http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(2): 131–133 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.906575
ORIGINAL ARTICLE
Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Connecticut on 04/01/15 For personal use only.
Senem Alkan, Esra Arun Ozer, Ozkan Ilhan, Sumer Sutcuoglu, and Mansur Tatli Department of Neonatology, Tepecik Training and Research Hospital, Yenisehir, Izmir, Turkey
Abstract
Keywords
Background: It is suggested that there may be expanded use of surfactant replacement for the neonatal diseases such as meconium aspiration syndrome (MAS), pneumonia and possibly bronchopulmonary dysplasia (BPD). Objective: To evaluate the characteristics and short-term outcome of the neonates given exogenous surfactant because of the diseases other than respiratory disease syndrome (RDS). Methods: This retrospective study included 35 neonates admitted to the neonatal intensive care unit from January 2012 to December 2012 for an expanded use of surfactant. Data related to gestational age, birth weight, gender and perinatal risk factors were obtained from the patients’ records. The short-term prognosis was also noted. Results: The diagnosis was sepsis in 16 patients, eight MAS, seven transient tachypnea of the newborns (TTN) and four BPD. Mean gestational age was 35.6 ± 4.5 weeks and mean birth weight was 2661 ± 981 g. Of overall cases, 65% were boys and 35% girls. The mortality rate was 17%. Of six fatal cases, three was with BPD, two with sepsis and one with MAS. Conclusion: We think that surfactant replacement may be life saver in the neonatal diseases other than RDS such as BPD, MAS and sepsis by rapidly improving oxygenation. Further investigation is necessary to validate the significance of expanded use of surfactant.
Mortality, newborn, respiratory distress, surfactant History Received 30 December 2013 Accepted 16 March 2014 Published online 9 April 2014
Introduction
Materials and methods
Pulmonary surfactant is a lipid–protein complex that forms a layer between the terminal airways/alveolar surfaces and the alveolar gas [1]. Efficacy of exogenous surfactant in the prevention and treatment of respiratory distress syndrome (RDS) has been well-documented in preterm babies. Reduced mortality rates and improved short-term respiratory status for preterm infants with surfactant-deficiency respiratory distress have been confirmed [2]. Apart from RDS, other neonatal lung diseases such as meconium aspiration syndrome (MAS), pneumonia, bronchopulmonary dysplasia (BPD) are characterized by inactivated or dysfunctional pulmonary surfactant. However, the efficacy of pulmonary surfactant replacement therapy for non-RDS lung diseases remains controversial. The aim of this retrospective study was to evaluate and define clinical characteristics of newborn infants in neonatal intensive care unit (NICU) who received surfactant treatment for non-RDS lung diseases.
Study design
Address for correspondence: Esra Arun Ozer, MD, Department of Neonatology, Tepecik Training and Research Hospital, Yenisehir, Izmir, Turkey. Fax: +90 232 4330756. E-mail: [email protected]
We conducted a retrospective study including newborn infants who received surfactant because of non-RDS lung diseases from January 2012 to December 2012. The hospital files and electronic medical records of the patients were evaluated. Clinical data Maternal data included major medical and obstetric diseases. Neonatal data included gestational age (according to last menstrual period), post-natal age, birth weight, gender, type of delivery, post-natal age of surfactant treatment (timing), the duration of supplemental oxygen and frequency of surfactant treatment. Diagnostic criteria for the lung diseases were as follows: (1) Transient tachypnea of the newborn (TTN): The criteria for the diagnosis of TTN were presence of tachypnea (respiratory rate460 breaths/min) and need of supplemental oxygen for at least 6 h, associated with a radiological pattern compatible with the diagnosis of TTN. (2) Meconium aspiration syndrome (MAS): Respiratory distress in an infant born through meconium-stained amniotic fluid whose respiratory and radiological signs cannot be otherwise explained. (3) Pneumonia: The presence of clinical signs of
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Connecticut on 04/01/15 For personal use only.
132
S. Alkan et al.
J Matern Fetal Neonatal Med, 2015; 28(2): 131–133
respiratory distress, supplemental oxygen and/or positive pressure ventilation (PPV) requirement, extrapulmonary clinical signs of sepsis, typical chest X-ray findings in the presence of any suspected/proven infection such as elevated or decreased leukocyte count, elevated serum C-reactive protein (CRP) level or positive blood or tracheal aspirate culture. (4) Bronchopulmonary dysplasia (BPD): Infants who require supplemental oxygen for at least 28 post-natal days and its severity is graded according to the oxygen concentration and positive pressure of respiratory support at near term [3]. Pulmonary hypertension was defined as elevated right ventricular and pulmonary artery pressure leading to rightto-left ductal or foramen shunt detected by echocardiography, a routine procedure in our NICU for the patients suffering from severe respiratory failure. Surfactant was prepared according to the methods described in a published trial and administrated at a dose of 100 mg/kg [4]. Beractant (SurvantaÕ , Abbott Laboratories, Abbott Park, IL) was used for all patients. Surfactants were administered to the babies if the FiO2 levels higher than 60% or low oxygenation index. Term cases with congenital anomalies incompatible for life were excluded. The primary outcome was death and secondary outcome was duration of the oxygen support. The research protocol was fully approved by local ethics committee. Statistical analysis Statistical data were analyzed by using the Statistical Package for the Social Sciences (SPSS) 15.0 software (SPSS Inc., Chicago, IL). Continuous variables were compared by using Mann–Whitney U-test. Categorical variables were analyzed by Chi-square test or Fisher’s exact test. A p value of 50.05 was accepted as statistically significant.
The effects of exogenous surfactant on mortality in newborns with respiratory disorders are evaluated in Table 2. Although it was not statistically significant, the gestational age was lower in non-survivors. The birth weight was significantly higher in survivors. All non-survivors were boys, however, gender was statistically insignificant. The surfactant treatment was administered more frequent to the non-survivors than survivors.
Discussion By 1990, exogenous surfactant was widely used throughout the developed world, and many large clinical trials have been conducted since then to refine and improve surfactant treatment and prevention of RDS. These trials have focused on the treatment of RDS in preterm babies. It is becoming increasingly clear that there are surfactant abnormalities in other respiratory disorders affecting infants which might, therefore, be amenable to surfactant treatment. The aim of this retrospective study is to evaluate the effects of surfactant treatment on mortality in patients with non-RDS lung diseases. The most indication of the study for surfactant treatment was sepsis/pneumonia. The surfactant system is impaired in pneumonia. There is reduction in surfactant activity due to injury to the type 2 pneumocytes [5]. Increased surface tension associated with reduced levels of surfactant protein A, lipids, lecithin/sphingomyelin ratio and phosphatidylglycerol has been demonstrated in pneumonia [6]. There is limited and mixed experience of surfactant treatment in infants with pneumonia. The exogenous surfactant administration resulted in an initial significant oxygenation improvement, but the
Results During the one-year period, 2250 infants were hospitalized in our NICU. Of those, 35 infants (1.55%) received surfactant replacement therapy for severe non-RDS lung disease. Demographic characteristics of the patients are given in Table 1. There were 16 infants with pneumonia, eight infants with MAS, seven infants with TTN and four infants with BPD. Pulmoner air leak syndrome was not seen whereas pulmonary hemorrhage occurred in three infants with BPD. Six patients died with a mortality rate of 17.1%. Mortality rate was higher in patients with BPD. All patients with TTN survived (Figure 1). Table 1. Demographic and patient characteristics (n ¼ 35).
*Data are presented as mean ± standard deviation.
Table 2. The effects of exogenous surfactant on mortality in newborns with respiratory disorders. Survivors (n ¼ 29)
Patient characteristics Gestational age (weeks)* Birth weight (g)* Gender (Male/female) Type of delivery (Normal/cesarean section) Postnatal age of surfactant treatment (day)* Frequency of surfactant treatment* Duration of oxygen support (day)* Mortality, n (%)
Figure 1. The respiratory diseases and survival of the patients received surfactant treatment.
35.6 ± 4.5 2661 ± 981 23/12 26/9 4.9 ± 9.7 2.1 ± 1.4 19.1 ± 22.2 6 (17)
Gestational age (weeks)* 37.2 ± 2.9 Birth weight (g)* 2952 ± 755 Gender (Male/female) 17/12 Type of delivery (Normal/ 23/6 cesarean section) Postnatal age of surfactant 4.5 ± 9.5 treatment (day)* Frequency of surfactant treatment* 1.9 ± 1.4 Duration of oxygen support (day)* 15.8 ± 20.7 *Data are presented as mean ± standard deviation.
Non-survivors (n ¼ 6)
p
32.6 ± 6.7 1841 ± 1047 6/0 3/3
0.11 0.02 0.052 0. 13
6.8 ± 11.6
0.74
3±1 34.6 ± 28.5
0.03 0.27
Expanded use of surfactant in newborns
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Connecticut on 04/01/15 For personal use only.
DOI: 10.3109/14767058.2014.906575
inspired oxygen concentration was back to baseline within 12 h. Gortner et al. [7] reported that, of the 15 infants with congenital pneumonia treated with surfactant, 10 died (four due to respiratory failure). In our study group, survival rate was higher in patients with pneumonia/sepsis. Animal models of meconium aspiration demonstrate inactivation of surfactants with increased surface tension and decreased lung volume, compliance and oxygenation [8,9]. Uncontrolled studies of surfactant treatment in infants with MAS suggest that surfactant may be of benefit in MAS. In a pilot study of seven infants with MAS treated with surfactant, all seven infants demonstrated an improvement in respiratory failure [10]. It is suggested that in infants with MAS leading to moderate to severe respiratory failure, surfactant administration will decrease the number of infants treated with extracorporeal membrane oxygenation [11]. TTN is a common cause of respiratory distress in early neonatal period. It has been attributed to delayed resorption of fetal alveolar fluid. However, evidence has been accumulated that the syndrome results from mild immaturity of the surfactant system [12]. Surfactant abnormality may be considered as a primary problem in TTN, as suggested by James et al. [13]. Machado et al. [14] demonstrated that term infants with TTN had impaired surfactant function. In our study group, seven patients with TTN survived. BPD is the most prevalent long-term morbidity in surviving preterm infants and linked to increased risk of reactive airways disease, pulmonary hypertension, post-neonatal mortality and adverse neurodevelopmental outcomes [15]. The prolonged exposure of infants with BPD to increased inspired oxygen concentrations can result in alterations in type 2 pneumocyte function and impaired surfactant biosynthesis via oxidant-induced lung injury [16]. There continues to be ongoing research into late surfactant replacement therapy. A pilot trial administered 2 or 3 booster doses of surfactant to a total of 87 infants who were ventilated at 7–10 days [17]. These doses were safe and transiently improved respiratory status as well as composition and function of endogeneous surfactant. However, there was no significant difference in the proportion of survivors without BPD with an increased number of late doses. Preliminary evidence suggests exogenous surfactant can at least temporarily improve the respiratory status of infants with ongoing oxygen dependency [18]. In the present study, three out of four newborns with BPD died. Although the number of patients is limited, we think that surfactant administration is of no significance on mortality in BPD. The retrospective nature of our study has known limitations. The present study was performed in a single unit and patient inclusion was based on the need for surfactant treatment. In addition, we are unable to compare the study group with controls who were treated without surfactant treatment. In conclusion, surfactant treatment may be of significant benefit in late preterm infants with serious respiratory distress
133
secondary to a number of diseases. However, the best preparation, technique and optimal timing and dose of administration are not so clear in these neonates. Additional randomized, controlled studies and evidence-based guidelines are needed for optimal surfactant treatment in neonatal respiratory disorders other than respiratory distress syndrome.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
References 1. Jobe A. Surfactant treatment for respiratory distress syndrome. Respir Care 1986;31:9. 2. Engle WA. American Academy of Pediatrics Committee on Fetus and Newborn. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;121: 419–33. 3. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723–9. 4. Enhorning G, Shennan A, Possmayer F, et al. Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial. Pediatrics 1985;76:145–53. 5. Stinson SF, Ryan DP, Hertweck MS, et al. Epithelial and surfactant changes in influenza pulmonary lesions. Arch Pathol Lab Med 1976;100:147–53. 6. Baughman RP, Sternberg RI, Hull W, et al. Decreased surfactant protein A in patients with bacterial pneumonia. Am Rev Respir Dis 1993;147:653–7. 7. Gortner L, Pohlandt F, Bartmann P. Effect of bovine surfactant in very low birthweight premature infants with congenital pneumonia. Monatsschr Kinderheilkd 1990;138:274–8. 8. Chen CT, Toung TJK, Rogers MC. Effect of intraalveolar meconium on intraalveolar meconium on pulmonary surface tension properties. Crit Care Med 1985;13:233–6. 9. Davey AM, Becker JD, Davis JM. Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model. Pediatr Pulmonol 1993;16:101–8. 10. Auten RL, Notter RH, Kendig JW, et al. Surfactant treatment of full-term newborns with respiratory failure. Pediatrics 1991;87: 101–7. 11. El Shahed AI, Dargaville P, Ohlsson A, Soll RF. Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 2007;CD002054. 12. Gross TL, Sokol RJ, Kwong MS, et al. Transient tachypnea of the newborn: the relationship to preterm delivery and significant neonatal morbidity. Am J Obstet Gynecol 1983;146:236–41. 13. James DK, Chiswick ML, Harkes A, et al. Non-specificity of surfactant deficiency in neonatal respiratory disorders. Br Med J 1984;288:1635–8. 14. Machado LU, Fiori HH, Baldisserotto M, et al. Surfactant deficiency in transient tachypnea of the newborn. J Pediatr 2011; 159:750–4. 15. Ghanta S, Leeman KT, Christou H. An update on pharmacologic approaches to bronchopulmonary dysplasia. Semin Perinat 2013; 37:115–23. 16. LaCagnin LB, Bowman L, Ma JYC, Miles PR. Metabolic changes in alveolar type II cells after exposure to hydrogen peroxide. Am J Physiol 1990;259:L57–65. 17. Merrill JD, Ballard PL, Courtney SE, et al. Pilot trial of late booster doses of surfactant for ventilated premature infants. J Perinatol 2011;31:599–606. 18. Pandit PB, Dunn MS, Kelly EN, Perlman M. Surfactant replacement in neonates with early chronic lung disease. Pediatrics 1995; 95:851–4.
ORIGINAL ARTICLE
Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Connecticut on 04/01/15 For personal use only.
Senem Alkan, Esra Arun Ozer, Ozkan Ilhan, Sumer Sutcuoglu, and Mansur Tatli Department of Neonatology, Tepecik Training and Research Hospital, Yenisehir, Izmir, Turkey
Abstract
Keywords
Background: It is suggested that there may be expanded use of surfactant replacement for the neonatal diseases such as meconium aspiration syndrome (MAS), pneumonia and possibly bronchopulmonary dysplasia (BPD). Objective: To evaluate the characteristics and short-term outcome of the neonates given exogenous surfactant because of the diseases other than respiratory disease syndrome (RDS). Methods: This retrospective study included 35 neonates admitted to the neonatal intensive care unit from January 2012 to December 2012 for an expanded use of surfactant. Data related to gestational age, birth weight, gender and perinatal risk factors were obtained from the patients’ records. The short-term prognosis was also noted. Results: The diagnosis was sepsis in 16 patients, eight MAS, seven transient tachypnea of the newborns (TTN) and four BPD. Mean gestational age was 35.6 ± 4.5 weeks and mean birth weight was 2661 ± 981 g. Of overall cases, 65% were boys and 35% girls. The mortality rate was 17%. Of six fatal cases, three was with BPD, two with sepsis and one with MAS. Conclusion: We think that surfactant replacement may be life saver in the neonatal diseases other than RDS such as BPD, MAS and sepsis by rapidly improving oxygenation. Further investigation is necessary to validate the significance of expanded use of surfactant.
Mortality, newborn, respiratory distress, surfactant History Received 30 December 2013 Accepted 16 March 2014 Published online 9 April 2014
Introduction
Materials and methods
Pulmonary surfactant is a lipid–protein complex that forms a layer between the terminal airways/alveolar surfaces and the alveolar gas [1]. Efficacy of exogenous surfactant in the prevention and treatment of respiratory distress syndrome (RDS) has been well-documented in preterm babies. Reduced mortality rates and improved short-term respiratory status for preterm infants with surfactant-deficiency respiratory distress have been confirmed [2]. Apart from RDS, other neonatal lung diseases such as meconium aspiration syndrome (MAS), pneumonia, bronchopulmonary dysplasia (BPD) are characterized by inactivated or dysfunctional pulmonary surfactant. However, the efficacy of pulmonary surfactant replacement therapy for non-RDS lung diseases remains controversial. The aim of this retrospective study was to evaluate and define clinical characteristics of newborn infants in neonatal intensive care unit (NICU) who received surfactant treatment for non-RDS lung diseases.
Study design
Address for correspondence: Esra Arun Ozer, MD, Department of Neonatology, Tepecik Training and Research Hospital, Yenisehir, Izmir, Turkey. Fax: +90 232 4330756. E-mail: [email protected]
We conducted a retrospective study including newborn infants who received surfactant because of non-RDS lung diseases from January 2012 to December 2012. The hospital files and electronic medical records of the patients were evaluated. Clinical data Maternal data included major medical and obstetric diseases. Neonatal data included gestational age (according to last menstrual period), post-natal age, birth weight, gender, type of delivery, post-natal age of surfactant treatment (timing), the duration of supplemental oxygen and frequency of surfactant treatment. Diagnostic criteria for the lung diseases were as follows: (1) Transient tachypnea of the newborn (TTN): The criteria for the diagnosis of TTN were presence of tachypnea (respiratory rate460 breaths/min) and need of supplemental oxygen for at least 6 h, associated with a radiological pattern compatible with the diagnosis of TTN. (2) Meconium aspiration syndrome (MAS): Respiratory distress in an infant born through meconium-stained amniotic fluid whose respiratory and radiological signs cannot be otherwise explained. (3) Pneumonia: The presence of clinical signs of
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Connecticut on 04/01/15 For personal use only.
132
S. Alkan et al.
J Matern Fetal Neonatal Med, 2015; 28(2): 131–133
respiratory distress, supplemental oxygen and/or positive pressure ventilation (PPV) requirement, extrapulmonary clinical signs of sepsis, typical chest X-ray findings in the presence of any suspected/proven infection such as elevated or decreased leukocyte count, elevated serum C-reactive protein (CRP) level or positive blood or tracheal aspirate culture. (4) Bronchopulmonary dysplasia (BPD): Infants who require supplemental oxygen for at least 28 post-natal days and its severity is graded according to the oxygen concentration and positive pressure of respiratory support at near term [3]. Pulmonary hypertension was defined as elevated right ventricular and pulmonary artery pressure leading to rightto-left ductal or foramen shunt detected by echocardiography, a routine procedure in our NICU for the patients suffering from severe respiratory failure. Surfactant was prepared according to the methods described in a published trial and administrated at a dose of 100 mg/kg [4]. Beractant (SurvantaÕ , Abbott Laboratories, Abbott Park, IL) was used for all patients. Surfactants were administered to the babies if the FiO2 levels higher than 60% or low oxygenation index. Term cases with congenital anomalies incompatible for life were excluded. The primary outcome was death and secondary outcome was duration of the oxygen support. The research protocol was fully approved by local ethics committee. Statistical analysis Statistical data were analyzed by using the Statistical Package for the Social Sciences (SPSS) 15.0 software (SPSS Inc., Chicago, IL). Continuous variables were compared by using Mann–Whitney U-test. Categorical variables were analyzed by Chi-square test or Fisher’s exact test. A p value of 50.05 was accepted as statistically significant.
The effects of exogenous surfactant on mortality in newborns with respiratory disorders are evaluated in Table 2. Although it was not statistically significant, the gestational age was lower in non-survivors. The birth weight was significantly higher in survivors. All non-survivors were boys, however, gender was statistically insignificant. The surfactant treatment was administered more frequent to the non-survivors than survivors.
Discussion By 1990, exogenous surfactant was widely used throughout the developed world, and many large clinical trials have been conducted since then to refine and improve surfactant treatment and prevention of RDS. These trials have focused on the treatment of RDS in preterm babies. It is becoming increasingly clear that there are surfactant abnormalities in other respiratory disorders affecting infants which might, therefore, be amenable to surfactant treatment. The aim of this retrospective study is to evaluate the effects of surfactant treatment on mortality in patients with non-RDS lung diseases. The most indication of the study for surfactant treatment was sepsis/pneumonia. The surfactant system is impaired in pneumonia. There is reduction in surfactant activity due to injury to the type 2 pneumocytes [5]. Increased surface tension associated with reduced levels of surfactant protein A, lipids, lecithin/sphingomyelin ratio and phosphatidylglycerol has been demonstrated in pneumonia [6]. There is limited and mixed experience of surfactant treatment in infants with pneumonia. The exogenous surfactant administration resulted in an initial significant oxygenation improvement, but the
Results During the one-year period, 2250 infants were hospitalized in our NICU. Of those, 35 infants (1.55%) received surfactant replacement therapy for severe non-RDS lung disease. Demographic characteristics of the patients are given in Table 1. There were 16 infants with pneumonia, eight infants with MAS, seven infants with TTN and four infants with BPD. Pulmoner air leak syndrome was not seen whereas pulmonary hemorrhage occurred in three infants with BPD. Six patients died with a mortality rate of 17.1%. Mortality rate was higher in patients with BPD. All patients with TTN survived (Figure 1). Table 1. Demographic and patient characteristics (n ¼ 35).
*Data are presented as mean ± standard deviation.
Table 2. The effects of exogenous surfactant on mortality in newborns with respiratory disorders. Survivors (n ¼ 29)
Patient characteristics Gestational age (weeks)* Birth weight (g)* Gender (Male/female) Type of delivery (Normal/cesarean section) Postnatal age of surfactant treatment (day)* Frequency of surfactant treatment* Duration of oxygen support (day)* Mortality, n (%)
Figure 1. The respiratory diseases and survival of the patients received surfactant treatment.
35.6 ± 4.5 2661 ± 981 23/12 26/9 4.9 ± 9.7 2.1 ± 1.4 19.1 ± 22.2 6 (17)
Gestational age (weeks)* 37.2 ± 2.9 Birth weight (g)* 2952 ± 755 Gender (Male/female) 17/12 Type of delivery (Normal/ 23/6 cesarean section) Postnatal age of surfactant 4.5 ± 9.5 treatment (day)* Frequency of surfactant treatment* 1.9 ± 1.4 Duration of oxygen support (day)* 15.8 ± 20.7 *Data are presented as mean ± standard deviation.
Non-survivors (n ¼ 6)
p
32.6 ± 6.7 1841 ± 1047 6/0 3/3
0.11 0.02 0.052 0. 13
6.8 ± 11.6
0.74
3±1 34.6 ± 28.5
0.03 0.27
Expanded use of surfactant in newborns
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Connecticut on 04/01/15 For personal use only.
DOI: 10.3109/14767058.2014.906575
inspired oxygen concentration was back to baseline within 12 h. Gortner et al. [7] reported that, of the 15 infants with congenital pneumonia treated with surfactant, 10 died (four due to respiratory failure). In our study group, survival rate was higher in patients with pneumonia/sepsis. Animal models of meconium aspiration demonstrate inactivation of surfactants with increased surface tension and decreased lung volume, compliance and oxygenation [8,9]. Uncontrolled studies of surfactant treatment in infants with MAS suggest that surfactant may be of benefit in MAS. In a pilot study of seven infants with MAS treated with surfactant, all seven infants demonstrated an improvement in respiratory failure [10]. It is suggested that in infants with MAS leading to moderate to severe respiratory failure, surfactant administration will decrease the number of infants treated with extracorporeal membrane oxygenation [11]. TTN is a common cause of respiratory distress in early neonatal period. It has been attributed to delayed resorption of fetal alveolar fluid. However, evidence has been accumulated that the syndrome results from mild immaturity of the surfactant system [12]. Surfactant abnormality may be considered as a primary problem in TTN, as suggested by James et al. [13]. Machado et al. [14] demonstrated that term infants with TTN had impaired surfactant function. In our study group, seven patients with TTN survived. BPD is the most prevalent long-term morbidity in surviving preterm infants and linked to increased risk of reactive airways disease, pulmonary hypertension, post-neonatal mortality and adverse neurodevelopmental outcomes [15]. The prolonged exposure of infants with BPD to increased inspired oxygen concentrations can result in alterations in type 2 pneumocyte function and impaired surfactant biosynthesis via oxidant-induced lung injury [16]. There continues to be ongoing research into late surfactant replacement therapy. A pilot trial administered 2 or 3 booster doses of surfactant to a total of 87 infants who were ventilated at 7–10 days [17]. These doses were safe and transiently improved respiratory status as well as composition and function of endogeneous surfactant. However, there was no significant difference in the proportion of survivors without BPD with an increased number of late doses. Preliminary evidence suggests exogenous surfactant can at least temporarily improve the respiratory status of infants with ongoing oxygen dependency [18]. In the present study, three out of four newborns with BPD died. Although the number of patients is limited, we think that surfactant administration is of no significance on mortality in BPD. The retrospective nature of our study has known limitations. The present study was performed in a single unit and patient inclusion was based on the need for surfactant treatment. In addition, we are unable to compare the study group with controls who were treated without surfactant treatment. In conclusion, surfactant treatment may be of significant benefit in late preterm infants with serious respiratory distress
133
secondary to a number of diseases. However, the best preparation, technique and optimal timing and dose of administration are not so clear in these neonates. Additional randomized, controlled studies and evidence-based guidelines are needed for optimal surfactant treatment in neonatal respiratory disorders other than respiratory distress syndrome.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
References 1. Jobe A. Surfactant treatment for respiratory distress syndrome. Respir Care 1986;31:9. 2. Engle WA. American Academy of Pediatrics Committee on Fetus and Newborn. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;121: 419–33. 3. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723–9. 4. Enhorning G, Shennan A, Possmayer F, et al. Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial. Pediatrics 1985;76:145–53. 5. Stinson SF, Ryan DP, Hertweck MS, et al. Epithelial and surfactant changes in influenza pulmonary lesions. Arch Pathol Lab Med 1976;100:147–53. 6. Baughman RP, Sternberg RI, Hull W, et al. Decreased surfactant protein A in patients with bacterial pneumonia. Am Rev Respir Dis 1993;147:653–7. 7. Gortner L, Pohlandt F, Bartmann P. Effect of bovine surfactant in very low birthweight premature infants with congenital pneumonia. Monatsschr Kinderheilkd 1990;138:274–8. 8. Chen CT, Toung TJK, Rogers MC. Effect of intraalveolar meconium on intraalveolar meconium on pulmonary surface tension properties. Crit Care Med 1985;13:233–6. 9. Davey AM, Becker JD, Davis JM. Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model. Pediatr Pulmonol 1993;16:101–8. 10. Auten RL, Notter RH, Kendig JW, et al. Surfactant treatment of full-term newborns with respiratory failure. Pediatrics 1991;87: 101–7. 11. El Shahed AI, Dargaville P, Ohlsson A, Soll RF. Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 2007;CD002054. 12. Gross TL, Sokol RJ, Kwong MS, et al. Transient tachypnea of the newborn: the relationship to preterm delivery and significant neonatal morbidity. Am J Obstet Gynecol 1983;146:236–41. 13. James DK, Chiswick ML, Harkes A, et al. Non-specificity of surfactant deficiency in neonatal respiratory disorders. Br Med J 1984;288:1635–8. 14. Machado LU, Fiori HH, Baldisserotto M, et al. Surfactant deficiency in transient tachypnea of the newborn. J Pediatr 2011; 159:750–4. 15. Ghanta S, Leeman KT, Christou H. An update on pharmacologic approaches to bronchopulmonary dysplasia. Semin Perinat 2013; 37:115–23. 16. LaCagnin LB, Bowman L, Ma JYC, Miles PR. Metabolic changes in alveolar type II cells after exposure to hydrogen peroxide. Am J Physiol 1990;259:L57–65. 17. Merrill JD, Ballard PL, Courtney SE, et al. Pilot trial of late booster doses of surfactant for ventilated premature infants. J Perinatol 2011;31:599–606. 18. Pandit PB, Dunn MS, Kelly EN, Perlman M. Surfactant replacement in neonates with early chronic lung disease. Pediatrics 1995; 95:851–4.
