Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely

Abstract

The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age. One hundred and seventy-nine children born at a mean gestational age of 26.9 (range 23–28) weeks were assessed at 11 to 14 years; 50 had received postnatal dexamethasone. Forced expiratory flow at 75% (FEF75), 50%, 25% and 25–75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes including total lung capacity and residual volume were assessed. Lung function outcomes were compared between children who had and had not been exposed to dexamethasone after adjustment for neonatal factors using linear mixed effects regression. After adjustment for confounders all the mean spirometry results were between 0.38 and 0.87 standard deviations lower in those exposed to dexamethasone compared to the unexposed. For example, the mean FEF75 z-score was 0.53 lower (95% CI 0.21 to 0.85). The mean lung function was lower as the number of courses of dexamethasone increased. In conclusion, postnatal dexamethasone exposure was associated with lower mean lung function at school age in children born extremely prematurely. Our results suggest the larger the cumulative dose the greater the adverse effect on lung function at follow-up.

Lung function and respiratory outcomes in teenage boys and girls born very prematurely

“…In addition, analysis of amniotic samples taken from 164 pregnant women with no maternal or fetal abnormalities demonstrated that the lecithin to sphingomyelin ratios reached phospholipid maturity at 33.7 weeks in female fetuses compared with 35.1 weeks in male fetuses . A further explanation for our results are that the males were more likely to be exposed to postnatal steroids which we have shown has a detrimental long term effect on lung function …”

“…31 A further explanation for our results are that the males were more likely to be exposed to postnatal steroids which we have shown has a detrimental long term effect on lung function. 32 The EPICURE follow-up study showed that lung function did not differ significantly between boys and girls at 10 to 12 years of age. 33 The majority of children included, however, had not been routinely exposed to antenatal steroids or postnatal surfactant.…”

Postnatal dexamethasone exposure and lung function in adolescents born very prematurely

“…Studies in animal models, however, have shown that postnatal corticosteroid administration can alter the lung development, resulting in delayed alveolarisation and emphysematous lungs with fewer air spaces [ 3 ]. We have previously reported that within the United Kingdom Oscillation Study (UKOS) cohort [ 4 ], postnatal dexamethasone exposure was associated with poorer respiratory outcomes at two years of age [ 5 ] and poorer lung function at 11 to 14 years of age in a dose dependent manner [ 6 ].…”

A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice

“…On the other hand, epidemiologic studies associate early and late postnatal administration of dexamethasone to preterm infants with a higher risk for prolonged hospitalization and poor lung function later in life. 96,97 Similarly, prenatal dexamethasone treatment in rats was found to impair alveolarization after birth. [98][99][100] These findings are in line with our results linking exposure to high maternal stress perception, and thus to excessive glucocorticoid levels, in midgestation with impaired lung development and maturation.…”