Development of lung diffusion to adulthood following extremely preterm birth.

BACKGROUND: Gas exchange in extremely preterm (EP) infants must take place in fetal lungs. Childhood lung diffusing capacity of the lung for carbon monoxide (D LCO) is reduced; however, longitudinal development has not been investigated. We describe the growth of D LCO and its subcomponents to adulthood in EP compared with term-born subjects. METHODS: Two area-based cohorts born at gestational age ≤28 weeks or birthweight ≤1000 g in 1982-1985 (n=48) and 1991-1992 (n=35) were examined twice, at ages 18 and 25 years and 10 and 18 years, respectively, and compared with matched term-born controls. Single-breath D LCO was measured at two oxygen pressures, with subcomponents (membrane diffusion (D M) and pulmonary capillary blood volume (V C)) calculated using the Roughton-Forster equation. RESULTS: Age-, sex- and height-standardised transfer coefficients for carbon monoxide (K CO) and D LCO were reduced in EP compared with term-born subjects, and remained so during puberty and early adulthood (p-values for all time-points and both cohorts ≤0.04), whereas alveolar volume (V A) was similar. Development occurred in parallel to term-born controls, with no signs of pubertal catch-up growth nor decline at age 25 years (p-values for lack of parallelism within cohorts 0.99, 0.65, 0.71, 0.94 and 0.44 for z-D LCO, z-V A, z-K CO, D M and V C, respectively). Split by membrane and blood volume components, findings were less clear; however, membrane diffusion seemed most affected. CONCLUSIONS: Pulmonary diffusing capacity was reduced in EP compared with term-born subjects, and development from childhood to adulthood tracked in parallel to term-born subjects, with no signs of catch-up growth nor decline at age 25 years.

Children Born Preterm at the Turn of the Millennium Had Better Lung Function Than Children Born Similarly Preterm in the Early 1990s.

OBJECTIVE: Compare respiratory health in children born extremely preterm (EP) or with extremely low birthweight (ELBW) nearly one decade apart, hypothesizing that better perinatal management has led to better outcome. DESIGN: Fifty-seven (93%) of 61 eligible 11-year old children born in Western Norway in 1999-2000 with gestational age (GA) <28 weeks or birthweight <1000 gram (EP1999-2000) and matched term-controls were assessed with comprehensive lung function tests and standardized questionnaires. Outcome was compared with data obtained at 10 years of age from all (n = 35) subjects born at GA <29 weeks or birthweight <1001 gram within a part of the same region in 1991-92 (EP1991-1992) and their matched term-controls. RESULTS: EP1999-2000 had significantly reduced forced expiratory flow in 1 second (FEV1), FEV1 to forced vital capacity (FEV1/FVC) and forced expiratory flow between 25-75% of FVC (FEF25-75), with z-scores respectively -0.34, -0.50 and -0.61 below those of the term-control group, and more bronchial hyperresponsiveness to methacholine (dose-response-slope 13.2 vs. 3.5; p<0.001), whereas other outcomes did not differ. Low birthweight z-scores, but not neonatal bronchopulmonary dysplasia (BPD) or low GA, predicted poor outcome. For children with neonatal BPD, important lung-function variables were better in EP1999-2000 compared to EP1991-1992. In regression models, improvements were related to more use of antenatal corticosteroids and surfactant treatment in the EP1999-2000. CONCLUSIONS: Small airway obstruction and bronchial hyperresponsiveness were still present in children born preterm in 1999-2000, but outcome was better than for children born similarly preterm in 1991-92, particularly after neonatal BPD. The findings suggest that better neonatal management not only improves survival, but also long-term pulmonary outcome.

Adult respiratory outcomes of extreme preterm birth. A regional cohort study.

RATIONALE: Lifetime respiratory function after extremely preterm birth (gestational age≤28 wk or birth weight≤1,000 g) is unknown. OBJECTIVES: To compare changes from 18-25 years of age in respiratory health, lung function, and airway responsiveness in young adults born extremely prematurely to that of term-born control subjects. METHODS: Comprehensive lung function investigations and interviews were conducted in a population-based sample of 25-year-old subjects born extremely prematurely in western Norway in 1982-1985, and in matched term-born control subjects. Comparison was made to similar data collected at 18 years of age. MEASUREMENTS AND MAIN RESULTS: At 25 years of age, 46/51 (90%) eligible subjects born extremely prematurely and 39/46 (85%) control subjects participated. z-Scores for FEV1, forced expiratory flow at 25-75% of vital capacity, and FEV1/FVC were significantly reduced in subjects born extremely prematurely by 1.02, 1.26, and 0.88, respectively, and airway resistance (kPa/L/s) was increased (0.23 versus 0.18). Residual volume to total lung capacity increased with severity of neonatal bronchopulmonary dysplasia. Responsiveness to methacholine (dose-response slope; 3.16 versus 0.85) and bronchial lability index (7.5 versus 4.8%) were increased in subjects born extremely prematurely. Lung function changes from 18 to 25 years and respiratory symptoms were similar in the prematurely born and term-born groups. CONCLUSIONS: Lung function in early adult life was in the normal range in the majority of subjects born extremely prematurely, but methacholine responsiveness was more pronounced than in term-born young adults, suggesting a need for ongoing pulmonary monitoring in this population.

Pulmonary gas transfer in children and adolescents born extremely preterm.

In extremely preterm-born infants, gas exchange takes place in developmentally fetal lungs, disturbing normal acinar growth and differentiation, potentially with long term negative consequences for lung function. The aim was to compare alveolar function in children and adolescents born extremely preterm and at term by measuring diffusing capacity of the lung for carbon monoxide (DLCO). Since this procedure may be challenging for subjects with shortcomings often seen after extremely preterm birth, we also assessed the reproducibility of the method. DLCO and DLCO adjusted for lung volume (KCO) were measured twice within 2 weeks in two population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g, aged 10.6 years (n = 35) and 17.7 years (n = 46), and in 81 term-born controls individually matched for sex, age and place of birth. Reproducibility of DLCO measurements was in the same range for preterm and term-born children and young adults, and coefficients of variation were below 10% for all subgroups. KCO was significantly reduced with 7.9% and 7.2% for the oldest and youngest preterm birth cohorts, respectively. Reproducibility of DLCO in children and young adults born extremely preterm was adequate. DLCO and KCO were modestly reduced, supporting recent reports suggesting continuing alveolar growth throughout childhood.