Advertisement

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

  • Aslam Qureshi
    Affiliations
    Innovative Neonatal and Infant Feeding Disorders Research Program, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio
    Search for articles by this author
  • Manish Malkar
    Affiliations
    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
    Search for articles by this author
  • Mark Splaingard
    Affiliations
    Division of Pulmonary Medicine, Sleep Laboratory, Nationwide Children's Hospital, Columbus, Ohio
    Search for articles by this author
  • Abdul Khuhro
    Affiliations
    Division of Pediatric Neurology, Department of Pediatrics, The Ohio State University, Columbus, Ohio
    Search for articles by this author
  • Sudarshan Jadcherla
    Correspondence
    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.
    Affiliations
    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
    Search for articles by this author

      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.

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Pediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jadcherla S.R.
        • Parks V.N.
        • Peng J.
        • et al.
        Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals.
        Am J Physiol Gastrointest Liver Physiol. 2012; 302: G134-G144
        • Jadcherla S.R.
        • Chan C.Y.
        • Fernandez S.
        • et al.
        Maturation of upstream and downstream esophageal reflexes in human premature neonates: the role of sleep and awake states.
        Am J Physiol Gastrointest Liver Physiol. 2013; 305: G649-G658
        • Carskadon M.A.
        • Dement W.C.
        Normal Human Sleep: An Overview.
        in: Kryger M.H. Roth T. Dement W.C. Priciples and Practice of Sleep Medicine. Elsevier Saunder, Phildelphia, PA, USA2005: 13-23
        • Peirano P.
        • Algarin C.
        • Uauy R.
        Sleep-wake states and their regulatory mechanisms throughout early human development.
        J Pediatr. 2003; 143: S70-S79
        • Curzi-Dascalova L.
        • Peirano P.
        • Morel-Kahn F.
        Development of sleep states in normal premature and full-term newborns.
        Dev Psychobiol. 1988; 21: 431-444
        • Graven S.
        Sleep and Brain Development.
        in: White R. Clin Perinatol. W. B. Saunders Company, Philadelphia, PA2006: 693-706
        • Eisermann M.
        • Kaminska A.
        • Moutard M.
        • et al.
        Normal EEG in Childhood: From neonates to adolescents.
        Clin Neurophysiol. 2013; 43: 35-65
        • Iber C.
        • Ancoli-Israel S.
        • Chesson A.L.J.
        • et al.
        • American Academy of Sleep Medicine
        The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications.
        Americal Academy of Sleep Medicine, Westchester, IL2007
        • Vandenplas Y.
        • Rudolph C.D.
        • Di Lorenzo C.
        • et al.
        Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).
        J Pediatr Gastroenterol Nutr. 2009; 49: 498-547
        • Lightdale J.R.
        • Gremse D.A.
        Gastroesophageal reflux: management guidance for the pediatrician.
        Pediatrics. 2013; 131: e1684-1695
        • Jadcherla S.R.
        • Rudolph C.D.
        Gastroesophageal Reflux in the Preterm Neonate.
        NeoReviews. 2005; 6: e87-e98
        • Jadcherla S.R.
        • Slaughter J.L.
        • Stenger M.R.
        • et al.
        Practice Variance, Prevalence, and Economic Burden of Premature Infants Diagnosed With GERD.
        Hosp Pediatr. 2013; 3: 335-341
        • Jadcherla S.R.
        • Peng J.
        • Chan C.Y.
        • et al.
        Significance of gastroesophageal refluxate in relation to physical, chemical, and spatiotemporal characteristics in symptomatic intensive care unit neonates.
        Pediatr Res. 2011; 70: 192-198
        • Jadcherla S.R.
        Gastroesophageal reflux in the neonate.
        in: Berseth C.L. Clin Perinatol. W.B. Saunders Company, Philadelphia, PA2002: 135-158
        • Malcolm W.F.
        • Cotten C.M.
        Metoclopramide, H2 blockers, and proton pump inhibitors: pharmacotherapy for gastroesophageal reflux in neonates.
        Clin Perinatol. 2012; 39: 99-109
        • van Wijk M.P.
        • Benninga M.A.
        • Omari T.I.
        Role of the multichannel intraluminal impedance technique in infants and children.
        J Pediatr Gastroenterol Nutr. 2009; 48: 2-12
        • Wenzl T.G.
        • Silny J.
        • Schenke S.
        • et al.
        Gastroesophageal reflux and respiratory phenomena in infants: status of the intraluminal impedance technique.
        J Pediatr Gastroenterol Nutr. 1999; 28: 423-428
        • Nunez J.
        • Cristofalo E.
        • McGinley B.
        • et al.
        Temporal association of polysomnographic cardiorespiratory events with GER detected by MII-pH probe in the premature infant at term.
        J Pediatr Gastroenterol Nutr. 2011; 52: 523-531
        • Weusten B.L.
        • Roelofs J.M.
        • Akkermans L.M.
        • et al.
        The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data.
        Gastroenterology. 1994; 107: 1741-1745
        • Omari T.
        Gastro-oesophageal reflux disease in infants and children: new insights, developments and old chestnuts.
        J Pediatr Gastroenterol Nutr. 2005; 41: S21-S23
        • Vandenplas Y.
        • De Wolf D.
        • Deneyer M.
        • et al.
        Incidence of gastroesophageal reflux in sleep, awake, fasted, and postcibal periods in asymptomatic and symptomatic infants.
        J Pediatr Gastroenterol Nutr. 1988; 7: 177-180
        • Schilter B.
        • Le Coultre C.
        • Belli D.C.
        Gastro-oesophageal reflux in children: comparison of different durations, positions and sleep-awake periods of pH monitoring in the same patient.
        Eur J Pediatr. 1993; 152: 880-883
        • Cresi F.
        • Locatelli E.
        • Maggiora E.
        • et al.
        Relationship between sleep/wakefulness and gastroesophageal reflux in symptomatic newborns.
        J Biol Regul Homeost Agents. 2012; 26: 83-85
        • Jeffery H.E.
        • Heacock H.J.
        Impact of sleep and movement on gastro-oesophageal reflux in healthy, newborn infants.
        Arch Dis Child. 1991; 66: 1136-1139
        • Ammari M.
        • Djeddi D.
        • Leke A.
        • et al.
        Relationship between sleep and acid gastro-oesophageal reflux in neonates.
        J Sleep Res. 2012; 21: 80-86
        • Jadcherla S.R.
        • Gupta A.
        • Fernandez S.
        • et al.
        Spatiotemporal characteristics of acid refluxate and relationship to symptoms in premature and term infants with chronic lung disease.
        Am J Gastroenterol. 2008; 103: 720-728
        • Hemmink G.J.
        • Weusten B.L.
        • Oors J.
        • et al.
        Ambulatory oesophageal pH monitoring: a comparison between antimony, ISFET, and glass pH electrodes.
        Eur J Gastroenterol Hepatol. 2010; 22: 572-577
        • Gupta A.
        • Jadcherla S.R.
        The relationship between somatic growth and In Vivo esophageal segmental and sphincteric growth in human neonates.
        J Pediatr Gastroenterol Nutr. 2006; 43: 35-41
        • Gupta A.
        • Gulati P.
        • Kim W.
        • et al.
        Effect of postnatal maturation on the mechanisms of esophageal propulsion in preterm human neonates: primary and secondary peristalsis.
        Am J Gastroenterol. 2009; 104: 411-419
        • Grigg-Damberger M.
        • Gozal D.
        • Marcus C.L.
        • et al.
        The visual scoring of sleep and arousal in infants and children.
        J Clin Sleep Med. 2007; 3: 201-240
        • Lee-Chiong Jr., T.
        Sleep in Infants, Children and Adolescents.
        in: Lee-Chiong Jr., T. Sleep Medicine: Essentials and Review. Oxford University Press, New York, NY, USA2008: 400-412
        • Rosen R.
        • Nurko S.
        The importance of multichannel intraluminal impedance in the evaluation of children with persistent respiratory symptoms.
        Am J Gastroenterol. 2004; 99: 2452-2458
        • Wiener G.J.
        • Richter J.E.
        • Copper J.B.
        • et al.
        The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring.
        Am J Gastroenterol. 1988; 83: 358-361
        • Breumelhof R.
        • Smout A.J.
        The symptom sensitivity index: a valuable additional parameter in 24-hour esophageal pH recording.
        Am J Gastroenterol. 1991; 86: 160-164
        • Omari T.I.
        • Barnett C.P.
        • Benninga M.A.
        • et al.
        Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease.
        Gut. 2002; 51: 475-479
        • Harper R.M.
        • Hoppenbrouwers T.
        • Sterman M.B.
        • et al.
        Polygraphic studies of normal infants during the first six months of life. I. Heart rate and variability as a function of state.
        Pediatr Res. 1976; 10: 945-948
        • Mittal R.K.
        • Holloway R.H.
        • Penagini R.
        • et al.
        Transient lower esophageal sphincter relaxation.
        Gastroenterology. 1995; 109: 601-610
        • Orlando R.C.
        The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms.
        Best Pract Res Clin Gastroenterol. 2010; 24: 873-882
        • Jadcherla S.R.
        • Hogan W.J.
        • Shaker R.
        Physiology and pathophysiology of glottic reflexes and pulmonary aspiration: from neonates to adults.
        Semin Respir Crit Care Med. 2010; 31: 554-560
        • Jadcherla S.R.
        Upstream effect of esophageal distention: effect on airway.
        Curr Gastroenterol Rep. 2006; 8: 190-194
        • Praud J.P.
        Upper airway reflexes in response to gastric reflux.
        Paediatr Respir Rev. 2010; 11: 208-212
        • Sheldon S.H.
        Anatomy of Sleep.
        in: Sheldon S.H. Principal and Practice of Pediatric Sleep Medicine. Elsevier Saunders, Philadelphia, PA, USA2005: 35-41
        • Verrier R.L.
        • Harper R.M.
        • Hobson J.A.
        Cardiovascular Physiology: Central and Autonomic Regulation.
        in: Kryger M.H. Roth T. Dement W.C. Principle and Practice of Medicine. Elsevier Saunders, Philadelphia, PA, USA2005: 192-195
        • Oren J.
        • Kubin L.
        Respiratory Physiology: Central Neural Control.
        in: Kryger M.H. Roth T. Dement W.C. Principle and Practice of Sleep Medicine. Elsevier Saunders, Philadelphia, PA, USA2005: 213-218
        • Machado R.
        • Woodley F.
        • Skaggs B.
        • et al.
        Gastroesophageal Reflux Causing Sleep Interruptions in Infants.
        J Pediatr Gastroenterol Nutr. 2013; 56: 431-435