Date Published: July 19, 2017
Publisher: Public Library of Science
Author(s): Gordon Qin, Jessica W. Lo, Neil Marlow, Sandy A. Calvert, Anne Greenough, Janet L. Peacock, Rory Edward Morty.
Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes.
Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors.
The study included 412 infants born at 23–28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken.
After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26).
Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.
Infants born prematurely usually require respiratory support which, although often essential for survival, can lead to lung damage, prolonged oxygen dependency and chronic respiratory morbidity. The administration of the corticosteroids can improve respiratory function and allow earlier extubation. Systematic review of randomised trials demonstrated that the administration of steroids before seven days facilitated extubation and reduced bronchopulmonary dysplasia (BPD) . Delayed corticosteroid treatment, i.e. after seven days, was also associated with reductions in failure to extubate and BPD . Corticosteroids, however, are linked to adverse neurological effects when given early [1, 3] or late  and linked to inhibited secondary septation .
In the UKOS trial, 797 babies were randomised to either high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) . Five hundred and ninety-two infants survived to hospital discharge; the 412 infants who were seen at two years of age formed this dataset (Fig 1). The UKOS trial and follow-up were approved by the London South Thames Multicentre Research Ethics Committee. Parents gave informed written consent for their infants to take part.
The baseline characteristics of those with and without complete data were similar apart from oxygen dependency at 36 weeks postmenstrual age (PMA) which was commoner in those with complete data, 58% vs 49% (Table 1). This was true in those with and without exposure to postnatal dexamethasone: 82% vs 75% were oxygen dependent at 36 weeks PMA among those exposed compared to 49% vs 39% in the unexposed. Oxygen dependency at 36 weeks PMA was included in both the multivariable analyses and the propensity score matching.
We have shown an association between exposure to early or late postnatal dexamethasone and respiratory hospital readmission. This association was reduced but remained statistically significant after adjustment for neonatal and infant factors and was robust to adjustment using two different statistical approaches. The proportion of infants who had had respiratory admissions increased with the number of courses. The associations with respiratory admissions remained statistically significant after adjustment using propensity score matching. We observed strong correlations between reported respiratory admission and cough, wheeze and use of chest medications, validating the use of respiratory admission as a marker of respiratory morbidity.