Cardiorespiratory Monitoring Data to Predict Respiratory Outcomes in Extremely Preterm Infants.

Rationale: Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. Objectives: To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA. Methods: The Prematurity-related Ventilatory Control (Pre-Vent) study was an observational multicenter prospective cohort study including infants born at <29 weeks of gestation with continuous cardiorespiratory monitoring. The primary outcome was either "favorable" (alive and previously discharged or inpatient and off respiratory medications/O2/support at 40 wk PMA) or "unfavorable" (either deceased or inpatient/previously discharged on respiratory medications/O2/support at 40 wk PMA). Measurements and Main Results: A total of 717 infants were evaluated (median birth weight, 850 g; gestation, 26.4 wk), 53.7% of whom had a favorable outcome and 46.3% of whom had an unfavorable outcome. Physiologic data predicted unfavorable outcome, with accuracy improving with advancing age (area under the curve, 0.79 at Day 7, 0.85 at Day 28 and 32 wk PMA). The physiologic variable that contributed most to prediction was intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <90%. Models with clinical data alone or combining physiologic and clinical data also had good accuracy, with areas under the curve of 0.84-0.85 at Days 7 and 14 and 0.86-0.88 at Day 28 and 32 weeks PMA. Intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <80% was the major physiologic predictor of severe bronchopulmonary dysplasia and death or mechanical ventilation at 40 weeks PMA. Conclusions: Physiologic data are independently associated with unfavorable respiratory outcome in extremely preterm infants.

Pulmonary function tests in extremely low gestational age infants at one year of age.

RATIONALE: Identifying neonatal and post-discharge exposures among extremely low gestational age newborns (ELGANs) that drive increased pulmonary morbidity and abnormal lung function at 1 year of age proves challenging. OBJECTIVE: The NIH-sponsored Prematurity and Respiratory Outcomes Program (PROP), evaluated infant pulmonary function tests (iPFTs) at 1 year corrected age to determine which demographic and clinical factors are associated with abnormal lung function. METHODS: iPFTs were performed on a PROP subcohort of 135 participants following Institutional Review Board (IRB)-approved written consent. Demographic data, Neonatal Intensive Care Unit (NICU) clinical care, and post-NICU exposures were analyzed for association with iPFTs. MAIN RESULTS: A significant decrease in forced expiratory volume at 0.5 s (FEV0.5 ) and/or forced expiratory flows at 75% of forced vital capacity (FEF75 ), were associated with male sex and African American race. Clinical factors including longer duration of ventilatory support, exposure to systemic steroids, and weight less than the 10th percentile at 36 weeks postmenstrual age were also associated with airflow obstruction, whereas supplemental oxygen requirement and bronchopulmonary dysplasia were not. Additionally, the need for respiratory medications, technology, or hospitalizations during the first year, ascertained by a quarterly survey, were the only post-NICU factors associated with decreased FEV0.5 and FEF75 . Only 7% of infants had reversible airflow obstruction. CONCLUSIONS: Neonatal demographic factors, respiratory support in the NICU, and a history of greater post-NICU medical utilization for respiratory disease had the strongest association with lower lung function at 1 year in ELGANs.

Postmenstrual age at discharge in premature infants with and without ventilatory pattern instability.

RATIONALE: To determine if ventilatory pattern instability, manifested as periodic breathing (PB) during physiologic challenge testing, affects postmenstrual age (PMA) at discharge. METHODS: Eighty infants underwent challenge testing at 36 weeks PMA. Infants breathing supplemental O2 received a room air challenge (RAC, N = 51); those breathing ambient air underwent a hypoxic challenge test (HCT, N = 29). Infants were assigned one of four ventilatory control phenotypes based on the presence or absence of PB during their test, and if they passed or failed because of hypoxemia during the challenge test. RESULTS: There were no clinical or demographic differences between groups. Infants who passed their challenge testing were, on average, discharged 1.6 weeks sooner than those who failed. The groups of ventilatory control phenotypes differed in PMA at discharge (p = 0.0020), but those with PB were younger by PMA at discharge. CONCLUSIONS: Ventilatory pattern instability did not prolong time to discharge. Passing either challenge was associated with earlier discharge, suggesting these tests might identify infants who can have nasal cannula support removed and be safely discharged sooner. Most of the infants who failed their challenge tests with PB were receiving nasal cannula support. Nasal cannula support may be not only treating hypoxemia due to bronchopulmonary dysplasia (BPD), but also mitigating their ventilatory pattern instability.

Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates.

RATIONALE: The relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined. OBJECTIVES: To test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with bronchopulmonary dysplasia (BPD) or respiratory disease in the first year of life and those without these conditions. METHODS: Study subjects were part of the PROP (Prematurity and Respiratory Outcomes Program) study, a longitudinal cohort study of infants born at less than 29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week before anticipated hospital discharge. Infants were breathing spontaneously and were receiving less than or equal to 1 L/min nasal cannula flow at 21% to 100% fraction of inspired oxygen. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without BPD (oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants. RESULTS: A total of 765 infants survived to 36 weeks postmenstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of postdischarge respiratory disease was 65.7%. Compared with a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no clinically significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared with those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life. CONCLUSIONS: Extremely premature infants receiving less than 1 L/min nasal cannula support at 21% to 100% fraction of inspired oxygen have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not. Clinical trial registered with www.clinicaltrials.gov (NCT01435187).

Stability of polysomnography for one year and longer in children with sickle cell disease.

STUDY OBJECTIVES: Serious morbidity may be linked to sleep disordered breathing (SDB) among children with sickle cell disease (SCD). We investigated the stability of polysomnography (PSG) results among children not having acute complications of SCD. METHODS: Two PSGs were performed on a subsample of 63 children 4 to 18 years of age from the Sleep and Asthma Cohort Study. All had Hb SS or HbSß(0) disease. Two PSGs were compared for 45 subjects. Excluded from comparison were 18 children who had begun transfusions or hydroxyurea, had an adenotonsillectomy between the PSGs, or had a pain crisis or the acute chest syndrome within 3 months of the second PSG. Sleep disordered breathing was identified using 2 thresholds for the apnea hypopnea index (AHI): ≥ 2 or ≥ 5 respiratory events per hour. RESULTS: Ages were 12.3 yrs ± 4.0, BMI, 18.2 ± 3.2. Interval between PSGs was 581 ± 119 days (19.1 ± 3.9 months). Ten of 45 changed from ≥ 2 events per hour to < 2; 3 of 45 from < 2 to ≥ 2; 7 of 45 had ≥ 2 on both nights. Six of 45 changed from ≥ 5 to < 5, 2 of 45 from < 5 to ≥ 5, and 1 had ≥ 5 on both nights (McNemar χ(2), p = 0.09, and p = 0.29). CONCLUSIONS: In the absence of acute SCD complications, overnight PSG usually remains stable or improves over a 12- to 30-month period. Only 6.7% subjects, or fewer, had AHI on a subsequent PSG that would re-classify the child as having SDB not identified in the earlier PSG.

Evaluation of ventilatory efficiency during exercise in patients with idiopathic scoliosis undergoing spinal fusion.

STUDY DESIGN: A prospective evaluation of ventilatory function following spinal fusion in adolescent idiopathic scoliosis. OBJECTIVES: To prospectively evaluate pulmonary function, maximal oxygen uptake, and ventilatory efficiency during exercise in patients with adolescent idiopathic scoliosis before surgery and a minimum of 2 years postoperation. SUMMARY OF BACKGROUND DATA: For reasons that are unclear, patients with untreated adolescent idiopathic scoliosis tend to avoid aerobic exercise. Their reluctance may be the result of low ventilatory efficiency, as they often approach their ventilatory ceiling at maximum oxygen uptake despite forced vital capacities that are near normal. This inefficiency of ventilation with exercise may explain the reluctance of patients with scoliosis to pursue aerobic fitness. No study has evaluated the effect spinal fusion has on the ventilatory function of patients with scoliosis during exercise. METHODS: Forty-two patients with adolescent idiopathic scoliosis (36 female and 6 male) at an average age of 14 +/- 3 years (range 10-18 years) underwent spinal fusion. Twenty patients underwent a posterior spinal fusion alone, 20 an anterior spinal fusion alone, and 2 an anterior spinal fusion and posterior spinal fusion. The average Cobb measurement was 55 degrees (range 40-85 degrees). Pulmonary function values (forced vital capacity, total lung capacity, maximum voluntary ventilation), maximum oxygen uptake (VO2max), and ventilatory efficiency were obtained before surgery and a minimum of 2 years postoperation. RESULTS: For all patients, forced vital capacity percent predicted decreased from 88.1% to 81.4% (P < 0.0001). Total lung capacity also declined from 90.5% to 88.5% but was not statistically significant (P = 0.189). Percent predicted maximum oxygen uptake (VO2max) declined from 93.6% to 85.1% (P = 0.00029). Ventilatory efficiency, as measured by VEmax/maximum voluntary ventilation, improved from 0.76 to 0.68 (P = 0.005), whereas measured by VEmax/FEV1 x 40 was unchanged from 0.69 to 0.70 (P = 0.172) postoperation. The choice of operative approach [anterior (n = 20) versus posterior (n = 20)] or whether rib graft was harvested (n = 33) versus iliac crest graft (n = 7) did not change these results. CONCLUSION: Improvement in ventilatory efficiency during exercise does not occur in the majority of patients with adolescent idiopathic scoliosis following spinal fusion and thus cannot be relied on to foster increases in aerobic activity.