Effects of Non-Nutritive Sucking on Gastroesophageal Reflux and Related Apneas in Symptomatic Preterm Infants

NCT02023216 | Completed

• 2 other identifiers: SO-2013-NNS16/2013/U/Oss
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Gastro-esophageal reflux (GER) is a common condition among preterm infants, due to several physiological promoting factors. To limit the potentially harmful widespread of pharmacological treatment, a step-wise approach, which firstly applies conservative strategies, is currently considered the best choice to manage GER in the preterm population. Among the most common conservative strategies, postural measures seem to represent an effective measure to reduce GER features in symptomatic preterm babies, whereas feed thickening is almost ineffective. Non-nutritive sucking (NNS) is a care strategy largely applied in the Neonatal Intensive Care Unit (NICU) settings. The act of swallowing is both reported to trigger the onset of transient lower esophageal sphincter relaxations (TLESRs), thereby eliciting to GER episodes, and to promote the esophageal clearance of refluxate. Hence, a possible effect of NNS on GER features might be hypothesized. This observational, prospective and explorative study primarily aims to explore the effect of NNS, applied by means of a pacifier, on acid and non-acid GER features, evaluated in symptomatic preterm infants (gestational age ≤32 weeks) undergoing a diagnostic combined pH and multiple intraluminal impedance (pH-MII). The secondary aim of this study is to evaluate, in the subgroup of patients with recurrent GER-related apneas, the effect of NNS on cardiorespiratory events, defined as bradycardias and total, central, obstructive, mixed apneas and detected by a simultaneous polysomnographic monitoring.

Conditions

Gastroesophageal Reflux; Apneas; Bradycardia

Keywords

Preterm infants; Non-nutritive sucking; Pacifier; Gastro-esophageal reflux; pH-multiple intraluminal impedance; Apneas; Bradycardias; Hypoxic episodes; Polysomnographic monitoring

Outcome Measures

Primary Outcomes (1)

• Changes in GER pH-MII features during NNS periods

  24 hours

Secondary Outcomes (1)

• Changes in the number of cardiorespiratory events occurring during NNS periods

  6 hours

Interventions

Pacifier DEVICE

The effect of NNS on GER features will be evaluated in preterm infants suffering from GER symptoms, for which a 24-hour pH-MII monitoring has been scheduled. During the monitoring period each infant will receive 8 meals: 4 meals will be followed by NNS, applied by pacifier, while the other 4 not. The sequence of NNS application will be consecutively alternated in study participants. At least 2 hours of NNS are required for the validity of each post-prandial evaluation; measures to fix the pacifier will be strictly forbidden. In the subgroup of babies with recurrent desaturations a simultaneous non-invasive 6-hour PSG monitoring comprehensive of 2 meals (one followed by NNS, the other not), will be performed to evaluate the effect of NNS on apneas, bradycardias and hypoxic episodes.

Eligibility Criteria

• Age: 7 Days - 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Due to the exploratory nature of this study, at least 30 preterm infants admitted to the Neonatal Intensive Care Unit of Sant'Orsola-Malpighi Universitary Hospital and fulfilling the inclusion criteria will be enrolled.

You may qualify if:

• Preterm newborns (GA ≤ 32 weeks) able to sustain a feeding of at least 100 ml kg-1 day-1 of fortified human milk or standard preterm formula, affected by severe/moderate GER symptomatology (recurrent regurgitations, feeding difficulties, failure to thrive and/or post-prandial desaturations) which usual treatment includes 24h pH-MII diagnostic evaluation.
• Preterm newborns able to sustain pacifier usage for at least 2h, as scheduled in our study plan.
• Weight ≥ 1100 g at the time of enrollment
• Obtained written parental consent.

You may not qualify if:

• Newborns with serious chronic pathology.
• Ongoing pharmacological treatment which could interfere with gastro-enteral motion functions (pro-kinetics) and/or with acid gastric secretion (H2 antagonists; proton pump inhibitors).
• Major congenital malformations (e.g. congenital heart diseases, gastrointestinal abnormalities, malformation syndromes).
• Neonatal necrotizing enterocolitis (NEC).
• Ongoing infections.
• Patients with severe clinical conditions which can hinder his/her participation in this trial (e.g. patent ductus arteriosus, intra-ventricular hemorrhage, hemodynamic instability).
• Administration of experimental medication treatment during the previous two weeks.

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

Neonatal Intensive Care Unit of the S.Orsola-Malpighi Hospital

Bologna, Italy, 40138, Italy

Location

Related Publications (19)

• Aceti A, Corvaglia L, Paoletti V, Mariani E, Ancora G, Galletti S, Faldella G. Protein content and fortification of human milk influence gastroesophageal reflux in preterm infants. J Pediatr Gastroenterol Nutr. 2009 Nov;49(5):613-8. doi: 10.1097/MPG.0b013e31819c0ce5.

  PMID: 19633575 BACKGROUND

• Boeckxstaens GE. The lower oesophageal sphincter. Neurogastroenterol Motil. 2005 Jun;17 Suppl 1:13-21. doi: 10.1111/j.1365-2982.2005.00661.x.

  PMID: 15836451 BACKGROUND

• Bremner RM, Hoeft SF, Costantini M, Crookes PF, Bremner CG, DeMeester TR. Pharyngeal swallowing. The major factor in clearance of esophageal reflux episodes. Ann Surg. 1993 Sep;218(3):364-9; discussion 369-70. doi: 10.1097/00000658-199309000-00015.

  PMID: 8373277 BACKGROUND

• Corvaglia L, Ferlini M, Rotatori R, Paoletti V, Alessandroni R, Cocchi G, Faldella G. Starch thickening of human milk is ineffective in reducing the gastroesophageal reflux in preterm infants: a crossover study using intraluminal impedance. J Pediatr. 2006 Feb;148(2):265-8. doi: 10.1016/j.jpeds.2005.09.034.

  PMID: 16492440 BACKGROUND

• Corvaglia L, Rotatori R, Ferlini M, Aceti A, Ancora G, Faldella G. The effect of body positioning on gastroesophageal reflux in premature infants: evaluation by combined impedance and pH monitoring. J Pediatr. 2007 Dec;151(6):591-6, 596.e1. doi: 10.1016/j.jpeds.2007.06.014. Epub 2007 Oct 24.

  PMID: 18035136 BACKGROUND

• Corvaglia L, Mariani E, Aceti A, Capretti MG, Ancora G, Faldella G. Combined oesophageal impedance-pH monitoring in preterm newborn: comparison of two options for layout analysis. Neurogastroenterol Motil. 2009 Oct;21(10):1027-e81. doi: 10.1111/j.1365-2982.2009.01301.x. Epub 2009 Mar 30.

  PMID: 19368657 BACKGROUND

• Corvaglia L, Zama D, Spizzichino M, Aceti A, Mariani E, Capretti MG, Galletti S, Faldella G. The frequency of apneas in very preterm infants is increased after non-acid gastro-esophageal reflux. Neurogastroenterol Motil. 2011 Apr;23(4):303-7, e152. doi: 10.1111/j.1365-2982.2010.01650.x. Epub 2010 Dec 22.

  PMID: 21175996 BACKGROUND

• Corvaglia L, Aceti A, Mariani E, Legnani E, Ferlini M, Raffaeli G, Faldella G. Lack of efficacy of a starch-thickened preterm formula on gastro-oesophageal reflux in preterm infants: a pilot study. J Matern Fetal Neonatal Med. 2012 Dec;25(12):2735-8. doi: 10.3109/14767058.2012.704440. Epub 2012 Jul 13.

  PMID: 22725606 BACKGROUND

• Dhillon AS, Ewer AK. Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units. Acta Paediatr. 2004 Jan;93(1):88-93.

  PMID: 14989446 BACKGROUND

• Harding C. An evaluation of the benefits of non-nutritive sucking for premature infants as described in the literature. Arch Dis Child. 2009 Aug;94(8):636-40. doi: 10.1136/adc.2008.144204.

  PMID: 19628881 BACKGROUND

• Malcolm WF, Gantz M, Martin RJ, Goldstein RF, Goldberg RN, Cotten CM; National Institute of Child Health and Human Development Neonatal Research Network. Use of medications for gastroesophageal reflux at discharge among extremely low birth weight infants. Pediatrics. 2008 Jan;121(1):22-7. doi: 10.1542/peds.2007-0381.

  PMID: 18166553 BACKGROUND

• More K, Athalye-Jape G, Rao S, Patole S. Association of inhibitors of gastric acid secretion and higher incidence of necrotizing enterocolitis in preterm very low-birth-weight infants. Am J Perinatol. 2013 Nov;30(10):849-56. doi: 10.1055/s-0033-1333671. Epub 2013 Jan 28.

  PMID: 23359235 BACKGROUND

• Orenstein SR. Effect of nonnutritive sucking on infant gastroesophageal reflux. Pediatr Res. 1988 Jul;24(1):38-40. doi: 10.1203/00006450-198807000-00010.

  PMID: 3412848 BACKGROUND

• Stokowski LA. A primer on Apnea of prematurity. Adv Neonatal Care. 2005 Jun;5(3):155-70; quiz 171-4. doi: 10.1016/j.adnc.2005.02.010.

  PMID: 16034738 BACKGROUND

• Schwartz R, Moody L, Yarandi H, Anderson GC. A meta-analysis of critical outcome variables in nonnutritive sucking in preterm infants. Nurs Res. 1987 Sep-Oct;36(5):292-5.

  PMID: 3650803 BACKGROUND

• van der Pol RJ, Smits MJ, Venmans L, Boluyt N, Benninga MA, Tabbers MM. Diagnostic accuracy of tests in pediatric gastroesophageal reflux disease. J Pediatr. 2013 May;162(5):983-7.e1-4. doi: 10.1016/j.jpeds.2012.10.041. Epub 2012 Dec 7.

  PMID: 23219449 BACKGROUND

• Wenzl TG. Investigating esophageal reflux with the intraluminal impedance technique. J Pediatr Gastroenterol Nutr. 2002 Mar;34(3):261-8. doi: 10.1097/00005176-200203000-00006. No abstract available.

  PMID: 11964948 BACKGROUND

• Zhao CX, Yue XH, Lu H, Xue XD. [Effects of nonnutritive sucking on gastric emptying and gastroesophageal reflux in premature infants]. Zhonghua Er Ke Za Zhi. 2004 Oct;42(10):772-6. Chinese.

  PMID: 16221350 BACKGROUND

• Corvaglia L, Martini S, Corrado MF, Mariani E, Legnani E, Bosi I, Faldella G, Aceti A. Does the Use of Pacifier Affect Gastro-Esophageal Reflux in Preterm Infants? J Pediatr. 2016 May;172:205-8. doi: 10.1016/j.jpeds.2016.01.022. Epub 2016 Feb 4.

  PMID: 26852181 DERIVED

MeSH Terms

Conditions

Gastroesophageal Reflux; Apnea; Bradycardia

Interventions

Pacifiers

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Infant Equipment; Equipment and Supplies

Study Officials

• Luigi T Corvaglia, AP

  Neonatal Intensive Care Unit of the S.Orsola-Malpighi Hospital, Bologna (Italy).

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, University of Bologna (Italy); NICU Medical Director

Study Record Dates

• First Submitted: December 23, 2013
• First Posted: December 30, 2013
• Study Start: May 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 15, 2015

Record last verified: 2015-10

Locations

IT (1)