflux events (weakly acidic or acidic) were categorized between sleep versus wake states: Symptom Index = number of symptoms with gastroesophageal reflux/total symptoms*100; Symptom Sensitivity Index = number of gastroesophageal reflux with symptoms/total gastroesophageal reflux*100; Symptom Association Probability = [(1 - probability of observed association between reflux and symptoms)*100]).

Results: We analyzed 317 gastroesophageal reflux events during 116 hours of polysomnography. During wake versus sleep, respectively, the median (interquartile range) frequency of impedance-positive gastroesophageal reflux was 4.9 (3.1-5.8) versus 1.4 (0.7-1.7) events/hour (P < 0.001) and the proximal migration was 2.6 (0.8-3.3) versus 0.2 (0.0-0.9) events/hour (P < 0.001). The Symptom Index for cardiorespiratory symptoms for impedance-positive events was 22.5 (0-55.3) versus 6.1 (0-13), P = 0.04, whereas the Symptom Sensitivity Index was 9.1 (0-23.1) versus 18.4 (0-50), P = 0.04, although Symptom Association Probability was similar (P = 0.68).

Conclusions: Contrary to our hypothesis, frequency of gastroesophageal reflux in sleep is lower; however, spatiotemporal and chemical characteristics of gastroesophageal reflux and symptom-generation mechanisms are distinct. For cardiorespiratory symptoms during sleep, a lower Symptom Index entails evaluation for etiologies other than gastroesophageal reflux disease, a higher Symptom Sensitivity Index implies heightened esophageal sensitivity, and similar Symptom Association Probability indicates other mechanistic possibilities.