Abstract
Rationale: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. Objective: We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. Methods: Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). Results: A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. Conclusions: Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 899-908 |
| Number of pages | 10 |
| Journal | Pediatric Pulmonology |
| Volume | 55 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2020 |
Funding
The authors would like to acknowledge the critical work of the PROP Site and Data Coordinating Center Investigators and research staff, the support of Lynn Taussig, MD, University of Arizona, and of Carol J. Blaisdell, MD, Division of Lung Diseases, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD for their guidance. The authors express their indebtedness to the generosity of our NICU families who consented to this and other research studies. This study was supported by NIH grants: 5R01 HL105702 (Duke University, Indiana University, Virginia Commonwealth University, Cincinnati Children's Hospital Medical Center), U01 HL101813 (University of Rochester and University at Buffalo), U01 HL101465 (Washington University), U01 HL101800 (Cincinnati Children's Hospital Medical Center), and U01 HL101794 (University of Pennsylvania). The authors would like to acknowledge the critical work of the PROP Site and Data Coordinating Center Investigators and research staff, the support of Lynn Taussig, MD, University of Arizona, and of Carol J. Blaisdell, MD, Division of Lung Diseases, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD for their guidance. The authors express their indebtedness to the generosity of our NICU families who consented to this and other research studies. This study was supported by NIH grants: 5R01 HL105702 (Duke University, Indiana University, Virginia Commonwealth University, Cincinnati Children's Hospital Medical Center), U01 HL101813 (University of Rochester and University at Buffalo), U01 HL101465 (Washington University), U01 HL101800 (Cincinnati Children's Hospital Medical Center), and U01 HL101794 (University of Pennsylvania).
Keywords
- bronchopulmonary dysplasia
- gastrin-releasing peptide
- reactive oxygen species
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Pulmonary and Respiratory Medicine