Volatile organic compounds in exhaled breath of newborns: a pilot study.

OBJECTIVE: To assess volatile organic compounds (VOCs) in breath samples collected non-invasively from preterm and full-term infants. METHODS: This was a pilot study included preterm and full-term infants who were not intubated or suspected or diagnosed with metabolic or gastrointestinal disorders. The samples were analyzed for VOCs using a selected-ion flow-tube mass spectrometer. RESULTS: Twenty infants were included; ten preterm and ten full-term infants. Twenty-two VOCs were detected and measurable in all samples. There was a significant difference between preterm and full-term infants for the 2-propanol, acetaldehyde, acetone, acetonitrile, benzene, ethanol, isoprene, pentane, 3-methylhexane, 2-nonene, ethane, triethylamine, and trimethylamine compounds. CONCLUSION: It is feasible to measure VOCs in breath samples of preterm and full-term non-intubated infants. Full-term infants express different concentrations than preterm infants. Further studies are needed to examine the utility and reproducibility of measuring VOCs to identify neonatal diseases and predict outcomes.

Chorioamnionitis, Cesarean Deliveries, and Racial Disparities in the USA.

BACKGROUND: Studies showed disparities in management and outcomes of African American when compared to Caucasian population. The presence of chorioamnionitis may affect the decision to have a cesarean delivery (CD); however, it is not known if such a decision is affected by the mothers' race/ethnicity. OBJECTIVE: To assess the interaction between African American race/ethnicity and CD in women with chorioamnionitis. METHODS: Utilizing the National Inpatient Sample dataset, we examined the association of CD with chorioamnionitis in the overall population and within Caucasian and African American. Logistic regression models were used to control for confounders. RESULTS: The study included 6,648,883 women who delivered 6,925,920 infants. The prevalence of chorioamnionitis was 0.78 and 1.1 in Caucasian and African American, respectively. CD with and without chorioamnionitis was 41.2% and 32.4%, respectively (aOR 1.46 (1.43-1.49), p < 0.001), in Caucasian population and 45.0% and 36.6% in African American population aOR 1.42 (1.37-1.47), p < 0.001. African American population had significantly higher CD after controlling for chorioamnionitis and other confounding variables (aOR of 1.18 (1.17-1.18), p < 0.001). CONCLUSION: Chorioamnionitis is associated with increased rate of CD. Ethnic disparities exist in CD rates regardless of the chorioamnionitis status. Such findings warrant further investigation to explore factors associated with this discrepancy.

PDA: Does it matter?

Management of persistent patent ductus arteriosus (PDA) continues to be a challenging issue. The attitude toward PDA has shifted in the opposite direction during the last 20 years, from advocating an aggressive and early closure toward a call for watchful observation. While persistent PDA may cause challenges in the medical management of preterm neonates secondary to volume overload, pulmonary edema or hemorrhage, hypotension, and impaired tissue perfusion, its contribution toward long-term neonatal morbidities including bronchopulmonary dysplasia (BPD), ROP, NEC, and NDI has not been substantiated. By advocating conservative management, it is clear now that the majority of the PDA cases show spontaneous closure and do not require treatment. However, there has not been agreement regarding what constitutes a hemodynamically significant PDA and when, if any, it should be targeted for treatment. With increasing concern regarding possible associated complications with PDA ligation, a new trend for transcatheter approach to PDA closure is expanding. In this review, we summarize current understanding of the pathophysiology, diagnosis, and management of PDA in preterm infants, and we make some recommendations regarding evidence-based approach.

Caffeine use in the neonatal intensive care unit.

Caffeine is the most frequently used medication in the neonatal intensive care unit. It is used for the prevention and treatment of apnea, although this has been associated with lower incidence of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus as well as intact survival at 18-21 months of life. Although neurodevelopmental advantage was no longer statistically significant at age 5 years, caffeine was associated with sustained improvement in co-ordination and less gross motor impairment than placebo. The mechanism of action of caffeine on prevention of apnea and activation of breathing seems to be through central inhibition of adenosine receptors. However, its impact on BPD and neurodevelopmental outcomes might be induced through its effects as anti-inflammatory mediator, protection of white matter, and induction of surfactant protein B. Whereas long-term studies have documented the safety of caffeine as used in current practice, further studies are clearly needed to identify optimum dosing, and time of starting and discontinuing caffeine.

Neonatal apnea: what's new?

Apnea of prematurity (AOP) remains a major clinical problem in present day neonatology that warrants frequent evaluations and imposes challenges in therapeutic strategies. Although the pathogenesis of AOP is poorly understood, it is probably a manifestation of physiologic immaturity of breathing control rather than a pathologic disorder. Immature breathing responses to hypoxia, hypercapnia and exaggerated inhibitory pulmonary reflexes in preterm infants might also contribute to the occurrence or severity of AOP. Recent data suggest a role for genetic predisposition. Although typically resolve with maturation, the role of bradycardia and desaturation episodes associated with AOP in the development of sleep disorder breathing and neurodevelopmental delay needs further clarification. Pharmacological treatment with methylxanthines and CPAP remain the mainstay for treatment of AOP. However, recent studies have implicated central inhibitory neuromodulators including prostaglandins, GABA and adenosine in its pathogenesis, the fact that might provide future specific targets for treatment. This review will summarize new insights involving these issues as well as others involving the pathogenesis, treatment strategies and consequences of apnea in premature infants.

Activation of central adenosine A(2A) receptors enhances superior laryngeal nerve stimulation-induced apnea in piglets via a GABAergic pathway.

Activation of the laryngeal mucosa results in apnea that is mediated through, and can be elicited via electrical stimulation of, the superior laryngeal nerve (SLN). This potent inhibitory reflex has been suggested to play a role in the pathogenesis of apnea of prematurity and sudden infant death syndrome, and it is attenuated by theophylline and blockade of GABA(A) receptors. However, the interaction between GABA and adenosine in the production of SLN stimulation-induced apnea has not been previously examined. We hypothesized that activation of adenosine A(2A) receptors will enhance apnea induced by SLN stimulation while subsequent blockade of GABA(A) receptors will reverse the effect of A(2A) receptor activation. The phrenic nerve responses to increasing levels of SLN stimulation were measured before and after sequential intracisternal administration of the adenosine A(2A) receptor agonist CGS (n = 10) and GABA(A) receptor blocker bicuculline (n = 7) in ventilated, vagotomized, decerebrate, and paralyzed newborn piglets. Increasing levels of SLN stimulation caused progressive inhibition of phrenic activity and lead to apnea during higher levels of stimulation. CGS caused inhibition of baseline phrenic activity, hypotension, and enhancement of apnea induced by SLN stimulation. Subsequent bicuculline administration reversed the effects of CGS and prevented the production of apnea compared with control at higher SLN stimulation levels. We conclude that activation of adenosine A(2A) receptors enhances SLN stimulation-induced apnea probably via a GABAergic pathway. We speculate that SLN stimulation causes endogenous release of adenosine that activates A(2A) receptors on GABAergic neurons, resulting in the release of GABA at inspiratory neurons and subsequent respiratory inhibition.

Control of breathing and neonatal apnea.

Great strides have been made in our understanding of developmental respiratory neurobiology. A clear picture is, therefore, emerging of the physiological mechanisms that underlie apnea of prematurity. The ventral surface of the medulla and adjacent areas play a key integrative function for central CO2 chemosensitivity and modulation of afferent inputs from peripheral chemoreceptors and laryngeal afferents. Maturational change in medullary neurotransmitter function appears to contribute to the physiological events that characterize apnea of prematurity. Despite this greater scientific insight, therapeutic strategies for neonatal apnea have changed little in 30 years. Xanthine therapy and continuous positive airway pressure remain the mainstay of therapy while other therapeutic approaches have been inadequately studied. Our understanding of a possible relationship between the triad of apnea, bradycardia and desaturation, and impaired neurodevelopmental outcome is also limited. These are all issues that need our attention if optimal therapy and outcome are to be provided for preterm infants with immature respiratory control.

Maturation of respiratory reflex responses in the fetus and neonate.

Respiratory control in the fetus and neonate is quite immature when compared to that of adults. This immaturity involves all facets of respiration including respiratory responses to hypoxia, hypercapnia, an exaggerated apnoeic response to laryngeal stimulation and immature responses to activation of pulmonary afferents. The net result of this immaturity of breathing responses is the vulnerability of neonates and especially preterm infants to apnoea and respiratory pauses. The mechanisms behind immature control of breathing are not fully understood, but seem to originate from a predominance of inhibitory input early in life on respiratory centres. The relative contribution of up-regulation of inhibitory pathways versus down-regulation of excitatory ones is not clear. Multiple neurotransmitters have been implicated in the regulation of breathing in mammals and some of them are discussed in this chapter.

Inhibition of Na(+)/H(+) exchanger type 3 reduces duration of apnea induced by laryngeal stimulation in piglets.

Reflexes from the larynx induce cessation of breathing in newborn animals. The magnitude of respiratory inhibition is inversely related to the level of central chemical input. Recent studies indicate that selective inhibition of Na(+)/H(+) exchanger type 3 (NHE3) activates CO(2)/H(+)-sensitive neurons, resembling the responses evoked by hypercapnic stimuli. Hence, the use of NHE3 inhibitors may reduce reflexly mediated respiratory depression and duration of apnea in the neonatal period. This possibility was examined in decerebrate, vagotomized, ventilated, and paralyzed piglets by testing the effects of i.v. administration of NHE3 blocker S8218 on the response of phrenic nerve amplitude, frequency, and duration of apnea induced by graded electrical stimulation of the superior laryngeal nerve. Superior laryngeal nerve stimulation caused a significant decrease in phrenic nerve amplitude, frequency, minute phrenic activity, and inspiratory time (all p < 0.01) that was proportional to the level of electrical stimulation. Increased levels of stimulation were more likely to induce apnea both during and after cessation of stimulation. NHE3 blocker S8218 reduced the superior laryngeal nerve stimulation-induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic nerve frequency (all p < 0.05) and reduced superior laryngeal nerve stimulation-induced apnea and duration of poststimulation apnea (p < 0.05). In six other pigs the brain concentrations of S8218 were measured at different intervals after i.v. administration of the drug and were found to be higher in the brain tissue than plasma at all intervals. These findings suggest that the use of NHE3 blockers may decrease the duration of apnea and possibly reduce the pathophysiologic consequences of potentially life-threatening apnea in infants.

Effects of hypoxia on respiratory neural output and lower esophageal sphincter pressure in piglets.

We have previously documented anatomic and functional relationships between ventilatory and autonomic neural output. Therefore, we hypothesized in this study that hypoxia-induced changes in respiratory neural output are associated with changes in autonomic regulation of lower esophageal sphincter (LES) pressure. Respiratory neural output, heart rate, and LES pressure were measured before and during a 3-min exposure to 8% oxygen (balance nitrogen) in 12 3- to 7-d-old piglets. Respiratory neural output was determined from diaphragmatic electromyogram and LES pressure from an esophageal catheter. Studies were repeated after atropine administration in eight animals. Hypoxic exposure resulted in significant increases in diaphragmatic amplitude, respiratory rate, and minute diaphragmatic activity as well as heart rate. The biphasic response of diaphragm amplitude peaked at 1 min, whereas the responses of respiratory frequency and heart rate were sustained. Hypoxia caused a 50% increase in LES pressure (p < 0.05), which was eliminated by i.v. atropine administration. Development of apnea during subsequent hyperoxic exposure was always followed by a decline in LES pressure. Hypoxia-induced increase in respiratory neural output and accompanying increase in heart rate are associated with enhanced constrictive output to the LES. Blockade by atropine implicates a peripheral cholinergic mechanism for this LES response. We speculate that whereas hypoxia in the presence of enhanced respiratory neural output seems to be protective against reflux, decreased respiratory drive and accompanying apnea may be associated with a decline in LES tone and predispose to gastroesophageal reflux.