Research Article: Exploring clinical, echocardiographic and molecular biomarkers to predict bronchopulmonary dysplasia

Date Published: March 6, 2019

Publisher: Public Library of Science

Author(s): Maria Alvarez-Fuente, Laura Moreno, Paloma Lopez-Ortego, Luis Arruza, Alejandro Avila-Alvarez, Marta Muro, Enrique Gutierrez, Carlos Zozaya, Gema Sanchez-Helguera, Dolores Elorza, Andrea Martinez-Ramas, Gema Villar, Carlos Labrandero, Lucia Martinez, Teresa Casado, Irene Cuadrado, Maria Jesus del Cerro, James West.


Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in childhood, related to prematurity, and the most common cause of pulmonary hypertension (PH) secondary to pulmonary disease in children. Moderate and severe BPD have a worse outcome and relate more frequently with PH. The prediction of moderate or severe BPD development in extremely premature newborns is vital to implement preventive strategies. Starting with the hypothesis that molecular biomarkers were better than clinical and echocardiographic factors, this study aims to explore the ability of clinical, echocardiographic and analytical variables to predict moderate or severe BPD in a cohort of extremely preterm infants.

We designed a prospective longitudinal study, in which we followed a cohort of preterm newborns (gestational age <28 weeks and weight ≤ 1250 grams). In these newborns we recorded weekly clinical and echocardiographic variables as well as blood and tracheal aspirate samples, to analyze molecular biomarkers (IL-6, IL-1, IP10, uric acid, HGF, endothelin-1, VEGF, CCL5). Variables and samples were collected since birth up to week 36 (postmenstrual age), time-point at which the diagnosis of BPD is established. We included 50 patients with a median gestational age of 26 weeks (IQR 25–27) and weight of 871 g (SD 161,0) (range 590-1200g). Three patients were excluded due to an early death. Thirty-five patients (74.5%) developed BPD (mild n = 14, moderate n = 15, severe n = 6). We performed a logistic regression in order to identify risk factors for moderate or severe BPD. We compared two predictive models, one with two variables (mechanical ventilation and inter-ventricular septum flattening), and another-one with an additional molecular biomarker (ET-1). The combination of clinical and echocardiographic variables is a valuable tool for determining the risk of BPD. We find the two variable model (mechanical ventilation and echocardiographic signs of PH) more practical for clinical and research purposes. Future research on BPD prediction should be oriented to explore the potential role of ET-1.

Partial Text

Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease in childhood and one of the most frequent sequel of prematurity [1]. The prevalence of BPD in very low birth weight infants (VLBWI) ranges between 15% and 50%, and is inversely related to birth weight and gestational age (GA) [2, 3].

The study was approved by the ethical committee of all participating hospitals (Hospital La Paz, Hospital Clinico (14/545-E), Hospital de Getafe, Hospital Puerta de Hierro and Complejo Hospitalario de Coruña (2015/001)). The hospital responsible was La Paz with the following approval number PI-1774. Written consent was obtained from all participants´ parents.

Fifty ELGAN were included between November 2014 and November 2016 (recruitment flow chart is available in Fig 1).

Our study shows that a very simple predictive model composed of 2 variables (MV and echocardiographic signs of PH), is able to predict moderate or severe BPD, with a reasonable sensibility and specificity. We also found that the addition of plasma ET-1 (a pathway not yet well explored in BPD), to that model, improved the predictive value.




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