Predictive value of increased C-reactive protein levels in preterm infants on respiratory function at five to six years of age

Abstract Background Chronic lung disease in very low birthweight infants involves complex, inflammation-driven lung injury. This study aimed to assess whether C-reactive protein levels during the first 28 days of life predict lung function at five to six years of age. Methods In this multicentre observational study, infants with a birthweight below 1500 grams and born between 2009 and 2015 were included. A C-reactive protein concentration above 10 mg/L was considered elevated. Recurrent elevations were defined as at least two values above this threshold separated by 14 days or more, with an interim decrease below 5 mg/L. Lung function was assessed by spirometry and running endurance at school age. Analyses included univariate tests and linear regression models adjusted for relevant risk factors. Results Here we show that among 268 infants with a median gestational age of 27.6 (25.7–29.4) weeks, those with recurrent C-reactive protein elevations had higher rates of bronchopulmonary dysplasia (56.3% versus 29.4%, p < 0.027) and a greater proportion of children with forced expiratory volume in one second below the fifth percentile (71.9% versus 61.8%, p < 0.001), and reduced running endurance. Recurrent elevations showed a high positive predictive value (71.9%) but low sensitivity (20.2%) for detecting severely reduced lung function. Conclusions The absence of recurrent C-reactive protein elevations in the neonatal period is associated with better long-term pulmonary outcomes and physical performance. These findings suggest that early inflammatory activity contributes to adverse lung development and support incorporating inflammatory biomarkers into multivariable models for early risk stratification.