Published online January 3, 2005
PEDIATRICS Vol. 115 No. 1 January 2005, pp. 199 (doi:10.1542/peds.2004-2366)

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Association Study of Gene Polymorphism and Bronchopulmonary Dysplasia: In Reply

S. Nadya J. Kazzi, MD, MPH
Department of Pediatrics,
Wayne State University,
Detroit, MI 48201

U. Olivia Kim, MD
Department of Pediatrics,
Medical College of Wisconsin,
Milwaukee, WI 53226-0509

Michael W. Quasney, MD, PhD
Department of Pediatrics,
University of Tennessee Health Science Center,
Memphis, TN 38103

Irina Buhimschi, MD
Department of Obstetrics and Gynecology,
Yale University,
New Haven, CT 06520-8063

In Reply.—

We thank Lin et al for their thoughtful comments on our study¹ and appreciate the opportunity to respond to their question. As they suggested, we conducted a multivariate logistic regression analysis to examine the contribution of potential confounders that were revealed in our univariate analysis to the development of bronchopulmonary dysplasia (BPD). After including birth weight, gestational age, antenatal steroids, prolonged rupture of fetal membranes for >18 hours, respiratory distress syndrome, pulmonary hemorrhage, pneumonia, patent ductus arteriosus, and late-onset sepsis as covariables in the logistic regression, pneumonia (odds ratio: 4.69; 95% confidence interval: 1.43–15.40; P = .011) and the absence of adenine allele of tumor necrosis factor- (TNF-)-238 (odds ratio: 0.056; 95% confidence interval: 0.006–0.57; P = .015) were the only variables that were significantly associated with the development of BPD. Our findings of no significant association between G/A alleles of TNF--308 and BPD among very low birth weight infants is in agreement with the report by Adcock et al² and Lin et al³ as they mention in their letter. Our study points to the novel perspective of a possible protective role that the A allele of TNF--238 or the haplotype with which it is in linkage disequilibrium may have in the development and severity of BPD. We agree with Lin et al that larger multicenter trials are needed to examine the contribution of genetic factors to the development of BPD. As we know, the survival of very low birth weight infants has improved over the past decade, with a significant number of these infants being afflicted with BPD.⁴ The observation of increased neurodevelopmental morbidity among BPD survivors^5–7 behooves us to focus our efforts on identifying any possible factors that may contribute to the risk and or severity of the disease. Because research into the genetics of BPD has been limited, we believe that exploring this aspect of the disease might help elucidate its pathogenesis and direct our preventative strategies toward at-risk infants.

REFERENCES

1. Kazzi SN, Kim UO, Quasney MW, Buhimschi I. Polymorphism of tumor necrosis factor- and risk and severity of bronchopulmonary dysplasia among very low birth weight infants. Pediatrics. 2004;114 (2). Available at: www.pediatrics.org/cgi/content/full/114/2/e243
2. Adcock K, Hedberg C, Loggins J, Kruger TE, Baier RJ. The TNF--308, MCP-1–2518 and TGF-ß1+915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants. Genes Immun. 2003;4 :420 –426[CrossRef][Web of Science][Medline]
3. Lin HC, Hsu CM, Tsai FJ, Tsai CH. Cytokines polymorphisms and chronic lung disease in small preterm infants. Arch Dis Child. 2005; in press
4. Fanaroff AA, Hack M, Walsh MC. The NICHD neonatal research network: changes in practice and outcomes during the first 15 years. Semin Perinatol. 2003;27 :281 –287[CrossRef][Web of Science][Medline]
5. Vohr BR, Bell EF, Oh W. Infants with bronchopulmonary dysplasia. Am J Dis Child. 1982;136 :443 –447[Abstract/Free Full Text]
6. Gregoire MC, Lefebvre F, Glorieux J. Health and developmental outcomes at 18 months in very preterm infants with bronchopulmonary dysplasia. Pediatrics. 1998;101 :856 –860[Abstract/Free Full Text]
7. Vohr BR, Wright LL, Dusick AM, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994. Pediatrics. 2000;105 :1216 –1226[Abstract/Free Full Text]

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PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kazzi, S. N. J. Articles by Buhimschi, I. Search for Related Content PubMed Articles by Kazzi, S. N. J. Articles by Buhimschi, I. Related Collections Premature & Newborn Social Bookmarking                         What's this?