Etiologies of apnea of infancy.

BACKGROUND: To date there are limited data in the literature to guide the initial evaluation for etiologies of apnea in full-term infants born at greater than or equal to 37 weeks conceptional age (apnea of infancy [AOI]). Pediatricians and pediatric pulmonologists are left to pursue a broad, rather than targeted and a stepwise approach to begin diagnostic evaluation. METHODS: We performed a retrospective chart review of 101 symptomatic full-term infants (age under 12 months) diagnosed with apnea with an inpatient multichannel pneumogram (six channels) or a fully attended overnight pediatric polysomnogram in our outpatient sleep center accredited by American Academy of Sleep Medicine (AASM), scored using the standards set forth by the AASM. The infant was diagnosed as having AOI if the apnea hypopnea index (AHI) was greater than 1 (AHI is defined as the number of apnea and hypopnea events per hour of sleep). The final diagnosis/etiology was determined based on physician clinical assessment and work up. We then determined the frequency for each diagnosis. RESULTS: We found that the three most common etiologies were gastroesophageal reflux disease (GERD) (48/101), upper airway abnormalities/obstruction (37/101), and neurological diseases (19/101). There were significant numbers of infants with multiple etiologies for AOI. CONCLUSION: Based on the frequencies obtained, pediatric practitioners caring for full-term infants with apnea of unknown etiology are advised to begin with evaluation of more likely causes such as GERD and upper airway abnormalities/obstruction before evaluating for less common causes.

Amelioration of ischemia-reperfusion injury in an isolated rabbit lung model using OXANOH.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality. Oxygen-free radicals (OFRs) produced during ischemia and reperfusion (IR) have been implicated as the final common pathway in the pathogenesis of this syndrome. Spin traps have been shown to decrease IR injury in several animal lung models. The hydroxylamine, OXANOH (2-ethyl-2,5,5-trimethyl-3-oxazolidine) has been proposed as an ideal spin trap that would trap extra- and intracellular OFRs producing the stable radical, OXANO• (2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl). Electron microscopy was used to investigate whether OXANOH would protect against IR injury in the rabbit lung. METHODS: OXANOH was obtained by hydrogenation of its stable radical, OXANO• using a safe laboratory technique. Several doses of OXANOH were tested to identify a nontoxic dose. Two quantitative methods were used based on the average surface area of the alveoli and average number of alveoli per unit surface area using scanning electron microscopy (SEM). A total of 20 animals were subjected to 2 hours of ischemia followed by 4 hours of reperfusion. On reperfusion, the 4 groups (N = 5) received no treatment, OXANOH, superoxide dismutase (SOD)/catalase, or oxypurinol. RESULTS: A therapeutic dose of 250 µmol/L of OXANO• was suggested in this in vitro model. All the 3 treatments showed significantly less injury compared to the control group and that SOD/catalase was significantly different from OXANOH and oxypurinol (P < .008). CONCLUSION: OXANOH ameliorated IR injury in the isolated rabbit lung, almost as effectively as SOD/catalase and oxypurinol.

Longitudinal assessment of hemoglobin oxygen saturation in preterm and term infants in the first six months of life.

OBJECTIVE: To report longitudinal home recordings of hemoglobin O(2) saturation by pulse oximetry (Spo(2)) during unperturbed sleep in preterm and term infants. STUDY DESIGN: We recorded continuous pulse oximetry during the first 3 minutes of each hour of monitor use (nonevent epochs) for 103 preterm infants born at <1750 g and ≤ 34 weeks postmenstrual age (PMA), and 99 healthy term infants. RESULTS: Median baseline Spo(2) was approximately 98% for both the preterm and term groups. Episodes of intermittent hypoxemia occurred in 74% of preterm and 62% of term infants. Among infants with intermittent hypoxemia, the number of seconds/hour of monitoring <90% Spo(2) was initially significantly greater in the preterm than the term group and declined with age at a similar rate in both groups. The 75(th) to 95(th) percentiles for seconds/hour of Spo(2) <90% in preterm infants were highest at 36 weeks PMA and progressively decreased until 44 weeks PMA, after which time they did not differ from term infants. CONCLUSIONS: Clinically inapparent intermittent hypoxemia occurs in epochs unperturbed by and temporally unrelated to apnea or bradycardia events, especially in preterm infants at 36 to 44 weeks PMA.

Ischemia-reperfusion injury in the lung: quantitation using electron microscopy.

BACKGROUND: The primary objectives of this study were to determine the time course of ischemia-reperfusion injury in an isolated rabbit lung model and to quantify this damage using electron microscopic methodology coupled with statistical analyses. MATERIALS AND METHODS: Eight groups of isolated rabbit lungs (n = 5 per group) were subjected to predetermined periods of ischemia-reperfusion. Two hours of ischemia and 4 hours of reperfusion were concluded to be necessary to induce optimal ischemia-reperfusion injury in this model. Four other groups were subjected to 2 hours of ischemia followed by selected periods of reperfusion. These groups were compared to 4 control groups that were perfused for comparable time periods but without the initial ischemia. New quantitative methods were developed based on the average surface area of the alveoli and average number of alveoli per unit surface area, using scanning electron microscopic examination. RESULTS: Ischemia per se caused substantial damage. Restoration of volume and nutrients reversed this damage at 1 hour of reperfusion, but severe damage was evident at 4 hours of reperfusion, as reported by subjective and blinded examination. By using the new quantitative methods, there was a significant difference between the groups (P < .005) according to the time of post-ischemia-reperfusion, which correlated with the subjective evaluation of damage. CONCLUSIONS: These 2 new quantitative techniques provide an objective assessment of damage in the isolated rabbit lung model, suggesting that they warrant further consideration in similar studies of ischemia reperfusion injury.

Precursors of cardiorespiratory events in infants detected by home memory monitor.

In 1,079 infants monitored for >700,000 hr at home for apnea or bradycardia, we found an association between infants having multiple events exceeding conventional or a priori defined more extreme thresholds and less favorable developmental outcome at 1 year of age than infants with few or no events. If it is necessary to prevent such events to minimize risk for developmental morbidity, there is reason to determine whether there are disturbances in advance of the apnea or bradycardia that herald their onset. In the 85 infants with at least 1 extreme event and 1 conventional event, we hypothesized that apnea and bradycardia do not occur de novo but rather are preceded by cardiorespiratory and hemoglobin O2 saturation changes. We compared recorded time intervals preceding these events, and we analyzed three preceding time intervals for each conventional and extreme event, and each non-event recording: Time-2 hr: up to 2 hr before; Time-1 hr: up to 1 hr before; and Time-75 sec: the 75 sec immediately preceding each event. O2 saturation progressively decreased preceding both conventional and extreme events, and progressive increases occurred in heart and breathing rate variability. Duration of respiratory pauses and of periodic breathing progressively increased preceding conventional events, respiratory rate variability increased immediately preceding conventional events and at 1 hr preceding extreme events, and O2 saturation decreased immediately preceding both conventional and extreme events. Thus, conventional and extreme events do not occur de novo but rather are preceded by autonomic instability of the cardiorespiratory system.

Factors that influence use of a home cardiorespiratory monitor for infants: the collaborative home infant monitoring evaluation.

BACKGROUND: As part of the Collaborative Home Infant Monitoring Evaluation, a home monitor was developed to record breathing, heart rate, other physiologic variables, and the time the monitor was used. OBJECTIVE: To determine the frequency of monitor use, factors that influence use, and validity of a model developed to predict use. DESIGN: We developed a model to predict monitor use using multiple linear regression analysis; we then tested the validity of this model to predict adherence for the first week of monitoring and for the subsequent 4-week period (weeks 2-5). SETTING: Clinical research centers in Chicago, Ill; Cleveland, Ohio; Honolulu, Hawaii; Los Angeles, Calif; and Toledo, Ohio. Patients Preterm infants, infants younger than 1 month with a history of autopsy-confirmed sudden infant death syndrome in a sibling, and infants with an idiopathic apparent life-threatening event were divided into 2 cohorts based on enrollment date. Main Outcome Measure Mean hours of monitor use per week. RESULTS: In cohort 1, the variables available before monitoring were only weakly associated with total hours of monitor use in weeks 2 to 5 (total model r(2) = 0.08). However, when hours of monitor use in week 1 were included as a variable to predict monitor use in weeks 2 to 5, the r(2) increased to 0.64 for hours of monitor use per week. CONCLUSIONS: Our data show that monitor use in the first week was the most important variable for predicting subsequent monitor use. The study suggests that a major focus of home monitoring should be adherence in the first week, although it remains to be tested whether this adherence can be altered.

Ontogeny of arousal.

Ontogeny of arousal data constitute a vital supplement to the sparse literature on spontaneous neuronal activity. These data demonstrate that measurable infant spontaneous arousals (SAs) with an inherent oscillatory entrainment occur six times more in active sleep than in quiet sleep of the same duration and are identifiable as a human neurobiologic function. These SAs are not significantly associated with race or ethnicity, gender, total hours spent sleeping, percent time spent in active or quiet sleep, preterm status, history of a life-threatening event, having had a sibling who died of sudden infant death syndrome (SIDS), or having had a mother who smoked during this pregnancy. As measurable neurophysiologic events, SAs establish parameters for research at molecular and molar levels focusing on several critical areas: (1) the neuronal control of SA related to neurotransmitters, (2) as a significant antecedent factor in clinical cardiorespiratory events occurring in infants at high epidemiologic risk for SIDS; (3) as a regulatory biologic factor underlying temperament and executive cognitive functioning, and (4) morbidity and mortality effects possibly related to therapeutic interventions that alter SA levels.

Cardiorespiratory events detected by home memory monitoring and one-year neurodevelopmental outcome.

OBJECTIVE: To determine if infants with cardiorespiratory events detected by home memory monitoring during early infancy have decreased neurodevelopmental performance. STUDY DESIGN: Infants (n = 256) enrolled in the Collaborative Home Infant Monitoring Evaluation also completed the Bayley Scales of Infant Development II at 92 weeks' postconceptional age. Infants were classified as having 0, 1 to 4, or 5+ cardiorespiratory events. Events were defined as apnea >or=20 seconds or heart rate <60 to 80 bpm or <50 to 60 bpm, for >or=5 to 15 seconds, depending on age. RESULTS: For term infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean Mental Developmental Index (MDI) values (+/-SD) of 103.6 (10.6), 104.2 (10.7), and 97.7 (10.9), respectively, and mean Psychomotor Developmental Index (PDI) values of 109.5 (16.6), 105.8 (16.5), and 100.2 (17.4). For preterm infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean MDI values of 100.4 (10.3), 96.8 (11.5), and 95.8 (10.6), respectively, and mean PDI values of 91.7 (19.2), 93.8 (15.5), and 94.4 (17.7). The adjusted difference in mean MDI scores with 5+ events compared with 0 events was 5.6 points lower in term infants ( P = .03) and 4.9 points lower in preterm infants ( P = .04). CONCLUSIONS: Having 5+ conventional events is associated with lower adjusted mean differences in MDI in term and preterm infants.

Infant polysomnography: reliability and validity of infant arousal assessment.

Infant arousal scoring based on the Atlas Task Force definition of transient EEG arousal was evaluated to determine (1). whether transient arousals can be identified and assessed reliably in infants and (2). whether arousal and no-arousal epochs scored previously by trained raters can be validated reliably by independent sleep experts. Phase I for inter- and intrarater reliability scoring was based on two datasets of sleep epochs selected randomly from nocturnal polysomnograms of healthy full-term, preterm, idiopathic apparent life-threatening event cases, and siblings of Sudden Infant Death Syndrome infants of 35 to 64 weeks postconceptional age. After training, test set 1 reliability was assessed and discrepancies identified. After retraining, test set 2 was scored by the same raters to determine interrater reliability. Later, three raters from the trained group rescored test set 2 to assess inter- and intrarater reliabilities. Interrater and intrarater reliability kappa's, with 95% confidence intervals, ranged from substantial to almost perfect levels of agreement. Interrater reliabilities for spontaneous arousals were initially moderate and then substantial. During the validation phase, 315 previously scored epochs were presented to four sleep experts to rate as containing arousal or no-arousal events. Interrater expert agreements were diverse and considered as noninterpretable. Concordance in sleep experts' agreements, based on identification of the previously sampled arousal and no-arousal epochs, was used as a secondary evaluative technique. Results showed agreement by two or more experts on 86% of the Collaborative Home Infant Monitoring Evaluation Study arousal scored events. Conversely, only 1% of the Collaborative Home Infant Monitoring Evaluation Study-scored no-arousal epochs were rated as an arousal. In summary, this study presents an empirically tested model with procedures and criteria for attaining improved reliability in transient EEG arousal assessments in infants using the modified Atlas Task Force standards. With training based on specific criteria, substantial inter- and intrarater agreement in identifying infant arousals was demonstrated. Corroborative validation results were too disparate for meaningful interpretation. Alternate evaluation based on concordance agreements supports reliance on infant EEG criteria for assessment. Results mandate additional confirmatory validation studies with specific training on infant EEG arousal assessment criteria.