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

  • Aslam Qureshi
    Innovative Neonatal and Infant Feeding Disorders Research Program, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio
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  • Manish Malkar
    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
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  • Mark Splaingard
    Division of Pulmonary Medicine, Sleep Laboratory, Nationwide Children's Hospital, Columbus, Ohio
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  • Abdul Khuhro
    Division of Pediatric Neurology, Department of Pediatrics, The Ohio State University, Columbus, Ohio
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  • Sudarshan Jadcherla
    Communications should be addressed to: Dr. Jadcherla; Professor of Pediatrics and Associate Division Chief of Neonatology, Academics, Division of Neonatology, Pediatric Gastroenterology and Nutrition; Center for Perinatal Research; The Research Institute at Nationwide Children's Hospital; 700 Children's Drive; Columbus, OH 43205.
    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
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      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.


      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.


      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]).


      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).


      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.


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