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Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants
Namasivayam Ambalavanan1, Waldemar A Carlo, Carl T D'Angio
1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35249, USA. ambal@uab.edu
Insights
Predicting bronchopulmonary dysplasia (BPD) or death in premature infants is possible using clinical data and cytokine levels. Specific cytokine patterns indicate an impaired immune response transition, aiding in early identification.
Area of Science:
- Neonatal immunology
- Respiratory medicine
- Biomarker discovery
Background:
- Bronchopulmonary dysplasia (BPD) and death are significant morbidities in extremely low birth weight (ELBW) infants.
- Early prediction of BPD/death is crucial for timely intervention and improved outcomes.
Purpose of the Study:
- To develop predictive models for BPD and/or death at 36 weeks postmenstrual age.
- To evaluate the utility of clinical and cytokine data in predicting BPD/death.
Main Methods:
- Multivariate logistic regression models were developed using clinical and cytokine data from 1067 ELBW infants.
- Cytokine levels were measured at multiple time points within the first 21 days of life.
- Stepwise regression identified key predictive variables, including cytokine concentrations.
Main Results:
- BPD/death was associated with elevated levels of IL-1β, IL-6, IL-8, IL-10, and IFN-γ, and decreased levels of IL-17, RANTES, and TNF-β.
- Inclusion of cytokine data significantly, though modestly, improved the predictive ability of models compared to clinical variables alone.
- 606 out of 1062 infants developed BPD or died.
Conclusions:
- The cytokine profile suggests a link between BPD/death and a disrupted innate to adaptive immune response transition.
- Cytokine patterns may serve as early indicators of BPD/death risk in ELBW infants.
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.
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