Perinatal inflammation relates to early respiratory morbidity and lung function at 12 years of age in children born very preterm

Abstract

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.

Lung function deficits and bronchodilator responsiveness at 12 years of age in children born very preterm compared with controls born at term

“…Children born preterm usually do not have an ongoing eosinophilic inflammation in the airways 29 . This was shown in one of our cohorts, where fraction of exhaled NO was normally low (<20 ppb) in 87% of the children and clearly elevated (>35 ppb) in 8% of the children only 18 …”

“…Not only airflow limitation 6,7,14 but also a reduced diffusion capacity, 2,7,18,25 has previously been reported in children born preterm and in young adults with a history of BPD. In this study, a significant reduction in diffusion capacity was seen in children born very preterm, but few children had a DL CO below the lower limit of normal.…”

“…In the first cohort (74 children born 2001–2003), inclusion criteria were gestational age <32 weeks, antenatal consent, and no congenital anomalies 16 . Of these children, 71 children survived until week 36 and 54 came for lung function measurement at 12 years of age 18 …”

Lung function deficits and bronchodilator reversibility at 12 years of age in children born very preterm compared with controls born at term

“…Airflow limitation (6,7) and reduced diffusion capacity (2,7,18,19) , has also previously been reported in children born preterm and in young adults with a history of BPD. In this study, a significant reduction in diffusion capacity was seen in children born very preterm, but few children had a DL CO below the lower limit of normal.…”

Association between ondansetron use and mortality of patients on mechanical ventilation in the intensive care unit: a retrospective cohort study

“…First, ondansetron may reduce excessive inflammatory reactions in the lungs. Inflammation plays a critical role in the need for invasive mechanical ventilation (37), ventilatorinduced lung injury (38)(39)(40), prolonged mechanical ventilation (41,42), and death risk of patients on mechanical ventilation (37,43). Recently, 5-HT 3 receptor antagonists were suggested as important potential agents for regulating inflammation and immune disorders (7).…”