Late permissive hypercapnia and respiratory stability among very preterm infants: a pilot randomised trial.

OBJECTIVE: Determine if targeting higher transcutaneous carbon dioxide improves respiratory stability among very preterm infants on ventilatory support. DESIGN: Single-centre pilot randomised clinical trial. SETTING: The University of Alabama at Birmingham. PATIENTS: Very preterm infants on ventilatory support after postnatal day 7. INTERVENTIONS: Infants were randomised to two different transcutaneous carbon dioxide levels targeting 5 mm Hg (0.67 kPa) changes with four sessions each lasting 24 hours for 96 hours: baseline-increase-baseline-increase or baseline-decrease-baseline-decrease. MAIN OUTCOME MEASURES: We collected cardiorespiratory data evaluating episodes of intermittent hypoxaemia (oxygen saturations (SpO2)<85% for ≥10 s), bradycardia (<100 bpm for ≥10 s), and cerebral and abdominal hypoxaemia on near-infrared spectroscopy. RESULTS: We enrolled 25 infants with a gestational age of 24 w 6 d±11 d (mean±SD) and birth weight 645±142 g on postnatal day 14±3. Continuous transcutaneous carbon dioxide values (56.8±6.9 in the higher group vs 54.5±7.8 in the lower group; p=0.36) did not differ significantly between groups during the intervention days. There were no differences in intermittent hypoxaemia (126±64 vs 105±61 per 24 hours; p=0.30) or bradycardia (11±16 vs 15±23 per hour; p=0.89) episodes between groups. The proportion of time with SpO2<85%, SpO2<80%, cerebral hypoxaemia or abdominal hypoxaemia did not differ (all p>0.05). There was moderate negative correlation between mean transcutaneous carbon dioxide and bradycardia episodes (r=-0.56; p<0.001). CONCLUSION: Targeting 5 mm Hg (0.67 kPa) changes in transcutaneous carbon dioxide did not improve respiratory stability among very preterm infants on ventilatory support but the intended carbon dioxide separation was difficult to achieve and maintain. TRIAL REGISTRATION NUMBER: NCT03333161.

Higher- or Usual-Volume Feedings in Infants Born Very Preterm: A Randomized Clinical Trial.

OBJECTIVE: To determine whether higher-volume feedings improve postnatal growth among infants born very preterm. STUDY DESIGN: Randomized clinical trial with 1:1 parallel allocation conducted from January 2015 to June 2018 in a single academic medical center in the US. In total, 224 infants with a birth weight 1001-2500 g born at <32 weeks of gestation were randomized to higher-volume (180-200 mL/kg/d) or usual-volume (140-160 mL/kg/d) feedings after establishing full enteral feedings (≥120 mL/kg/d). The primary outcome was growth velocity (g/kg/d) from randomization to study completion at 36 weeks of postmenstrual age or hospital discharge if earlier. RESULTS: Growth velocity increased among infants in the higher-volume group compared with the usual-volume group (mean [SD], 20.5 [4.5] vs 17.9 [4.5] g/kg/d; P < .001). At study completion, all measurements were higher among infants in the higher-volume group compared with the usual-volume group: weight (2365 [324] g, z score -0.60 [0.73] vs 2200 [308] g, z score -0.94 [0.71]; P < .001); head circumference (31.9 [1.3] cm, z score -0.30 [0.91] vs 31.4 [1.3] cm, z score -0.53 [0.84]; P = .01); length (44.9 [2.1] cm, z score -0.68 [0.88] vs 44.4 [2.0], z score -0.83 [0.84]; P = .04); and mid-arm circumference (8.8 [0.8] cm vs 8.4 [0.8] cm; P = .002). Bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or other adverse outcomes did not differ between groups. CONCLUSIONS: In infants born very preterm weighing 1001-2500 g at birth, higher-volume feedings increased growth velocity, weight, head circumference, length, and mid-arm circumference compared with usual-volume feedings without adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02377050.