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

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.