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Abstract
Near infrared spectroscopy (NIRS) is an imaging-based diagnostic tool that provides non-invasive and continuous evaluation of regional tissue oxygenation in real-time. In recent years, NIRS has shown promise as a useful monitoring technology to help detect relative tissue ischemia that could lead to significant morbidity and mortality in preterm infants. However, some issues inherent in NIRS technology use on neonates, such as wide fluctuation in signals, signal dropout and low limit of detection of the device, pose challenges that may obscure reliable interpretation of the NIRS measurements using current methods of analysis. In this paper, we propose new nonparametric statistical methods to analyze mesenteric rSO2 (regional oxygenation) produced by NIRS to evaluate oxygenation in intestinal tissues and investigate oxygenation response to red blood cell transfusion (RBC) in preterm infants. Specifically, we present a mean area under the curve (MAUC) measure and a slope measure to capture the mean rSO2 level and temporal trajectory of rSO2, respectively. We develop estimation methods for the measures based on multiple imputation and spline smoothing and further propose novel nonparametric testing procedures to detect RBC-related changes in mesenteric oxygenation in preterm infants. Through simulation studies, we show that the proposed methods demonstrate improved accuracy in characterizing the mean level and changing pattern of mesenteric rSO2 and also increased statistical power in detecting RBC-related changes, as compared with standard approaches. We apply our methods to a NIRS study in preterm infants receiving RBC transfusion from Emory University to evaluate the pre- and post-transfusion mesenteric oxygenation in preterm infants.
References
| 1. | Sood, BG, McLaughlin, K, Cortez, J. Near-infrared spectroscopy: applications in neonates. Semin Fetal Neonatal Med 2015; 20: 164–172. Google Scholar | Crossref | Medline | ISI |
| 2. | Marin, T, Moore, J. Understanding near-infrared spectroscopy. Adv Neonatal Care 2011; 11: 382–388. Google Scholar | Crossref | Medline |
| 3. | Mintzer, J, Parvez, B, Chelala, M, et al. Quiescent variability of cerebral, renal, and splanchnic regional tissue oxygenation in very low birth weight neonates. J Neonatal-Perinatal Med 2014; 7: 199–206. Google Scholar | Medline |
| 4. | Bailey, SM, Mally, PN. Review of splanchnic oximetry in clinical medicine. J Biomed Optics 2016; 21: 091306–091306. Google Scholar | Crossref | Medline |
| 5. | da Costa CS, Greisen G and Austin T. Is near-infrared spectroscopy clinically useful in the preterm infant? Archives of Disease in Childhood-Fetal and Neonatal Edition 2015; 100: 558–561. Google Scholar |
| 6. | Lin, PW, Stoll, BJ. Necrotising enterocolitis. Lancet 2006; 368: 1271–1283. Google Scholar | Crossref | Medline | ISI |
| 7. | Neu, J, Walker, WA. Necrotizing enterocolitis. New Engl J Med 2011; 364: 255–264. Google Scholar | Crossref | Medline | ISI |
| 8. | Patel, RM, Denning, PW. Intestinal microbiota and its relationship with necrotizing enterocolitis. Pediatric Res 2015; 78: 232–232. Google Scholar | Crossref | Medline |
| 9. | Patel, RM, Knezevic, A, Shenvi, N, et al. Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants. JAMA 2016; 315: 889–897. Google Scholar | Crossref | Medline |
| 10. | Fortune, P-M, Wagstaff, M, Petros, A. Cerebro-splanchnic oxygenation ratio (CSOR) using near infrared spectroscopy may be able to predict splanchnic ischaemia in neonates. Intens Care Med 2001; 27: 1401–1407. Google Scholar | Crossref | Medline | ISI |
| 11. | Gay, AN, Lazar, DA, Stoll, B, et al. Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets. J Pediatric Surg 2011; 46: 1034–1040. Google Scholar | Crossref | Medline |
| 12. | Epelman, M, Daneman, A, Navarro, OM, et al. Necrotizing enterocolitis: review of state-of-the-art imaging findings with pathologic correlation. Radiographics 2007; 27: 285–305. Google Scholar | Crossref | Medline | ISI |
| 13. | Mohamed, A, Shah, PS. Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics 2012; 129: 529–540. Google Scholar | Crossref | Medline | ISI |
| 14. | Marin, T, Josephson, CD, Kosmetatos, N, et al. Feeding preterm infants during red blood cell transfusion is associated with a decline in postprandial mesenteric oxygenation. J Pediatr 2014; 165: 464–471.e461. Google Scholar | Crossref | Medline |
| 15. | McNeill, S, Gatenby, J, McElroy, S, et al. Normal cerebral, renal and abdominal regional oxygen saturations using near-infrared spectroscopy in preterm infants. J Perinatol 2011; 31: 51–51. Google Scholar | Crossref | Medline | ISI |
| 16. | Hastie, T, Tibshirani, R. Generalized additive models, New York, NY: Wiley Online Library, 1990. Google Scholar |
| 17. | Marin, T, Moore, J, Kosmetatos, N, et al. Red blood cell transfusion–related necrotizing enterocolitis in very‐low‐birthweight infants: a near‐infrared spectroscopy investigation. Transfusion 2013; 53: 2650–2658. Google Scholar | Crossref | Medline | ISI |
| 18. | Ruppert D, Wand MP and Carroll RJ. Semiparametric regression. Cambridge series in statistical and probabilistic mathematics 12. Cambridge: Cambridge University Press. Mathematical Reviews (MathSciNet): MR1998720 2003. Google Scholar |
| 19. | Hutchinson, MF, De Hoog, F. Smoothing noisy data with spline functions. Numerische Mathematik 1985; 47: 99–106. Google Scholar | Crossref | ISI |
| 20. | Succop, PA, Clark, S, Chen, M, et al. Imputation of data values that are less than a detection limit. J Occup Environment Hygiene 2004; 1: 436–441. Google Scholar | Crossref | Medline |
| 21. | Hopke, PK, Liu, C, Rubin, DB. Multiple imputation for multivariate data with missing and below‐threshold measurements: time‐series concentrations of pollutants in the Arctic. Biometrics 2001; 57: 22–33. Google Scholar | Crossref | Medline | ISI |
| 22. | McMurry, TL, Politis, DN. Banded and tapered estimates for autocovariance matrices and the linear process bootstrap. J Time Series Analysis 2010; 31: 471–482. Google Scholar | Crossref |
