title: The relationship between reticulated platelets, intestinal alkaline phosphatase, and necrotizing enterocolitis.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) affects up to 10% of extremely-low-birthweight infants, with a 30% mortality rate. Currently, no biomarker reliably facilitates early diagnosis. Since thrombocytopenia and bowel ischemia are consistent findings in advanced NEC, we prospectively investigated two potential biomarkers: reticulated platelets (RP) and intestinal alkaline phosphatase (iAP).
  
  
  METHODS
  Infants born ≤ 32 weeks and/or ≤ 1500 g were prospectively enrolled from 2009 to 2012. Starting within 72 hours of birth, 5 weekly whole blood specimens were collected to measure RP and serum iAP. Additional specimens were obtained at NEC onset (Bell stage II or III) and 24 hours later. Dichotomous cut-points were calculated for both biomarkers. Non-parametric (Mann-Whitney) and Chi-square tests were used to test differences between groups. Differences in Kaplan-Meier curves were examined by log-rank test. The Cox proportional hazards model estimated hazard ratios.
  
  
  RESULTS
  A total of 177 infants were enrolled in the study, 15 (8.5%) of which developed NEC (40% required surgery and 20% died). 14 (93%) NEC infants had "low" (≤ 2.3%) reticulated platelets, and 9 (60%) had "high" iAP (>0 U/L) in at least one sample before onset. Infants with "low" RP were significantly more likely to develop NEC [HR=11.0 (1.4-83); P=0.02]. Infants with "high" iAP were at increased risk for NEC, although not significant [HR=5.2 (0.7-42); P=0.12]. Median iAP levels were significantly higher at week 4 preceding the average time to NEC onset by one week (35.7 ± 17.3 days; P=0.02).
  
  
  CONCLUSIONS
  Decreased RP serves as a sensitive marker for NEC onset, thereby enabling early preventative strategies. iAP overexpression may signal NEC development.
authors: Loyola University Medical Center, Maywood, IL, USA.
authors: Richard
authors: R
authors: Kampanatkosol
authors: Loyola University Medical Center, Maywood, IL, USA.
authors: Tricia
authors: T
authors: Thomson
authors: Hutt Valley District Health Board, Wellington, New Zealand.
authors: Omar
authors: O
authors: Habeeb
authors: Ann and Robert H. Lurie Children's Hospital at Cadence Health, Winfield, IL, USA.
authors: Loretto
authors: L
authors: Glynn
authors: Loyola University Medical Center, Maywood, IL, USA.
authors: Phillip J
authors: PJ
authors: Dechristopher
authors: Loyola University Medical Center, Maywood, IL, USA.
authors: Sherri
authors: S
authors: Yong
authors: Loyola University Medical Center, Maywood, IL, USA.
authors: Walter
authors: W
authors: Jeske
authors: University of Illinois at Chicago, Chicago, IL, USA.
authors: Akhil
authors: A
authors: Maheshwari
authors: Loyola University Medical Center, Maywood, IL, USA. Electronic address: jmurask@lumc.edu.
authors: Jonathan
authors: J
authors: Muraskas
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology*; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase
keywords: Biomarker; Extremely-low-birthweight; Necrotizing enterocolitis; Premature