Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Global State of the Art and Science of Childhood Dysphagia: Similarities and Disparities in Burden.

Feeding/swallowing and airway protection are complex functions, essential for survival, and continue to evolve throughout the lifetime. Medical and surgical advances across the globe have improved the long-term survival of medically complex children at the cost of increasing comorbidities, including dysfunctional swallowing (dysphagia). Dysphagia is prominent in children with histories of preterm birth, neurologic and neuromuscular diagnoses, developmental delays, and aerodigestive disorders; and is associated with medical, health, and neurodevelopmental problems; and long-term socioeconomic, caregiver, health system, and social burdens. Despite these survival and population trends, data on global prevalence of childhood dysphagia and associated burdens are limited, and practice variations are common. This article reviews current global population and resource-dependent influences on current trends for children with dysphagia, disparities in the availability and access to specialized multidisciplinary care, and potential impacts on burdens. A patient example will illustrate some questions to be considered and decision-making options in relation to age and development, availability and accessibility to resources, as well as diverse cultures and family values. Precise recognition of feeding/swallowing disorders and follow-up intervention are enhanced by awareness and knowledge of global disparities in resources. Initiatives are needed, which address geographic and economic barriers to providing optimal care to children with dysphagia.

Comparison of direct effects of rice-thickened formula vs routine feeds on symptoms and gastroesophageal reflux indices: A crossover cohort study.

BACKGROUND: We compared the direct effects of routine vs rice-thickened formula on 24-h pH-impedance and symptom characteristics and then examined if dietary effects were modified by acid reflux index severity in infants. METHODS: Forty infants under consideration for gastroesophageal reflux disease and therapies were evaluated at 43 ± 1 weeks postmenstrual age. Each infant was equally fed routine diet and thickened formula during evaluations. Postprandial sessions were analyzed for acid reflux index, reflux events, clearance times, distal baseline impedance, and symptoms. RESULTS: Thickened formula has no effect (P ≥ 0.05) on acid reflux events' characteristics or overall symptom frequency. However, refluxate height and frequency of weakly acidic events and cough were decreased (P < 0.05). Prolonged bolus clearance and a decrease in distal baseline impedance were noted with thickened feeds (vs routine feeds) when acid reflux index was >7 (P < 0.05). CONCLUSION: Our pH-impedance testing protocol identifies direct effects of potential therapies at the point of care. Acutely, thickened formula does not impact acid-specific reflux indices but decreases full-column reflux and cough reflexes. In those with an acid reflux index of >7, thickened formula prolongs the distal esophageal bolus clearance (the mechanisms of which are uncertain). Clinical trials are needed to clarify objective indications and therapeutic use of thickened formulas for infants with gastroesophageal reflux disease, along with short- and long-term side effects.

Characteristics of esophageal refluxate and symptoms in infants compared between pre-treatment and on treatment with proton pump inhibitors.

OBJECTIVE: To examine longitudinal pH-impedance characteristics from those infants who remained on proton pump inhibitors therapy for gastroesophageal reflux disease (GERD) as parents/providers refused to discontinue therapy after 4 weeks. STUDY DESIGN: Eighteen infants with acid reflux index >3% underwent treatment, and pH-impedance data were compared prior to and on proton pump inhibitors at 42 ± 1 and 46 ± 1 weeks' postmenstrual age, respectively. Esophageal acid and bolus exposure, symptoms and swallowing characteristics were examined. RESULTS: Proton pump inhibitors reduces the acid-mediated effects of reflux but modifies impedance and clearance mechanisms (P < 0.05). Prolonged therapy did not reduce symptoms (P > 0.05). Infants evaluated while on proton pump inhibitors were 1.8 times more likely to have swallows before and after reflux. CONCLUSIONS: Prescription of proton pump inhibitors for objectively determined GERD should have time limits, as prolonged treatment can result in prolonged esophageal bolus clearance time without relieving symptoms.

Proton pump inhibitor therapy may alter the sensory motor characteristics of pharyngoesophageal motility in infants with suspected GERD.

BACKGROUND: Acid reflux index (ARI) is a biomarker for gastroesophageal reflux disease (GERD). The effects of short-term proton pump inhibitor (PPI) therapy on pharyngoesophageal motility and clearance mechanisms in infants remain unknown. We hypothesized that pharyngoesophageal reflexes and response to PPI are distinct between infants with 3%-7% and >7% ARI. METHODS: Secondary analysis was performed from a subset of infants who participated in a randomized controlled trial (NCT: 02486263). Infants (N = 36, 29.9 ± 4.3 weeks gestation) underwent 4 weeks of PPI therapy, 1 week of washout, and longitudinal testing to assess: (a) clinical outcomes; (b) pH-impedance and symptom metrics including ARI, distal baseline impedance, clearance time, refluxate height, symptoms, I-GERQ-R scores, symptom association probability; (c) pharyngoesophageal motility reflexes and sensory motor characteristics. Comparisons were performed between infants with 3%-7% versus >7% ARI. KEY RESULTS: From the 36 hospitalized infants treated: Pharyngoesophageal reflex latencies were prolonged (p > 0.05) and duration in ARI 3%-7% group only (p = 0.01); GER frequency, proximal ascent and clearance increased (ARI 3%-7%); weight gain velocity, oral feeding success, and fine motor score decreased while length of hospital stays increased in the ARI >7% group despite the decrease in symptoms and I-GERQ-R scores. CONCLUSIONS & INFERENCES: Distinct changes in pharyngoesophageal sensory motor aspects of motility and reflex mechanisms exist after using PPI therapy in infants. Contributory factors may include the effects of maturation and aerodigestive comorbidities (GERD and BPD). Controlled studies incorporating placebo are needed to delineate the effects of PPI on causal and adaptive GERD mechanisms in infants with aerodigestive and feeding-related comorbidities.

The Irritable Infant in the Neonatal Intensive Care Unit: Risk Factors and Biomarkers of Gastroesophageal Reflux Disease.

OBJECTIVES: To determine risk factors for arching/irritability in high-risk infants and examine the significance of comorbidity and gastroesophageal reflux (GER) characteristics. STUDY DESIGN: Retrospective analysis of 24-hour pH-impedance studies of symptomatic infants in a neonatal intensive care unit (ICU) (n = 516, 30.1 ± 4.5 weeks of gestation, evaluated at 41.7 ± 3.2 weeks postmenstrual age) was conducted. Comparisons were made between infants with >72 vs ≤72 arching/irritability events per day. We characterized risk factors for arching/irritability along with clinical, pH-impedance, and outcome correlates. RESULTS: Of 39 973 arching/irritability events and 42 155 GER events, the averages per day were 77.6 ± 41.0 and 81.7 ± 48.2, respectively. Acid reflux and impedance bolus characteristics were not significantly different between infants with >72 and ≤72 arching/irritability events (P ≥ .05). The odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for postmenstrual age and weight at evaluation were significant for risk factors of preterm birth (2.3 [1.2-4.4]), moderate or severe neuropathology (2.0 [1.1-3.6]), and presence of oral feeding at testing (1.57 [1.07-2.30]). CONCLUSIONS: Acid GER disease is unlikely the primary cause of arching/irritability and empiric treatment should not be used when arching/irritability is present. Prematurity and neurologic impairment may be more likely the cause of the arching/irritability. Arching/irritability may not be a concern in orally fed infants.

A decade of evidence: standardized feeding initiative targeting feeding milestones and predicting NICU stays in premature infants in an all-referral level IV NICU.

OBJECTIVE: Ten-year data from the simplified, individualized, milestone-targeted, pragmatic, longitudinal and educational (SIMPLE) feeding initiative were examined by gestational age (GA) category to characterize the feeding milestones, length of hospital stays (LOHS), annual variability and predictive models for LOHS. STUDY DESIGN: Preterm infants (≤32 weeks GA, N = 434) in level-IV NICU had milestone-targeted feeding plans. Continuous data were analyzed for outcomes. RESULTS: Over 93% successfully attained full oral feedings. Earlier acquisition of feeding milestones correlated with earlier discharge (P < 0.05). Year-wise analysis showed sustained maintenance of milestones (P < 0.05). Milestones and outcomes (P < 0.001) were significantly correlated with different GA categories. Prediction models for LOHS were derived using GA, BPD, age at full enteral, postmenstrual age (PMA) at 1st and full oral feeds. CONCLUSIONS: The SIMPLE feeding program minimized variability and promoted acquisition of feeding milestones consistently. LOHS is predictable using feeding milestones, co-morbidities, GA, and PMA at feeding milestones.

Pharyngeal biorhythms during oral milk challenge in high-risk infants: Do they predict chronic tube feeding?

BACKGROUND: Eating difficulties are common in high-risk neonatal intensive care unit (NICU) infants; mechanisms remain unclear. Crib-side pharyngo-esophageal motility testing is utilized to assess contiguous swallowing physiology, and cross-system interplay with cardio-respiratory rhythms. Aims were to: (1) identify whether distinct pharyngeal rhythms exist during oral milk challenge (OMC), and (2) develop a chronic tube feeding risk prediction model in high-risk infants. METHODS: Symptomatic NICU infants (N = 56, 29.7 ± 3.7 weeks birth gestation) underwent pharyngo-esophageal manometry with OMC at 40.9 ± 2.5 weeks postmenstrual age (PMA). Exploratory cluster data analysis (partitioning around k-medoids) was performed to identify patient groups using pharyngeal contractile rhythm data (solitary swallows and swallows within bursts). Subsequently, (a) pharyngeal-esophageal, cardio-respiratory, and eating method characteristics were compared among patient groups using linear mixed models, and (b) chronic tube feeding prediction model was created using linear regression. RESULTS: Three distinct patient groups were identified with validity score of 0.6, and termed sparse (high frequency of solitary swallows), intermediate, or robust (high swallow rate within bursts). Robust group infants had: lesser pharyngeal and esophageal variability, greater deglutition apnea, pharyngeal activity, and esophageal activity (all p < 0.05), but less frequent heart rate decreases (p < 0.05) with improved clinical outcomes (milk transfer rate, p < 0.001, and independent oral feeding at discharge, p < 0.03). Chronic tube feeding risk = -11.37 + (0.22 × PMA) + (-0.73 × bronchopulmonary dysplasia) + (1.46 × intermediate group) + (2.57 × sparse group). CONCLUSIONS: Robust pharyngeal rhythm may be an ideal neurosensorimotor biomarker of independent oral feeding. Differential maturation of cranial nerve-mediated excitatory and inhibitory components involving foregut, airway, and cardiac rhythms distinguishes the physiologic and pathophysiologic basis of swallowing and cardio-respiratory adaptation.

Symptom Scores and pH-Impedance: Secondary Analysis of a Randomized Controlled Trial in Infants Treated for Gastroesophageal Reflux.

BACKGROUND AND AIMS: To evaluate and compare gastro-esophageal reflux (GER) symptom scores with pH-impedance and test the effects of acid-suppressive medications with or without feeding modifications on pH-impedance in high-risk infants. METHODS: Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) and 24-hour pH-impedance data were analyzed from 94 infants evaluated in a tertiary care setting for GER disease. Longitudinal data from 40 infants that received randomized GER therapy (proton pump inhibitor [PPI] with or without feeding modifications) for 4 weeks followed by 1-week washout were analyzed. Relationships between I-GERQ-R and pH-impedance metrics (acid reflux index, acid and bolus GER events, distal baseline impedance, and symptoms) were examined and effects of treatments compared. RESULTS: (A) Correlations between I-GERQ-R and pH-impedance metrics were weak. (B) I-GERQ-R sensitivity, specificity, and positive predictive values were suboptimal when correlated with pH-impedance metrics. I-GERQ-R negative predictive value (NPV) was high for acid symptom-association probability (NPV = 84%) and distal baseline impedence (NPV = 86%) thresholds. (C) PPI with feeding modifications (vs PPI alone) did not alter pH-impedance metrics or symptom scores (P > .05); however, bolus clearance metrics worsened for both treatment groups (P < .05). CONCLUSIONS: In high-risk infants (1) I-GERQ-R may be a helpful clinical screening tool to exclude acid-GER disease diagnosis and minimize unnecessary acid-suppressive treatment, but further testing is needed for diagnosis. (2) Acid-suppressive therapy with feeding modifications has no effect on symptom scores or pH-impedance metrics. Clearance of refluxate worsened despite PPI therapy, which may signal development of pharyngoesophageal dysmotility and persistence of symptoms. (3) Placebo-controlled trials are needed in high-risk infants with objective pH-impedance criteria to determine efficacy, safety, and underlying mechanisms. Clinicaltrials.gov ID: NCT02486263.

Bronchodilator responsiveness and dysanapsis in bronchopulmonary dysplasia.

Background: The incidence of bronchopulmonary dysplasia (BPD) following preterm birth is increasing. Bronchodilators are often used to treat patients with BPD with little evidence to guide therapy. The aim of this study was to test the hypothesis that there are infant pulmonary function test (iPFT) parameters that can predict subsequent bronchodilator response in infants with BPD. Methods: Subjects in this study were part of a patient group in which we reported three BPD phenotypes (obstructive, restrictive and mixed) based on iPFT data. From that group, a cohort of 93 patients with iPFT data including bronchodilator response was eligible for this study. Results: Bronchodilator responsiveness was found in 59 people (63%) in the cohort. There were no differences in demographics between the responders and non-responders. There was no difference in forced vital capacity (FVC) between the two groups. Responders had significantly lower forced expiratory volume in 0.5 s (FEV0.5) and FEV0.5/FVC (p<0.005) and greater indices of hyperinflation than did non-responders (p<0.005). Logistic regression modelling found that pre-bronchodilator FEV0.5 and functional residual capacity/total lung capacity were significantly associated with bronchodilator response. The magnitude of response to bronchodilators was negatively correlated (R= -0.49, R2= 0.24, p<0.001) with the FEV0.5. The median dysanapsis ratio in responders (0.08, 95% CI 0.05-0.19) was significantly (p=0.005) smaller than in non-responders (0.18, 95% CI 0.06-0.38). Conclusion: These findings demonstrate that there are pulmonary function test parameters associated with bronchodilator response. Responders had evidence of greater dysanaptic lung growth than non-responders.

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

Esophageal distal baseline impedance (DBI) is an indicator of mucosal integrity; lower values suggest increased permeability. Aims were to characterize the (1) effect of DBI category (<900 Ω, 900-2000 Ω, and >2000 Ω) on sensory-motor characteristics of mid-esophageal provocation-induced motility reflexes, and (2) clinical outcomes among high-risk human infants evaluated for gastroesophageal reflux disease. Symptomatic infants (N = 49, 41 ± 3 weeks postmenstrual age) underwent pH-impedance testing to characterize acid reflux index (ARI) and DBI, and pharyngo-esophageal manometry to examine upper esophageal sphincter (UES), peristaltic, and lower esophageal sphincter (LES) functions. Sensory-motor response characteristics included response threshold (ml), occurrence (%), latency (s), duration (s), and magnitude (mmHg) upon mid-esophageal stimulations (0.1-2.0 ml of air, water, and apple juice). Motility and clinical outcomes were compared among DBI groups. In infants with DBI <900 Ω and 900-2000 Ω (vs. >2000 Ω): (a) Long-term feeding milestones did not differ (p > 0.05); (b) complete peristaltic propagation decreased in 900-2000 Ω (p < 0.05), polymorphic waveforms increased in <900 Ω and 900-2000 Ω (p < 0.05); (c) media effects were noted with liquids (vs. air) wherein UES and esophageal contractility were prolonged in <900 Ω and 900-2000 Ω (p < 0.05), and esophageal sensitivity heightened for <900 Ω with water and for 900-2000 Ω with air (both p < 0.05). ARI was not correlated with DBI in infants with chronic lung disease (r = 0.05, p = 0.82). We conclude that pharyngo-esophageal motility sensory-motor characteristics in infants are modified by DBI category. These preliminary findings pave-the-way for further physiological testing in convalescing high-risk infants to ascertain potential mechanisms of airway-digestive reflex interactions and symptom generation, which may lead to targeted therapies.

Evidence-Based Approaches to Successful Oral Feeding in Infants with Feeding Difficulties.

Infants in the neonatal intensive care unit (NICU) frequently have feeding difficulties with the root cause remaining elusive to identify. Evaluation of the provider/parent/infant feeding process may provide objective clues to sources of feeding difficulty. Specialized testing may be necessary to determine if the infant's swallowing skills are dysfunctional, immature, or maldeveloped, and to determine the risk of feeding failure or chronic tube feeding. Current evidence-based diagnostic and management approaches resulting in successful oral feeding in the NICU infant are discussed.

What Are the Factors Affecting Total Sleep Time During Video Polysomnography in Infants?

OBJECTIVE: The aim of the study is to investigate factors affecting total sleep time (TST) during infant polysomnography (PSG) and assess if <4 hours of TST is sufficient for accurate interpretation. STUDY DESIGN: Overall, 242 PSGs performed in 194 infants <6 months of chronological age between March 2013 and December 2015 were reviewed to identify factors that affect TST, including age of infant, location and timing of study, presence of medical complexity, and presence of nasal tubes. A continuum of apnea-hypopnea index (AHI) in relation to TST was reviewed. Data were examined in infants who had TST <4 hours and low AHI. RESULTS: Greater TST (p < 0.001) was noted among infants during nocturnal PSGs, at older chronological and post-menstrual ages, and without medical complexity. The presence of nasogastric/impedance probes reduced TST (p = 0.002). Elevated AHIs were identified even in PSGs with TST <4 hours. Short TST may have affected interpretation and delayed initial management in one infant without any inadvertent complications. CONCLUSION: Clinical factors such as PMA and medical complexity, and potentially modifiable factors such as time of day and location of study appeared to affect TST during infant PSGs. TST < 4 hours can be sufficient to identify high AHI allowing physician interpretation. KEY POINTS: · Less than 4 hours of TST is enough for interpretation of infant polysomnography.. · Shorter TST appears related to infant age, medical complexity, and higher apnea-hypopnea index.. · Modifiable factors seen with higher TST were time of day, environment, and presence of nasal tubes..

Predictive ability of postnatal growth failure for adverse feeding-related outcomes in preterm infants: an exploratory study comparing Fenton with INTERGROWTH-21st preterm growth charts.

BACKGROUND: Postnatal growth failure (PGF) can impact the short- and long-term health outcomes in preterm infants. However, PGF rates vary according to the way it is defined and the growth chart used to monitor the postnatal growth. Fenton-2013 growth charts which suggest following intrauterine fetal growth compared to INTERGROWTH-21st, one specifically constructed for monitoring preterm extrauterine growth. OBJECTIVE: Exploratory study to determine the PGF definition at first per oral (PO) that is most predictive of adverse oral feeding-related outcomes in preterm infants. METHODS: Prospectively collected data of preterm infants 24-32 weeks gestation, who were started on cue-based oral feeds at ≤34 weeks gestation were reviewed. Anthropometric data at first PO (weight, length, and head circumference) were compared according to Fenton and INTERGROWTH-21st growth charts. PGF was defined either as <10th percentile, Z-score change (ZSC) of ≥-1.5 from birth, or ZSC of ≥-2.0. Top-quartile (Q4) of feeding-related outcomes (days from first PO to full PO, post-menstrual age at full PO, days from first PO to discharge, and length of hospital stay) was considered as adverse outcome. RESULTS: Of the 125 infants included, the median birth gestation and weight were 29.4 weeks and 1235 g, respectively. Incidence of appropriate, small, and large for gestational age was similar at birth by both growth charts. ZSC -1.5 for weight by Fenton was significantly higher at first PO vs. INTERGROWTH-21st (p=.02), while percentile <10th and ZSC -2.0 rates were similar. The PGF definition based on individual anthropometrics at first PO that has the best area under the curve (AUC) for adverse feeding-related outcomes was used to create a combined PGF definition for each growth chart. The AUC for the combined PGF for the Fenton and INTERGROWTH-21st was similar (p>.05) and both have moderate sensitivity and negative predictive value, but have low specificity, positive predictive value, and positive likelihood ratio for adverse feeding-related outcomes. CONCLUSIONS: The tested definitions of PGF at first PO have only small to moderate predictive ability for adverse feeding-related outcomes in preterm infants.

Characterization of Esophageal and Sphincter Reflexes across Maturation in Dysphagic Infants with Oral Feeding Success vs Infants requiring Gastrostomy.

To test the hypothesis that esophageal and sphincteric sensory-motor reflexes are distinct across maturation in infants with dysphagia receiving gastrostomy-tube (G-tube). This is a retrospective review of 29 dysphagic infants (N = 15 study requiring gastrostomy, N = 14 age matched control achieving oral feeds) that underwent longitudinal pharyngeal-esophageal manometry at 42.3 (37-50.2) weeks postmenstrual age (PMA) and 48.9 (43.3-57.9) weeks PMA. Graded stimuli (0.1-5 mL) of varying media (air, water, and apple juice) tested esophageal peristaltic reflex, upper esophageal sphincter contractile reflex (UESCR), and lower esophageal sphincter relaxation reflex (LESRR). Comparisons were performed between study and controls and across maturation (time-1 vs time-2). Data represented as mean ± SE or OR (95% CI). Across maturation (time-1 vs time-2): Study infants did not exhibit significant differences across in peristaltic, UES, or LES reflexes (all p > 0.05). In contrast, controls exhibited increased UES resting pressure (13 ± 3 vs 17 ± 3 mmHg, p = 0.001), LES resting pressure (22 ± 3 vs 25 ± 3 mmHg, p < 0.009), LES nadir pressure (0.5 ± 1 vs 4.3 ± 1 mmHg, p = 0.001), and esophago-deglutition responses [2.5 (1.23-4.88), p = 0.04], and decreased secondary peristalsis [0.44 (0.31-0.61), p = 0.001], UESCR [0.4 (0.25-0.65), p = 0.001], LESRR [0.4 (0.24-0.75), p = 0.01], and symptoms [0.6 (0.45-0.83), p = 0.005]. Among infants with dysphagia, esophageal provocation induced peristaltic reflex, UESCR, and LESRR advance with longitudinal maturation when infants are oral-fed successfully, but not in those who received gastrostomy. Underlying mechanisms may be related to esophageal sensitivity, afferent or efferent transmission, and coordination of upstream excitation and downstream inhibition, which can be potential therapeutic targets for improving feeding capabilities after gastrostomy placement in infants with dysphagia.

Developing a Quality Improvement Feeding Program for NICU Patients.

Practices in NICUs vary widely, particularly when clinical decisions involve complex tasks and multiple disciplines, which occurs with feeding preterm infants. Neonatal feeding difficulties in preterm infants often lead to prolonged tube feeding and therefore lengthened hospital stays. Education and compliance with evidence-based protocols and guidelines are needed on the initiation of feedings and feeding advancement to transform enteral and oral feeding practices and thus reduce practice variation and improve clinical outcomes.

Mechanisms and management considerations of parent-chosen feeding approaches to infants with swallowing difficulties: an observational study.

Videofluoroscopy swallow studies (VFSS) and high-resolution manometry (HRM) methods complement to ascertain mechanisms of infant feeding difficulties. We hypothesized that: (a) an integrated approach (study: parent-preferred feeding therapy based on VFSS and HRM) is superior to the standard-of-care (control: provider-prescribed feeding therapy based on VFSS), and (b) motility characteristics are distinct in infants with penetration or aspiration defined as penetration-aspiration scale (PAS) score ≥ 2. Feeding therapies were nipple flow, fluid thickness, or no modification. Clinical outcomes were oral-feeding success (primary), length of hospital stay and growth velocity. Basal and adaptive HRM motility characteristics were analyzed for study infants. Oral feeding success was 85% [76-94%] in study (N = 60) vs. 63% [50-77%] in control (N = 49), p = 0.008. Hospital-stay and growth velocity did not differ between approaches or PAS ≥ 2 (all P > 0.05). In study infants with PAS ≥ 2, motility metrics differed for increased deglutition apnea during interphase (p = 0.02), symptoms with pharyngeal stimulation (p = 0.02) and decreased distal esophageal contractility (p = 0.004) with barium. In conclusion, an integrated approach with parent-preferred therapy based on mechanistic understanding of VFSS and HRM metrics improves oral feeding outcomes despite the evidence of penetration or aspiration. Implementation of new knowledge of physiology of swallowing and airway protection may be contributory to our findings.

Pharyngoesophageal motility reflex mechanisms in the human neonate: importance of integrative cross-systems physiology.

Swallowing is a critical function for survival and development in human neonates and requires cross-system coordination between neurological, airway, and digestive motility systems. Development of pharyngoesophageal motility is influenced by intra- and extrauterine development, pregnancy complications, and neonatal comorbidities. The primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biological conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiological and pathophysiological neonatal aerodigestive functions.

Prophylactic Indomethacin in extremely preterm infants: association with death or BPD and observed early serum creatinine levels.

OBJECTIVES: To identify the relationship between prophylactic indomethacin (PI) administration and (1) mortality and bronchopulmonary dysplasia (BPD) at 36-week postmenstrual age (PMA) (primary outcome), and (2) to evaluate for PI-associated acute kidney injury. STUDY DESIGN: Retrospective cohort investigation of 22-28 weeks gestation infants (N = 1167) who were admitted to Nationwide Children's Hospital on postnatal days 0-1 between May 2009 and September 2017 and survived ≥24-h postnatal. The associations of PI treatment with mortality or BPD, and other secondary outcomes, were evaluated via multivariable robust-error-variance Poisson regression. RESULTS: The adjusted risks of death or BPD (1.02, 95% CI: 0.83, 1.25), BPD (0.97, 95% CI: 0.77, 1.21), and death 1.33 (95% CI: 0.84, 2.10) by 36-week PMA were unchanged following PI treatment after multivariable adjustment. No changes in mean creatinine levels were detected in exposed versus unexposed infants to suggest PI-induced AKI. CONCLUSION: Prophylactic indomethacin treatment was unrelated to mortality or BPD outcomes.

Body adiposity and oral feeding outcomes in infants: a pilot study.

BACKGROUND: Prevalence of oral feeding difficulties in high-risk infants is increasing. Desire to take orally can be influenced by hunger and satiety, which may influence growth and body fat. OBJECTIVE: To determine the association between body adiposity and infant oral feeding. METHODS: Retrospective case-control study of infants ≥37-week postmenstrual age (PMA). Infants on tube feeding (cases) compared to birth gestation-matched infants on full oral feeding (controls). Body composition was determined by air displacement plethysmography. RESULTS: Overall, 16 cases vs. 16 controls. At study, cases vs. controls had similar PMA, weight and length z-scores, and calorie intake. The mean oral intake was significantly less in cases vs. controls (66 vs. 168 ml/kg/day, p < 0.001). Cases had significantly higher percentage of fat mass (18.7 vs. 10.9) and fat-mass z-score (1.62 vs. 0.08) (p < 0.05), but similar fat-free mass vs. controls. Five case infants required gastrostomy. CONCLUSIONS: Higher body adiposity may worsen the infant oral feeding outcomes.