Background
Methods
Study selection
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Studies were included for analysis if satisfying all following criteria: (1) full English written publications, (2) with a prospective or retrospective cohort study or nested case-control design (3) identifying (neonatal or non-neonatal) prognostic factors for NEC (primary or secondary outcome), (4) using multivariable data analysis including more than 2 co-variates, (5) in a study population of neonates/newborns, preterm infants, very low birth weight (VLBW) or extremely low birth weight (ELBW) infants. No explicit use of the term prognostic was required for inclusion.
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Excluded were studies (1) only reporting on associative models of one or two variables with NEC (also if adjustment for potential confounders was performed), or (2) focusing only on risk factors for other abdominal problems than NEC such as spontaneous focal intestinal perforation, viral enteritis and allergic colitis.
Quality assessment
Data extraction and reporting
Results
Search and inclusion
Study characteristics
Study | Study participation (max. 15) | Study attrition (max. 15) | Prognostic factor measurement (max. 15) | Outcome measurement (max. 15) | Statistical analysis and reporting (max. 15) | Quality score (max. 75) |
---|---|---|---|---|---|---|
Gephart et al. (2014) [18] | 15 | 5 | 12.5 | 15 | 15 | 62.5 |
Lee et al. (2016) [38] | 15 | 5 | 12.5 | 12.5 | 15 | 60 |
Youn et al. (2015) [30] | 15 | 5 | 12.5 | 12.5 | 15 | 60 |
Boo et al. (2012) [21] | 15 | 5 | 12.5 | 10 | 15 | 57.5 |
Drenckpohl et al. (2010) [36] | 15 | 5 | 10 | 12.5 | 15 | 57.5 |
Guthrie et al. (2003) [23] | 15 | 5 | 10 | 12.5 | 15 | 57.5 |
Yee et al. (2012) [27] | 15 | 5 | 12.5 | 10 | 15 | 57.5 |
Gagliardi et al. (2008) [28] | 15 | 5 | 12.5 | 7.5 | 15 | 55 |
Manogura et al. (2008) [39] | 15 | 5 | 10 | 10 | 15 | 55 |
Yamoto et al. (2016) [26] | 15 | 5 | 10 | 10 | 15 | 55 |
Faustini et al. (2003) [37] | 13.5 | 5 | 10 | 12.5 | 12.5 | 53.5 |
Carter et al. (2008) [22] | 15 | 5 | 10 | 10 | 12.5 | 52.5 |
Luig et al. (2004) [25] | 15 | 5 | 10 | 7.5 | 15 | 52.5 |
Uauy et al. (1991) [24] | 12 | 5 | 10 | 10 | 12.5 | 49.5 |
Author | Country (year) | Design | Type of analysis |
N included | Male (%) | Study population | Outcome | NEC type | Significant prognostic factors from multivariable analysis with p < 0.05 |
---|---|---|---|---|---|---|---|---|---|
Boo et al. (2012) [21] | Malaysia (2007) | Retrospective | Multivariable | 3601 | 52% | VLBW (≤1500 g) | NEC | II, III | Maternal age, BW, surfactant, intrapartum antibiotics, indomethacin, surfactant, congenital pneumonia |
Carter et al. (2008) [22] | United States (unknown) | Retrospective | Multivariable | 134 | 54% | GA <35 weeks, BW <1500 g or requiring mechanical ventilation at birth | NEC | II, III | Number of infections, ventilation |
Drenckpohl et al. (2010) [36] | United States (2002–2008) | Retrospective | Multivariable | 324 | 54% | GA 23–36 weeks | NEC | II, III | Ethnicity, PROM, sepsis, H2 blockers in TPN |
Faustini et al. (2003) [37] | Italy (1999) | Retrospective | Multivariable | 221 | 49% | Live births of the university hospital in Rome | NEC | I, II | Any neonatal pathological condition, first time feeding with formula, any invasive procedure |
Gagliardi et al. (2008) [28] | Italy (1999–2002) | Prospective | Multivariable | 2035 | 51% | VLBW (<1500 g), GA 23–37 weeks | NEC-medical, NEC-surgical | II, III | Assisted ventilation, PDA, surfactant, Late-onset sepsis |
Gephart et al. (2014) [18] | United States (2007–2011) | Retrospective | Multivariable (Prediction model) | 35,013 | 50% | BW <1500 g and GA < 36 weeks | NEC-surgical, NEC-medical | II, III | GA, outborn, ethnicity, dopamine, dobutamine or milrinone combined with hypotension, metabolic acidosis, probiotics, late sepsis, PRBC transfusion, 2 or more positive cultures (blood, urine, other), human milk at day 7 and 14 of life, unit NEC rate |
Guthrie et al. (2003) [23] | United States (1998–2000) | Retrospective | Multivariable | 15,072 | 53% | GA 23–34 weeks | NEC-surgical, NEC-medical | II, III | BW, antenatal glucocorticoids, umbilical vessel catheterization, assisted ventilation, type of delivery, exposed both glucocorticoids and indomethacin during first week of life, Apgar score 5 min. |
Lee et al. (2016) [38] | South Korea (2003–2014) | Retrospective | Multivariable | 354 | 53% | GA 23–31(+6) weeks | NEC | II, III | Maternal blood NLR, multiparity, BW, GA |
Luig et al. (2004) [25] | Australia (1994–1999) | Retrospective | Multivariable | 4649 | 55% | All NICU admissions | NEC | II, III | Placental abruption, GA (weeks), SGA, year of birth, hyaline membrane disease, hypertensive disease of pregnancy |
Manogura et al. (2008) [39] | United States (1997–2006) | Prospective | Multivariable | 404 |
a
| Neonates with suspected IUGR | NEC | II, III | BW, base deficit |
Uauy et al. (1991) [24] | United States (1988–1989) | Prospective | Multivariable | 2681 |
a
| Infants admitted to one of the network centers <1500 g | NEC | II, III | Center of birth, ethnicity/gender, BW, maternal haemorrhage, duration of ROM, cesarean section |
Yamoto et al. (2016) [26] | Japan (2006–2015) | Retrospective | Multivariable | 323 | 53% | BW <1000 g | NEC, FIP, MRI | II, III | Gestational age of <26 weeks, severe cardiac malformations, not received EAP |
Yee et al. (2012) [27] | Canada (2003–2008) | Retrospective | Multivariable | 16,669 | 54% | GA <33 weeks | Early-Onset NEC, Late-Onset NEC | II, III | GA, SGA, outborn/inborn, congenital anomalies, narcotic use in <3 days, postnatal glucocorticoids |
Youn et al. (2015) [30] | Korea (2013–2014) | Prospective | Multivariable | 2326 | 50% | VLBW (<1500 g) | NEC | II, III | hypotension ≤1 week |
Prognostic factors
Prognostic factor | High quality | Moderate quality | Low quality |
---|---|---|---|
Birth weight | 1× | 4× | - |
Gestational age (weeks) | 1× | 3× | - |
Sepsis | 1× | 2× | - |
Ethnicity | 1× | 2× | - |
Hypotension | 1× | 1× | - |
Outborn | 1× | 1× | - |
Assisted ventilation | - | 3× | - |
Cesarean section | - | 2× | - |
PROM | - | 2× | - |
Small for gestational age | - | 2× | - |
Surfactant | - | 2× | - |
First author: | Boo | Carter | Drenckpohl | Faustini | Gagliardi | Gephart | Guthrie | Lee | Luig | Manogura | Uauy | Yamoto | Yee | Youn |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(Low) birth weightb
| OR 0.999 [0.998,0.999]c
| OR 1.001 [p = 0.164]d,e
| OR 1 [1.000,1.001] | . | . | . |
p < 0.001f
| OR 0.07 [0.01,0.53]g
| . |
p < 0.001f
| OR 0.999 [p < 0.001]c,d,h
| . | . | . |
Gestational age (weeks)b
| . | . | . | . | . | OR 2.37 [1.78,3.16]i
| . | OR 1.14 [0.85,1.54]g
| OR 0.82 [0.77,0.89]g
| . | . | OR 19.32 [3.27,370.43]j
| OR 0.84 [0.81,0.87]g
| . |
Sepsis | . | . | OR 4.98 [2.2,11.27]a
| . | OR 5.38 [2.86,10.14]k
| OR 1.49 [1.30,1.72]k
| . | OR 1.41 [0.42,4.67]a
| . | . | . | . | . | OR 1.75 [0.71,2.86]l
|
Ethnicity | . | OR 0.571 [p = 0.317]d,m
| OR 0.36 [0.17,0.78]n
| . | . | OR 1.22 [1.09,1.35]m
| . | . | . | . | OR 1.68 [p < 0.001]d,h,m
| . | . | . |
Hypotension | . | . | . | . | . | OR 1.51 [1.36,1.69]o
| . | . | . | . | . | . | . | OR 2.00 [1.001,3.999]o
|
Outborn | . | . | . | . | . | OR 1.31 [1.17,1.46] | . | . | . | . | . | . | OR 1.55 [1.31,1.83] | . |
Assisted ventilation | . | OR 1.053 [p = 0.047]d,a
| . | . | OR 2.71 [1.03,7.15]a
| . | OR 3.5 [2.5,4.7]p
| . | . | . | . | . | . | . |
Cesarean section | . | . | . | . | . | . | OR 0.60 [0.50,0.80] | . | . | . | OR 0.60 [p < 0.001]d,h
| . | . | . |
PROM | . | . | OR 2.06 [1.02,4.16] | . | . | . | . | . | . | . | OR 1.10 [p < 0.009]d,h
| . | . | . |
Small for gestational ageb
| . | . | . | . | . | . | . | . | OR 1.97 [1.19,3.26]a
| . | . | . | OR 1.35 [1.08,1.69]q
| . |
Surfactant | OR 1.59 [1.17,2.16] | . | . | . | OR 0.41 [0.19,0.90] | . | . | . | . | . | . | . | . | . |