title: The Role of Sleep in the Modulation of Gastroesophageal Reflux and Symptoms in NICU Neonates.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Innovative Neonatal and Infant Feeding Disorders Research Program, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Aslam
authors.initials: A
authors.lastname: Qureshi
authors.affiliation: Innovative Neonatal and Infant Feeding Disorders Research Program, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Manish
authors.initials: M
authors.lastname: Malkar
authors.affiliation: Division of Pulmonary Medicine, Sleep Laboratory, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Mark
authors.initials: M
authors.lastname: Splaingard
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, The Ohio State University, Columbus, Ohio.
authors.forename: Abdul
authors.initials: A
authors.lastname: Khuhro
authors.affiliation: Innovative Neonatal and Infant Feeding Disorders Research Program, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio; Pediatric Gastroenterology and Nutrition, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio. Electronic address: sudarshan.jadcherla@nationwidechildrens.org.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Jadcherla
mesh_terms: D017097:Electric Impedance; D005260:Female; D005764:Gastroesophageal Reflux / Q000503:physiopathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology; D007363:Intensive Care Units, Neonatal; D008297:Male; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
keywords: gastroesophageal reflux; neonates; pH impedance; sleep; symptoms