Juliann M. Di Fiore

A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity.

OBJECTIVE Retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina in preterm infants, is associated with multiple factors, including oxygenation level. We explored whether the common intermittent hypoxemic events in preterm infants are associated with the development of ROP. STUDY DESIGN Oxygen desaturation events were quantified in 79 preterm infants (gestational age, 24 to 27-6/7 weeks) during the first 8 weeks of life. Infants were classified as requiring laser treatment for ROP versus having less severe or no ROP. A linear mixed model was used to study the association between the incidence of intermittent hypoxia and laser treatment of ROP, controlling for gestational age, sex, race, multiple births, and initial severity of illness. RESULTS For all infants, hypoxemic events increased with postnatal age (P<.001). Controlling for all covariates, a higher incidence of oxygen desaturation events was found in the infants undergoing laser therapy for ROP (P<.001), males (P<.02), and infants of younger gestational age (P<.003). CONCLUSIONS The incidence of hypoxemic events was higher in infants with ROP requiring laser therapy. Therapeutic strategies to optimize oxygenation in preterm infants should include minimization of desaturation episodes, which may in turn decrease serious morbidity in this high-risk population.

Intermittent Hypoxic Episodes in Preterm Infants: Do They Matter?

Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks 6–8. Such episodic hypoxia/reoxygenation has the potential to sustain a proinflammatory cascade with resultant multisystem morbidity. This morbidity includes retinopathy of prematurity and impaired growth, as well as possible longer-term cardiorespiratory instability and poor neurodevelopmental outcome. Therapeutic approaches for intermittent hypoxic episodes comprise determination of optimal baseline saturation and careful titration of supplemental inspired oxygen, as well as xanthine therapy to prevent apnea of prematurity. In conclusion, characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.

Apnea Is Not Prolonged by Acid Gastroesophageal Reflux in Preterm Infants

Objective. To examine the temporal relationship between apnea and gastroesophageal reflux (GER) and to assess the effect of GER on apnea duration. Methods. A total of 119 preterm infants underwent 12-hour cardiorespiratory monitoring studies using respiratory inductance plethysmography, heart rate, oxygen saturation (SaO2), and esophageal pH. The studies were scored for GER (pH <4 for ≥5 seconds) and apnea ≥15 seconds or ≥10 seconds that occurred within 30 seconds of GER. Apnea ≥10 seconds was used to assess whether GER would prolong apnea duration. Results. There were 6255 episodes of GER. Only 1% of GER episodes were associated with apnea ≥15 seconds, and there was no difference in apnea rate before, during, or after GER. There was also no difference in rate of apnea ≥10 seconds before versus during GER; however, there was a decrease in apnea rate immediately after GER. The presence of GER during apnea did not prolong apnea duration, and GER had no effect on the lowest SaO2 or heart rate during apnea. Conclusion. There is no evidence of a temporal relationship between acid-based GER and apnea in preterm infants. In addition, GER does not prolong apnea duration and does not exacerbate the resultant decrease in heart rate and SaO2.

Low Oxygen Saturation Target Range is Associated with Increased Incidence of Intermittent Hypoxemia

OBJECTIVE To test the hypothesis that preterm infants randomized to a low vs high O(2) saturation target range have a higher incidence of intermittent hypoxemia. STUDY DESIGN A subcohort of 115 preterm infants with high resolution pulse oximetry enrolled in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial were randomized to low (85%-89%) or high (91%-95%) O(2) saturation target ranges. Oxygen saturation was monitored until 36 weeks postmenstrual age or until the infant was breathing room air without respiratory support for ≥72 hours. RESULTS The low target O(2) saturation group had a higher rate of intermittent hypoxemia (≤80% for ≥10 seconds and ≤3 minutes) prior to 12 days and beyond 57 days of life (P < .05). The duration shortened (P < .0001) and the severity increased (P < .0001) with increasing postnatal age with no differences between target saturation groups. The higher rate of intermittent hypoxemia events in the low target group was associated with a time interval between events of <1 minute. CONCLUSION A low O(2) saturation target was associated with an increased rate of intermittent hypoxemia events that was dependent on postnatal age. The duration and severity of events was comparable between target groups. Further investigation is needed to assess the role of intermittent hypoxemia and their timing on neonatal morbidity.

Apnea of prematurity – Perfect storm☆

With increased survival of preterm infants as young as 23 weeks gestation, maintaining adequate respiration and corresponding oxygenation represents a clinical challenge in this unique patient cohort. Respiratory instability characterized by apnea and periodic breathing occurs in premature infants because of immature development of the respiratory network. While short respiratory pauses and apnea may be of minimal consequence if oxygenation is maintained, they can be problematic if accompanied by chronic intermittent hypoxemia. Underdevelopment of the lung and the resultant lung injury that occurs in this population concurrent with respiratory instability creates the perfect storm leading to frequent episodes of profound and recurrent hypoxemia. Chronic intermittent hypoxemia contributes to the immediate and long term co-morbidities that occur in this population. In this review we discuss the pathophysiology leading to the perfect storm, diagnostic assessment of breathing instability in this unique population and therapeutic interventions that aim to stabilize breathing without contributing to tissue injury.

Characteristics of hypoxemic episodes in very low birth weight infants on ventilatory support

OBJECTIVE To characterize hypoxemic episodes in very low birth weight infants with mechanically ventilated lungs and to describe their natural history and the effect of body position. STUDY DESIGN Tidal volume, respiratory rate, oxygen saturation, heart rate, and body movement were continuously recorded in 10 very low birth weight infants who exhibited episodes of hypoxemia during mechanical ventilation (birth weight, 810 +/- 133 gm; postconceptional age at study, 30 +/- 1.6 weeks). Frequency of hypoxemic episodes was compared in both prone and supine positions. RESULTS Seventy-eight percent of hypoxemic episodes began in association with body movement as well as heart rate acceleration. Thereafter the spontaneous and delivered minute ventilation both decreased during the first 15 seconds of hypoxemia. The former decrease was due to a significant decrease in frequency of spontaneous respiration, whereas the latter was associated with a significant decrease in delivered tidal volume. Minute ventilation returned to normal before recovery of oxygenation. A change in body position from supine to prone significantly decreased the frequency of hypoxemic episodes. CONCLUSION Hypoxemic episodes in infants who are on ventilatory support are characterized by (1) movement and cardioacceleration at initiation; (2) a decrease in both spontaneous and delivered minute ventilation, and (3) a lower incidence in the prone position. We speculate that spontaneous movement during sleep can trigger cardiopulmonary reflex responses that initiate and propagate these episodes.

Does Gastroesophageal Reflux Cause Apnea in Preterm Infants

Gastroesophageal reflux (GER) and apnea are both common occurrences in premature infants but their relationship is controversial. We present the evidence for and against an association between GER and apnea and discuss the merits and limitations of the various methodologies employed in characterizing such a relationship. Overall, GER and apnea do not appear temporally related in preterm infants, despite strong physiologic evidence that stimulation of laryngeal afferents elicits central apnea and laryngeal adduction. In a subpopulation of infants with neurodevelopmental compromise, there may be an increased incidence of both apnea and GER, although the direct association between GER and apnea in this population is unclear. Therefore, we believe there is no evidence to support widespread use of anti-reflux medications in the treatment of apnea in preterm infants. Further studies are needed to clarify the existence of a small subpopulation of infants who may have GER-induced apnea, to identify potential triggering mechanisms, and to document benefit from newer pharmacological approaches.

The relationship between patterns of intermittent hypoxia and retinopathy of prematurity in preterm infants

Background:We have previously shown an increased incidence of intermittent hypoxemia (IH) events in preterm infants with severe retinopathy of prematurity (ROP). Animal models suggest that patterns of IH events may play a role in ROP severity as well. We hypothesize that specific IH event patterns are associated with ROP in preterm infants.Methods:Variability in IH event duration, severity, and the time interval between IH events (≤80%, ≥10 s, and ≤3 min) along with the frequency spectrum of the oxygen saturation (SpO2) waveform were assessed.Results:Severe ROP was associated with (i) an increased mean and SD of the duration of IH event (P < 0.005), (ii) more variability (histogram entropy) of the time interval between IH events (P < 0.005), (iii) a higher IH nadir (P < 0.05), (iv) a time interval between IH events of 1–20 min (P < 0.05), and (v) increased spectral power in the range of 0.002–0.008 Hz (P < 0.05), corresponding to SpO2 waveform oscillations of 2–8 min in duration. Spectral differences were detected as early as 14 d of life.Conclusion:Severe ROP was associated with more variable, longer, and less severe IH events. Identification of specific spectral components in the SpO2 waveform may assist in early identification of infants at risk for severe ROP.

Cardiopulmonary monitoring at home: The CHIME monitor

A new physiologic monitor for use in the home has been developed and used for the Collaborative Home Infant Monitor Evaluation (CHIME). This monitor measures infant breathing by respiratory inductance plethysmography and transthoracic impedance; infant electrocardiogram, heart rate and R-R interval; haemoglobin O2 saturation of arterial blood at the periphery and sleep position. Monitor signals from a representative sample of 24 subjects from the CHIME database were of sufficient quality to be clinically interpreted 91.7% of the time for the respiratory inductance plethysmograph, 100% for the ECG, 99.7% for the heart rate and 87% for the 16 subjects of the 24 who used the pulse oximeter. The monitor detected breaths with a sensitivity of 96% and a specificity of 65% compared to human scorers. It detected all clinically significant bradycardias but identified an additional 737 events where a human scorer did not detect bradycardia. The monitor was considered to be superior to conventional monitors and, therefore, suitable for the successful conduct of the CHIME study.

Technical limitations in detection of gastroesophageal reflux in neonates.

Objective: Characterize the incidence and possible etiologies of acid reflux events detected by pH and not identified by multiple intraluminal impedance (MII) monitoring. Materials and Methods: Acid reflux events detected by pH but not identified by MII (pH-only) were documented in 80 preterm and 39 term infants. Reasons for failure of MII to detect these events were classified as failure to meet MII scoring criteria, presence of an air bolus, technical artifact, and no change in impedance. Events with no change in impedance were stratified to low impedance throughout the study (possible esophageal inflammation), transient decrease in pre-event impedance (presence of refluxate), occurrence <30 seconds of a preceding event, and no explanation. Results: A total of 2572 events were detected by pH, with 59% of events not identified by MII. A higher incidence of pH-only events occurred in preterm versus term infants (54 ± 27% versus 42 ± 23%, P = .025, respectively). Thirteen percent of pH-only events were missed due to MII scoring criteria, 12% due to technical artifact, 11% due to an air bolus, and 64% had no change in impedance. Of the 978 events with no change in impedance, 154 were associated with low impedance throughout the study, 430 with a transient decrease in pre-event impedance, and 175 were preceded by a reflux episode within 30 seconds. Conclusions: There was a high incidence of acid reflux events detected by pH but not identified by MII. This occurred more often in the least mature infants, and we speculate that delayed esophageal fluid clearance is the major underlying mechanism.