Background. An abnormally high incidence (44%) of bronchopulmonary dysplasia with variations in rates among cities was observed in Colombia among premature infants. Objective. To identify risk factors that could explain the observed high incidence and regional variations of bronchopulmonary dysplasia. Study Design. A case-control study was designed for testing the hypothesis that differences in the disease rates were not explained by differences in city-of-birth specific population characteristics or by differences in respiratory management practices in the first 7 days of life, among cities. Results. Multivariate analysis showed that premature rupture of membranes, exposure to mechanical ventilation after received nasal CPAP, no surfactant exposure, use of rescue surfactant (instead of early surfactant), PDA, sepsis and the median daily FIO2, were associated with a higher risk of dysplasia. Significant differences between cases and controls were found among cities. Models exploring for associations between city of birth and dysplasia showed that being born in the highest altitude city (Bogotá) was associated with a higher risk of dysplasia (OR 1.82 95% CI 1.31–2.53). Conclusions. Bronchopulmonary dysplasia was manly explained by traditional risk factors. Findings suggest that altitude may play an important role in the development of this disease. Prenatal steroids did not appear to be protective at high altitude. 1. Introduction Despite all the advances in the care of premature infants with respiratory distress syndrome (RDS), including the use of antenatal steroids and early management with surfactant, bronchopulmonary dysplasia (BPD) continues to be a major cause of chronic morbidity among this population. There are large variations in the incidence and severity of this disease. According to the National Institutes of Health of USA (NICHD) consensus [1], mild BPD is defined as a need for supplemental oxygen for ≥28 days at 36 weeks postmenstrual age (wPMA) or discharge, moderate BPD as supplemental oxygen for ≥28 days plus treatment with <30% oxygen at 36？wPMA, and severe BPD as supplemental oxygen for ≥28 days plus ≥30% oxygen and/or positive pressure at 36？wPMA. Currently, the estimated incidence of BPD defined as need for supplemental oxygen at 36？wPMA in the United States is approximately 30% for premature infants with a birth weight <1000 grams and <7% in infants with a birth weight >1250 grams or who were at least 30 weeks of gestation at birth [1, 2]. Previous epidemiological studies have identified prematurity, oxygen toxicity, and mechanical
References
[1]
A. H. Jobe and E. Bancalari, “Bronchopulmonary dysplasia,” American Journal of Respiratory and Critical Care Medicine, vol. 163, no. 7, pp. 1723–1729, 2001.
[2]
R. A. Ehrenkranz, M. C. Walsh, B. R. Vohr et al., “Validation of the National Institutes of health consensus definition of bronchopulmonary dysplasia,” Pediatrics, vol. 116, no. 6, pp. 1353–1360, 2005.
[3]
A. A. Hislop, J. S. Wigglesworth, R. Desai, and V. Aber, “The effects of preterm delivery and mechanical ventilation on human lung growth,” Early Human Development, vol. 15, no. 3, pp. 147–164, 1987.
[4]
M. Palta, D. Gabbert, M. R. Weinstein et al., “Multivariate assessment of traditional risk factors for chronic lung disease in very low birth weight neonates,” Journal of Pediatrics, vol. 119, no. 2, pp. 285–292, 1991.
[5]
L. J. Van Marter, M. Pagano, E. N. Allred, A. Leviton, and K. C. K. Kuban, “Rate of bronchopulmonary dysplasia as a function of neonatal intensive care practices,” Journal of Pediatrics, vol. 120, no. 6, pp. 938–946, 1992.
[6]
T. Farstad and D. Bratlid, “Incidence and prediction of bronchopulmonary dysplasia in a cohort of premature infants,” Acta Paediatrica, International Journal of Paediatrics, vol. 83, no. 1, pp. 19–24, 1994.
[7]
D. D. Marshall, M. Kotelchuck, T. E. Young, C. L. Bose, P. A. C. Lauree Kruyer, and T. M. O'Shea, “Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants,” Pediatrics, vol. 104, no. 6, pp. 1345–1350, 1999.
[8]
P. J. Sanchez and J. A. Regan, “Ureaplasma urealyticum colonization and chronic lung disease in low birth weight infants,” Pediatric Infectious Disease Journal, vol. 7, no. 8, pp. 542–546, 1988.
[9]
E. E. L. Wang, H. Frayha, J. Watts et al., “Role of Ureaplasma urealyticum and other pathogens in the development of chronic lung disease of prematurity,” Pediatric Infectious Disease Journal, vol. 7, no. 8, pp. 547–551, 1988.
[10]
A. H. Jobe and M. Ikegami, “Antenatal infection/inflammation and postnatal lung maturation and injury,” Respiratory Research, vol. 2, no. 1, pp. 27–32, 2001.
[11]
L. J. Van Marter, O. Dammann, E. N. Allred et al., “Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants,” Journal of Pediatrics, vol. 140, no. 2, pp. 171–176, 2002.
[12]
M. A. Rojas, A. Gonzalez, E. Bancalari, N. Claure, C. Poole, and G. Silva-Neto, “Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease,” Journal of Pediatrics, vol. 126, no. 4, pp. 605–610, 1995.
[13]
T. Farstad and D. Bratlid, “Pulmonary effects of closure of patent ductus arteriosus in premature infants with severe respiratory distress syndrome,” European Journal of Pediatrics, vol. 153, no. 12, pp. 903–905, 1994.
[14]
L. J. Van Marter, A. Leviton, E. N. Allred, M. Pagano, and K. C. K. Kuban, “Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants,” Journal of Pediatrics, vol. 116, no. 6, pp. 942–949, 1990.
[15]
A. R. Spitzer, W. W. Fox, and M. Delivoria-Papadopoulos, “Maximum diuresis—a factor in predicting recovery from respiratory distress syndrome and the development of bronchopulmonary dysplasia,” Journal of Pediatrics, vol. 98, no. 3, pp. 476–479, 1981.
[16]
B. A. Darlow and P. J. Graham, “Vitamin A supplementation to prevent mortality and short and long-term morbidity in very low birthweight infants,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD000501, 2007.
[17]
K. L. Watterberg, J. S. Gerdes, C. H. Cole et al., “Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial,” Pediatrics, vol. 114, no. 6, pp. 1649–1657, 2004.
[18]
P. Kwinta, M. Bik-Multanowski, Z. Mitkowska, T. Tomasik, M. Legutko, and J. J. Pietrzyk, “Genetic risk factors of bronchopulmonary dysplasia,” Pediatric Research, vol. 64, no. 6, pp. 682–688, 2008.
[19]
J. L. Tapia, D. Agost, A. Alegria et al., “Bronchopulmonary dysplasia: incidence, risk factors and resource utilization in a population of South American very low birth weight infants,” Jornal de Pediatria, vol. 82, no. 1, pp. 15–20, 2006.
[20]
M. A. Rojas, J. M. Lozano, M. X. Rojas et al., “Very early surfactant without mandatory ventilation in premature infants treated with early continuous positive airway pressure: a randomized, controlled trial,” Pediatrics, vol. 123, no. 1, pp. 137–142, 2009.
[21]
J. M. Lozano, O. R. Duque, T. Buitrago, and S. Behaine, “Pulse oximetry reference values at high altitude,” Archives of Disease in Childhood, vol. 67, no. 3, pp. 299–301, 1992.
[22]
S. Balasubramanian, N. Suresh, R. Raeshmi, and K. Kaarthigeyan, “Comparison of oxygen saturation levels by pulse oximetry in healthy children aged 1 month to 5 years residing at an altitude of 1500 metres and at sea level,” Annals of Tropical Paediatrics, vol. 28, no. 4, pp. 267–273, 2008.
[23]
J. L. Ballard, J. C. Khoury, K. Wedig, L. Wang, B. L. Eilers-Walsman, and R. Lipp, “New Ballard Score, expanded to include extremely premature infants,” Journal of Pediatrics, vol. 119, no. 3, pp. 417–423, 1991.
[24]
G. F. Gonzales and V. Tapia, “Birth weight charts for gestational age in 63 620 healthy infants born in Peruvian public hospitals at low and at high altitude,” Acta Paediatrica, International Journal of Paediatrics, vol. 98, no. 3, pp. 454–458, 2009.
[25]
M. M. Levy, M. P. Fink, J. C. Marshall et al., “2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference,” Critical Care Medicine, vol. 31, no. 4, pp. 1250–1256, 2003.
[26]
L. A. Papile, J. Burstein, R. Burstein, and H. Koffler, “Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm,” Journal of Pediatrics, vol. 92, no. 4, pp. 529–534, 1978.
[27]
D. K. Richardson, J. D. Corcoran, G. J. Escobar, and S. K. Lee, “SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores,” Journal of Pediatrics, vol. 138, no. 1, pp. 92–100, 2001.
[28]
K. De Meer, H. S. A. Heymans, and W. G. Zijlstra, “Physical adaptation of children to life at high altitude,” European Journal of Pediatrics, vol. 154, no. 4, pp. 263–272, 1995.
[29]
K. De Meer, R. Bergman, J. S. Kusner, and H. W. A. Voorhoeve, “Differences in physical growth of Aymara and Quechua children living at high altitude in Peru,” American Journal of Physical Anthropology, vol. 90, no. 1, pp. 59–75, 1993.
[30]
R. Gamboa and E. Marticorena, “Pulmonary arterial pressure in newborn infants in high altitude,” Archivos del Instituto de Biologia Andina, vol. 4, no. 2, pp. 55–66, 1971.
[31]
F. Sime, N. Banchero, D. Pe？aloza, R. Gamboa, J. Cruz, and E. Marticorena, “Pulmonary hypertension in children born and living at high altitudes,” American Journal of Cardiology, vol. 11, no. 2, pp. 143–149, 1963.
[32]
S. Niermeyer, E. M. Shaffer, E. Thilo, C. Corbin, and L. G. Moore, “Arterial oxygenation and pulmonary arterial pressure in healthy neonates and infants at high altitude,” Journal of Pediatrics, vol. 123, no. 5, pp. 767–772, 1993.
[33]
R. Lavadenz, E. Palmero, F. Loma, and R. Carreon, “Patent ductus arteriosus with pulmonary hypertension,” Arquivos Brasileiros de Cardiologia, vol. 47, no. 5, pp. 323–327, 1986.
[34]
C. Y. Miao, J. S. Zuberbuhler, and J. R. Zuberbuhler, “Prevalence of congenital cardiac anomalies at high altitude,” Journal of the American College of Cardiology, vol. 12, no. 1, pp. 224–228, 1988.
[35]
S. Niermeyer, “Cardiopulmonary transition in the high altitude infant,” High Altitude Medicine and Biology, vol. 4, no. 2, pp. 225–239, 2003.
[36]
S. Niermeyer, P. A. Mollinedo, and L. Huicho, “Child health and living at high altitude,” Archives of Disease in Childhood, vol. 94, no. 10, pp. 806–811, 2009.
[37]
A. Gonzalez, I. R. S. Sosenko, J. Chandar, H. Hummler, N. Claure, and E. Bancalari, “Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less,” Journal of Pediatrics, vol. 128, no. 4, pp. 470–478, 1996.
[38]
G. Rocha, O. Ribeiro, and H. Guimar？es, “Fluid and electrolyte balance during the first week of life and risk of bronchopulmonary dysplasia in the preterm neonate,” Clinics, vol. 65, no. 7, pp. 663–674, 2010.
[39]
B. H. Yoon, R. Romero, K. S. Kim et al., “A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia,” American Journal of Obstetrics and Gynecology, vol. 181, no. 4, pp. 773–779, 1999.
[40]
R. F. Soll and C. J. Morley, “Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD000510, 2001.
[41]
T. P. Stevens, E. W. Harrington, M. Blennow, and R. F. Soll, “Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD003063, 2007.
