Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants

Abstract

Objective: The goal was to develop multivariate logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at postmenstrual age of 36 weeks by using clinical and cytokine data from the first 28 days.

Methods: For 1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development, levels of 25 cytokines were measured in blood collected within 4 hours after birth and on days 3, 7, 14, and 21. Stepwise regression analyses using peak levels of the 25 cytokines and 15 clinical variables identified variables associated with bronchopulmonary dysplasia/death. Multivariate logistic regression analysis was performed for bronchopulmonary dysplasia/death by using variables selected through stepwise regression. Similar analyses were performed by using average cytokine values from days 0 to 21, days 0 to 3, and days 14 to 21.

Results: Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. On the basis of results from all models combined, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukin 1beta, 6, 8, and 10 and interferon gamma and lower concentrations of interleukin 17, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor beta. Compared with models with only clinical variables, the addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude.

Conclusions: The overall cytokine pattern suggests that bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T lymphocytes.

Figure 1

Temporal profile of cytokines associated with BPD and/or Death by multi-variable logistic regression analysis in ELBW infants. Values shown are median values, unadjusted for other cytokine or clinical variables.

Figure 2

Temporal profile of cytokines not associated with the combined outcome of Death or BPD by multi-variable logistic regression analysis in ELBW infants. Values shown are median values, unadjusted for other cytokine or clinical variables.

Figure 3

Figure showing temporal profile of IL-8 serum concentrations in infants who died or developed BPD (25^th to 75^th centiles enclosed by pink shading) and in infants who survived without BPD (25^th to 75^th centiles enclosed by green shading). The IL-8 expression profile as chosen as a representative example to demonstrate the marked overlap of cytokine concentrations in infants with BPD/Death and in those surviving without BPD.