More than half of children who were born very early -- at 25 weeks or less (normal gestation is around 40 weeks) -- have abnormal lung function and are twice as likely as their full-term peers to have a diagnosis of asthma, according to U.K. researchers, who followed a national cohort of extremely preterm infants to age 11.
"Following extremely preterm birth, impaired lung function and increased respiratory morbidity persist into middle childhood, especially those with bronchopulmonary dysplasia," said principal investigator, Janet Stocks, Ph.D., professor of respiratory physiology at the University College London, Institute of Child Health. "Many of these children may not be receiving appropriate treatment."
The research was published online ahead of the print edition of the American Journal of Respiratory and Critical Care Medicine.
The researchers used data from the Medical Research Council-funded EPICure study, which tracked all babies born in the U.K. or Ireland at or below 25 completed weeks' gestation between March and December 1995. The children were assessed for lung function and respiratory health at 2.5, 6 and 11 years of age and compared to age-, gender- and race-matched peers at school who were randomly selected to serve as controls.
"For a variety of reasons, rates of preterm birth are increasing in developed countries," explained Dr. Stocks. "Despite sophisticated medical interventions, we know that preterm birth is often associated with serious respiratory problems. We wanted to look at the longer-term implications of the complications as these children grow up"
Of 307 children who survived to age 11, 182 completed satisfactory baseline spirometry at school, 129 (71 percent) of whom had had bronchopulmonary dysplasia (BPD). In addition to the finding that 56 percent of extremely preterm (EP) children had abnormal baseline spirometry, indicating impaired lung function and that one in four had a diagnosis of asthma, 27 percent had a positive bronchodilator response, indicating that their airway obstruction was at least partially reversible. Furthermore, while nearly two-thirds (65 percent) had not had any respiratory symptoms for the past 12 months, nearly one-half (48 percent) of non-symptomatic EP children had abnormal spirometry results.
"The fact that many EP children were asymptomatic despite lung function impairment reflects the fact that there is considerable lung reserve during middle childhood. As the lungs grow and airway caliber increase, such children will be far less prone to wheezing episodes and will appear to have 'grown out' of their symptoms," explained Dr. Stocks. "However, there is concern that such symptoms may reappear in later life in the form of early onset chronic obstructive lung disease. Even if asymptomatic, those who enter adulthood with impaired lung function will be at increased risk of subsequent chronic lung disease. There is therefore a continuing need to monitor these children for respiratory problems. While we do not yet know what effects EP birth has beyond the age of 11, one can surmise that respiratory problems will likely get worse, not better, and that early monitoring and appropriate treatment could minimize greater problems down the line. Similarly, adult chest physicians need to become more aware of the potential long-term respiratory impact of preterm birth and include neonatal details when taking medical histories."
While medical treatment of preterm infants has vastly improved, the respiratory problems that are associated with extremely preterm birth may be a product of the early birth itself. "In theory, preterm survivors of modern neonatal care, who have been treated with ante-natal steroids and postnatal surfactant and subjected to far gentler ventilatory regimes than in the past, should have far less evidence of airway injury than their predecessors," said Dr. Stocks. "The persistence of airway obstruction in these children is likely multi-factorial in nature, potentially reflecting the impact of extreme preterm birth per se and the vulnerability of such immature lungs even to low ventilatory pressures or oxygen concentrations. It is, however, important to note that amongst the minority (29 percent) of children who survived EP birth without BPD (long-term oxygen dependency), respiratory outcome is encouraging."
Dr. Stocks further noted that "a sizeable proportion of EP children in this study may have benefited from closer surveillance and medication, particularly those with prior BPD." Among the 48 EP children with respiratory symptoms during the past 12 months, 8 (17 percent) had not received any medication. Similarly, of the 33 EP children with prior BPD who, despite being asymptomatic, had evidence of reversible airways obstruction (abnormal spirometry and a positive bronchodilator response) 19 (58 percent) were not receiving any treatment.
"These results indicate that despite improvements in obstetric and neonatal care that have resulted in increased survival of extremely preterm infants, airway obstruction remains a common long-term outcome," she said. "Children born extremely preterm remain at high risk for respiratory morbidity, airway obstruction and increased bronchial responsiveness. There needs to be long term surveillance of this population, and appropriate treatment throughout childhood with a special emphasis on a healthy lifestyle with respect to diet, exercise and smoking prevention in order to preserve available lung function for as long as possible."
- J. Fawke, S. Lum, J. Kirkby, E. Hennessy, N. Marlow, V. Rowell, S. Thomas, J. Stocks. Lung Function and Respiratory Symptoms at 11 Years in Extremely Preterm Children: The EPICure Study. American Journal of Respiratory and Critical Care Medicine, 2010; DOI: 10.1164/rccm.200912-1806OC
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