Effect of Tube Feeding on Gastroesophageal Reflux in Preterm Infants
Condition: Gastroesophageal Reflux
MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic
Study type: Observational

Summary: 
      Due to several promoting factors, gastro-esophageal reflux (GER) is very frequent in preterm
      infants. To limit the potentially harmful widespread of pharmacological treatment, a
      step-wise approach, which firstly undertakes 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 effectively reduce GER features in symptomatic preterm
      babies, whereas feed thickening is almost ineffective.

      Due to their prematurity, preterm infants <34 weeks gestation are often unable to coordinate
      sucking, swallowing and breathing, thus requiring a feeding tube to ensure adequate enteral
      intakes. Continuous feeding and boluses are the most common techniques of enteral tube
      feeding in Neonatal Intensive Care Units; at present, however, the effects of these
      techniques on GER features have not been clearly established.

      This observational, prospective and explorative study primarily aims to evaluate the effect
      of different techniques of enteral tube feeding on GER frequency and features in symptomatic
      preterm infants (gestational age ≤33 weeks) undergoing a diagnostic combined pH and multiple
      intraluminal impedance (pH-MII) for GER evaluation.
    

Detailed description: 
      Due to several promoting factors related to the physiological immaturity of the
      gastro-intestinal tract, gastro-esophageal reflux (GER) is a frequent condition among preterm
      infants.

      GER clinical presentation may vary within a wide range of symptoms, being vomiting,
      regurgitations and cardiorespiratory events the most common in the preterm population.

      Combined pH and multiple intraluminal impedance (pH-MII) is currently considered the best
      choice for GER diagnosis in preterm infants. While pH monitoring is limited to the detection
      of acid reflux, combined pH-MII effectively identifies both acid and non-acid GER, which is
      predominant in preterm infants. Moreover, it allows to evaluate the height reached by the
      refluxate within the esophageal lumen and to distinguish retrograde fluid bolus movements
      (reflux) from the anterograde ones (swallows).

      In the last decade, GER pharmacological treatment has increasingly widespread in Neonatal
      Intensive Care Units (NICUs). The provision of anti-histamine2 blockers and proton pump
      inhibitors in the preterm population, however, might lead to such adverse effects as an
      increased incidence of necrotizing enterocolitis and infections. Hence, to avoid a useless
      and potentially harmful pharmacological overtreatment, a step-wise approach, firstly
      promoting conservative strategies, is currently considered the most advisable choice for GER
      management in symptomatic preterm infants.

      Postural and dietary interventions are the most common conservative strategies and their
      efficacy in improving GER symptoms and features has been largely investigated.

      As previously assessed by pH-MII, both prone and left-side positions were more effective than
      the right-side or supine ones to significantly improve both acid and non-acid GER features.

      Feed thickening is widely employed to reduce vomiting and regurgitations in symptomatic term
      infants; with regard to the preterm population, however, little data is currently available.
      The efficacy of thickened fortified human milk on preterm infants with GER symptoms has been
      previously investigated, observing no benefits. Furthermore, standard human milk
      fortification itself has been shown to increase GER frequency in preterm infants.

      With regard to anti-regurgitation (AR) formulas, the effectiveness of a specific AR formula,
      thickened with amylopectin and specifically tailored for preterm infants' nutritional needs,
      has been recently evaluated; the tested thickened formula effectively reduced the number of
      acid GERs, but no difference was observed in the frequency of non-acid GERs and in the mean
      esophageal acid exposure, which is known to be the main determinant for the development of
      gastro-esophageal reflux disease (GERD). Thus, according to these data, feed thickening seem
      to be almost ineffective in improving GER symptoms and features in preterm infants.

      Due to their prematurity, preterm infants <34 weeks gestation are unable to coordinate
      sucking, swallowing and breathing; thus, to ensure adequate enteral intakes, they are usually
      fed via an intragastric tube. Continuous and bolus feeding are the most common techniques of
      enteral tube feeding in NICU settings.

      The latter is shown to stimulate cyclical surges of gastrointestinal hormones, thus being
      considered more physiological. It entails the administration of the meal by gravity or
      through an infusion pump for a total duration of about 10 minutes, after which the feeding
      tube could be removed. However, the short time elapsing between the tube insertion for bolus
      administration and its subsequent removal might provoke a vagal response, characterized by
      bradycardia and temporary reduction of cardiac output. Moreover, the rapid gastric distension
      following bolus administration could increase the pressure of lower esophageal sphincter
      (LES), thus contributing to the refluxate of gastric contents into the esophageal lumen.

      On the other hand, continuous feeding allows administering enteral feeds over a longer period
      (e.g. 2 or 3 hours), at a slower flow rate. It has been associated with better absorption of
      nutrients and faster gastric emptying, thus it may be preferable in case of delayed gastric
      motility, gastric residuals and abdominal distension. Moreover, its slow rate of infusion
      prevents a rapid gastric distension; however, this feeding method requires the permanence of
      the feeding tube through the LES for the whole feeding period, and this could predispose to
      the occurrence of gastro-esophageal reflux.

      The effect of bolus and continuous feeding on cardio-respiratory events, which could
      represent clinical atypical manifestations of GER, has been recently evaluated, observing a
      slight but significant increase of apneic episodes during continuous feeding.

      A recent systematic review has aimed to evaluate which of these tube-feeding methods could be
      more suitable in low birth weight infants with GER symptoms; however, current data are scarce
      and controversial and do not allow to draw any definitive conclusion.

      The aim of this study is to evaluate the effect of different enteral tube feeding modalities,
      such as bolus and continuous feeding, on pH-MII GER features in tube-fed preterm infants ≤33
      weeks gestation, undergoing a diagnostic pH-MII evaluation.

      Overall, thirty preterm infants ≤33 weeks gestation will be enrolled if suffering from
      moderate/severe GER symptoms and if a diagnostic 24-hour pH-MII monitoring has been scheduled
      to evaluate GER features, according to our clinical practice.

      During the 24-h pH-MII monitoring, each infant will receive his meals (usually 8) according
      to the following sequence:

        -  1st meal: optional modality (not considered for statistical analysis);

        -  2nd meal: continuous feeding over 3 hours;

        -  3rd meal: bolus feeding; the feeding tube remains in place for the whole post-prandial
           period;

        -  4th meal: bolus feeding; the feeding tube is removed after feed administration;

        -  5th: continuous feeding over 3 hours;

        -  6th : bolus feeding; the feeding tube remains in place for the whole post-prandial
           period;

        -  7th: bolus feeding; the feeding tube is removed after feed administration;

        -  8th: optional modality (not considered for statistical analysis). Healthcare assistants
           will inspect the correct application of this sequence.

      The pH-MII device in use for this study (Comfortec pH-MII Sandhill Scientific®) is a
      nasogastric probe with seven rings, composed by six dipolar impedance channels and one
      antimony electrode responsible for pH detection and placed in the middle of the distal
      impedance dipole. Due to these characteristics, pH-MII is able to measure the esophageal
      height reached by refluxate and to identify the direction of esophageal bolus movements,
      thereby distinguish between a retrograde flow (reflux) and an anti-retrograde flow (swallow).

      The distance between the infant's nose and LES will be determined with Strobel's formula:
      [baby length (cm) x 0.252 + 5)] - 13%. After placement, the probe's position will be
      radiographically confirmed.

      Data from the pH-MII recording will be automatically acquired on a portable Sleuth Sandhill
      Scientific system and then stored in a personal computer containing a specific software
      (BioVIEW Analysis Sandhill Scientific, version 5.0.9). Data analysis will be performed by the
      aforementioned software and confirmed by direct visual evaluation.

      Statistical analysis will be performed by SPSS 20 (Statistical Package for the Social
      Sciences, SPSS Inc., Chicago, IL, USA) for Windows. Differences between the different
      modalities in terms of GER frequency and features will be tested by Friedman test (level of
      significance: p <0.05).
    

Intervention name(s): Tube feeding
Intervention type(s): Other
Intervention description(s): During the study period, enteral feeds will be administered according to different tube feeding modalities: bolus feeding followed by the removal of the feeding tube; bolus tube feeding with permanence of the feeding tube for the whole post-prandial period; continuous feeding over a 3-hour period.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Due to the exploratory nature of this study, at least 30 preterm infants fulfilling the
        inclusion criteria will be enrolled.
      
Keywords: gastroesophageal reflux; tube enteral feeding; preterm infants