Prognostic Factors in Preterm Infants with Neonatal Gastrointestinal Perforation: A Retrospective Cohort Study

doi:10.21203/rs.3.rs-1445391/v1

Download PDF

Research Article

Prognostic Factors in Preterm Infants with Neonatal Gastrointestinal Perforation: A Retrospective Cohort Study

https://doi.org/10.21203/rs.3.rs-1445391/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Gastrointestinal perforation (GIP) among neonates is a major clinical emergency associated with high mortality, which is severe and life-threatening, especially in preterm infants. This study aimed to describe the clinical features of preterm neonatal gastrointestinal perforation and evaluate the potential prognostic factors.

Methods

A total of 191 preterm neonates with gastrointestinal perforation were included in this retrospective cohort study and assigned to survival and non-survival groups. Information containing clinical and demographic data, laboratory and imaging features, and outcomes were collected and recorded by retrospective medical records review. The independent factors associated with death risk were determined by univariate and multivariate logistic regression analyses.

Results

The overall mortality in the study cohort was 25.1%. The median age of onset of gastric perforation was 3 days (range: 1–11 days), while the median age of onset of intestinal perforation was 7.5 days (range: 1–30 days). Abdominal distension (184 [96.3%] patients) was the most common symptom, followed by absent bowel sounds (157 [82.2%] patients), lethargy (148 [77.5%] patients), and shortness of breath (60 [59.4%] patients). Finally, three independent mortality risk factors were identified: severe acidosis (OR,7.604; 95% CI, 1.424‒51.910; p = 0.025), shock (5.131; 2.419‒11.266; p < 0.001) and coagulopathy (3.269; 1.511–7.431; p = 0.003).

Conclusions

Severe acidosis, shock, and coagulopathy are independently and significantly associated with an increased risk of death in preterm infants with neonatal gastrointestinal perforation. The identification of novel risk factors will facilitate the development of therapeutic strategies for preterm neonates with gastrointestinal perforation.

gastrointestinal perforation

neonate

mortality

coagulopathy

shock

acidosis.

Gastrointestinal perforation (GIP) among neonates is a common but major clinical emergency, which carries a mortality of 20–63% and occurs in a large heterogeneous population ranging from preterm and low-birth-weight neonates to healthy term neonates[1–4]. Despite the continuous development in neonatal intensive care units and improvement of surgical and anesthetic techniques, gastrointestinal perforation is still causing significant morbidity and mortality in neonates, especially in preterm groups [1, 5, 6]. The major causes of GIP in neonates have been ascribed to preterm, low birth weight, bacterial colonization, an early and fast increase in meal volume, and intestinal ischemia according to recent studies [7–10]. Many theories have been proposed for the pathogenesis of gastrointestinal perforation; however, the etiology is still controversial. The prevention of GIP remains challenging because of the multifactorial etiology and poorly understood pathogenesis.

Several studies attempted to identify risk factors that impact the prognosis for neonates with GIP in recent years. Some studies have found that necrotizing enterocolitis (NEC), low birth weight, premature birth, intervention time, surgical procedure, location of the perforation, and sepsis were unfavorable prognostic factors [1, 2, 4, 11–16].

The etiology, the pattern of presentation, and surgical findings were suggested to be different between preterm and term infants with GIP in the study of Kara et al. Some previous studies have found that preterm birth was a common poor prognostic factor[1, 2, 12]. With the development of neonatal intensive care and the improvements in obstetrics, the premature infants’ survival rate has been rising in recent years, which increased the number of preterm infants with GIP during the neonatal periods. Therefore, it is necessary to further explore the prognostic factors of GIP in preterm infants and develop better treatment plans for these infants.

This retrospective study aimed to evaluate the etiologies, clinical findings, and potential factors affecting the outcomes of GIP in preterm neonates operated in our hospital with a large sample-sized analysis.

2.1. Participants

This study was approved by the Ethics Committee of our hospital(approval no.2021 − 329). All the patients’ guardians or parents provided written informed consent to use the clinical data of their children in our research. The study retrospectively included 191 neonates with gastrointestinal perforation who were admitted to our hospital’s neonatal intensive care unit (NICU) between April 2009 and October 2021. Patients were divided into the survival and non-survival groups according to the vital status at hospital discharge.

2.2. Inclusion and exclusion criteria

Inclusion criteria: (1) Gestational age is fewer than 37 weeks; (2) Age at onset ≤ 30d; (3) Gastrointestinal perforation was postoperative confirmed and diagnosed.

Exclusion criteria: (1) Patients received treatment before admission to other hospitals or transferred to other hospitals during treatment; (2) Patients complicated with major chromosomal and congenital anomalies; (3) Patients with incomplete clinical data.

2.2. Data Collection

The baseline clinical and biological characteristics were retrospectively collected and recorded in an electronic case report form, which includes patient demographics (gestational age, sex, birth weight, history of perinatal asphyxia, mode of delivery, age of onset), primary symptoms and signs, imaging features, preoperative laboratory findings (hemoglobin, count of leukocyte and platelet, arterial pH, C-reactive protein, concentration of sodium, and serum lactic acid), intraoperative findings (the number of ascites, the perforation sites, and perforation number), surgical intervention time (time between the onset of GIP to any surgical intervention), and complications. All included patients were followed up until in-hospital death or hospital discharge.

2.3. Definitions

According to previous studies, we defined GIP as the destruction of the integrity of the digestive tract. Preterm born was defined as birth before 37 weeks gestation, respectively. NEC The severity of thrombocytopenia was defined as mild (100–150×10⁹/L), moderate (50–100×10⁹/L), and severe (< 50×10⁹/L))[17], [18]. Severe acidosis was defined as arterial blood pH༜7.05 in this study, while hyponatremia was defined as the concentration of serum sodium (Na+) was less than 130 mEq/L [18][19]. Shock and sepsis were diagnosed based on the Pediatric Sepsis Consensus (PSC) criteria while fever was defined as an axillary temperature was no less than 37.3°C. According to previous literature, coagulopathy was defined as platelet count < 1×10⁵/mm³or activated prothrombin time > 60 sec or INR > 1.5, as well as the high PCT level was diagnosed with age-specific cut-off values[18]. Infants with suspected NEC (stage I), moderate NEC (stage II), or severe NEC (stage III) were categorized according to Bell’s classification standard[19]. In this study, confirmed NEC was defined as NEC stage II and III. Spontaneous intestinal perforation (SIP) was diagnosed by the fellow criteria: (1) no clinical evidence of NEC; (2) isolated intestinal perforation confirmed by surgery and/or pathological examination (without surrounding ischemia, inflammation, pneumatosis, or necrosis); (3) no intestinal anomalies, such as intestinal atresia, volvulus, imperforate anus or traumatic perforations[9, 20–22]. Gastrointestinal(GI) anomalies were also confirmed by surgery and/or pathological examination.

2.4. Statistical analysis

Descriptive statistics were analyzed by SPSS software version 25.0 (SPSS, Chicago, IL, USA.), with probability levels of 0.05 considered statistically significant. Categorical variables were described by frequency rates and percentages and compared by use of the Fisher exact test or χ2 test. A Shapiro-Wilk test was used for the baseline variable to estimate whether the continuous data followed a normal distribution. Based on the Shapiro–Wilk test’s results, continuous variables were expressed as mean ± standard deviation (SD) if they were normally distributed or median (interquartile range [IQR]) if they were not. Comparisons were determined thanks to the Mann-Whitney U test or Student’s t-test for continuous variables as appropriate. The association of potential predictors and unfavorable outcomes was explored by univariate and multivariate logistic regression. Multivariate logistic regression models were derived based on the incorporated baseline variables, which were considered clinically relevant or showed a univariate relationship with outcome. Given the number of events available, the variables for inclusion were carefully selected to make sure the parsimony of the final models.

3.1. Demographic and clinical characteristics

A total of 191 preterm neonates had surgically diagnosed neonatal gastrointestinal perforation between April 2009 and October 2021. As shown in Table 1, the overall mortality rate of the whole cohort was 25.1%. The median age of onset of gastric perforation was 3 days (range: 1–11 days), while the median age of onset of intestinal perforation was 7.5 days (range: 1–30 days), respectively. Among the total population, abdominal distension was the most frequent presentation at admission, which was followed by absent bowel sounds, lethargy, and shortness of breath. There were no significant differences in clinical presentation between the two groups. The detailed demographic and clinical characteristics in the derivation and test cohorts were described in Table 1.

Table 1

Demography and clinical presentation of 191 preterm neonates.
	Total (n = 191)	Survivors (n = 143)	Non-survivors (n = 48)	p value
Male gender, n (%)	99(51.8)	77(53.8)	22(45.8)	0.336
GA (wk)^a	34 [32, 35]	34 [32, 35]	34 [33, 35]	0.754
BW (g)^a	2000 [1670, 2340]	2000 [1735, 2310]	2000 [1635, 2385]	0.594
LBW, n (%)	157 (82.2)	118 (82.5)	39 (81.2)	1
Cesarean section, n (%)	146 (76.4)	112 (78.3)	34 (70.8)	0.389
Primegravidity, n (%)	63 (33.0)	45 (31.5)	18 (37.5)	0.554
Primipara, n (%)	93 (61.6)	64 (57.7)	29 (72.5)	0.143
Feeding before onset, n (%)	130 (71.0)	97 (70.3)	33 (73.3)	0.84
History of perinatal asphyxia, n (%)	91 (47.6)	68 (47.6)	23 (47.9)	1
Age of onset (d)^b	5 [2, 8.5]	5 [2, 9]	5 [2, 6.25]	0.185
Symptom, n (%)
Abdominal distension	184 (96.3)	138 (96.5)	46 (95.8)	1
Lethargy	148 (77.5)	111 (77.6)	37 (77.1)	1
Shortness of breath	87 (45.5)	68 (47.6)	19 (39.6)	0.428
Cyanosis	87 (45.5)	68 (47.6)	19 (39.6)	0.428
Vomiting	54 (28.3)	39 (27.3)	15 (31.2)	0.731
Feeding intolerance	41 (21.5)	32 (22.4)	9 (18.8)	0.744
Fever	25 (13.1)	16 (11.2)	9 (18.8)	0.273
Bloody stool	45 (23.6)	36 (25.2)	9 (18.8)	0.477
Signs, n (%)
Absent bowel sounds	157 (82.2)	116 (81.1)	41 (85.4)	0.649
Prominent abdominal veins	74 (38.7)	52 (36.4)	22 (45.8)	0.32
Abdominal erythema	47 (24.6)	32 (22.4)	15 (31.2)	0.298
Abbreviations: IQR, interquartile range; GA, Gestational age; LBW, Low Birth weight.
^aMean and standard deviation.
^bMedian and interquartile range.

3.2. Laboratory findings and imaging features

As shown in Table 2, leukopenia, elevated serum lactic acid, thrombocytopenia, and acidosis were statistically associated with severe sequelae, while the other laboratory findings were not. Pneumoperitoneum (95%) was the most frequent finding during preoperative radiological evaluations, but there was no statistical difference.

Table 2

Laboratory findings and imaging features of 191 preterm neonates.
	Total (n = 191)	Survivors (n = 143)	Non-survivors (n = 48)	p value
Laboratory findings
WBC count, 10⁹cells/L^a	6.83 [3.53, 11.57]	7.29 [3.85, 12.85]	4.69 [2.65, 9.47]	0.009
< 5*10⁹cells/L	72 (37.7)	47 (32.9)	25 (52.1)	0.027
Hb, g/L^a	138 [115, 163.5]	136 [113, 163]	147 [130, 168.75]	0.096
PLT count, 10⁹cells/L^b	190 [117, 261]	201 [127.5, 276]	168.5 [96, 204.75]	0.028
Thrombocytopenia	70 (36.6)	50 (35.0)	20 (41.7)	0.509
CRP༞8mg/L, n(%)	120 (62.8)	92 (64.3)	28 (58.3)	0.567
pHa	7.3 [7.23, 7.37]	7.31 [7.23, 7.38]	7.28 [7.14, 7.34]	0.048
pH༜7.05, n (%)	10 (5.3)	3 (2.1)	7 (14.9)	0.003
Lac, mmol/L^b	1.5 [1, 2.7]	1.4 [0.9, 2.2]	2.1 [1.2, 4.10]	0.005
Lac༞5mmol/L, n (%)	17 (8.9)	8 (5.6)	9 (18.8)	0.013
SC, mEq/L^a	136 [134, 139]	137 [134, 139]	135.9 [133.2, 137.6]	0.18
Hyponatremia, n(%)	18 (9.4)	12 (8.4)	6 (12.5)	0.577
Imaging features
Pneumoperitoneum, n(%)	178(93.2)	134(93.7)	44(91.7)	0.877
Abbreviations: WBC, White blood cell; Hb, Haemoglobin; PLT, Platelet; CRP, C-reactive protein; PCT, procalcitonin; Lac, lactic acid; SC, Sodium concentration.
^aMean and standard deviation.
^bMedian and interquartile range.

3.3. Surgical findings

As depicted in Table 3, gastric perforation has a higher mortality rate than intestinal perforation (29.5% vs. 22.5%), but statistically significant difference was not found between the two groups (p = 0.359). 50 of 191 cases were diagnosed with multiple perforations (2 or more), and 36 of them were from the intestines as well as 14 of them were from the stomach. The number of ascites and the incidences of multiple perforations in the survival group were lower than those in the non-survival group, but there was no significant difference either(p = 0.507), which was same in the situation of surgical intervention time (p = 0.637).

Table 3

Surgical intervention time and intraoperative findings of 191 preterm neonates.
	Total (n = 191)	Survivors (n = 143)	Non-survivors (n = 48)	p value
Surgical intervention time, h				0.637
≤ 4 hours, n(%)	122	93	29
4–12 hours, n(%)	50	35	15
༞ 24 hours, n(%)	19	15	4
Perforation site, n(%)				0.359
Stomach	71 (37.2)	50 (35.0)	21 (43.8)
Intestinal	120 (62.8)	93 (65.0)	27 (56.2)
Amount of ascites (ml)^a				0.507
༜100, n(%)	137 (70.2)	105 (71.9)	32 (65.2)
≥ 100, n(%)	54 (29.8)	38 (28.1)	16 (34.8)
Multiple perforations, n(%)	50 (26.2)	37 (25.9)	13 (27.1)	1

Among the 71 premature neonates with gastric perforation, 25 of them were confirmed with congenital absence of gastric musculature after surgery, and 6 cases were combined with congenital GI malformations that could cause distal obstruction, including Merkel's diverticulum(three), annular pancreas(two), and intestinal atresia(one). In the population of 120 neonates with intestinal perforation, 61 of their primary causes were NEC, as well as 36 neonates were diagnosed with SIP. Twenty-three neonates were associated with GI anomalies, including Merkel's diverticulum perforation(five), intestinal atresia(five), acute perforated appendicitis(four), Hirschsprung disease(three), volvulus(two), imperforate anus(two), malrotation(one), and intestinal stenosis(one).

3.4. Complications

Among all complications, pneumonia was the most frequently observed one which was followed by sepsis and coagulopathy. In the meanwhile, NEC, shock, and coagulopathy were more frequent in the non-survival group and there were significant differences in the latter two indexes (all p༜0.05), which is illustrated in Table 4.

Table 4

Complications of 191 preterm neonates.
		Total (n = 191)		Survivors (n = 143)		Non-survivors (n = 48)		p value
Complications, n(%)
Sepsis		134 (70.2)		95 (66.4)		39 (81.2)		0.079
Pneumonia		165 (86.4)		124 (86.7)		41 (85.4)		1
Respiratory failure		62 (32.5)		43 (30.1)		19 (39.6)		0.298
Shock		65 (34.0)		34 (23.8)		31 (64.6)		< 0.001
Coagulopathy		96 (50.3)		60 (42.0)		36 (75.0)		< 0.001
NEC	91 (47.6)		67 (46.9)		24 (50.0)		0.833
Abbreviations: NEC, necrotizing enterocolitis.

3.5. Predictors of mortality

In univariable analysis, patients with leukopenia (leukocyte < 5×10⁹/L), decreased platelet count, severe acidosis (pH < 7.05), elevated lactic acid (serum lactic acid > 5mmol/L), shock, and coagulopathy had higher odds of poor prognosis than others. The above significant variables were included in the multivariable logistic regression model of all 191 subjects, which showed that pH < 7.05, shock, and coagulopathy were associated with increased odds of death (Table 5).

Table 5

Risk factors associated with mortality.
	Univariable OR (95% CI)	p value	Multivariable OR (95% CI)	p value
WBC count < 5*10⁹ cells/L	2.220 (1.143–4.344)	0.019
Plt count, 10⁹cells/L	0.996 (0.993–0.999)	0.025
pH < 7.05	8.050 (2.134–38.682)	0.003	7.604 (1.424–51.910)	0.025
Lactate > 5mmol/L	3.894 (1.401–11.032)	0.009
Shock	5.846 (2.924–12.065)	< 0.001	5.131 (2.419–11.266)	< 0.001
Coagulopathy	4.150 (2.043–8.938)	< 0.001	3.269 (1.511–7.431)	0.003
Abbreviations: CI, confidence interval; OR, odd ratio; WBC, white blood cell.

In our study, the total mortality of preterm neonates with gastrointestinal perforation was 25.1%, which was similar to previous studies[1, 11, 15, 22–24]. With the development of intensive care measures, operative techniques, and anesthesiology procedures during the neonatal period, the survival rate of premature infants has been increasing, however, gastrointestinal perforation still leads to high neonatal mortality, especially in premature groups[1, 11, 22]. Compared with full-term infants, preterm infants are physiologically and metabolically immature. Therefore, their condition may change more rapidly and the prognosis may be worse than the term-born neonates. As early detection, diagnosis, and access to treatment can improve the infants’ survival, it is necessary to determine the major risk factors in high-risk infants for early intervention.

The symptoms of gastrointestinal perforations during the initial stages are usually non-specific. In our study, abdominal distension was the most common presentation at admission, followed closely by absent bowel sounds, lethargy, and shortness of breath, which is consistent with previous studies. However, these symptoms and signs had no significant indication of the severity of the disease.

In our study, the median age of onset of gastric perforation was 3 days (range: 1–11 days) and the median age of onset of intestinal perforation was 7.5 days (range: 1–30 days). Saracli et al.’s study has reported that NGP generally occurs between 2 and 7 days after birth, which was in line with our study[25]. It’s also reported that the majority of perforated-NEC onset occurs between 2 and 8 weeks following birth, as well as SIP mainly occurs within 10 days after birth[22]. In Calisti et al.’s previous study, the mean age of intestinal perforation in neonates was about 10 days, which is later than the onset age in our study [26]. We speculate that this is due to the higher proportion of intestinal structural abnormalities (such as intestinal atresia, malrotation, volvulus, etc.) in our cohort.

Our study confirmed that severe acidosis (arterial blood pH༜7.05) was associated with an unfavorable outcome of death, which is consistent with the previous finding[27]. Acidosis is a well-known indicator of high mortality. In this study, ten neonates developed severe acidosis and seven of them died. As far as we’ve known, changes in pH can influence vascular tone (i.e., intracellular acidosis is associated with vasodilation)[28]. Vasovagal reactions without effective treatment probably led to irreversible shock and even death. Second, acidosis causes damage to cardiomyocytes through altered cellular Ca2 + fluxes as well as by modifying the functional properties of myofilament proteins, which in turn affects myocardial contractility[29]. The decline in cardiac contractility causes a circulatory disturbance, reduces gastrointestinal mucosal perfusion, which hinders the repair of perforations. In our study, elevated lactic acid is another important independent risk factor of mortality of GIP. This has been reported in our previous study [30].

We observed that shock was a risk factor for in-hospital mortality in patients with GIP. In a shock state, blood flow is redistributed and shunted preferentially to the brain and heart at the gradual expense of peripheral vascular beds. Decreased blood perfusion leads to insufficient oxygen delivery of intestinal mucosa, resulting in tissue hypoxia, which is associated with increased enterocyte damage and integrity loss. The destruction of the digestive tract barrier leads to bacterial translocation, which leads to severe sepsis and multiple organ dysfunction.

Our study also confirmed that coagulopathy was associated with mortality of GIP, which has not been reported in previous studies. This result is consistent with our previous study[30]. It is well known that blood coagulation plays a major role in the process of protecting the damaged tissue and vessel following repair. In the meanwhile, dysfunctional coagulation may also lead to bleeding in patients with blood coagulation disorders or undergoing surgery. On the one hand, it hinders the repair of the perforation site, on the other hand, the increase of bleeding leads to the decrease of blood perfusion, which further aggravates the damage of gastrointestinal mucosa.

Leukopenia has been reported to be a poor prognostic factor in previous studies, although it has not been confirmed in our study[24, 31]. The decisive diagnostic value of leukopenia in neonatal infectious diseases is still controversial. It’s suggested in a previous cohort study focusing on WBC counts in febrile neonates that any WBC count threshold was not recommended to identify bacterial infections for the modest discriminatory power in identifying neonates with bacterial infections and the substantial overlap among groups[32].

Surgical intervention time (time from symptoms and surgical intervention) was reported to be a risk factor for postoperative death, which is contrary to our present study[11, 24, 33]. Our results are consistent with a previous study in another hand [31], which warrants some further thoughts.

There are two main advantages to this study. Firstly, to the best of our knowledge, this is the largest sample size study on the risk factors of GIP in preterm neonates. Secondly, we collected available data from all aspects and comprehensively evaluated its relationship with death.

Our study also has several limitations. First, the present study has the inherent limitations of a retrospective, single-center investigation. Our data were collected retrospectively, which may produce a population bias. The findings reported here will require verification in a prospective, multicenter trial. Secondly, considering that our hospital is the largest tertiary referral center for children in southwest China, the neonates in this cohort are relatively seriously ill and most of them were referred from other hospitals, which means the prehospital treatment regimens cannot be accurately collected, such as the history of indomethacin, paracetamol, etc. Finally, confounding factors, such as the welfare systems, medical environment, and socio-behavioral factors, may also need to be considered.

In conclusion, gastrointestinal perforation is a major neonatal emergency, which is life-threatening and especially severe in preterm infants. In our study, the factors affecting the prognosis of preterm GIP patients were severe acidosis (arterial blood pH < 7.05), shock, and coagulopathy. It is hoped that early diagnosis and timely intervention can improve the prognosis.

Interest

None.

Acknowledgments

We thank our patients for entrusting us with their care and for giving us the opportunity to learn and understand their disease and hopefully help others who may suffer from this disease in the future. And we thank all participants and staff of this study and the physicians for their work.

Funding

This study is supported by the Foundation for Science & Technology Research Project of Chongqing(CSTC 2018jcyjAX0230) and the Science-Health Joint Medical Scientific Research Project of Chongqing [No.2019ZDXM021].

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Asabe K, Oka Y, Kai H, Shirakusa T: Neonatal gastrointestinal perforation. The Turkish journal of pediatrics 2009, 51(3):264-270.
Tan C, Kiely EM, Agrawal M, Brereton RJ, Spitz L: Neonatal gastrointestinal perforation. Archives of Disease in Childhood Fetal & Neonatal Edition 2003, 24(9):888-892.
Sakellaris G, Partalis N, Dede O, Alegakis A, Seremeti C, Korakaki E, Giannakopoulou C: Gastrointestinal perforations in neonatal period: experience over 10 years. Pediatric emergency care 2012, 28(9):886-888.
Eltayeb AA, Hashem M: Management and Outcome of Neonatal Bowel Perforation. Ann pediatr surg 2008.
Nakamura H, Hirano K, Watanabe K, Iwasaki I, Tada H, Yamaguchi M, Komazawa T: Gastrointestinal Perforation in 31 Neonates With Surgical Treatment : Satistical Analysis by Quantification Theory Type III. Journal of the Japanese Society of Pediatric Surgeons 2003, 39(6):748-757.
St-Vil D, LeBouthillier G, Luks F, Bensoussan A, Blanchard H, Youssef S: Neonatal gastrointestinal perforations. Journal of pediatric surgery 1992, 27(10):1340-1342.
Irles C, González-Pérez G, Carrera Muiños S, Michel Macias C, Sánchez Gómez C, Martínez-Zepeda A, Cordero González G, Laresgoiti Servitje E: Estimation of Neonatal Intestinal Perforation Associated with Necrotizing Enterocolitis by Machine Learning Reveals New Key Factors. International journal of environmental research and public health 2018, 15(11).
Jr R, Krasna IH: 'Spontaneous' neonatal gastric perforation: is it really spontaneous? Journal of Pediatric Surgery 2000, 35(7):1066-1069.
Olaloye O, Swatski M, Konnikova L: Role of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review. Nutrients 2020, 12(5).
Lloyd JR: The etiology of gastrointestinal perforations in the newborn. Journal of Pediatric Surgery 1969, 4(1):77-84.
Ekwunife H, Jideofor U, Victor M, Andrew O: Gastrointestinal Perforation in Neonates: Aetiology and Risk Factors. Journal of Neonatal Surgery 2013, 2(3):30.
Essam A E, Ahmed F E, Nagy I E, Hamada H D, Moustafa A, Manal E B: Neonatal gastrointestinal perforations. 2000.
Lohfa, B., Chirdan, Emmanuel, A., Ameh: Neonatal intestinal perforation in a developing country. Annals of Tropical Paediatrics International Child Health 2001.
Holland A, Shun A, Martin H, Cooke-Yarborough C, Holland J: Small bowel perforation in the premature neonate: congenital or acquired? Pediatric Surgery International 2003, 19(6):489-494.
Sandra, Prgomet, Boris, Lukšić, Zenon, Pogorelić, Ivo, Jurić, Vesna, Arapović: Perinatal risk factors in newborns with gastrointestinal perforation. World journal of gastrointestinal surgery 2017.
Sarac M, Bakal Ü, Aydın M, Tartar T, Orman A, Taşkın E, Canpolat S, Kazez A: Neonatal Gastrointestinal Perforations: the 10-Year Experience of a Reference Hospital. Indian Journal of Surgery 2017.
Liu D, Wu J, Xiong T, Yue Y, Tang J: Platelet transfusion for neonates with thrombocytopaenia: protocol for a systematic review. BMJ Open 2020, 10(10):e039132-e039132.
Noah Z, Budek C, De WM, Weesemayer DE: Nelson Textbook of Pediatrics 20th edition. 2015.
Bell M, Ternberg J, Feigin R, Keating J, Marshall R, Barton L, Brotherton T: Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Annals of surgery 1978, 187(1):1-7.
Shin S, Kim E, Kim S, Kim H, Kim H: Head Growth and Neurodevelopment of Preterm Infants with Surgical Necrotizing Enterocolitis and Spontaneous Intestinal Perforation. Children (Basel, Switzerland) 2021, 8(10).
Attridge J, Herman A, Gurka M, Griffin M, McGahren E, Gordon P: Discharge outcomes of extremely low birth weight infants with spontaneous intestinal perforations. Journal of perinatology : official journal of the California Perinatal Association 2006, 26(1):49-54.
Clyman RI, Jin C, Hills NK: A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis. Journal of Perinatology 2020, 40(11):1662-1670.
Iacusso C, Boscarelli A, Fusaro F, Bagolan P, Morini F: Pathogenetic and Prognostic Factors for Neonatal Gastric Perforation: Personal Experience and Systematic Review of the Literature. Frontiers in Pediatrics 2018, 6:61.
Yang CY, Lien R, Fu RH, Chu SM, Hsu JF, Lai JY, Minoo P, Chiang MC: Prognostic factors and concomitant anomalies in neonatal gastric perforation. J Pediatr Surg 2015, 50(8):1278-1282.
Saracli T, Mann M, French DM, Booker CR, Scott RB: Rupture of the Stomach in the Newborn Infant: Report of Three Cases and Review of the World Literature. Clinical Pediatrics 1967, 6(10):583-588.
Calisti A, Perrelli L, Nanni L, Vallasciani S, Maragliano G: Surgical approach to neonatal intestinal perforation. An analysis on 85 cases (1991-2001). Minerva Pediatrica 2004, 56(3):335-339.
Chung MT, Kuo CY, Wang JW, Hsieh WS, Huang CB, Lin JN: Gastric perforation in the neonate: clinical analysis of 12 cases. Zhonghua Minguo xiao er ke yi xue hui za zhi [Journal] Zhonghua Minguo xiao er ke yi xue hui 1994, 35(5):460-465.
Crimi E, Taccone F, Infante T, Scolletta S, Crudele V, Napoli C: Effects of intracellular acidosis on endothelial function: An overview. Journal of critical care 2011, 27:108-118.
Sheehan KA, Arteaga GM, Hinken AC, Dias FA, Ribeiro C, Wieczorek DF, Solaro RJ, Wolska BM: Functional effects of a tropomyosin mutation linked to FHC contribute to maladaptation during acidosis. J Mol Cell Cardiol 2011, 50(3):442-450.
Huang Y, Lu Q, Peng N, Wang L, Song Y, Zhong Q, Yuan P: Risk Factors for Mortality in Neonatal Gastric Perforation: A Retrospective Cohort Study. Frontiers in Pediatrics 2021, 9(432).
Yang T, Huang Y, Li J, Zhong W, Tan T, Yu J, Li L, Pan J, Hu C, Yang J et al: Neonatal Gastric Perforation: Case Series and Literature Review. World Journal of Surgery 2018, 42(8):2668-2673.
Atıcı A, Karaman A, Zenciroğlu A, Karaman I, Afşarlar C, Yılmaz E, Okumuş N, Cavuşoğlu Y, Ozgüner I, Erdoğan D: Factors affecting mortality in stage 3b necrotizing enterocolitis. The Turkish journal of pediatrics 2014, 56(2):133-137.
Byun J, Kim H, Noh S, Kim S, Jung S, Lee S, Park K: Neonatal gastric perforation: A single center experience. World journal of gastrointestinal surgery 2014, 6:151-155.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Prognostic Factors in Preterm Infants with Neonatal Gastrointestinal Perforation: A Retrospective Cohort Study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

1. Introduction

2. Methods

2.1. Participants

2.2. Inclusion and exclusion criteria

2.2. Data Collection

2.3. Definitions

2.4. Statistical analysis

3. Results

3.1. Demographic and clinical characteristics

3.2. Laboratory findings and imaging features

3.3. Surgical findings

3.4. Complications

3.5. Predictors of mortality

4. Discussion

5. Conclusion

Declarations

References

Additional Declarations

Status:

Version 1