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Am J Physiol Endocrinol Metab 292: E308-E313, 2007. First published September 5, 2006; doi:10.1152/ajpendo.00251.2006
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Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

Ettore Capoluongo,1,2 Franco Ameglio,1 Paola Lulli,1 Angelo Minucci,1 Concetta Santonocito,1 Paola Concolino,1 Enrico Di Stasio,1 Simona Boccacci,3 Valentina Vendettuoli,3 Giuseppe Giuratrabocchetta,3 Angela De Cunto,3 Milena Tana,3 Costantino Romagnoli,3 Cecilia Zuppi,1 and Giovanni Vento3

1Institute of Biochemistry and Clinical Biochemistry and 2International Scientific Institute "Paolo VI" Catholic University of the Sacred Heart and 3Division of Neonatology, Department of Pediatrics, Catholic University of the Sacred Heart, Rome, Italy

Submitted 25 May 2006 ; accepted in final form 28 August 2006

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O2 dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

insulin-like growth factor I; pregnancy-associated plasma protein-A


Address for reprint requests and other correspondence: E. Capoluongo, Laboratory of Molecular Biology, Dept. of Biochemistry and Clinical Biochemistry, Catholic University, Largo F. Vito 1, 00168, Rome, Italy (e-mail: ecapoluongo{at}rm.unicatt.it)






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