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Serum Neurotrophin Levels at Birth Are Associated with Respiratory Illness in the First Three Years of Life

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A6982 - Serum Neurotrophin Levels at Birth Are Associated with Respiratory Illness in the First Three Years of Life
Author Block: I. A. Sammour1, V. Munjapara1, M. Alejandro-Rodriguez1, S. L. Simpson1, M. Allen2, W. L. Spencer3, S. Worley4, A. S. Tang4, F. Rezaee1, G. Piedimonte1; 1Center for Pediatric Research, Cleveland Clinic Children's, Cleveland, OH, United States, 2Center for Clinical Research, Cleveland Clinic, Cleveland, OH, United States, 3Center for Cardiovascular Research, Cleveland Clinic, Cleveland, OH, United States, 4Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States.
RATIONALE
Children with bronchopulmonary dysplasia (BPD) are twice as likely to require rehospitalization in the first two years. Although all infants born preterm have higher rates of pulmonary problems than their term counterparts, infants with BPD continue to experience sequelae into adolescence and adulthood.
METHODS
A prospective cohort of infants in neonatal intensive care units within Cleveland Clinic Children’s were identified. Serum samples were obtained at birth, and highly-sensitive immunoassays were used to measure BDNF and NGF protein concentrations. Participants consented to be followed for 18 years, completing annual telephone follow-up calls.
Results at each follow-up time were analyzed separately. Subjects with and without BPD were compared on outcomes at 1, 2, and 3 year follow-up surveys using Kruskal-Wallis, Chi-square, and Fisher’s exact tests. The associations between outcomes and serum neurotrophins were assessed using Kruskal-Wallis tests and Spearman’s rank correlation coefficients.
RESULTS
This is an interim analysis of 32, 35, and 19 patients who have completed the 12, 24, and the 36-month follow-up questionnaires respectively. In each cohort respectively, 8, 10, and 8 patients had a history of BPD.
At one year, subjects with BPD had significantly fewer sick visits (p=0.042) and upper respiratory tract infections (URTI) (p=0.012) than subjects with BPD; this unexpected finding is likely due to the extended NICU length of stay in the BPD group. They also were significantly more likely to require home oxygen therapy (6/8=75% vs 5/24=21%, p=0.010). At two years, subjects with BPD were more likely to have a new diagnosis of asthma than subjects without BPD (3/10=30% vs 2/25=8%, p=0.043). At three years, subjects with BPD were more likely to have sick visits for wheezing/breathing problems than those without BPD (p=0.038).
Higher serum BDNF at birth was significantly associated with greater numbers of URTI in the first year (correlation =0.37, p=0.042), whereas higher serum NGF at birth was significantly associated with fewer admissions and numbers of sick visits in the first year (correlations -0.40 and -0.42, p-values 0.028, 0.020 respectively).
CONCLUSIONS
Infants with BPD are at an increased risk of being diagnosed with asthma, or seeking medical attention for respiratory symptoms by 2 years. Serum levels of BDNF and NGF obtained at birth may provide valuable insight into the postnatal course of these children. These early biomarkers may help set expectations for a child’s long-term pulmonary outlook. Further analysis and adjustment for other patient characteristics is needed as more data is collected.
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