Role of feeding strategy bundle with acid-suppressive therapy in infants with esophageal acid reflux exposure: a randomized controlled trial

Abstract

Objective To test the hypothesis that a feeding bundle concurrent with acid suppression is superior to acid suppression alone in improving gastroesophageal reflux disease (GERD) attributed-symptom scores and feeding outcomes in neonatal ICU infants. Methods Infants (N = 76) between 34 and 60 weeks’ postmenstrual age with acid reflux index > 3% were randomly allocated to study (acid-suppressive therapy + feeding bundle) or conventional (acid-suppressive therapy only) arms for 4 weeks. Feeding bundle included: total fluid volume < 140 mL/kg/day, fed over 30 min in right lateral position, and supine postprandial position. Primary outcome was independent oral feeding and/or ≥6-point decrease in symptom score (I-GERQ-R). Secondary outcomes included growth (weight, length, head circumference), length of hospital stay (LOHS, days), airway (oxygen at discharge), and developmental (Bayley scores) milestones. Results Of 688 screened: 76 infants were randomized and used for the primary outcome as intent-to-treat, and secondary outcomes analyzed for 72 infants (N = 35 conventional, N = 37 study). For study vs. conventional groups, respectively: (a) 33% (95% CI, 19−49%) vs. 44% (95% CI, 28−62%), P = 0.28 achieved primary outcome success, and (b) secondary outcomes did not significantly differ (P > 0.05). Conclusions Feeding strategy modifications concurrent with acid suppression are not superior to PPI alone in improving GERD symptoms or discharge feeding, short-term and long-term outcomes. Impact Conservative feeding therapies are thought to modify GERD symptoms and its consequences. However, in this randomized controlled trial in convalescing neonatal ICU infants with GERD symptoms, when controlling for preterm or full-term birth and severity of esophageal acid reflux index, the effectiveness of acid suppression plus a feeding modification bundle (volume restriction, intra- and postprandial body positions, and prolonged feeding periods) vs. acid suppression alone, administered over a 4-week period was not superior in improving symptom scores or feeding outcomes. Restrictive feeding strategies are of no impact in modifying GERD symptoms or clinically meaningful outcomes. Further studies are needed to define true GERD and to identify effective therapies in modifying pathophysiology and outcomes. The improvement in symptoms and feeding outcomes over time irrespective of feeding modifications may suggest a maturational effect. This study justifies the use of placebo-controlled randomized clinical trial among NICU infants with objectively defined GERD.

Race and Ethnicity of Infants Enrolled in Neonatal Clinical Trials

“…We identified 120 studies that were entered into Cochrane CENTRAL 2017 to 2021 and met our inclusion criteria (eFigure 1 in Supplement 1). There was a range in the articles’ availability via electronic publication (2016-2021) and publication year (2017-2023).…”

“…There were 75 studies (62.5%) that included participant race and ethnicity data of any kind (eTable in Supplement 1). Most studies reported race and ethnicity as a single combined variable (eg, non-Hispanic White), while some reported them as separate variables (eg, non-Hispanic and White).…”

“…Among the 75 studies that reported race and ethnicity, there was a pooled sample of 10 650 participants. This pooled sample was classified as 1.2% Asian participants, 33.0% Black participants, 11.2% Hispanic participants, 0.2% Indigenous, 0.8% participants identifying as multiple races, 49.3% White participants, and 10.3% participants identifying as other race or ethnicity (eFigure 2 in Supplement 1).…”

Impact of esophageal mucosal permeability markers on provocation‐induced esophageal reflexes in high‐risk infants

“…In infants, DBI had been shown to improve with PPI therapy, but symptoms did not improve (Loots et al, 2012 ). Recently, we have shown that in infants treated with PPI, perception of symptom burden decreased (Jadcherla, Hasenstab, Wei, et al, 2020 ), but pharyngeal‐esophageal motility mechanisms worsened (Jadcherla, Hasenstab, Gulati, et al, 2020 ). It is unknown if PPI improves esophageal motility and symptoms in infants with DBI <900 Ω.…”

Pediatric Laryngopharyngeal Reflux: An Evidence-Based Review

“…To date, there is no randomized controlled trial comparing the effectiveness of PPIs over placebo in pediatric population. In recent prospective studies, Li et al reported a success rate of PPIs in 53% of P-LPR patients [ 66 ], while Jadcherla et al reported 33% of symptom improvement in young infants [ 102 ]. The poor efficacy of PPIs in the P-LPR treatment and the lack of confidence by practitioners were supported in the recent survey of the American Society of Pediatric Otolaryngology.…”