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Aim: Very preterm birth may be associated with lung function impairment later in life. It is not known if this is caused by prematurity per se or by associated perinatal events, such as maternal–foetal inflammation and severity of early neonatal lung disease. We assessed these factors in a prospective cohort of very preterm infants followed from birth to middle school age. Methods: In 71 infants with a gestational age of median 27.4 (range 23.9–31.7) weeks, pro-inflammatory and modulatory cytokines were measured in umbilical cord blood and in arterial blood sampled at 6, 24 and 72 h after birth, and cumulated cytokine concentrations were calculated as area under the curve (AUC). At median 12.6 (range 12.3–13.5) years of age, pulmonary function testing was done in 53 children. Results: There was a positive correlation between days on mechanical ventilation and AUC for IL-6 (p = 0.001), IL-8 (p = 0.015) and IL-10 (p = 0.006). Infants with bronchopulmonary dysplasia (BPD; n = 32) had higher AUC for the cytokines IL-6, IL-8 and IL-10 than those without BPD (all p < 0.01). Higher levels of AUC for IL-6 at birth correlated with lower forced expiratory volume in 1 s (p = 0.030) and lower mean expiratory flow rate between 25 and 75% of forced vital capacity (p = 0.034). Conclusion: Perinatal inflammation, assessed by circulating cytokines in the first three days of life, was associated with BPD and with airway obstruction at 12 years of age. (Less)

Background: Club cell secretory protein (CC16) probably has a role in protecting the lung from inflammation. Aim: To evaluate if low levels of CC16 in gastric fluid at birth, reflecting low levels of CC16 in the lung, would be associated with lung inflammation and respiratory morbidity. Methods: A study of 64 infants with mean gestational age 26.1 weeks. CC16 was analyzed in gastric fluid at birth. CC16, pro-inflammatory cytokines, and MMP-9 were analyzed in tracheal aspirate within 24 h from birth. Results: CC16 in gastric fluid increased with gestational age (P = 0.033). Lower concentrations of CC16 in gastric fluid at birth were associated with higher concentrations of IL-1β (P = 0.028), TNF-α (P = 0.034), and MMP-9 (P = 0.015) in tracheal aspirate. Infants who needed mechanical ventilation at 24 and 72 h of age had lower CC16 in gastric fluid than those not ventilated at these ages (P = 0.011 and P = 0.024, respectively). Lower CC16 in gastric fluid was associated with higher FiO2 at 6 h (P = 0.009), higher PaCO2 at 24 h (P = 0.03), more ventilator days (P = 0.012) and more days with supplemental oxygen (P = 0.03). Infants who had either died or were still treated with supplemental oxygen at 36 weeks postmenstrual age had lower CC16 in gastric fluid than infants with none of these outcomes (P = 0.049). Conclusion: A low CC16 concentration in gastric fluid at birth was associated with increased inflammation in the trachea within the first 24 h of life and with more need for respiratory support in the neonatal period. (Less)