Wang et al. BMC Pediatrics(2024) 24:512
https://doi.org/10.1186/s12887-024-04978-7

BMC Pediatrics

RESEARCH

Open AccessInfluencing factors for surgical treatment
in neonatal necrotizing enterocolitis:a systematic review and meta-analysis
Dandan Wang1, Fanhui Zhang1, Jiarong Pan1, Tianming Yuan1 and Xuefeng Jin2*
Abstract
Background Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation andis one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical
treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited
and largely dependent on the surgeon’s experience, leading to variability in outcomes. The primary aim of this study is
to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for
surgical intervention.
Methods A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control
studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, anddata analysis was performed using R Studio 4.3.2.
Results 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatmentgroup. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower
gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45,
95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07,
1.39)] are significant risk factors for surgical treatment in neonatal NEC.
Conclusions High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, andhyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential
clinical significance for predicting surgical risk.
Keywords Neonate, Necrotizing enterocolitis, Risk factors, Meta-analysis*Correspondence:
Xuefeng Jin
82152025@163.com
1
Department of Neonatology, Children’s Hospital, Zhejiang University
School of Medicine, National Clinical Research Center for Child Health,3333#, Bin Sheng Road, Hangzhou, Zhejiang 310052, P.R. China
2
Department of Gastroenterology, Hangzhou Children’s Hospital, 195#,
Wen Hui Road, Gong Shu Distric, Hangzhou, Zhejiang 310014, P.R. China© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified thelicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to thematerial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation
or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/.

Wang et al. BMC Pediatrics(2024) 24:512

Introduction
Necrotizing enterocolitis (NEC) is a complex diseasecharacterized by gastrointestinal inflammation and is
one of the most common gastrointestinal emergencies
in neonates. The disease is marked by mucosal ischemic
necrosis, abdominal mass, erythema of the abdominal
wall, pneumatosis intestinalis, portal venous gas, and, insevere cases, pneumoperitoneum [1]. NEC is notorious
for its rapid onset, diagnostic challenges, and high mortality rate, posing a severe threat to neonatal life.
Due to the absence of reliable epidemiological data,
the true incidence of neonatal NEC remains unclear [2].
However, estimates from various reports in the UnitedStates suggest an incidence rate of 0.1-0.3% [3, 4], withover 30-50% of NEC patients requiring surgical intervention [5–7]. The overall mortality rate post-surgery ranges
from 20 to 30% [8] and up to 50% in some reports [2, 9].
Survivors often suffer from multiple complications, leading to lifelong disabilities such as intestinal stricture,
short bowel syndrome, malnutrition, and neurodevelopmental delays, which significantly decrease the qualityof life for the patients and their families due to the highcosts of ongoing treatment [10–13].
The treatment for NEC depends on the severity of thecondition. Medical treatment for mild to moderate cases
includes cessation of enteral feeds, empirical antibiotic
therapy, supportive care, and close monitoring of vital
signs. Severe cases require surgical intervention, suchas intestinal resection, peritoneal drainage, and medical
treatment [1]. Intestinal perforation is an absolute indication for surgery for NEC. However, evidence for othersurgical indications is scarce and largely dependent on
the surgeon’s experience, leading to outcome variability.
The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which
will aid in predicting the optimal timing for surgicalintervention, allowing these patients to benefit from earlier surgery, preserving more viable intestinal segments,
reducing complications, and improving outcomes.
Methods
The primary aim of this study is to identify the main factors leading to surgical treatment in NEC and lay thegroundwork for early preventive measures. This study
was registered in the PROSPERO International Prospective Register of Systematic Reviews (Registration number: CRD42023424160) and is reported following thePreferred Reporting Items for Systematic Reviews andMeta-Analyses (PRISMA) guidelines [14].
Search strategy

A comprehensive search was conducted in the PubMed,
Embase, and Web of Science databases for case-control studies on the risk factors for NEC requiring

Page 2 of 10

surgical treatment up to June 16, 2024. The search strategy involved a combination of MeSH terms and free text
terms, including “neonate,” “preterm,” “surgery,” “Peritoneal drainage,” “Intestinal Resection,” and “Necrotizing Enterocolitis.” Manual searches of references fromrelevant articles and reviews were also conducted toensure comprehensiveness. The detailed search strategy
is described in Supplementary Material 1.
Inclusion and exclusion criteria

Inclusion criteria:

1. The study population consists of patients with NEC.
2. The study design includes case-control.
3. The focus of the study is on risk factors or
influencing factors for surgical treatment of NEC.
4. Clear outcome indicators are obtainable fromthe original articles, including but not limited tocomputable outcome measures such as odds ratios(ORs).
5. The most comprehensive or recent publication is
selected when articles have similar authors andcontent.
6. The article is published in English.
Exclusion criteria:
1. Conference abstracts, meta-analyses, protocols,letters, systematic reviews, and animal studies.
2. Non-English publications.
3. Studies for which the full text is not available.
4. Studies with duplicate data.
Studies with incomplete data records that cannot betransformed or studies with significant errors in researchor statistical methods.
Data extraction

Two researchers independently screened the literature,
extracted data, and reviewed titles, abstracts, and fulltexts, directly filtering easily evaluated articles. Expert
opinions were sought for studies with potential disputes,
and full texts were directly downloaded for screening.
During the screening process, inclusion and exclusion
criteria were strictly followed. Relevant indicators fromthe studies were extracted, and the extracted data werecross-checked to ensure consistency. The primary data
extraction content included the first author, year of publication, country, sample size, study period, type of study,
influencing factors, and outcome indicators. The main
outcome indicators included results from both univariate and multivariate analyses. When a paper reported
univariate and multivariate results, the adjusted risk values from the multivariate analysis were prioritized for

Wang et al. BMC Pediatrics(2024) 24:512

extraction; otherwise, the univariate results were used if
only univariate analysis were available.
Risk of bias

The Newcastle-Ottawa Scale (NOS) was used to assess
the quality of the case-control studies, including theselection of study groups (4 points), comparability ofgroups (2 points), and ascertainment of either the exposure or outcome of interest (3 points) [15]. The total scoreis 9 points, with ≤ 4 points indicating low quality, 5–6
points indicating medium quality, and ≥ 7 points indicating high quality. If there was a disagreement between thetwo researchers during the evaluation process, the decision will be discussed through all authors.
Statistical analysis

R Studio version 4.3.2 was used for statistical analysis.
The risk value of each study was described by the OR
value. The OR value and 95% confidence interval (CI)were taken as the effect size, and the effect sizes werepooled for the same factor mentioned in three or more
original studies. Depending on the heterogeneity test
I² statistic result, an appropriate model was selected to
calculate the pooled OR value. A random-effects model
was used if I² > 50%; a fixed-effects model was used if I²≤ 50% [16–18]. The significance level was set at α = 0.05,
with P < 0.05 considered statistically significant. If there
were ≥ 10 original studies for the same factor, funnel plots
combined with Egger’s test were used to assess publication bias.

Results
Literature search results

A preliminary search of the PubMed, Embase, and Web
of Science databases yielded 6,632 articles. After deduplication, 3,181 articles remained. By reviewing titles andabstracts, 83 articles were preliminarily selected, and 18
were finally included after a full-text review [7, 19–35].
The specific search process is illustrated in Fig. 1.
Characteristics of the included studies

Eighteen studies were included, originating from China(nine studies), and one study each from the USA, Canada, the UK, Poland, Italy, Spain, Tunisia, Korea, anda collaborative study between Belgium and the Netherlands. There were 1,104 patients in the surgery group and1,686 in the medical treatment group. The characteristicsof the included studies are detailed in Table 1.
The NOS was used to evaluate the included articles,with 13 studies rated 7–8 and the remaining five rated
5–6, indicating that the overall quality of the included
studies was high. The specific quality ratings are shownin Table 1.

Page 3 of 10

Factors influencing neonatal surgery in NEC
C-Reactive protein (CRP)

CRP was examined in nine studies and analyzed using arandom-effects model due to significant heterogeneity(I² = 82.43%, P < 0.001). The analysis indicated that elevated CRP levels are a significant risk factor for surgery
in neonatal NEC, with a statistically significant difference[OR = 1.42, 95% CI (1.01, 1.99)] (Fig. 2 and Table 2).
Gestational age

Gestational age was discussed in seven studies, and a random-effects model was employed for heterogeneity analysis (I² = 80.4%, P < 0.001). The results suggest that lower
gestational age is a significant risk factor for surgery inneonatal NEC, with a statistically significant difference[OR = 0.52, 95% CI (0.3, 0.91)] (Fig. 3 and Table 2).
Serum sodium

Serum sodium was mentioned in four studies and analyzed using a random-effects model due to significant
heterogeneity (I² = 82.4%, P < 0.001). The analysis indicated that hyponatremia is a significant risk factor for
surgical intervention in neonatal NEC, with a statistically significant difference [OR = 1.22, 95% CI (1.07, 1.39)](Fig. 4 and Table 2).
Sepsis

Sepsis was mentioned in three studies and analyzed
using a fixed-effects model due to low heterogeneity (I²= 19.9%, P = 0.287). The findings indicate that sepsis is asignificant risk factor for surgery in neonatal NEC, witha statistically significant difference [OR = 2.94, 95% CI(1.87, 4.60)] (Fig. 5and Table 2).
Coagulation disorders

Coagulation disorders were mentioned in three studies and analyzed with a fixed-effects model given noheterogeneity (I² = 0%, P = 0.629). The analysis suggeststhat coagulation disorders are a significant risk factor
for surgery in neonatal NEC, with a statistically significant difference [OR = 3.45, 95% CI (1.81, 6.58)] (Fig. 6 andTable 2).
Enteral Feeding

Enteral feeding was discussed in three studies and analyzed using a fixed-effects model due to no heterogeneity (I² = 0%, P = 0.567). The results suggest that the lackof enteral feeding is a significant risk factor for surgery
in neonatal NEC, with a statistically significant difference[OR = 3.18, 95% CI (1.37, 7.35)] (Fig. 7 and Table 2).
Meta-analysis of other factors

Factors such as gender, multiple births, birth weight,
delivery mode, WBC, PCT, PLT, and timing of NEC

Wang et al. BMC Pediatrics(2024) 24:512

Page 4 of 10

Fig. 1 Flowchart of literature search

onset showed no statistically significant impact on thenecessity for surgery in neonatal NEC (Table 2).
Publication bias

When fewer than ten studies were included as an influencing factor, the power of meta-analysis funnel plots,
Egger’s test, and Begg’s test for assessing publication bias
were low. No publication bias analysis was conductedsince all influencing factors in this study involved fewer
than ten articles.

Discussion
In this meta-analysis, we identified high CRP, coagulation
disorders, sepsis, lower gestational age, the lack of enteralfeeding, and hyponatremia as significant risk factors forsurgery in NEC.
CRP, an acute-phase protein, surges in response toinflammation, injury, or infection driven by cytokines.
Higher CRP levels are associated wit more severe theinflammatory responses [36, 37]. Inflammation involving
cytokine and chemokine release is a pathogenic mechanism in NEC, where an excessive inflammatory responsecompromises the integrity of the intestinal mucosa,
preventing self-repair and leading to NEC progression,
culminating in full-thickness intestinal necrosis and perforation [38]. Moreover, inflammation reduces mucosal

Wang et al. BMC Pediatrics(2024) 24:512

Page 5 of 10

Table 1 Literature characteristics table
Study

Year

PeriodCountry

GenderMale Female
136
113
81
73
115
89
27
22
104
91

Study design

NOS

Factors

China
China
China
AmericanCanadaSample size
sNEC mNEC
111
138
51
103
113
91
16
33
69
126

Zhang G
Chen L
Shi B
Liebe H
Cowap
M
Kang C
Yu L
Feng W
Zouari M
Cho A
GalazkaP
El Manouni El
HassaniS
Sharif SP

2024
2024
2023
2023
2023

2008–2022
2013.2-2023.2
2018.10-2022.12
2010.01-2022.01
1991–2016

Case-control
Case-control
Case-control
Case-control
Case-control

7
6
8
6
7

1,3,9,25,29,
25,30,31,32,33
1,19,22,27
4
13,14

2023
2022
2022
2022
2021
2021

2018.01-2020.12
2015.01-2019.12
2019.08-2020.06
2010.01-2022.03
2003.03-2016.09
-

China
China
China
Tunisia
Korea
Poland

78
41
46
25
87
56

57
143
68
77
102
20

70
101
61
66
110
43

65
83
53
36
79
33

Case-control
Case-control
Case-control
Case-control
Case-control
Case-control

8
7
8
7
8
5

2,3,4,5,8,11,13,17,25,26,27
2,4
3,19
1,2,5,6,10,12,24,28
23,24
5

2021

2014.10-2017.08

Netherlands
and Belgium

41

32

40

33

Case-control

8

1,2,3,5,6,7,8,9,10,12,14,15,16,21,28

20202009.01-2015.12

68

64

74

58

Case-control

7

2,5,6,72019

2003–2015

UnitedKingdom
Spain

GarciaGonzalez M
Duci M
He Y

47

77

77

47

Case-control

7

1,2,4,6,7,10,11,13,15,16,18,20,21,23,25,26

2018
2016

2002.01-2015.12
2000.01-2014.12

Italy
China

53
54

102
184

94
144

61
94

Case-control
Case-control

6
5

1,12,22
1,3,8,9,11,17,20

Notes: mNEC, NEC treated medically only; sNEC, NEC requiring surgery; 1, C-reactive protein (CRP); 2, gestational age; 3, platelet; 4, procalcitonin (PCT); 5,
birth weight; 6, gender; 7, multiple births; 8, sepsis; 9, white blood cell (WBC); 10, delivery mode; 11, coagulation disorder; 12, NEC onset days; 13, enteral feed;
14, corticosteroids (neonatal); 15, corticosteroids (maternal); 16, age mother at birth; 17, abdominal erythema; 18, glucose; 19, prothrombin time (PT); 20, bloodtransfusion; 21, haemoglobin (Hb); 22, intestinalis pneumatosis; 23, RDS; 24, breast milk feeding; 25, natremia; 26, kalemia; 27, acidosis; 28, mechanic ventilation
exposure; 29, fibrinogen; 30, increased bloody stools within 24 h; 31, oxygen inhalation; 32, using vasoconstrictors; 33, portal venous gas.

Fig. 2 Forest plot analysis of CRP

Wang et al. BMC Pediatrics(2024) 24:512

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Table 2 Analysis of factors influencing surgery in neonatal NEC
Factor

CRP
Gestational age
Platelet
PCT
Birth weight
GenderWBC
Natremia
Multiple births
SepsisWBC
Delivery mode
Coagulation disorder
NEC onset days
Enteral feed

GroupsHigh vs. Low
High vs. Low
High vs. Low
High vs. Low
High vs. Low
Male vs. Female
High vs. Low
Low vs. HighYes vs. No
With vs. Without
High vs. Low
Natural vs. CesareanWith vs. Without
Long vs. shortWith vs. Without

No of study

9
7
5
5
5
4
4
4
3
3
3
3
3
3
3

Sample size

1562
1017
827
642
518
431
827
662
329
446
578
435
497
330
454

OR (95%CI)

1.42(1.01, 1.99)
0.52(0.30, 0.91)
0.54(0.23, 1.27)
4.09(0.93, 17.94)
0.73(0.23, 2.25)
1.19(0.77, 1.83)
1.04(0.98, 1.11)
1.22 (1.07, 1.39)
1.43(0.84, 2.45)
2.94(1.87, 4.60)
1.32(0.73, 2.37)
1.31(0.79, 2.17)
3.45(1.81, 6.58)
0.58(0.23, 1.46)
3.18(1.37, 7.35)

Effects model

R
R
R
R
R
F
R
R
F
F
R
F
F
R
F

Global Effects
test
Z
P
2.04
0.041
2.31
0.021
0.6
0.551
1.87
0.062
0.56
0.579
0.77
0.44
1.41
0.157
2.92
0.004
1.32
0.186
4.7
< 0.001
0.92
0.358
1.06
0.288
3.76 < 0.001
1.16
0.247
2.70
0.007

heterogeneity
I2(%)
82.3
80.4
91.7
80.0
83.2
0.0
80.5
82.4
0.0
19.9
80.5
19.5
0.0
83.3
0.0

P
< 0.001< 0.001< 0.001
0.001< 0.001
0.442
0.002< 0.001
0.907
0.287
0.006
0.289
0.629
0.003
0.567

R: Random effects model; F: Fixed effects modelFig. 3 Forest plot analysis of gestational age

blood perfusion, leading to intestinal hypoxia and microcirculatory dysfunction, further exacerbating NEC [39,40]. Our study’s finding of a significant association
between elevated CRP and surgical risk [OR = 1.55, 95%
CI (1.02, 2.34)] suggests that persistently high CRP levels
usually indicate a hazardous condition, constituting a risk
factor for surgical intervention in neonatal NEC.
Coagulation disorders, defined by a deficiency orabnormal function of clotting factors, are increasingly
recognized for the extensive crosstalk between the
inflammatory and coagulation systems. The activationof one system can amplify the other, potentially leading
to tissue damage or multiorgan failure if unaddressed[39, 41]. NEC, an inflammatory intestinal necrosis,
exhibits signs of disseminated intravascular coagulation(DIC) in one-third of patients. DIC is characterized bydecreased plasma fibrinogen levels, positive fibrin degradation products (FDP) tests, and prolonged prothrombin time (PT) and activated partial thromboplastin time
(APTT), leading to mesenteric microthrombosis, intestinal hypoxia, and damage, including perforation [25, 42,43]. Our study indicates that coagulation dysfunction[OR = 3.45, 95%CI (1.81, 6.58)] is also a risk factor for
NEC surgery, suggesting that a dynamic understanding of
coagulation parameters can help clinicians preliminarily

Wang et al. BMC Pediatrics(2024) 24:512

Fig. 4 Forest plot analysis of serum sodium

Fig. 5 Forest plot analysis of sepsis

Fig. 6 Forest plot analysis of coagulation disorders

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Wang et al. BMC Pediatrics(2024) 24:512

Page 8 of 10

Fig. 7 Forest plot analysis of enteral feeding

decide on the necessity for surgery and formulate intervention strategies.
When NEC is accompanied by sepsis, pathogenic bacteria can directly damage the intestinal mucosa throughtoxin production and activate immune cells to release
many cytokines like tumor necrosis factor and interleukins. This cascade alters vascular permeability and tissue
damage, promotes platelet and leukocyte aggregation,
increases blood viscosity and inflammatory response,
exacerbates intestinal mucosal damage, and increases therisk of intestinal perforation [8]. This study found that
NEC infants with sepsis have a 2.94-fold higher risk ofrequiring surgical intervention compared to those without sepsis [95% CI (1.87, 4.60)]. Therefore, it is crucial tomaintain heightened vigilance and implement proactive
measures in NEC infants with sepsis to reduce the incidence of poor outcomes.
Gestational age is pivotal for the maturation of theintestinal barrier [44]. Preterm infants have immature
gastrointestinal development and lack effective protective mechanisms, such as gastric acid, digestive enzymes,
mucus, poor intestinal motility and incomplete intestinal physical and chemical barrier functions. These features increase susceptibility to intestinal diseases, making
them prone to intestinal perforation under triggering andenvironmental factors [45, 46]. Additionally, the immature immune system of preterm infants is prone to theoveractive inflammatory response associated with NEC,causing mucosal necrosis and perforation, resulting insevere NEC [27, 47]. Our findings indicate that lower gestational age is significantly associated with an increased
risk of surgical intervention in NEC [OR = 0.52, 95% CI(0.3, 0.91)].
Although many cases of NEC occur after the initiationof feeding, early minimal enteral feeding has been shown
to promote gut maturation [48]. Studies have found thatadministering initial minimal enteral feedings of 10–20
mL/(kg·d) for 3–7 days can reduce the incidence of NEC

in very low birth weight (VLBW) infants [49]. Enteralfeeding, particularly breastfeeding, is associated with alower risk of severe NEC. This protective effect is attributed to the presence of beneficial bacteria such as Lactobacillus and Bifidobacterium, as well as various bioactive
substances in breast milk, including immunoglobulins,
lactoferrin, lysozyme, and cytokines [50–52]. Infants who
do not receive enteral feeding, many of whom are fasted
from birth, are often in poorer condition and more likely
to develop severe NEC requiring surgical intervention[7]. In our study, NEC infants who did not receive enteralfeeding had a 3.18-fold higher risk of surgery than those
who did receive enteral feeding [OR = 3.18, 95% CI (1.37,
7.35)]. Therefore, enteral feeding, especially with breast
milk, has a protective effect against the progression ofNEC.
Hyponatremia is also significantly associated with anincreased risk of surgical intervention in NEC [OR = 1.22,
95% CI (1.07, 1.39)]. The precise pathophysiologicalmechanisms remain unclear, but the theory of antidiuretic hormone (ADH) secretion abnormalities causing
hyponatremia is widely accepted. As NEC progresses, asubstantial release of pro-inflammatory cytokines, suchas IL-1β, IL-6, and IL-8, occurs. These cytokines stimulate the secretion of ADH, resulting in impaired water
excretion and subsequent hyponatremia [53–55]. Therefore, serum sodium levels can indirectly reflect the severity of the disease.
Low birth weight often accompanies low gestational
age. However, in this study, birth weight was not identified as a risk factor for surgical intervention (P = 0.579).
The increased anesthetic and surgical risks for extremely
low birth weight neonates often lead surgeons to prefermedical management. This preference for non-surgicalintervention paradoxically protects against surgical intervention for NEC [28].
Half of the studies included in this research originatedfrom China, reflecting the country’s active contribution

Wang et al. BMC Pediatrics(2024) 24:512

to this field. It is important to acknowledge that differences in neonatal care facilities, professional training,
and treatment approaches exist across countries, which
may influence NEC treatment strategies and overall outcomes. Future research should consider these regional
differences and explore how to develop personalized
NEC management strategies based on the local healthcare environment and available resources.
Limitations of the study

This study has several limitations. First, we only included
studies published in English, potentially omitting significant research published in other languages. Second,although many influencing factors were analyzed, manystudies addressing the same factor were limited, reducing the statistical power and the likelihood of identifying
positive associations. Third, the inclusion of both univariate and multivariate results may have introduced bias
into the findings. Fourth, there was heterogeneity in thefactors of CRP, serum sodium, and gestational age, but
the limited number of studies prevented us from exploring the sources of this heterogeneity. Finally, the included
studies were observational and potentially subject toresidual confounding bias.

Conclusion
Our analysis indicates that high CRP, coagulation disorders, sepsis, lower gestational age, the lack of enteralfeeding, and hyponatremia are significant risk factors for
surgical intervention in neonatal NEC. These risk factors
hold potential clinical significance for predicting surgicalrisk, aiding in early treatment, reducing complications,and improving prognosis.
Abbreviations
NEC	Necrotizing enterocolitis
CRP	C-reactive protein
PRISMA	Preferred Reporting Items for Systematic Reviews andMeta-Analyses
ORs	odds ratios
NOS	Newcastle-Ottawa ScaleCI	confidence interval
DIC	disseminated intravascular coagulation
PCT	procalcitoninWBC	white blood cellPT	prothrombin timeHb	haemoglobin
ADH	antidiuretic hormone
VLBW	very low birth weight
FDP	fibrin degradation products

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-04978-7.
Supplementary Material 1
Supplementary Material 2
Supplementary Material 3

Page 9 of 10

Acknowledgements
Not applicable.
Author contributions
D. W., Conceptualization, Formal analysis, Investigation, Visualization, Writingoriginal draft, Writing-review & editing. F. Z., Formal analysis, Investigation,
Methodology. T. Y., Formal analysis, Investigation, Methodology. J. P.,
Investigation, Methodology. X. J., Conceptualization, Formal analysis, Funding
acquisition, Methodology, Project administration, Resources, Supervision,
Validation, Visualization, Writing - review & editing.
Funding
This work was supported by A Project Supported by Scientific Research Fundof Zhejiang Provincial Education Department (Y202353843) and Hangzhou
Medical Science and Technology Program Project (A20200779).
Data availability
All data relevant to the study are included in the article or uploaded as
supplemental information.

Declarations
Ethics approval and consent to participate
The current study is a meta-analysis and review, without collecting internal
data from patients or files, so no formal IRB approval was requested by theuniversity.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Conflict of interest
The authors declare that the research was conducted without commercial or
financial relationships construed as a potential conflict of interest.
Received: 21 April 2024 / Accepted: 29 July 2024

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