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Observational Study
. 2020 Apr;55(4):899-908.
doi: 10.1002/ppul.24665. Epub 2020 Jan 29.

Urine gastrin-releasing peptide in the first week correlates with bronchopulmonary dysplasia and post-prematurity respiratory disease

Judith A Voynow  1   2 , Kimberley Fisher  3 , Mary E Sunday  4 , Charles M Cotten  3 , Aaron Hamvas  5   6 , Karen D Hendricks-Muñoz  7 , Brenda B Poindexter  8   9 , Gloria S Pryhuber  10 , Clement L Ren  11   12 , Rita M Ryan  13   14 , Jack K Sharp  1   15   16 , Sarah P Young  17 , Haoyue Zhang  17 , Rachel G Greenberg  18 , Amy H Herring  19 , Stephanie D Davis  12   20
Affiliations
Observational Study

Urine gastrin-releasing peptide in the first week correlates with bronchopulmonary dysplasia and post-prematurity respiratory disease

Judith A Voynow et al. Pediatr Pulmonol. 2020 Apr.

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.

Keywords: bronchopulmonary dysplasia; gastrin-releasing peptide; reactive oxygen species.

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Figures

Figure 1.
Figure 1.
Study flow diagram. *Eligible infants in the GRP and BPD study who had urine GRP levels determined in the first week, and for infants only in the GRP and BPD study (167 of 198), at 36 weeks postmenstrual age (PMA): 44/55 from Duke University, 91/97 infants from Indiana University, 11/18 infants from Medical College of Virginia, and 21/28 infants from Cincinnati hospitals.
Figure 2.
Figure 2.
GRP levels (median (25th-75th percentile) pmol/mg Creatinine) are 90 (56-136) for bronchopulmonary dysplasia (BPD) (n= 109) and 67 (40-112) for No BPD (n= 148) status. Comparison by Wilcoxon rank sum test. *P=0.005
Figure 3.
Figure 3.
Postmenstrual age (PMA) in weeks on (A) the last day of invasive ventilation (n=240; R2=0.04; P=0.002), (B) the last day of non-invasive ventilation (n=258; R2=0.03; P=0.005), and (C) the last day of oxygen support (n=272; R2=0.02; P=0.012) by GRP level (pmol/mg Creatinine). Significance testing by linear regression.
Figure 3.
Figure 3.
Postmenstrual age (PMA) in weeks on (A) the last day of invasive ventilation (n=240; R2=0.04; P=0.002), (B) the last day of non-invasive ventilation (n=258; R2=0.03; P=0.005), and (C) the last day of oxygen support (n=272; R2=0.02; P=0.012) by GRP level (pmol/mg Creatinine). Significance testing by linear regression.
Figure 3.
Figure 3.
Postmenstrual age (PMA) in weeks on (A) the last day of invasive ventilation (n=240; R2=0.04; P=0.002), (B) the last day of non-invasive ventilation (n=258; R2=0.03; P=0.005), and (C) the last day of oxygen support (n=272; R2=0.02; P=0.012) by GRP level (pmol/mg Creatinine). Significance testing by linear regression.
Figure 4.
Figure 4.
Relationship of other laboratory values to GRP (pmol/mg Creatinine). Significance testing by linear regression for (A) allantoin (n=214; R2=0.04; P=0.003), (B) isoprostane (n=208; R2<0.01; P=0.87), and (C) 8-hydroxydeoxyguanosine (n=222; R2=0.02; P=0.014).
Figure 4.
Figure 4.
Relationship of other laboratory values to GRP (pmol/mg Creatinine). Significance testing by linear regression for (A) allantoin (n=214; R2=0.04; P=0.003), (B) isoprostane (n=208; R2<0.01; P=0.87), and (C) 8-hydroxydeoxyguanosine (n=222; R2=0.02; P=0.014).
Figure 4.
Figure 4.
Relationship of other laboratory values to GRP (pmol/mg Creatinine). Significance testing by linear regression for (A) allantoin (n=214; R2=0.04; P=0.003), (B) isoprostane (n=208; R2<0.01; P=0.87), and (C) 8-hydroxydeoxyguanosine (n=222; R2=0.02; P=0.014).
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References

    1. McEvoy CT, Jain L, Schmidt B, Abman S, Bancalari E, Aschner JL. Bronchopulmonary dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 2014; 11 Suppl 3: S146–153. - PMC - PubMed
    1. Islam JY, Keller RL, Aschner JL, Hartert TV, Moore PE. Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia. Am J Respir Crit Care Med 2015; 192: 134–156. - PMC - PubMed
    1. Martinez FD. Early-Life Origins of Chronic Obstructive Pulmonary Disease. N Engl J Med 2016; 375: 871–878. - PubMed
    1. Poindexter BB, Feng R, Schmidt B, Aschner JL, Ballard RA, Hamvas A, Reynolds AM, Shaw PA, Jobe AH, Prematurity, Respiratory Outcomes P. Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program. Annals of the American Thoracic Society 2015; 12: 1822–1830. - PMC - PubMed
    1. Steinhorn R, Davis JM, Gopel W, Jobe A, Abman S, Laughon M, Bancalari E, Aschner J, Ballard R, Greenough A, Storari L, Thomson M, Ariagno RL, Fabbri L, Turner MA, International Neonatal C. Chronic Pulmonary Insufficiency of Prematurity: Developing Optimal Endpoints for Drug Development. J Pediatr 2017; 191: 15–21 e11. - PubMed

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