Extended Continuous Positive Airway Pressure in Preterm Infants Increases Lung Growth at 6 Months: A Randomized Controlled Trial

Abstract

Rationale: Extended continuous positive airway pressure (eCPAP) in the neonatal ICU (NICU) for stable preterm infants increases lung volumes. Its effect on lung growth after discharge is unknown. Objectives: To assess whether 2 weeks of eCPAP in stable preterm infants is associated with increased alveolar volume (Va) at 6 months corrected age. Methods: This randomized controlled trial was conducted at Oregon Health & Science University. Outpatient assessors were unaware of treatment assignment. One hundred infants were randomized to eCPAP versus CPAP discontinuation (dCPAP) to room air. Measurements and Main Results: The primary outcome was Va by the single breath hold technique at 6 months corrected age. Secondary outcomes included Dl_CO and forced expiratory flows (FEFs). FRC was measured in the NICU. Infants randomized to eCPAP (n = 54) versus dCPAP (n = 46) had the following measurements shown as adjusted mean (SE): Va (500.2 [24.9] vs. 418.1 [23.4] ml; adjusted mean difference, 82.1 [95% confidence interval (CI), 8.3-155.9]; P = 0.033); Dl_CO (3.4 [0.2] vs. 2.8 [0.1] ml/min/mm Hg; adjusted mean difference, 0.6 [95% CI, 0.1-1.1]; P = 0.018); measurement of FEF at 50% of the expired volume (500.6 [18.2] vs. 437.9 [17.9] ml/s; adjusted mean difference, 62.7 [95% CI, 4.5-121.0]; P = 0.039); FEF between 25% and 75% of expired volume (452.0 [17.4] vs. 394.4 [17.4] ml/s; adjusted mean difference, 57.5 [95% CI, 1.3-113.8]; P = 0.046). Conclusions: Infants randomized to eCPAP versus dCPAP had significantly increased Va at 6 months corrected age. Dl_CO and FEFs were also increased. Extending CPAP in stable preterm infants in the NICU may be a nonpharmacologic and safe therapy to promote lung growth. Clinical trial registered with www.clinicaltrials.gov (NCT04295564).

Keywords: airway function; alveolar volume; lung diffusion capacity; nasal continuous positive airway pressure; preterm infants.

Figure 1.

CONSORT diagram for infants in the extended continuous positive airway pressure (eCPAP) study. Screening, enrollment, randomization, and follow-up of infants randomized to eCPAP compared with dCPAP through outpatient testing. For twin pairs allocated in the study, the first twin was randomized and the second twin was assigned to the same treatment arm when CPAP respiratory stability criteria were met. *Withdrawn by the principal investigator after discharge from the neonatal ICU because of diagnosis of a rare ARID1B chromosomal mutation after discharge. dCPAP = discontinuation of continuous positive airway pressure; IUGR = intrauterine growth restriction; PI = principal investigator; PMA = postmenstrual age; Va = alveolar volume.

Figure 2.

FRC measurements in the neonatal ICU. Data are shown as mean ± SE. P values for the difference in FRC at allocation and at the end of the 2-week treatment period are based on generalized multivariable linear mixed models to account for the covariance structure with twin sets and to adjust for gestational age at birth (allocation stratification variable), sex, and length at allocation to treatment arm. *P < 0.01 for comparison at 2 weeks. dCPAP = discontinuation of continuous positive airway pressure; eCPAP = extended continuous positive airway pressure.

Figure 3.

Alveolar volume, Dl_CO, and forced expiratory flows (FEFs) in infants at outpatient testing. (A and B) Data are shown as mean ± SE. P values for the difference in alveolar volume (P = 0.033) and Dl_CO (P = 0.018) between the treatment groups are based on generalized multivariable linear mixed models to account for the correlation between twin pairs and to adjust for gestational age at birth (stratification variable), sex, and length at outpatient testing. Both measurements are obtained from the same lung function maneuver. (C) FEFs in 38 infants assigned to eCPAP and 38 infants assigned to dCPAP. P values for the difference in FEFs between the treatment groups are based on generalized multivariable linear mixed models to account for the correlation between twin pairs and to adjust for gestational age at birth (stratification variable), sex, and length at outpatient testing. dCPAP = discontinuation of continuous positive airway pressure; eCPAP = extended continuous positive airway pressure; FEF_25–75 = FEF between 25% and 75% of the expired volume; FEF₅₀ = FEF at 50% of the expired volume; FEF₇₅ = FEF at 75% of the expired volume.