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Journal of Neonatal-Perinatal Medicine 7 (2014) 101–105 DOI 10.3233/NPM-1476613 IOS Press
Original Research
Cord blood fibroblast growth factor-10 as a possible predictor of bronchopulmonary dysplasia in preterm infants Walid A. Mohameda,b,∗ and Mohamed A. Aseeric a Department
of Pediatrics, Faculty of Medicine, Minia University, Minia, Egypt of Pediatrics, College of Medicine, King Khalid University, Abha, Saudi Arabia c Department of Biochemistry, Abha General Hospital, Abha, Saudi Arabia b Department
Received 22 November 2013 Revised 20 April 2014 Accepted 13 May 2014
Abstract. OBJECTIVE: To evaluate fibroblast growth factor-10 (FGF-10) levels in cord blood as a possible predictor of the subsequent development of bronchopulmonary dysplasia (BPD) in preterm infants. PATIENTS AND METHODS: A total of 269 preterm (≤32 weeks gestation) infants (76 infants developed BPD and 193 had no BPD) were enrolled. FGF-10 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Preterm infants who subsequently developed BPD had significantly lower cord serum levels of FGF-10 than those who did not (p < 0.001). Cord blood levels of FGF-10 were significantly lower in infants with severe BPD than those with moderate or mild disease (p < 0.001). Logistic regression analysis demonstrated that low cord blood FGF-10 level was independently associated with the subsequent risk of BPD (OR = 0.978 [95 % CI: 0.959 – 0.997]; p = 0.02). CONCLUSION: Low cord blood FGF-10 levels may predict the subsequent development of BPD in preterm infants. Keywords: Fibroblast growth factor, bronchopulmonary dysplasia, preterm infants
1. Introduction Bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants, is defined as oxygen dependence with continuing radiologic or clinical evidence of lung disease at 36 weeks postmenstrual age [1, 2]. The pathogenesis of BPD is multifactorial, with contributing factors including oxygen toxicity, barotrauma, inflammation, infection and lung immaturity ∗ Corresponding author: Dr. Walid Abdel Wahab Mohamed, Department of Pediatrics, College of Medicine, King Khalid University, Abha, P.O. Box 641, Saudi Arabia. Tel.: +966 502507894; Fax: +966 72418194; E-mail: [email protected].
[3–5]. Gestational age, birth weight, respiratory distress syndrome (RDS) and mechanical ventilation are known risk factors for BPD development [6]. BPD is associated with increased risk of mortality, growth failure, and neurodevelopmental delay [7]. The rate of BPD among surviving extreme preterm infants has increased in association with the availability of exogenous surfactant therapy for RDS treatment and the resulting improved survival of the most vulnerable babies [8, 9]. Early prediction of BPD has proven challenging. Identification of a predictive marker would provide the chance for both early prevention and possibly a treatment specifically directed at one or
1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
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W.A. Mohamed and M.A. Aseeri / Cord blood fibroblast growth factor-10 and BPD
more steps in the pathophysiologic cascade leading to chronic lung disease [6]. BPD is characterized by abnormal lung development, with arrested saccular airway branching and fewer, larger alveoli. Infants born between 24 and 28 weeks gestation are at high risk of BPD; the lungs of infants at this gestational age are transitioning from the canalicular to the saccular stage of lung development. Although many factors regulating branching morphogenesis of the airways have been identified, less is known about branching during the saccular stage of lung development [10]. Fibroblast growth factor-10 (FGF-10) is expressed by mesenchymal cells and regulates branching morphogenesis during the earliest stages of lung development [11, 12]. FGF-10 promotes elongation and branching of developing airways. Mice lacking either FGF-10 or its receptor FGFR-2 do not develop lungs [13, 14]. Evidence from animal models showed that decreased FGF-10 expression was associated with impaired lung development in chronic lung disease of infancy [15]. The aim of the current study was to evaluate FGF-10 levels in cord blood as a possible marker for predicting the subsequent development of BPD in preterm infants.
2. Patients and methods 2.1. Study design A prospective study was conducted at the neonatal intensive care unit of Abha General Hospital, Saudi Arabia between July 2011 and June 2013. The study was approved by the ethics committee of the Hospital. Written informed consent was obtained for each patient before enrollment. The study included all preterm infants (≤32 weeks gestation) who were consecutively admitted to the NICU. Infants with congenital malformations, developed sepsis within the first 72 hours after birth, whose mothers had preeclampsia, prenatal infection, prolonged rupture of membranes (≥18 hours) or diabetes were excluded from the study. 2.2. Definition of bronchopulmonary dysplasia and respiratory distress syndrome In 2001 the National Institute of Child Health and Human Development defined and classified BPD by gestational age and supplemental oxygen requirement
as preterm infants
Journal of Neonatal-Perinatal Medicine 7 (2014) 101–105 DOI 10.3233/NPM-1476613 IOS Press
Original Research
Cord blood fibroblast growth factor-10 as a possible predictor of bronchopulmonary dysplasia in preterm infants Walid A. Mohameda,b,∗ and Mohamed A. Aseeric a Department
of Pediatrics, Faculty of Medicine, Minia University, Minia, Egypt of Pediatrics, College of Medicine, King Khalid University, Abha, Saudi Arabia c Department of Biochemistry, Abha General Hospital, Abha, Saudi Arabia b Department
Received 22 November 2013 Revised 20 April 2014 Accepted 13 May 2014
Abstract. OBJECTIVE: To evaluate fibroblast growth factor-10 (FGF-10) levels in cord blood as a possible predictor of the subsequent development of bronchopulmonary dysplasia (BPD) in preterm infants. PATIENTS AND METHODS: A total of 269 preterm (≤32 weeks gestation) infants (76 infants developed BPD and 193 had no BPD) were enrolled. FGF-10 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Preterm infants who subsequently developed BPD had significantly lower cord serum levels of FGF-10 than those who did not (p < 0.001). Cord blood levels of FGF-10 were significantly lower in infants with severe BPD than those with moderate or mild disease (p < 0.001). Logistic regression analysis demonstrated that low cord blood FGF-10 level was independently associated with the subsequent risk of BPD (OR = 0.978 [95 % CI: 0.959 – 0.997]; p = 0.02). CONCLUSION: Low cord blood FGF-10 levels may predict the subsequent development of BPD in preterm infants. Keywords: Fibroblast growth factor, bronchopulmonary dysplasia, preterm infants
1. Introduction Bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants, is defined as oxygen dependence with continuing radiologic or clinical evidence of lung disease at 36 weeks postmenstrual age [1, 2]. The pathogenesis of BPD is multifactorial, with contributing factors including oxygen toxicity, barotrauma, inflammation, infection and lung immaturity ∗ Corresponding author: Dr. Walid Abdel Wahab Mohamed, Department of Pediatrics, College of Medicine, King Khalid University, Abha, P.O. Box 641, Saudi Arabia. Tel.: +966 502507894; Fax: +966 72418194; E-mail: [email protected].
[3–5]. Gestational age, birth weight, respiratory distress syndrome (RDS) and mechanical ventilation are known risk factors for BPD development [6]. BPD is associated with increased risk of mortality, growth failure, and neurodevelopmental delay [7]. The rate of BPD among surviving extreme preterm infants has increased in association with the availability of exogenous surfactant therapy for RDS treatment and the resulting improved survival of the most vulnerable babies [8, 9]. Early prediction of BPD has proven challenging. Identification of a predictive marker would provide the chance for both early prevention and possibly a treatment specifically directed at one or
1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
102
W.A. Mohamed and M.A. Aseeri / Cord blood fibroblast growth factor-10 and BPD
more steps in the pathophysiologic cascade leading to chronic lung disease [6]. BPD is characterized by abnormal lung development, with arrested saccular airway branching and fewer, larger alveoli. Infants born between 24 and 28 weeks gestation are at high risk of BPD; the lungs of infants at this gestational age are transitioning from the canalicular to the saccular stage of lung development. Although many factors regulating branching morphogenesis of the airways have been identified, less is known about branching during the saccular stage of lung development [10]. Fibroblast growth factor-10 (FGF-10) is expressed by mesenchymal cells and regulates branching morphogenesis during the earliest stages of lung development [11, 12]. FGF-10 promotes elongation and branching of developing airways. Mice lacking either FGF-10 or its receptor FGFR-2 do not develop lungs [13, 14]. Evidence from animal models showed that decreased FGF-10 expression was associated with impaired lung development in chronic lung disease of infancy [15]. The aim of the current study was to evaluate FGF-10 levels in cord blood as a possible marker for predicting the subsequent development of BPD in preterm infants.
2. Patients and methods 2.1. Study design A prospective study was conducted at the neonatal intensive care unit of Abha General Hospital, Saudi Arabia between July 2011 and June 2013. The study was approved by the ethics committee of the Hospital. Written informed consent was obtained for each patient before enrollment. The study included all preterm infants (≤32 weeks gestation) who were consecutively admitted to the NICU. Infants with congenital malformations, developed sepsis within the first 72 hours after birth, whose mothers had preeclampsia, prenatal infection, prolonged rupture of membranes (≥18 hours) or diabetes were excluded from the study. 2.2. Definition of bronchopulmonary dysplasia and respiratory distress syndrome In 2001 the National Institute of Child Health and Human Development defined and classified BPD by gestational age and supplemental oxygen requirement
as preterm infants
