This study analyzed data from over 663,000 premature infants to compare outcomes of surgical necrotizing enterocolitis (SNEC) in infants who received blood transfusions (BT) versus those who did not. Using propensity score matching, infants who received BT had higher rates of SNEC (1.21% vs 0.17%) and lower survival rates for SNEC cases (58.1% vs 66.7%) compared to non-BT infants. SNEC cases in the BT group also had shorter hospital stays and lower treatment costs. Multivariate analysis found higher SNEC mortality risks for BT infants with lower gestational age, male sex, African American race, and comorbidities like bronchopulmonary

1. ÔØ Å ÒÙ× Ö ÔØ
Blood Transfusions, Increased Rates of Surgical NEC, and Survival: A
Propensity-Score Matched Analysis
Arash J. Sayari, Jun Tashiro, Juan E. Sola, Eduardo A. Perez
PII: S0022-3468(16)00140-8
DOI: doi: 10.1016/j.jpedsurg.2016.02.052
Reference: YJPSU 57592
To appear in: Journal of Pediatric Surgery
Received date: 17 February 2016
Accepted date: 26 February 2016
Please cite this article as: Sayari Arash J., Tashiro Jun, Sola Juan E., Perez
Eduardo A., Blood Transfusions, Increased Rates of Surgical NEC, and Survival:
A Propensity-Score Matched Analysis, Journal of Pediatric Surgery (2016), doi:
10.1016/j.jpedsurg.2016.02.052
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

2. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
1
Blood Transfusions, Increased Rates of Surgical NEC, and Survival: A
Propensity-Score Matched Analysis.
Authors: Arash J. Sayari BS, Jun Tashiro MD MPH, Juan E. Sola MD, Eduardo A. Perez MD
Author Affiliations: Division of Pediatric Surgery, DeWitt-Daughtry Department of Surgery,
Leonard M. Miller School of Medicine, University of Miami, Miami, FL
Address for Correspondence:
Eduardo A. Perez MD
Associate Professor, Division of Pediatric Surgery
DeWitt-Daughtry Family Department of Surgery
Leonard M. Miller School of Medicine
University of Miami
1120 NW 14th Street, Suite 450K
Miami, FL 33136
Telephone: (305) 243-2247
Fax: 305-243-5731
E-Mail: EPerez3@med.miami.edu.
Author Disclosure Statement: The authors have no financial affiliations to disclose.

3. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
2
Abbreviations: BT – blood transfusion; SNEC – surgical necrotizing enterocolitis; PS –
propensity score; MVA – multivariate analysis; GA – gestational age; OR – odds ratio; BPD –
bronchopulmonary dysplasia; LOS – length of stay; TC – total charges; PDA – patent ductus
arteriosus.

4. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
3
Abstract:
Purpose: We sought to investigate the association between blood transfusions (BT), rates of
necrotizing enterocolitis requiring surgical intervention (SNEC), and survival.
Methods: BT in premature infants were identified in the Kids’ Inpatient Database (2003-2009).
Propensity score (PS) matched analysis compared SNEC outcomes in BT vs. non-BT groups.
Multivariate analyses (MVA) were performed to determine independent predictors of outcome.
Results: Overall, 663,740 cases were identified, and 4.9% received BT. SNEC occurred in 493
cases in the BT group, while SNEC occurred in 1049 cases in the non-BT group.
PS analysis of 20,991 BT and 20,988 non-BT cases demonstrated higher SNEC rates with BT
(OR: 1.21) vs. non-BT. SNEC with BT had lower survival rates (58%) vs. non-BT (67%). SNEC
with BT had lower length of stay and total charges vs. non-BT.
On MVA, SNEC mortality with BT increased for lower gestational age (GA), males (OR: 45.7),
African Americans (OR: 64.4), and infants with cardiac anomalies (OR: 50.8) or
bronchopulmonary dysplasia (OR: 177; BPD). Non-BT SNEC demonstrated higher mortality
with lower GA and infants with BPD (OR: 6.56) or sepsis (OR: 3.66).
Conclusion: On PS matched analysis, SNEC occurs at higher rates after BT and is associated
with lower survival and lower resource utilization vs. SNEC without BT.
Keywords: blood transfusion, necrotizing enterocolitis, neonatal prematurity

5. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
4
Introduction
Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal medical
emergencies in newborns, and the incidence is inversely related to birth weight and gestational
age. The incidence of NEC has been reported to range from 1 to 7.7% of admissions to the
neonatal intensive care unit (NICU), almost exclusively in premature infants.1
Appropriate
measures should be taken to minimize the risk of developing NEC, because when NEC
necessitates surgery (SNEC), the mortality reaches higher than 50%.2,3
Anemia of prematurity is another common entity in the NICU and is often seen in
premature infants weighing less than 1000 g.4
When neonates require blood transfusions (BT),
there is a reported risk of NEC. Since the first suggested association between packed red blood
cell (pRBC) transfusions and NEC in 1987,5
a multitude of case-control and cohort studies have
emerged supporting this notion, primarily in the last decade.6-16
In their meta-analysis, Mohamed and Shah observed that there was an increased risk of
NEC within 48 hours of a BT.17
The meta-analysis only included 12 studies, and all but two were
single or double center studies. Large population based studies are needed to provide multi-
center data that can better estimate the overall incidence. To the best of our knowledge, the
present study is the largest to evaluate the association between BT and NEC, and the first study
to examine this relationship in cases of NEC that require surgery. We hypothesized that there
would be a higher rate of SNEC in premature infants who received a BT.
Methods
We used the Kids’ Inpatient Database (KID) to search for cases of packed red blood cell
transfusions (BT) in premature (<37 weeks’ gestation) infants admitted at less than 8 days of life.

6. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
5
The KID samples national pediatric admissions, with information on up to 7.6 million weighted
cases per year. For this study, we used data releases from 2003, 2006, and 2009. Diagnoses and
procedures were coded using the International Classification of Diseases, 9th revision, Clinical
Modification (ICD-9-CM). Cases were weighted to project national estimates, and all analyses
were limited to available data.
We defined cases as surgical NEC (SNEC) in this analysis where infants with NEC (ICD-
9-CM 777.5x) required surgical intervention. A patient with NEC was considered to receive
surgical intervention (SNEC) when they underwent laparotomy, bowel resection/ostomy, or
peritoneal drain placement, whereas all other cases of NEC were considered to be medically
managed.18
For the BT (ICD-9-CM 99.04) group, only SNEC cases occurring within 7 days
post-BT were included, as these were cases of SNEC likely to be associated with BT. Cases of
SNEC occurring outside of this window (prior to BT or ≥ 8 days post-BT) were excluded from
analyses. For the non-BT group, all cases of SNEC were considered. Cases with disposition
coded as ‘transfer to short term hospital’ or ‘other transfers, including skilled nursing facility,
intermediate care, and another type of facility’ were excluded from analyses.
Propensity score (PS)-matched analyses BT vs. non-BT were performed using the 1:1
nearest neighbor method. For each comparison group, a dataset containing a total of 58 variables
were matched according to 47 covariates to construct a 1:1 fixed ratio matched cohort to
compare cases of premature infants who received BT vs. those who did not receive BT. Between
these matched cohorts, we compared rates of SNEC and outcomes following this diagnosis. PS
values were assigned via multivariate logistic regression, according to demographic (gender,
race), socioeconomic (payer status, median income quartile), hospital characteristics (bed size,
location/teaching status, region, type), birth weight (in grams), gestational age (in weeks), as well

7. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
6
as common comorbidities, specifically cardiac anomalies, bronchopulmonary dysplasia,
intraventricular hemorrhage, sepsis, respiratory distress syndrome, and multiple gestation, as
performed in a previous analysis.18
Additional risk-adjustment was performed using the
Elixhauser method, which is a standard set of comorbid conditions that has been validated in
previous retrospective outcome studies.18-21
PS value assignment, case sorting, and matching
were performed using MatchIt, version 2.4-20 (Cambridge, MA), a supplemental module for R,
version 2.14.2 (R foundation for Statistical Computing; Vienna, Austria). After constructing two
risk-adjusted comparison groups (BT vs. non-BT), we compared rates and outcomes (mortality,
length of stay [LOS], and total charges [TC]) of SNEC in the BT vs. non-BT group.
In a separate analysis, we used risk-adjusted multivariate analysis (MVA) to identify
predictors of in-hospital mortality and higher resource utilization (LOS, TC) among cases of
SNEC within BT or non-BT categories. Demographic, clinical, and hospital characteristic
variables were used to construct logistic regression models. The binary, backward step-wise
method was used to identify determinants of mortality, whereas ordinal regression models were
constructed for determinants of resource utilization endpoints. Adjustment for comorbid risk
factors were performed in a manner similar to the PS analysis, including variables for
demographic, socioeconomic, hospital, and neonatal and Elixhauser comorbidities. TC values
were standardized to 2009 US dollars (USD), according to inflation rates provided by the US
Bureau of Labor Statistics.22
We set the significance level at α = 0.05, and SPSS Statistics,
version 21.0 (IBM; Armonk, NY) was used to analyze data.
This retrospective analysis was exempt from Institutional Review Board review.

8. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
7
Results
Overall, 663,740 premature infants were identified, of which 32,241 (4.9%) received BT.
SNEC occurred in 493 (1.53%) cases in the BT group, while 1049 (0.17%) developed SNEC in
the non-BT group. For detailed demographic characteristics, see Table 1.
On 1:1 PS matched analysis of 41,979 cases, comprised of 20,991 BT (50.0%) and
20,988 non-BT (50.0%) cases. The BT group demonstrated a significantly higher odds of SNEC
(odds ratio [95% confidence interval]: 1.21 [1.03, 1.42]) vs. the non-BT group, p=0.017. SNEC
in the BT group (58.1%) had a lower survival rate vs. SNEC in the non-BT group (66.7%),
p=0.026. SNEC in the BT group had lower length of stay (median [interquartile range]: 47 [74])
vs. SNEC in the non-BT group (88 [70]), p<0.001. SNEC in the BT group (351,381 [578,577]
USD) had lower total charges vs. SNEC in the non-BT group (557,481 [535,191] USD),
p<0.001. For a tabular representation of these results, see Table 2.
On MVA, SNEC mortality for BT group increased for lower gestational age (GA), male
gender (OR: 45.7), African Americans (OR: 64.4), and associated comorbidities (cardiac
anomalies [OR: 50.8], bronchopulmonary dysplasia [OR: 177; BPD]), p<0.05. Non-BT SNEC
demonstrated higher mortality with lower GA and infants with BPD (OR: 6.6) or sepsis (OR:
3.7), p<0.05. For a graphic representation of these results, see Figure 1.
Discussion
BT in premature neonates are not without risks, and there has been recent awareness of
the risk of NEC after BT. Overall, 4.9% of the 663,740 premature infants in our study received a
BT. This is significantly lower than a previous randomized trial in 2005 that reported transfusion

9. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
8
rates as high as 90%, although they only included patients less than 1300 g.23
A separate trial by
Strauss et al. found that 5 to 6% of premature infants will receive at least one blood transfusion.24
In our study, of the premature infants who received a BT, 1.53% developed SNEC,
versus 0.17% in the group that did not receive a BT, which is consistent with only one previous
study.12
Paul et al.12
found that when compared to infants not receiving a BT, 1.4% of premature
infants developed NEC within 48 hours of a PRBC transfusion (OR: 2.3). In contrast to the low
incidence in our study, a retrospective study by El-Dib et al.10
found that 56% of premature
infants with NEC had received a BT within 48 hours preceding their diagnosis. Other studies
reported rates of NEC after BT to be between 15.5% and 38%, all of which were found to be
significantly higher than cases of NEC that did not involve a preceding BT.6,8,9,11,14-16
These
studies examined rates of NEC, and we do not expect all patients with NEC to necessitate
surgery,1
which may explain the lower rate of SNEC seen in our study.
Premature infants with SNEC in the BT group had a significantly lower survival rate than
the SNEC cases in the non-BT group. Christensen et al.7
reported a large, but non-significant
difference in mortality rate in infants with NEC following BT versus those with NEC unrelated
to a BT (40% versus 28%, respectively). Another study by Couselo et al.25
reported a mortality
rate of 50% in infants with SNEC after within 48 hours of a BT versus those with SNEC who did
not receive a BT, supporting the notion that survival is lower in patients with SNEC who had
previously received a BT.
Patients who developed SNEC in the BT group had lower length of stay and total charges
vs. the non-BT group, p<0.001. This may reflect the differing pathophysiological manifestations
of NEC in those who previously received a BT versus those who had not. Surgically reported
findings in infants with NEC revealed an odds ratio of 0.5 for developing advanced disease in the

10. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
9
SNEC after BT versus SNEC without BT group.25
This supports the notion that the patients with
SNEC after BT would have a shorter hospital stay. The same study also explained that more
ventilation support was provided to the SNEC group that received BT, which may hasten
recovery.25
However, the database used in this study precludes us from confirming a causative
association.
The suggestion that mortality increases with a lower gestational age and associated
comorbidities has been extensively reported, and our results confirmed this in the SNEC after BT
group. Interestingly, mortality was higher in the male gender (OR: 45.7) and in African
Americans (OR: 64.4), associations not previously reported in this population. The MVA for the
BT SNEC group also showed higher mortality in patients with associated comorbidities, such as
cardiac anomalies. The relationship between an existing patent ductus arteriosus (PDA) and the
development of NEC after a BT was reported as a case series by Sellmer et al.,26
which revealed
a mortality rate of 75%. Furthermore, Baxi et al.27
examined rates of NEC in infants with
congenital heart disease (CHD). They reported a higher death rate in the CHD and NEC group
when compared to matched controls (p = 0.04), and found that 84.4% had received a BT prior to
the diagnosis of NEC. BPD is another recognized complication of BTs in premature infants, and
the present study found higher mortality in premature infants in both BT and non-BT groups,
which suggests that BPD is associated with SNEC.
There are limitations in the present study that should be addressed. There are obvious
biases in a retrospective study that are avoided in a prospective, randomized study. However,
there are ethical concerns with randomization of neonates,28
and retrospective studies provide
valuable information on rare complications. Secondly, the data in the KID is made up by ICD-9
codes, which is dependent on appropriate billing and limits our inclusion and exclusion criteria,

11. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
10
such as gestational age or birth weight. Regardless, database studies are essential in pooling
national data, and results may be more generalizable to the population as a whole. The KID
specifically provides detailed data regarding pediatric disease, and its advantages have been
previously reported.18,29,30
The complex pathophysiology of NEC leaves no surprise of the significant morbidity and
mortality. With improving guidelines on transfusion practices, reports have suggested a
relationship between PRBC transfusions and the development of NEC. Using a national database
and using a PS matched analysis, we found that SNEC occurs at higher rates with BT and
confers lower survival and worse outcomes, but results in lower resource utilization when
compared to cases of SNEC without BT.
References
1. Kosloske AM. Epidemiology of necrotizing enterocolitis. Acta Paediatr Suppl.
1994;396:2-7.
2. Gephart SM, McGrath JM, Effken JA, Halpern MD. Necrotizing enterocolitis risk: state
of the science. Adv Neonatal Care. Apr 2012;12(2):77-87; quiz 88-79.
3. Derienzo C, Smith PB, Tanaka D, Bandarenko N, Campbell ML, Herman A, et al.
Feeding practices and other risk factors for developing transfusion-associated necrotizing
enterocolitis. Early Hum Dev. May 2014;90(5):237-240.
4. Widness JA. Pathophysiology of Anemia During the Neonatal Period, Including Anemia
of Prematurity. Neoreviews. Nov 1 2008;9(11):e520.
5. McGrady GA, Rettig PJ, Istre GR, Jason JM, Holman RC, Evatt BL. An outbreak of
necrotizing enterocolitis. Association with transfusions of packed red blood cells. Am J
Epidemiol. Dec 1987;126(6):1165-1172.
6. Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, et al.
Association of necrotizing enterocolitis with elective packed red blood cell transfusions
in stable, growing, premature neonates. Am J Perinatol. Nov 2006;23(8):451-458.
7. Christensen RD, Lambert DK, Henry E, Wiedmeier SE, Snow GL, Baer VL, et al. Is
"transfusion-associated necrotizing enterocolitis" an authentic pathogenic entity?
Transfusion. May 2010;50(5):1106-1112.
8. Josephson CD, Wesolowski A, Bao G, Sola-Visner MC, Dudell G, Castillejo MI, et al.
Do red cell transfusions increase the risk of necrotizing enterocolitis in premature
infants? J Pediatr. Dec 2010;157(6):972-978 e971-973.

12. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
11
9. Singh R, Visintainer PF, Frantz ID, 3rd, Shah BL, Meyer KM, Favila SA, et al.
Association of necrotizing enterocolitis with anemia and packed red blood cell
transfusions in preterm infants. J Perinatol. Mar 2011;31(3):176-182.
10. El-Dib M, Narang S, Lee E, Massaro AN, Aly H. Red blood cell transfusion, feeding and
necrotizing enterocolitis in preterm infants. J Perinatol. Mar 2011;31(3):183-187.
11. Blau J, Calo JM, Dozor D, Sutton M, Alpan G, La Gamma EF. Transfusion-related acute
gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red
blood cell transfusion. J Pediatr. Mar 2011;158(3):403-409.
12. Paul DA, Mackley A, Novitsky A, Zhao Y, Brooks A, Locke RG. Increased odds of
necrotizing enterocolitis after transfusion of red blood cells in premature infants.
Pediatrics. Apr 2011;127(4):635-641.
13. Holder GL, Dohert D, Patole S. Elective red cell transfusion for anemia of prematurity
and development of necrotizing enterocolitis in previously well preterm neonates:
incidence and difficulties in proving a cause-effect association. J Neonat Perinat Med.
2009;2(3):181-186.
14. Stritzke AI, Smyth J, Synnes A, Lee SK, Shah PS. Transfusion-associated necrotising
enterocolitis in neonates. Arch Dis Child Fetal Neonatal Ed. Jan 2013;98(1):F10-14.
15. Valieva OA, Strandjord TP, Mayock DE, Juul SE. Effects of transfusions in extremely
low birth weight infants: a retrospective study. J Pediatr. Sep 2009;155(3):331-337 e331.
16. Wan-Huen P, Bateman D, Shapiro DM, Parravicini E. Packed red blood cell transfusion
is an independent risk factor for necrotizing enterocolitis in premature infants. J
Perinatol. Oct 2013;33(10):786-790.
17. Mohamed A, Shah PS. Transfusion associated necrotizing enterocolitis: a meta-analysis
of observational data. Pediatrics. Mar 2012;129(3):529-540.
18. Tashiro J, Perez EA, Sola JE. Reduced Hospital Mortality With Surgical Ligation of
Patent Ductus Arteriosus in Premature, Extremely Low Birth Weight Infants: A
Propensity Score-matched Outcome Study. Ann Surg. Mar 27 2015.
19. Stone ML, Lapar DJ, Kane BJ, Rasmussen SK, McGahren ED, Rodgers BM. The effect
of race and gender on pediatric surgical outcomes within the United States. J Pediatr
Surg. Aug 2013;48(8):1650-1656.
20. Stone ML, LaPar DJ, Mulloy DP, Rasmussen SK, Kane BJ, McGahren ED, et al. Primary
payer status is significantly associated with postoperative mortality, morbidity, and
hospital resource utilization in pediatric surgical patients within the United States. J
Pediatr Surg. Jan 2013;48(1):81-87.
21. Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity measures for use with
administrative data. Med Care. Jan 1998;36(1):8-27.
22. Consumer Price Index Inflation Calculator. 2014;
http://www.bls.gov/data/inflation_calculator.htm. Accessed June 1, 2015.
23. Bell EF, Strauss RG, Widness JA, Mahoney LT, Mock DM, Seward VJ, et al.
Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in
preterm infants. Pediatrics. Jun 2005;115(6):1685-1691.
24. Strauss RG. Anaemia of prematurity: pathophysiology and treatment. Blood Rev. Nov
2010;24(6):221-225.
25. Couselo M, Fonseca R, Mangas L, Vila JJ. Surgical Findings in Transfusion-Associated
Necrotizing Enterocolitis. Eur J Pediatr Surg. May 26 2015.

13. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
12
26. Sellmer A, Tauris LH, Johansen A, Henriksen TB. Necrotizing enterocolitis after red
blood cell transfusion in preterm infants with patent ductus arteriosus: a case series. Acta
Paediatr. Dec 2012;101(12):e570-572.
27. Baxi AC, Josephson CD, Iannucci GJ, Mahle WT. Necrotizing enterocolitis in infants
with congenital heart disease: the role of red blood cell transfusions. Pediatr Cardiol.
Aug 2014;35(6):1024-1029.
28. Modi N. Ethical pitfalls in neonatal comparative effectiveness trials. Neonatology.
2014;105(4):350-351.
29. Sola JE, Bronson SN, Cheung MC, Ordonez B, Neville HL, Koniaris LG. Survival
disparities in newborns with congenital diaphragmatic hernia: a national perspective. J
Pediatr Surg. Jun 2010;45(6):1336-1342.
30. Tashiro J, Wang B, Sola JE, Hogan AR, Neville HL, Perez EA. Patent ductus arteriosus
ligation in premature infants in the United States. J Surg Res. Feb 12 2014;190(2):613-
622.

14. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
13
Figure Legend
Figure 1. Prognostic indicators of mortality in premature infants with surgical necrotizing
enterocolitis (SNEC) by comorbidity and transfusion, Kids’ Inpatient Database, 2003-2009.
NEC – necrotizing enterocolitis. Plots represent selected mortality odds ratio (OR) values
derived from binary logistic regression models for mortality; error bars represent 95%
confidence intervals for ORs. OR plots not shown were not significant determinants at α = 0.05.
Area under the curve (95% confidence interval) demonstrating overall model performance: 0.982
(0.962, 0.999) for transfusion, 0.940 (0.911, 0.968) for no blood transfusion group.

15. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
14
SNEC with blood
transfusion
n=493 (1.53% of BT)
SNEC with no blood
transfusion
n=1049 (0.17% of non-BT)
Baseline
Comparison
p
Length of stay, days 51 (76) 81 (88) <0.001
Total cost, US $ 329,911 (550,834) 458,626 (582,048) 0.002
Survival
Alive 287 (58%) 727 (69%) <0.001
Dead 206 (42%) 322 (31%) Ref
Year
2003 91 (19%) 259 (25%) <0.001
2006 147 (30%) 348 (33%) 0.013
2009 255 (52%) 442 (42%) Ref
Sex
Male 287 (58%) 628 (60%) NS
Female 206 (42%) 420 (40%) Ref
Race
White 182 (41%) 311 (44%) Ref
African American 98 (22%) 175 (25%) NS
Hispanic 103 (23%) 140 (20%) NS
Asian/PI 25 (6%) 22 (3%) 0.028
Native American * (< 2%) * (< 2%) *
Other 29 (6%) 52 (7%) NS
Payer
Medicaid 240 (49%) 585 (56%) 0.015
PI/HMO 216 (44%) 399 (38%) Ref
Self-pay * (< 2%) * (< 2%) *
Other 26 (5%) 43 (4%) NS
Median income
First quartile 169 (35%) 333 (32%) Ref
Second quartile 92 (19%) 276 (27%) 0.006
Third quartile 111 (23%) 253 (25%) NS
Fourth quartile 105 (22%) 164 (16%) NS
Hospital bed size
Small 52 (11%) 93 (10%) NS
Medium 121 (26%) 156 (17%) <0.001
Large 295 (63%) 680 (73%) Ref
Location/teaching
Rural * (< 2%) * (< 2%) *
Urban nonteaching 54 (11%) 95 (10%) NS
Urban teaching 415 (89%) 827 (89%) Ref
NACHRI type
NIACH 180 (39%) 283 (31%) 0.001
CGH 116 (25%) 215 (24%) NS
CUGH 171 (37%) 414 (45%) Ref
Region
Northeast 149 (30%) 123 (12%) <0.001
Midwest 84 (17%) 387 (37%) <0.001
South 63 (13%) 223 (21%) <0.001
West 197 (40%) 316 (30%) Ref

16. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
15
Gestational age, week
<24 34 (7%) 33 (3%) 0.001
24 48 (10%) 138 (13%) NS
25-26 111 (22%) 257 (25%) Ref
27-28 70 (14%) 208 (20%) NS
29-30 52 (10%) 150 (14%) NS
31-32 66 (13%) 102 (10%) 0.037
33-34 67 (14%) 101 (10%) 0.027
35-36 46 (9%) 60 (6%) 0.011
Birth weight, grams
<500 12 (2%) 19 (2%) NS
500-749 113 (23%) 225 (23%) NS
750-999 103 (21%) 236 (24%) Ref
1000-1249 48 (10%) 135 (14%) NS
1250-1499 46 (9%) 122 (13%) NS
1500-1749 40 (8%) 63 (6%) NS
1750-1999 22 (5%) 57 (6%) NS
2000-2499 65 (13%) 86 (9%) 0.006
≥ 2500 34 (7%) 37 (4%) 0.004
Cardiac anomalies 19 (4%) 10 (1%) <0.001
BPD 91 (18%) 272 (26%) 0.001
IVH 160 (32%) 226 (22%) <0.001
Sepsis 254 (52%) 620 (59%) 0.005
RDS 299 (61%) 658 (63%) NS
Multiple gestation 68 (14%) 177 (17%) NS
Table 1. Characteristics of surgical necrotizing enterocolitis (SNEC) occurring in blood
transfusion (BT) vs. non-blood transfusion (non-BT) cases. Continuous variables are presented
as median (interquartile range), whereas categorical variables are presented as n (%). Baseline
comparison analyses were performed; NS – not significant at α = 0.05. Asterisks (*) represent
values censored in accordance with HCUP Data Use Agreement. Asian/PI – Asian or Pacific
Islander; PI/HMO – private insurance / health maintenance organization; NACHRI – National
Association of Children’s Hospitals and Related Institutions, NIACH – not identified as a
children’s hospital, CGH – freestanding children’s general hospital, CUGH – children’s unit in a
general hospital; BPD – bronchopulmonary dysplasia, IVH – intraventricular hemorrhage, RDS
– respiratory distress syndrome.

17. ACCEPTED
MANUSCRIPT
ACCEPTED MANUSCRIPT
16
Blood transfusion
(n = 20,991)
No blood transfusion
(n = 20,988)
n % n % p
SNEC rate 351 1.67% 291 1.39% 0.017
Survival 204/351 58.1% 194/291 66.7% 0.026
LOS, days 47 (74) 88 (70) <0.001
TC, US $ 351,381 (578,577) 557,481 (535,191) <0.001
Table 2. Results of propensity score-matched analyses of surgical necrotizing enterocolitis
occurring in blood transfusion vs. non-blood transfusion cases. SNEC – surgical necrotizing
enterocolitis, LOS – length of stay, TC – total charges.