Differentiating esophageal sensitivity phenotypes using pH-impedance in intensive care unit infants referred for gastroesophageal reflux symptoms.

BACKGROUND: To identify esophageal sensitivity phenotypes relative to acid (SAcid), bolus (SBolus), acid and bolus (SAcid+Bolus), and none (SNone) exposures in infants suspected with gastroesophageal reflux disease (GERD). METHODS: Symptomatic infants (N = 279) were evaluated for GERD at 42 (40-45) weeks postmenstrual age using 24-h pH-impedance. Symptom-associated probability (SAP) for acid and bolus components defined esophageal sensitivity: (1) SAcid as SAP ≥ 95% for acid (pH < 4), (2) SBolus as SAP ≥ 95% for bolus, (3) SAcid+Bolus as SAP ≥ 95% for acid and bolus, or (4) SNone as SAP < 95% for acid and bolus. RESULTS: Esophageal sensitivity prevalence (SAcid, SBolus, SAcid+Bolus, SNone) was 28 (10%), 94 (34%), 65 (23%), and 92 (33%), respectively. Emesis occurred more in SBolus and SAcid+Bolus vs SNone (p < 0.05). Magnitude (#/day) of cough and emesis events increased with SBolus and SAcid+Bolus vs SNone (p < 0.05). SAcid+Bolus had increased acid exposure vs SNone (p < 0.05). Distributions of feeding and breathing methods were distinct in infants with SBolus vs SNone (both, p < 0.05). Multivariate analysis revealed that arching and irritability events/day were lesser at higher PMAs (p < 0.001) and greater for infants on NCPAP (p < 0.01) with SBolus and SAcid+Bolus (p < 0.05). Coughs/day was greater at higher PMAs (p < 0.001) for infants with gavage and transitional feeding methods (p < 0.02) with SBolus and SAcid+Bolus (p < 0.05) but lesser with Trach (p < 0.001). Number of emesis events/day were greater with SBolus and SAcid+Bolus (p < 0.001). Sneezes/day decreased for infants on Trach (p = 0.02). CONCLUSIONS: Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. We differentiated esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms using pH-impedance. Acid sensitivity alone was rare, which may explain poor response to acid suppressives; aerodigestive symptoms were predominantly linked with bolus spread. Magnitude of esophageal acid exposure and esophageal sensitivity to bolus spread may explain the pathophysiological basis for symptoms. IMPACT: Objective GERD diagnosis and reasons for symptoms in NICU infants remains unclear. Differentiation of esophageal sensitivities by acid and bolus components of GER reveal distinct symptom profiles, specifically the bolus component of GER significantly contributes to symptom occurrence. Acid only sensitivity to GER is rare, and acid-suppressive therapy alone may not improve symptoms in a majority of NICU infants. Magnitude of esophageal acid exposure and esophageal sensitivity to any bolus spread may explain the pathophysiological basis for symptoms. Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. GERD treatments should be individualized to the patient's GERD phenotype and likely also target the bolus component of GER.

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

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.

Impact of Feeding Strategies With Acid Suppression on Esophageal Reflexes in Human Neonates With Gastroesophageal Reflux Disease: A Single-Blinded Randomized Clinical Trial.

INTRODUCTION: Aims were to test hypothesis that esophageal provocation-induced reflexes are superior with acid suppression plus feeding modifications vs acid suppression alone among infants treated for gastroesophageal reflux disease (GERD). METHODS: Infants (N = 49, 41.3 ± 2.6 of postmenstrual age) with acid reflux index >3% underwent longitudinal motility testing (weeks 0 and 5) with graded midesophageal provocation to test randomly allocated therapies (4 weeks' proton pump inhibitor [PPI] ± feeding modifications) on sensory-motor aerodigestive reflexes. Feeding modification included restricted fluid volume <140 mL/kg per day, fed over 30 minutes in right lateral position and supine postprandial position. Primary motility outcome was frequency-occurrence of peristaltic reflex. Secondary outcomes included upper esophageal sphincter contractile reflex, lower esophageal sphincter (LES) relaxation reflex, respiratory change, and symptom characteristics. RESULTS: Treatment groups did not differ for primary outcome (odds ratio = 0.8, 95% confidence interval 0.4-1.6, P = 0.99) or secondary outcomes (all P > 0.05). For both treatment groups at follow-up, distal esophageal contraction and LES tone decreased, and LES relaxation reflex occurrence is less frequent (all P < 0.05). In a subgroup analysis, comparing infants with PPI washout (N = 40) vs with continued (N = 9) PPI therapy, no differences were noted for aerodigestive reflex response frequency-occurrence (all P > 0.05). DISCUSSION: In infants with GERD, feeding modification with acid suppression is not superior to acid suppression alone in modifying aerodigestive reflexes (frequency, sensation, or magnitude). Contiguous areas targeted by GER, i.e., LES and distal esophageal functions, worsened at follow-up for both groups despite PPI therapy. Maturation is likely the key factor for GERD resolution in infants, justifying the use of placebo in clinical trials for objectively determined GERD.

Approach to Feeding Difficulties in Neonates and Infants: A Comprehensive Overview.

Deglutition disorders (DD) can be transient and considered as physiologic during normal maturation. However, when oral feeding milestones are impaired and bothersome symptoms and aerodigestive consequences are associated, it is interpreted as DD with varying specific entities, such as feeding difficulties, swallowing disorders, aerodigestive illness, and aspiration syndromes. Symptoms related to DD are heterogeneous and managed empirically. This article clarifies current controversies, explains the potential role of safe feeding and physiologic and pathophysiologic perspectives, and highlights current advances in the field. Evidence basis for diagnostic strategies is discussed, and involves evaluation for structure and function tests, and nutrition and feeding assessment.

Impact of SIMPLE Feeding Quality Improvement Strategies on Aerodigestive Milestones and Feeding Outcomes in BPD Infants.

BACKGROUND AND OBJECTIVES: Delays with enteral and oral feeding milestones among premature infants with bronchopulmonary dysplasia (BPD) can be due to provider variation or infant-dependent factors. Our objectives with this study were to compare aerodigestive milestones and length of stay in BPD infants after implementing a quality improvement program to improve feeding outcomes. METHODS: Using the Institute for Healthcare Improvement model for quality improvement, we implemented the simplified, individualized, milestone-targeted, pragmatic, longitudinal, and educational (SIMPLE) feeding strategy to enhance feeding and aerodigestive milestones among BPD infants. The key interventions addressed were as follows: (1) enteral feed initiation and advancement protocol; (2) oral feeding progression guidelines, optimization of respiratory support, feeding readiness scores, nonnutritive breastfeeding, and cue-based feeding; (3) active multidisciplinary collaboration; and (4) family-centered care. Comparisons were made between baseline (January 2009 to March 2010) and SIMPLE feeding strategy (May 2010 to December 2013) groups. Both groups included infants between 23 0/7 and 32 6/7 weeks' birth gestation, and ≤34 weeks' postmenstrual age at admission and discharge. RESULTS: The baseline group and SIMPLE feeding group included 92 patients and 187 patients, respectively. Full enteral feeding, first oral feeding, full oral feeding, and length of stay milestones were (all P < .05) achieved sooner in the SIMPLE feeding group. Although the overall prevalence of BPD in the 2 groups is similar, the incidence of moderate BPD has decreased (P < .05) and severe BPD has increased (P < .05) in the SIMPLE feeding group. CONCLUSIONS: SIMPLE feeding strategy advances postnatal maturation and acquisition of feeding milestones irrespective of the severity of BPD and impacts the length of stay, thereby lowering resource use.

Gastroesophageal Reflux Disease in the Neonatal Intensive Care Unit Infant: Who Needs to Be Treated and What Approach Is Beneficial?

Gastroesophageal reflux (GER) and GER disease (GERD) pertaining to infants in the neonatal intensive care unit (NICU) are reviewed, based on research in this specific population. The developmental biology of the gastroesophageal junction, physiology of GER, and pathophysiology of GERD in this setting are summarized, and risk factors for GER and GERD identified. The epidemiology, economic burden, and controversies surrounding GERD in NICU infants are addressed, and an approach to GER and GERD in these patients formulated. Recent advancements in individual assessment of GER and GERD in the NICU infant are examined, and evidence-based guidelines for their adoption provided.

Brain Lesions among Orally Fed and Gastrostomy-Fed Dysphagic Preterm Infants: Can Routine Qualitative or Volumetric Quantitative Magnetic Resonance Imaging Predict Feeding Outcomes?

INTRODUCTION: The usefulness of qualitative or quantitative volumetric magnetic resonance imaging (MRI) in early detection of brain structural changes and prediction of adverse outcomes in neonatal illnesses warrants further investigation. Our aim was to correlate certain brain injuries and the brain volume of feeding-related cortical and subcortical regions with feeding method at discharge among preterm dysphagic infants. MATERIALS AND METHODS: Using a retrospective observational study design, we examined MRI data among 43 (22 male; born at 31.5 ± 0.8 week gestation) infants who went home on oral feeding or gastrostomy feeding (G-tube). MRI scans were segmented, and volumes of brainstem, cerebellum, cerebrum, basal ganglia, thalamus, and vermis were quantified, and correlations were made with discharge feeding outcomes. Chi-squared tests were used to evaluate MRI findings vs. feeding outcomes. ANCOVA was performed on the regression model to measure the association of maturity and brain volume between groups. RESULTS: Out of 43 infants, 44% were oral-fed and 56% were G-tube fed at hospital discharge (but not at time of the study). There was no relationship between qualitative brain lesions and feeding outcomes. Volumetric analysis revealed that cerebellum was greater (p < 0.05) in G-tube fed infants, whereas cerebrum volume was greater (p < 0.05) in oral-fed infants. Other brain regions did not show volumetric differences between groups. CONCLUSION: This study concludes that neither qualitative nor quantitative volumetric MRI findings correlate with feeding outcomes. Understanding the complexity of swallowing and feeding difficulties in infants warrants a comprehensive and in-depth functional neurological assessment.

Feeding Methods at Discharge Predict Long-Term Feeding and Neurodevelopmental Outcomes in Preterm Infants Referred for Gastrostomy Evaluation.

OBJECTIVE: To test the hypothesis that oral feeding at first neonatal intensive care unit discharge is associated with less neurodevelopmental impairment and better feeding milestones compared with discharge with a gastrostomy tube (G-tube). STUDY DESIGN: We studied outcomes for a retrospective cohort of 194 neonates <37 weeks' gestation referred for evaluation and management of feeding difficulties between July 2006 and July 2012. Discharge milestones, length of hospitalization, and Bayley Scales of Infant Development-Third Edition scores at 18-24 months were examined. χ2, Mann-Whitney U, or t tests and multivariable logistic regression models were used. RESULTS: A total of 60% (n = 117) of infants were discharged on oral feedings; of these, 96% remained oral-fed at 1 year. The remaining 40% (n = 77) were discharged on G-tube feedings; of these, 31 (40%) remained G-tube dependent, 17 (22%) became oral-fed, and 29 (38%) were on oral and G-tube feedings at 1 year. Infants discharged on a G-tube had lower cognitive (P <.01), communication (P = .03), and motor (P <.01) composite scores. The presence of a G-tube, younger gestation, bronchopulmonary dysplasia, or intraventricular hemorrhage was associated significantly with neurodevelopmental delay. CONCLUSIONS: For infants referred for feeding concerns, G-tube evaluations, and feeding management, the majority did not require a G-tube. Full oral feeding at first neonatal intensive care unit discharge was associated with superior feeding milestones and less long-term neurodevelopmental impairment, relative to full or partial G-tube feeding. Evaluation and feeding management before and after G-tube placement may improve long-term feeding and neurodevelopmental outcomes.

Effects of birth asphyxia on the modulation of pharyngeal provocation-induced adaptive reflexes.

Perinatal asphyxia and aerodigestive symptoms are troublesome. We tested the hypothesis that pharyngeal provocation alters proximal and distal aerodigestive reflex coordination and kinetics in infants with hypoxic ischemic encephalopathy (HIE), compared with healthy controls. Specifically, we characterized the sensory-motor properties of pharyngeal provocation-induced effects on upper esophageal sphincter (UES) and lower esophageal sphincter (LES) reflexes. Ten orally fed controls (32.0 ± 1.5 wk gestation) and 25 infants with HIE (38.1 ± 0.4 wk gestation) were evaluated at 39.7 ± 0.9 and 41.9 ± 0.6 wk postmenstrual age respectively. Pharyngo-esophageal reflexes evoked upon graded water stimuli were tested using water-perfusion micromanometry methods. Analysis included sensory-motor characteristics of pharyngeal reflexive swallow (PRS), pharyngo-UES-contractile reflex (PUCR), esophageal body-waveform kinetics, and pharyngo-LES-relaxation reflex (PLESRR). For controls vs. infants with HIE, median appearance, pulse, grimace, activity, respiration (APGAR) scores were 6 vs. 1 at 1 min (P < 0.001) and 8 vs. 3 at 5 min (P < 0.001). Upon pharyngeal- stimulation, HIE infants (vs. controls) had frequent PUCR (P = 0.01); increased UES basal tone (P = 0.03); decreased LES basal tone (P = 0.002); increased pharyngeal-waveforms per stimulus (P = 0.03); decreased frequency of LES relaxation (P = 0.003); and decreased proximal esophageal contractile amplitude (P = 0.002), with prolonged proximal esophageal contractile duration (P = 0.008). Increased tonicity and reactivity of the UES and dysregulation of LES may provide the pathophysiological basis for pooling of secretions, improper bolus clearance, and aspiration risk. Deficits in function at the nuclear or supranuclear level involving glossopharyngeal and vagal neural networks and respiratory regulatory pathways involved with aerodigestive protection may be contributory.

Upper and lower esophageal sphincter kinetics are modified during maturation: effect of pharyngeal stimulus in premature infants.

BACKGROUND: We hypothesized that changes in proximal and distal esophageal sphincter kinetics evoked upon pharyngeal provocation undergo longitudinal maturation. METHODS: Pharyngeal stimulation-induced reflexes were characterized using novel pharyngo-esophageal motility methods in 19 healthy premature neonates, studied at 34.7 ± 0.8 wk (time-1) and 39.3 ± 1.1 wk postmenstrual age (time-2). Graded volumes of air (290 infusions) and sterile water (172 infusions) were infused to define sensory-motor characteristics of upstream (pharyngeal reflexive swallow, PRS) and downstream (pharyngo-lower esophageal sphincter relaxation reflex, PLESRR) esophageal reflexes. Data displayed as mean ± SE. RESULTS: Threshold volumes were similar with air and water for PRS and PLESRR at time-1 and time-2. Multiple PRS responses were noted with water stimulus and were different between the media (time-1 vs. air, P < 0.0001; time-2 vs. air, P = 0.0003). Dose-response relationships for water were significant (P < 0.01 for PRS and PLESRR time-1 and time-2), but not with air. CONCLUSION: Significantly, the recruitment frequency of PRS and PLESRR increases with maturation, liquid is a superior medium for evoking such swallowing reflexes, and stimulus-response relationships for these reflexes are evident. These changes in aerodigestive protective reflexive activity may indicate differences in modulation of excitatory and inhibitory pathways during longitudinal postnatal maturation.

Effect of umbilical cord milking in term and near term infants: randomized control trial.

OBJECTIVE: The objective of the study was to investigate the effect of umbilical cord milking as compared with early cord clamping on hematological parameters at 6 weeks of age among term and near term neonates. STUDY DESIGN: This was a randomized control trial. Eligible neonates (>35 weeks' gestation) were randomized in intervention and control groups (100 each). Neonates of both groups got early cord clamping (within 30 seconds). The cord of the experimental group was milked after cutting and clamping at 25 cm from the umbilicus, whereas in control group cord was clamped near (2-3 cm) the umbilicus and not milked. Both groups got similar routine care. Unpaired Student t and Fisher exact tests were used for statistical analysis. RESULTS: Baseline characteristics were comparable in the 2 groups. Mean hemoglobin (Hgb) (11.9 [1.5] g/dL and mean serum ferritin 355.9 [182.6] µg/L) were significantly higher in the intervention group as compared with the control group (10.8 [0.9] g/dL and 177.5 [135.8] µg/L), respectively, at 6 weeks of age. The mean Hgb and hematocrit at 12 hours and 48 hours was significantly higher in intervention group (P = .0001). The mean blood pressure at 30 minutes, 12 hours, and 48 hours after birth was significantly higher but within normal range. No significant difference was observed in the heart rate, respiratory rate, polycythemia, serum bilirubin, and need of phototherapy in the 2 groups. CONCLUSION: Umbilical cord milking is a safe procedure and it improved Hgb and iron status at 6 weeks of life among term and near term neonates.