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PEDIATRICS Vol. 114 No. 2 August 2004, pp. e243-e248

ELECTRONIC ARTICLE

Polymorphism of Tumor Necrosis Factor- and Risk and Severity of Bronchopulmonary Dysplasia Among Very Low Birth Weight Infants

S. Nadya J. Kazzi, MD, MPH^*, U. Olivia Kim, MD^*, Michael W. Quasney, MD, PhD and Irina Buhimschi, MD

^* Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Hutzel Women’s Hospital, Detroit, Michigan
Department of Pediatrics, Division of Critical Care, Le Bonheur Children’s Medical Center, University of Tennessee Health Science Center, Memphis, Tennessee
Department of Obstetrics and Gynecology, Yale University, New Haven, Connecticut

Background. Preterm infants with bronchopulmonary dysplasia (BPD) exhibit prolonged elevation of inflammatory indices in their tracheal aspirates. Tumor necrosis factor- (TNF-) is a central mediator of the inflammatory response. The adenine-containing alleles of TNF-–308 and lymphotoxin-+250 have been associated with increased levels of TNF-, whereas the adenine allele of TNF-–238 produces lower levels of TNF- after stimulation. High levels of TNF- may promote chronic inflammation by overwhelming counter-regulatory mechanisms and may lead to the development of BPD. Low levels of TNF- may decrease the risk and/or severity of BPD.

Objective. To determine whether alleles of TNF- play a role in the susceptibility and/or severity of BPD among very low birth weight infants.

Methods. Infants with birth weights of 1250 g were included. Genotypic analyses (polymerase chain reaction-restriction fragment length polymorphism assays) were performed with DNA extracted from whole-blood samples.

Results. Infants who developed BPD (fraction of inspired oxygen at postconceptional age of 36 weeks of >0.21, n = 51) had a younger gestational age (mean ± SD: 27 ± 4 vs 29 ± 2 weeks) and lower birth weight (853 ± 184 vs 997 ± 193 g) than did infants without BPD (n = 69). The genotypic distributions of lymphotoxin-+250 and TNF-–308 were comparable among the groups of infants. However, the AA and GA TNF-–238 genotypes were much less likely to occur among infants with BPD than among infants without BPD. The adenine allele of TNF-–238 was absent among infants with severe BPD and occurred significantly less often among infants with moderate or severe BPD, compared with infants with mild BPD. The number of adenine alleles of TNF-–238 was correlated inversely with the severity of BPD (r = –.341).

Conclusion. The adenine allele of TNF-–238 may reduce the risk and severity of BPD.

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Key Words: tumor necrosis factor- • cytokines • bronchopulmonary dysplasia • polymorphism • low birth weight infants

Abbreviations: TNF-, tumor necrosis factor- • VLBWI, very low birth weight infant • BPD, bronchopulmonary dysplasia • LT-, lymphotoxin- • PCA, postconceptional age

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Received for publication Mar 25, 2004; Accepted Apr 5, 2004.

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