Rebecca K. Moore

Impact of Personalized Feeding Program in 100 NICU Infants: Pathophysiology-based Approach for Better Outcomes

Objectives: In neonatal intensive care unit infants referred for home-tube feeding methods, we evaluated the effect of an innovative diagnostic and management approach on feeding outcomes at discharge and 1 year, by comparing data from historical controls; we hypothesized that clinical and aerodigestive motility characteristics at evaluation were predictive of feeding outcomes at discharge; we assessed the economic impact of feeding outcomes. Patients and Methods: Patients (N = 100) who were referred for development of long-term feeding management strategy at 46.4 ± 13.1 weeks’ postmenstrual age were compared with 50 historical controls that received routine care. The focused approach included swallow-integrated pharyngoesophageal manometry, individualized feeding strategy, and prospective follow-up. Feeding success was defined as ability to achieve oral feedings at discharge and 1 year. Motility characteristics were evaluated in relation to feeding success or failure at discharge. Results: Higher feeding success was achieved in the innovative feeding program (vs historical controls) at discharge (51% vs 10%, P < 0.0001) and at 1 year (84.3% vs 42.9%, P < 0.0001), at a reduced economic burden (P < 0.05). Contributing factors to the innovative programs feeding success (vs feeding failure) were earlier evaluation and discharge (both P < 0.05), greater peristaltic reflex-frequency to provocation (P < 0.05), normal pharyngeal manometry (P < 0.05), oral feeding challenge success (P < 0.05), and suck-swallow-breath-esophageal swallow sequence (P < 0.05). Probability of feeding success demonstrated a prediction rate of 79.6%. Conclusions: Short-term and long-term feeding outcomes in complex neonates can be significantly improved with innovative feeding strategies at a reduced cost. Clinical and aerodigestive motility characteristics were predictive of outcomes.

Significance of gastroesophageal refluxate in relation to physical, chemical, and spatiotemporal characteristics in symptomatic intensive care unit neonates.

Gastroesophageal reflux disease (GERD) is a frequent consideration in intensive care unit neonates. We tested the hypothesis that symptoms in GERD are dependent on the spatiotemporal and physicochemical characteristics of reflux events by evaluating the symptom sensitivity index (SSI) and symptom index (SI) in relation to the refluxate characteristics. Thirty symptomatic neonates (30.7 ± 0.8 wk gestation) were evaluated using manometry and pH-impedance methods. During 704.3 h of recordings, 2063 gastroesophageal reflux (GER) were observed; 54% of the GER were associated with symptoms. Defined by physical characteristics, there were 51.3% liquid, 29.1% gas, and 19.6% mixed GER. Defined by chemical characteristics, there were 48.5% acid and 51.5% nonacid GER. Defined by most proximal extent, 79.2% were supra-UES (upper esophageal sphincter) and 20.8% were infra-UES. Higher SSI was noted with pH-only events (p < 0.0001 versus pH-impedance events). Higher SI was noted with movement symptoms (versus sensory, p = 0.04). In a subset analysis, the frequencies of GER events, acid clearance time, and SSI were all greater in chronic lung disease versus none (p < 0.001). In conclusion, clinical significance of symptoms as measured by SSI and SI and characterization of spatial-temporal-physical-chemical nature of GER events as defined by pH-impedance methods clarifies the definition of GERD.

Gestational and postnatal modulation of esophageal sphincter reflexes in human premature neonates

Background:Effects of gestational age (GA) and postnatal maturation on upper and lower esophageal sphincter (UES and LES) reflex development remain unclear. We hypothesized very-preterm (VPT) born neonates (< 32 wk GA) have delayed maturation of UES contractile reflex (UESCR) and LES relaxation reflex (LESRR) vs. preterm (PT) born (32–37 wk GA) neonates.Methods:Using provocative manometry, effects of 1,263 graded mid-esophageal stimuli (air, liquid) on sensory-motor characteristics of UESCR and LESRR were investigated in 24 VPT-born and 12 PT-born neonates (37.8 ± 0.6 vs. 38.9 ± 0.4 wk postmenstrual age respectively, P = 0.14).Results:In response to liquid stimuli (vs. air), VPT-born neonates displayed prolonged UESCR and LESRR response latencies (P < 0.001) and prolonged UESCR and LESRR durations (P < 0.01); unlike PT-born neonates, who exhibit prolonged LESRR response latency (P < 0.01), but similar UESCR and LESRR durations (P = 0.2). Differences were noted in LESRR duration in VPT vs. PT neonates for air stimuli (P = 0.04). With liquid stimuli, increasing GA was associated with decreasing response onset latencies to UESCR and LESRR (P < 0.05), and increasing LESRR duration (P = 0.02).Conclusion:Using GA as categorical or continuous variable, vagus-mediated mechano-sensitive and liquid-sensitive reflex characteristics of UESCR and LESRR are distinct; LESRR differs with varying intrauterine maturation suggesting inhibitory modulation progresses with advancing maturation.

Physiology of esophageal sensorimotor malfunctions in neonatal neurological illness

We aimed to define the sensorimotor characteristics of aero-digestive reflexes evoked upon midesophageal provocations in neuropathology infants. Provocative esophageal motility testing was performed in 20 neuropathology infants and 10 controls at 42.3 ± 0.6 and 38.9 ± 0.9 wk postmenstrual age. Data from 1,073 infusions were examined for the sensory thresholds, response frequencies, response magnitude of upper esophageal sphincter (UES) contractile reflexes, lower esophageal sphincter (LES) relaxation reflexes, and peristaltic reflexes using mixed statistical models. Threshold volumes for air and liquid in neuropathology and control infants were similar for all reflexes. Graded air- and liquid volume-dependent UES contractile reflex, LES relaxation reflex, and peristaltic reflex frequency recruitment were present in neuropathology and control subjects for the media (P < 0.0001) and the reflexes (P < 0.0001). In neuropathology infants (vs. controls), UES contractile magnitude is higher (P < 0.0001); LES relaxation reflex occurred earlier (P = 0.008); LES nadir duration lasted longer (P = 0.006); secondary peristalsis is the chief method of esophageal clearance (P < 0.0001); pharyngeal swallows and deglutition apneas are less frequent (P = 0.001); proximal, midesophageal waveform magnitudes and duration are exaggerated (P < 0.008). UES contractile reflex was longer with liquid than air in both groups (P = 0.03). We concluded that 1) perception to midesophageal provocation remains preserved in neuropathology neonates; 2) sustained and exaggerated myogenic response from afferent activation is evident by increased excitatory efferent outputs to the UES and esophageal body and increased inhibitory efferent outputs to the LES; 3) dysfunctional regulation of pharyngeal swallowing and infrequent deglutition responses indicate the possibility of impaired descending modulation and central malfunctions of brainstem and vagal nuclei.

Su1170 Relationship Between Discharge Feeding Method and Neuro-Developmental Outcomes At 18-24 Months of Age in Former Preterm Infants

BACKGROUND: Preterm neonates commonly encounter oral feeding difficulties. We have previously shown that a personalized feeding management approach yields improved oral feeding outcomes at NICU discharge. The association of feeding outcome at discharge to long term neuro-developmental outcomes is not known. AIMS: In preterm infants, we characterized and compared aerodigestive and neurodevelopmental (cognitive, communicative, and motor) outcomes at 18-24 months corrected age of successful (full oral at discharge) feeders vs unsuccessful (gastrostomy tube at discharge) feeders. METHODS: Retrospective analysis was performed on 105 preterm infants (<37 weeks gestation) who were referred to the Neonatal and Infant Feeding Disorders program between July 2006 and July 2012, and also had a neuro-developmental evaluation at 18-24 months corrected age. Aerodigestive outcomes included: first oral feed attainment, weight velocity at 36 wks postmenstrual age (PMA), gastrostomy frequency, feeding method at discharge (full oral or g-tube fed), oxygen at 36 wks PMA, duration of ventilation, tracheostomy frequency, and oxygen at discharge. Neuro-developmental outcomes included: composite Bayley Scales of Infant Development (BSID)-III that were comprised of cognitive, communication, and motor scores. BSID-III composite scores were corrected for gestational immaturity. Statistical comparisons were made using Chi-Square, Mann-Whitney U, or t-tests comparing the two groups (full oral vs. g-tube). Data presented as mean ± SD, median (IQR), or %. RESULTS: Subjects (N = 105, 52 male) were born at 27 ± 3 weeks gestational age, weighing 968 ± 428 grams. Clinical characteristics, aerodigestive milestones, and neuro-developmental outcomes of the 105 infants are shown (Table 1). CONCLUSIONS: Inability to attain full oral feeding milestones at discharge is associated with mild cognitive neuro-developmental delays at 1824 months of age, sparing communication and motor outcomes. Delays in aerodigestive milestones and complex interplay of neurologic and behavioral areas controlling feeding and cognitive functions can be contributory. Timely initiation of oro-motor stimulation and oral feeding may provide opportunities for enhanced feeding skills and improvement in neuro-developmental outcomes. *Supported in part by R01 DK068158 (Jadcherla) and P01 DK068051 (Jadcherla/Shaker)

Sa1453 Mechanisms of Origin and Resolution of Cough Reflex in Human Neonates

BACKGROUND: Cough and swallowing are important protective mechanisms that maintain the integrity of the aero-digestive tract across the age spectrum. Premature neonates commonly experience swallowing and breathing problems. Consequently, anterograde or retrograde aspiration is a frequent concern in neonates with chronic lung disease such as bronchopulmonary dysplasia (BPD). AIMS: Our aims were to define the cough-initiating and subsequent post-tussive mechanisms that restore aero-digestive normalcy (defined as return of respiratory rhythm to baseline along with esophageal quiescence) in human premature infants suffering from BPD. METHODS: Ten premature neonates (born at 25.5 ± 0.6 wks gestation, studied at 42.2 ± 1.2 wks post-menstrual age), diagnosed with BPD underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography (using Respitrace) and nasal air flow (using thermistor) methods to determine the relationships between esophageal motility and respiratory phases using a specially designed manometric catheter with upper and lower esophageal sphincter (UES and LES) sleeves and 5 recording pressure ports from pharynx, proximal-, middle-, and distalesophagus, and stomach. Cough was recognized as forceful exhalation preceded by deep inhalation on the respiratory waveforms along with audible cough marked during the study. The dynamic characteristics were analyzed preceding and following cough events defined by manometry and Respitrace. RESULTS: 1) Cough initiating mechanisms during 59 cough episodes are shown (Table). 2) Post-tussive mechanisms that restored aero-digestive normalcy were primary peristalsis in 81.4% (48/59), secondary peristalsis in 15.3 % (9/59), and not recognizable in 3.4 % (2/59). CONCLUSIONS: 1) In premature neonates with BPD, non-propagating swallows and UES contractile reflexes are the dominant reasons for the origin of the cough reflex, indicating the majority of cough events have upper aero-digestive origins. 2) Primary peristalsis is the most important clearance mechanism for post-tussive restoration of respiratory normalcy and pharyngo-esophageal quiescence. 3) These phenomena underscore the importance of postnatal development of esophagus-airway reciprocal communications mediated by Glossopharyngeal and Vagal nerves in human premature neonates with BPD. *Supported by PPG-PO1 DK 068051 Mechanisms triggering cough in neonates.

Influence of Acid Gastroesophageal Reflux Disease (GERD) on Lower Esophageal Sphincter (LES) Relaxation Reflex Kinetics in Human Infants

Background: Standard methods for assessment of meal induced gastric secretion are invasive, unphysiological and may themselves alter gastric secretion. Recently, a MRI technique for the quantitative assessment of intragastric secretion and meal dilution was developed [1]. Using this technique and a purpose-built physiologic test meal, this pilot study aimed on the non-invasive quantification of meal induced secretion and its effect on caloric emptying. Methods: Six healthy fasted volunteers (4males, age: 22-45 years (mean 31.8 years), BMI 24.2±1.9 kg/m2) were examined in right lateral position in a 1.5T whole body MRI System after ingestion of a purpose-made, secretogenic test meal. The meal consisted of a 400 ml viscous chocolate drink (450kcal) containing the following ingredients: 90 g carbohydrates, 40 g cacao powder, 100 mg Calcium, 16 g amino acids, 3 g locust bean gum, 133 μl GdDOTA. Gastric content volume (GCV), meal volume (MV) and secretion volume (SV) as well as distribution of secretion were assessed at 10 min intervals for 100 min, whereby MV emptying curves reflected caloric emptying. Previous in-vitro experiments confirmed acid stability and low buffer capacity of the test meal. Data were expressed as means ± SD. Results: The applied test meal continuously stimulated gastric secretion, resulting in a linear SV increase and maximum SV of 240ml at 100min (Figure 1). MV decreased linearly over time with a caloric emptying rate of 1.9±0.3 kcal/min, whereas GCV did not significantly change over time (Figure 1). T50 of caloric emptying was 108±34 min. Mixing of meal and secretion was heterogeneous and an increasing secretion layer on top of the meal was observed. The secretion dynamics resulted in a maximal meal dilution of 48±7 % after 100 min. Caloric emptying rate was negatively correlated to the secretion production rate (r= 0.73, p=0.06). Conclusion: A non-invasive, quantitative MR assessment of gastric secretion volume and distribution of secretions within the stomach is presented. The physiologic test meal induced large volumes of gastric secretion, attaining almost 50% of total gastric content volume at 100min. As a result changes in total gastric content volume (meal and secretion) systematically underestimated meal emptying and, therefore, caloric delivery to the small bowel. These findings highlight the need for concurrent assessment of secretion with gastric content volume if accurate assessment of meal emptying is to be obtained (at least in meals that stimulate secretion). This technique should provide new insight into the effects of acid secretion on gastric function in health and disease (e.g. gastro-esophageal reflux and peptic ulcer disease)” References: 1. Treier et al. JMRI 28:96-102 (2008)