Short running head: Physiology of impaired gas exchange in BPD Descriptor: 14.3 Manuscript Body Word Count: 3639 At a Glance Commentary: Scientific Knowledge on the Subject: Assessment of impaired gas exchange may provide a continuous outcome measure for sensitive and equitable determination of severity of bronchopulmonary dysplasia (BPD). Previous gas exchange studies in BPD infants used small cohorts and targeted moderate-severe BPD. These studies show right shift of the peripheral oxyhemoglobin saturation (SpO2) versus inspired oxygen partial pressure (PIO2) curve and reduced ventilation-perfusion ratio reliably predict hypoxaemia in preterm infants breathing air, and further, that many infants also have a right-left shunt. What This Study Adds to the Field: We provide measures of right shift, ventilation/perfusion and shunt, across the full spectrum of lung disease in a large (n=219) group of preterm infants. Shift increases and ventilation/perfusion decreases with increased severity of BPD as defined by the NIH classification of BPD. Shunt is primarily a feature of infants with moderate-severe BPD who require supplemental oxygen. Non-invasive bedside assessment of shift, ventilation/perfusion and shunt provide physiological continuous outcome measures of severity of respiratory disease in very preterm infants with/without BPD independent of altitude and unit practices. Routine analysis of the SpO2/PIO2 curve may improve accuracy of BPD severity classification and provide a sensitive continuous outcome measure for clinical trials evaluating pulmonary outcomes.

BACKGROUND AND OBJECTIVES: Evidence suggests that intramuscular vitamin A reduces the risk of bronchopulmonary dysplasia (BPD) in preterm infants. Our objective was to compare enteral water-soluble vitamin A with placebo supplementation to reduce the severity of BPD in extremely preterm infants. METHODS: We conducted a double-blind randomized controlled trial in infants <28 weeks’ gestation who were to receive either enteral water-soluble vitamin A (5000 IU per day) or a placebo. Supplementation was started within 24 hours of introduction of feeds and continued until 34 weeks’ postmenstrual age (PMA). The primary outcome was the severity of BPD, assessed by using the right shift of the pulse oximeter saturation versus the inspired oxygen pressure curve. RESULTS: A total of 188 infants were randomly assigned. The mean ± SD birth weight (852 ± 201 vs 852 ± 211 g) and gestation (25.8 ± 1.49 vs 26.0 ± 1.39 weeks) were comparable between the vitamin A and placebo groups. There was no difference in the right shift (median [25th–75th percentiles]) of the pulse oximeter saturation versus inspired oxygen pressure curve (in kilopascals) between the vitamin A (11.1 [9.5–13.7]) and placebo groups (10.7 [9.5–13.1]) (P = .73). Enteral vitamin A did not affect diagnosis of BPD or other clinical outcomes. Plasma retinol levels were significantly higher in the vitamin A group versus the placebo group on day 28 and at 34 weeks’ PMA. CONCLUSIONS: Enteral water-soluble vitamin A supplementation improves plasma retinol levels in extremely preterm infants but does not reduce the severity of BPD.

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