Submitted on May 25, 2006
Accepted on August 28, 2006
Epithelial Lining Fluid free IGF-1/PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants
Ettore Capoluongo1*, Franco Ameglio1, Paola Lulli1, Angelo Minucci2, Concetta Santonocito1, Paola Concolino1, Enrico Di Stasio1, Simona Boccacci3, Valentina Vendettuoli3, Giuseppe Giuratrabocchetta3, Angela De Cunto3, Milena Tana3, Costantino Romagnoli3, Cecilia Zuppi1, and Giovanni Vento3
1 Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, ROME, Italy, Italy
2 ROME, Italy, Italy; Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, ROME, Italy, Italy
3 Department of Pediatrics, Division of Neonatology, Catholic University of the Sacred Heart, ROME, Italy, Italy
* To whom correspondence should be addressed. E-mail: ecapoluongo{at}rm.unicatt.it.
Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-1 (IGF-1) in sera. They also present higher free IGF-1 concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase which dissociates three binding proteins from the active form of IGF-1, namely free IGF-1.
The present study analyses the ELFs concentrations of free IGF-1, PAPP-A and their ratios in preterm newborns developing or not BPD, defined as O2 dependence at 36 weeks postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without, and 7 with BPD) were analysed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELFs free IGF-1 and decreased PAPP-A concentrations on both days 2 and 4, as compared with newborns without BPD. A not significant trend between these two days was observed for free IGF-1 (increasing) and PAPP-A (decreasing). On the same days, the free IGF-1/PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-1 or PAPP-A, when individually evaluated. A multivariate analysis confirmed the significance for free IGF-1 on day 4, while the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indices of disease severity, such as hours of oxygen administration, days of hospitalisation, and ROP severity scores. Finally, the ratio between ELF free IGF-1 and PAPP-A appears to be a useful marker for lung injury of premature newborns.
