title: Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants.
abstract: 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 O(2) 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.
authors.affiliation: Laboratory of Molecular Biology, Dept. of Biochemistry and Clinical Biochemistry, Catholic University, Largo F. Vito 1, 00168, Rome, Italy. ecapoluongo@rm.unicatt.it
authors.forename: Ettore
authors.initials: E
authors.lastname: Capoluongo
authors.forename: Franco
authors.initials: F
authors.lastname: Ameglio
authors.forename: Paola
authors.initials: P
authors.lastname: Lulli
authors.forename: Angelo
authors.initials: A
authors.lastname: Minucci
authors.forename: Concetta
authors.initials: C
authors.lastname: Santonocito
authors.forename: Paola
authors.initials: P
authors.lastname: Concolino
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Stasio
authors.forename: Simona
authors.initials: S
authors.lastname: Boccacci
authors.forename: Valentina
authors.initials: V
authors.lastname: Vendettuoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giuratrabocchetta
authors.forename: Angela
authors.initials: A
authors.lastname: De Cunto
authors.forename: Milena
authors.initials: M
authors.lastname: Tana
authors.forename: Costantino
authors.initials: C
authors.lastname: Romagnoli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zuppi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vento
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D015999:Multivariate Analysis; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects / Q000379:methods; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy; D014508:Urea / Q000032:analysis / Q000097:blood
chemical_list: D007334:Insulin-Like Growth Factor I; D014508:Urea; D011266:Pregnancy-Associated Plasma Protein-A