Pharyngeal stimulus-induced reflexes are impaired in infants with perinatal asphyxia: Does maturation modify?

BACKGROUND: Development of pharyngo-esophageal protective reflexes among infants with hypoxic ischemic encephalopathy (HIE) is unclear. Our aim was to distinguish these reflexes from controls and examine the maturational changes in HIE infants. METHODS: We evaluated 14 HIE infants (seven males) at 41.4±0.6 (HIE Time-1) and 46.5±0.6 (HIE Time-2) weeks postmenstrual age (PMA). Seven controls (three males) were evaluated at 43.5±1.3 weeks PMA. Graded pharyngeal stimulation with liquids (0.1, 0.3, 0.5 mL in triplicate) concurrent with high-resolution manometry was used to analyze sensory-motor components of pharyngeal reflexive swallowing (PRS), upper esophageal sphincter (UES), contractile reflex (PUCR), and esophageal body characteristics. Linear mixed and generalized estimating equation models were used for comparison among groups. KEY RESULTS: Compared to controls, HIE infants (Time-1 and Time-2) exhibited decreased number of pharyngeal peaks and latency to terminal swallow. HIE Time-1 infants showed increased UES resting tone and distal latency, compared to controls and HIE Time-2. Contractile vigor was increasingly abnormal during maturation, compared to healthy controls. Threshold volumes and frequency distribution of primary responses (PRS: PUCR: None) were not significant among all groups. CONCLUSIONS & INFERENCES: Compared to controls, HIE infants display significant hypertonicity of skeletal muscle components, impairment of pharyngeal provocation-induced reflexes and smooth muscle contractile vigor, reflecting poor propagation with maturation. These mechanisms may be responsible for inadequate clearance of secretions, ascending refluxate, and oropharyngeal bolus in HIE infants.

Effects of pacifier and taste on swallowing, esophageal motility, transit, and respiratory rhythm in human neonates.

BACKGROUND: Pacifier use is widely prevalent globally despite hygienic concerns and uncertain mechanistic effects on swallowing or airway safety. AIMS: The effects of pacifier and taste interventions on pharyngo-esophageal motility, bolus transit, and respiratory rhythms were investigated by determining the upper esophageal sphincter (UES), esophageal body, esophagogastric junction (EGJ) motor patterns and deglutition apnea, respiratory rhythm disturbances, and esophageal bolus clearance. METHODS: Fifteen infants (six males; median gestation 31 weeks and birth weight 1.4 kg) underwent high-resolution impedance manometry at 43 (41-44) weeks postmenstrual age. Manometric, respiratory, and impedance characteristics of spontaneous swallows, pacifier-associated dry swallowing and taste (pacifier dipped in 3% sucrose)-associated swallowing were analyzed. Linear mixed and generalized estimating equation models were used. Data are presented as mean ± SEM, %, or median (IQR). KEY RESULTS: Pharyngo-esophageal motility, respiratory, and impedance characteristics of 209 swallows were analyzed (85 spontaneous swallows, 63 pacifier- swallows, 61 taste- swallows). Basal UES and EGJ pressures decreased upon pacifier (p < 0.05) and taste interventions (p < 0.05); however, esophageal motility, respiratory rhythm, and impedance transit characteristics were similar with both interventions. CONCLUSIONS & INFERENCES: Oral stimulus with pacifier or taste interventions decreases UES and EGJ basal pressure, but has no effects on pharyngo-esophageal motility, airway interactions, or esophageal bolus transit. A decrease in central parasympathetic-cholinergic excitatory drive is likely responsible for the basal effects.

Death by neurologic criteria in a neonate: Implications for organ donation.

We illustrate a unique case of neonatal organ donation in a full-term newborn with severe hypoxic ischemic encephalopathy (HIE) and multi-organ dysfunction that underwent therapeutic hypothermia. Prolonged hypothermia permitted adequate time for recovery of certain end-organs before such time that death by neurologic criteria was declared. Parental values aligned with the opportunity for organ donation.

Inhaled bronchodilator use for infants with bronchopulmonary dysplasia.

OBJECTIVE: To identify factors associated with bronchodilator administration to infants with bronchopulmonary dysplasia (BPD) and evaluate inter-institutional prescribing patterns. STUDY DESIGN: A retrospective cohort study of <29-week-gestation infants with evolving BPD defined at age 28 days within the Pediatric Health Information System database. Controlling for observed confounding with random-effects logistic regression, we determined demographic and clinical variables associated with bronchodilator use and evaluated between-hospital variation. RESULT: During the study period, 33% (N=469) of 1429 infants with BPD received bronchodilators. Lengthening mechanical ventilation duration increased the odds of receiving a bronchodilator (odds ratio 19.6 (11 to 34.8) at ⩾ 54 days). There was profound between-hospital variation in use, ranging from 0 to 81%.C ONCLUSION: Bronchodilators are frequently administered to infants with BPD at US children's hospitals with increasing use during the first hospital month. Increasing positive pressure exposure best predicts bronchodilator use. Frequency and treatment duration vary markedly by institution even after adjustment for confounding variables.

The role of the superior laryngeal nerve in esophageal reflexes.

The aim of this study was to determine the role of the superior laryngeal nerve (SLN) in the following esophageal reflexes: esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-lower esophageal sphincter (LES) relaxation reflex (ELIR), secondary peristalsis, pharyngeal swallowing, and belch. Cats (N = 43) were decerebrated and instrumented to record EMG of the cricopharyngeus, thyrohyoideus, geniohyoideus, and cricothyroideus; esophageal pressure; and motility of LES. Reflexes were activated by stimulation of the esophagus via slow balloon or rapid air distension at 1 to 16 cm distal to the UES. Slow balloon distension consistently activated EUCR and ELIR from all areas of the esophagus, but the distal esophagus was more sensitive than the proximal esophagus. Transection of SLN or proximal recurrent laryngeal nerves (RLN) blocked EUCR and ELIR generated from the cervical esophagus. Distal RLN transection blocked EUCR from the distal cervical esophagus. Slow distension of all areas of the esophagus except the most proximal few centimeters activated secondary peristalsis, and SLN transection had no effect on secondary peristalsis. Slow distension of all areas of the esophagus inconsistently activated pharyngeal swallows, and SLN transection blocked generation of pharyngeal swallows from all levels of the esophagus. Slow distension of the esophagus inconsistently activated belching, but rapid air distension consistently activated belching from all areas of the esophagus. SLN transection did not block initiation of belch but blocked one aspect of belch, i.e., inhibition of cricopharyngeus EMG. Vagotomy blocked all aspects of belch generated from all areas of esophagus and blocked all responses of all reflexes not blocked by SLN or RLN transection. In conclusion, the SLN mediates all aspects of the pharyngeal swallow, no portion of the secondary peristalsis, and the EUCR and ELIR generated from the proximal esophagus. Considering that SLN is not a motor nerve for any of these reflexes, the role of the SLN in control of these reflexes is sensory in nature only.

Impact of prematurity and co-morbidities on feeding milestones in neonates: a retrospective study.

OBJECTIVE: Feeding problems are an important area of neonatal morbidity that requires attention. We defined the feeding milestones related to transition to per oral feeding among premature infants based on gestational (GA) and postmenstrual ages (PMA), and elucidated the co-morbidity variables affecting with these skills. STUDY DESIGN: Feeding progress was tracked during the first hospitalization in a retrospective study involving 186 infants. We measured the age at acquisition of first feedings, maximum gavage feedings and maximum oral feedings. Resource usage measures included the total length of hospital stay (LOS), duration of gavage tube and duration of respiratory support. Effects of perinatal and co-morbidity factors on the acquisition of feeding milestones were evaluated. ANOVA, t-test, Wilcoxon rank sum test, chi(2) test, univariate and multivariate analysis, stepwise linear regression analysis and logistic regression analysis were applied as appropriate. Data were presented as mean+/-s.d., or as stated. P<0.05 was considered significant. RESULT: We stratified the data into three groups based on GA at birth: <28.0 weeks (group-1), 28.0 to 32.0 weeks (group-2) and 32.0 to 35.0 weeks (group-3). Compared with group-3, group-1 needed four-fold more ventilation and five-fold more continuous positive airway pressure (CPAP) duration (all P<0.001); whereas group-2 needed two-fold more CPAP duration. Age at first feed correlated with age at full gavage feedings and age at full oral feedings (r=0.53 and r=0.71, both P<0.0001). Age at full gavage feedings correlated with age at full oral feedings (r=0.81, P<0.0001). Univariate analysis was significant for GA age, hypotension, the effects of gastroesophageal reflux, and duration of ventilation and CPAP on the PMA at maximal oral feedings (all P<0.05); multivariate analysis for these variables was also significant (R (2)=0.58, P<0.0001). The success rate for oral feedings at discharge accelerated with GA maturation and caffeine use; on the other hand, the need for respiratory support and management of positive blood culture were associated with failure rates (P<0.05). CONCLUSION: Infants < 28 weeks GA have significant feeding delays with respect to initiation and progression to maximal gavage and oral feedings, as well as prolonged LOS. Infants >28 weeks GA attained successful feeding milestones by similar PMA. Specific aero-digestive co-morbidities significantly affected maximal oral feeding milestone. Delays in achieving maximum gavage and maximum oral feeding milestones suggest delays with the development of control and regulation of foregut motility.

Feeding abilities in neonates with congenital heart disease: a retrospective study.

OBJECTIVE: An important area concerning morbidity among infants with congenital heart defects (CHD) is related to feeding problems. Our objectives were to characterize the evolution of feeding milestones related to transition to per oral feeding among infants with CHD, and to identify associated variables impacting the feeding abilities. Specifically, we differentiated the feeding characteristics in neonates with acyanotic vs cyanotic CHD. STUDY DESIGN: Feeding progress was tracked during the first hospitalization in a retrospective chart review study involving 76 infants (29 acyanotic, 47 cyanotic CHD). The ages at which the following milestones attained were recorded: first feeds, maximum gavage feeds, first nipple feeds and maximum nipple feeds, in addition to the length of hospital stay. Effects of perinatal factors, duration of respiratory support, vasopressor and narcotic use and use of cardiopulmonary bypass on the feeding milestones were also evaluated. ANOVA, t-test, and stepwise linear regression analysis were applied as appropriate. Data stated as mean+/-s.e.m., or %; P<0.05 was considered significant. RESULT: Prenatal and birth characteristics were similar (P=NS) between the neonates with acyanotic and cyanotic CHD. Cyanotic CHD required three times prolonged use of ventilation, narcotics and vasopressor use (all P<0.05, compared to the acyanotic group). In the acyanotic group, prolonged respiratory support correlated linearly with time to attain maximal gavage feeds and nippling (both, R2=0.8). In the cyanotic group, delayed initiation of gavage feeds and prolonged respiratory support both correlated linearly with time to attain maximal gavage feeds and nippling (both, R2=0.8). Age at first gavage feed correlated with maximum gavage feeds among neonates with cyanotic CHD, and first nipple feed correlated with maximum nipple feeds among all groups (P<0.01). Use of cardiopulmonary bypass in cyanotic CHD delayed the feeding milestones and prolonged the length of stay (both, P<0.05 vs non-bypass group); similar findings were not seen in the acyanotic group. CONCLUSION: In contrast to neonates with acyanotic CHD, cyanotic CHD group had significant delays with (a) feeding readiness, (b) successful gastric feeding, (c) oromotor readiness and (d) successful oromotor skills. Co-morbid factors that may directly influence the delay in feeding milestones include the (a) duration of respiratory support and (b) use of cardiopulmonary bypass. Delays in achieving maximum gavage and maximum nippling may suggest foregut dysmotility and oropharyngeal dysphagia.

Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults.

We evaluated the upper oesophageal sphincter (UOS) relationship with oesophageal body during primary peristalsis (PP) sequences in healthy human neonates during maturation and compared with that of healthy adult volunteers. Forty-nine studies were performed using a water perfusion manometry system and a specially designed oesophageal catheter with a UOS sleeve concurrent with submental electromyogram in 31 subjects in supine position (18 preterm neonates, 29.9 +/- 2.5 weeks gestation; four full-term neonates, 39.3 +/- 1.0 weeks gestation; and nine adults, 18-65 years). The preterm neonates were studied longitudinally at 33 and 36 weeks postmenstrual age (PMA) and full-term born at 40 weeks PMA. Data were compared between the groups to recognize the effects of gestation, postnatal age and ageing. We evaluated 403 consecutive spontaneous solitary swallows during maturation (preterm at time-1 vs time-2) and growth (preterm and full-term vs adults) and observed significant (P < 0.05) differences in the basal UOS resting pressure, UOS relaxation characteristics, proximal and distal oesophageal body amplitude, duration, propagation and peristaltic velocity. Characteristics of UOS and PP are well-developed by 33 weeks PMA and undergo further maturation during the postnatal period, and are significantly different from that of adult.

Esophageal and upper esophageal sphincter motor function in babies.

The incidence of concomitant feeding and airway-related disorders is high among premature infants and babies with congenital anomalies. The cause of these disorders is commonly attributed to foregut dysfunction, and the approach to diagnosis and management is largely empiric. Management strategies usually are based on the failure to improve feeding tolerance with advancing maturation and the presence of supraesophageal complications of reflux disease. Very little information exists about the functional development of deglutitive and airway-protective mechanisms in neonates. The purpose of this article is to review the available information on esophageal and upper esophageal sphincter (UES) motor function in human infants. Understanding the maturation of the motor functions of the pharynx-UES and esophagus and related airway-protection responses is essential for determining the pathophysiologic basis of feeding-related airway disorders.

Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants.

In adults, migrating motor complexes (MMCs) appear to be partially under hormonal modulation by motilin and pancreatic polypeptide. Preterm infants do not exhibit MMCs until 32 wk of gestation. Although plasma concentrations of motilin are similar in infants and adults, it is not known if actual hormonal modulation of MMCs is present in infants. In the first study we assessed whether plasma concentrations of motilin and pancreatic polypeptide surge with the occurrence of MMCs in term infants. In the second study we assessed whether erythromycin, a motilin receptor agonist, could induce migrating motor activity in preterm and term infants. In the first study we recorded motor activity in nine term infants who had never been fed. We determined plasma concentrations of motilin and pancreatic polypeptide in the presence and absence of MMCs. In the second study we gave the motilin agonist erythromycin intragastrically to 21 infants at a range of 24-42 wk of gestation to assess whether migrating activity could be induced via the motilin receptor. In the first study, plasma concentrations of motilin were similar during the presence and absence of MMCs, as were plasma concentrations of pancreatic polypeptide. In the second study, the administration of erythromycin induced the appearance of migrating activity in 7 of 14 infants who were older than 32 wk but in none of the infants who was younger than 32 wk. Although the motilin receptor appears to be functionally present beyond 32 wk of gestation, as assessed by in indirect pharmacologic challenge, hormonal modulation of migrating activity in the neonate by plasma motilin and pancreatic polypeptide is absent.

Acute and chronic intestinal motor activity responses to two infant formulas.

OBJECTIVE: Preterm formulas are nutritionally better for preterm infants; however, it has been observed that these formulas cause more feeding intolerance than do regular formulas. Because intestinal motor activity is responsible for the aboral movement of intraluminal nutrients, the purpose of this study was to evaluate intestinal motor activity responses to two infant formulas: 84 and 100.8 J/oz. STUDY DESIGN AND RESULTS: Intestinal motor activity was recorded in 52 preterm infants who had never been fed and who were randomly assigned to receive small enteral feedings (24 mL/kg per day) for 10 days with one of two commonly used infant formulas. In a subset of 26 of these infants, acute motor responses to both formulas were also evaluated. At the end of the study period, motor activity during fasting did not differ between the two groups of infants. However, motor responses during feeding to the two formulas differed significantly. When infants were fed for the first time, their motor activity increased compared with fasting when they were fed the 84-J/oz formula but decreased when they were fed the 100.8-J/oz formula. These differences in motor responses to the two formulas were not present 10 days later. These differences in motor responses to the 100.8- and 84-J/oz formulas were even more pronounced among the 7 infants who subsequently developed feeding intolerance to the 100.8-J/oz formula during the 10-day study period. CONCLUSION: Inhibition of motor responses to calorically denser formulas during active feeding in a subset of preterm infants may underlie the feeding intolerance they experience when they are fed these formulas. However, this inhibitory response diminishes with age, suggesting that denser formulas can be reintroduced later in life to these infants.