Risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease

doi:10.21203/rs.2.13787/v1

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Research article

Risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease

https://doi.org/10.21203/rs.2.13787/v1

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published 21 Jan, 2020

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Background: The aim of our study was to analyze the risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease (CHD). Methods: We performed a retrospective cohort study, and children with CHD who underwent open-heart surgeries at Shanghai Children’s Medical Center from January 1, 2012 to December 31, 2018 were included. The baseline characteristics of these patients of different ages, including neonates (0-1 months old), infants (1-12 months old) and children (1-10 years old), were analyzed, and the association of risk factors with postoperative nosocomial infection were assessed. Results: A total of 11937 subjects were included in the study. The overall nosocomial infection rate was 11.10%. Nosocomial infection rates in neonates, infants, and children with congenital heart disease were 25.41%, 15.78%, and 5.31%, respectively. Multivariate logistic regression analysis found age (OR 0.804, 95%CI: 0.776-0.834; P<0.001), STS risk grade (OR 1.308, 95%CI: 1.203-1.423; P<0.001), body mass index (BMI)

Infectious Diseases

Nosocomial infection

Cardiac surgery

Children

In-hospital infections have an adverse effect on the clinical outcomes of pediatric patients after thoracotomy, which can cause morbidity, mortality, prolonged hospital stay[1-4]. The prevalence of nosocomial infections in children with open-heart surgery remains high. Among patients who admitted into the ICU, 50% or more of the patients were affected by nosocomial infections, compared with about 5% to 15% of inpatients in the conventional ward[5]. In developing countries, the severity of nosocomial infections is still underestimated, mainly due to lack of good surveillance system which requires expertise and resources[6].

In-hospital infections after cardiac surgery in patients with congenital heart disease are affected by many factors. A prospective cohort study found that diabetes mellitus and obesity are associated with surgical site infection in valve surgery, and diabetes mellitus and reoperation for bleeding are associated with surgical site infection in coronary revascularization[7]. Younger age and ventilator or ECMO use at time of heart transplant are attribute to bacterial infections of pediatric patients[8].

A 4-year survey found that age <2 months, congenital malformations, post-operative complications, and open-chest procedure are associated with nosocomial infections in pediatric cardiovascular surgery patients[9]. Surgery-related risk factors include age, longer preoperative hospitalizations, higher American Society of Anesthesiologist (ASA) score, preoperative ventilation, longer duration of surgical procedures, blood transfusions, continuation of antimicrobial prophylaxis more than 48 hours, longer ICU time and longer hospitalization time, open chest, surgical risk grade, and duration of central line placement are associated with hospital-acquired infections in pediatric cardiac surgical patients[10]. The study founded that risk factors for nosocomial infection after neonatal cardiac surgery include lower Apgar score, higher incidence of other congenital malformations, longer hospital stay, central venous catheter indwelling time > 14 days, mechanical ventilation time > 7 days, blood product transfusion > 5 times[11].

Previous studies on risk factors for nosocomial infection in children with CHD have often focused on a specific age group, and few studies have detailed analysis of risk factors for nosocomial infections after CHD in children of different ages, especially in China. Therefore, the aim of this study was to explore the risk factors of post-operative in-hospital infection in children with CHD classified according to age.

Patient and study design

Children with CHD who underwent cardiac surgery at Shanghai Children’s Medical Center from January 1, 2012 to December 31, 2018 were included in this retrospective cohort study. For patients with multiple surgery records within 30 days, only the last open-heart surgery was included and the previous surgery records were considered as operation history. The inclusion criteria include patient with CHD, age ≤10 years old. The exclusion criteria include surgery without cardiopulmonary bypass (CPB), infection within preoperative 30 days, preoperative ventilator support, and no complete blood count (CBC) within 48hours before CPB. Demographic characteristics and pre-operation test data were extracted from a clinical database. The study was approved by the Ethical Committee of Shanghai Children’s Medical Center. All children with congenital heart disease were divided into neonates (0-1 months old), infants (1-12 months old) and children (1-10 years old) according to age. We analyzed the in-hospital infection rate of all CHD children after cardiac surgery. The baseline characteristics of these patients of different ages were analyzed, and the association of risk factors with postoperative nosocomial infection were assessed.

Definition and variables

Nosocomial infection was defined according to draft version of the hospital infection diagnosis standard of Chinese Ministry of Health[12]. The variables of interest in the study included preoperative demographic data of the patient, laboratory test data after admission, surgical related variables, etc. All these study data were obtained from the hospital’s electronic medical record. All laboratory testing was done at Shanghai Children’s Medical Center.

Statistical analysis

Continuous variables were described as Mean ± SD or Median (Range) according to their distributions and categorical data were presented as frequency (%). For between group comparison, T tests or Mann-Whitney U tests were used for continuous variables and Chi-squared tests or Fisher’s exact tests for categorical data, as appropriate.

To identify risk factors for nosocomial infection, univariate logistic regression was used first and multiple logistic regression were applied for significant variables in the univariate analysis to select the significant risk factors. Finally, nomograms were established for the risk predictive models for nosocomial infection.

All tests were two-sided and p<0.05 were regarded as statistically significant.

A total of 11937 subjects were included in the study. Among them, there are 122 newborns, 6368 infants, and 5447 children (figure 1). Nosocomial infection rates in neonates, infants, and children with congenital heart disease were 25.41%, 15.78%, and 5.31%, respectively. The overall nosocomial infection rate was 11.10%.

Newborns

Baseline characteristics of newborns with and without nosocomial infection

Of all 122 neonatal CHD patients (median age 14d, range: 2-30d), there were 31 nosocomial infections and 91 non-nosocomial infections. General characteristics were similar for nosocomial infection and non-nosocomial infection CHD newborns. Significant differences were found in age (20d vs. 13d, P=0.002), CPB time (85 min vs. 109min, P=0.006) between of nosocomial infection and non-nosocomial infection CHD newborns (table 1).

Infants

Baseline characteristics of infants with and without nosocomial infection

Among 6368 CHD infants (median age 187d, range: 30-365d), there were 1005 nosocomial infections, and 5363 non-nosocomial infections. Among baseline characteristics, CPB time (68 min vs. 53 min, P<0.001) of nosocomial infections infant was significantly higher than non- nosocomial infections group, but age (137d vs. 195d, P<0.001) was significantly younger. BMI, STS risk grade, delayed sternal closure, serum creatinine level, lymphocyte count, neutrophil count, lymphocyte/white blood cell (WBC) ratio and neutrophil/WBC ratio were all significantly different between nosocomial infection and non-nosocomial infection CHD newborns (table 2).

Univariate and multivariate analysis of risk factors for nosocomial infection in CHD infants

Significant risk factors in the univariate analysis associated with nosocomial infection were age, STS risk grade, delayed sternal closure, BMI (<P5 percentile), CPB time, high lymphocyte count, lymphocyte/WBC ratio, high neutrophil count, neutrophil/WBC ratio and high serum creatinine (table 3).

After adjusted confounding factors, the study found age (OR 0.804, 95%CI: 0.776-0.834; P<0.001), STS risk grade (OR 1.308, 95%CI: 1.203-1.423; P<0.001), BMI <P5 percentile (OR 1.287, 95%CI: 1.026-1.615; P=0.029), BMI ＞P95 percentile (OR 0.802, 95%CI: 0.661-0.974; P=0.026), CPB time (OR 1.007, 95%CI: 1.005-1.009; P<0.001) and high neutrophil/WBC ratio (OR 1.456, 95%CI: 1.103-1.923; P=0.008) were significantly associated with nosocomial infection in CHD infants (table 3).

Nomograms predicting nosocomial infection risk of CHD infant after cardiac surgery

Nosocomial infection probability can be estimated with the nomograms (figure 2). In order to calculate the probability of nosocomial infection after heart surgery in infants with congenital heart disease, each parameter has a corresponding score on the point axis, and the sum of the scores is plotted on the “total point” axis. The probability of nosocomial infection is the value at a vertical line from corresponding total points.

Children

Baseline characteristics of children with and without nosocomial infection

Among 5447 CHD children (median age 930d, range: 365-3650d), there were 289 nosocomial infections and 5158 non-nosocomial infections. Few characteristics were similar for nosocomial infection and non-nosocomial infection patients. Nosocomial infection CHD children had longer CPB time (88min vs. 48min, P<0.001) and younger age (824d vs. 934d, P=0.027). Characteristics of nosocomial infection CHD children including proportion of patients with a history of cardiac surgery, BMI, STS risk grade, proportion of patients with delayed sternal closure, abnormal ALT, WBC counts, lymphocyte counts, neutrophil count, lymphocyte/WBC ratio and neutrophil/WBC ratio were all significantly different with those of non-nosocomial infection CHD children (table 4).

Univariate and multivariate analysis of risk factors for nosocomial infection in CHD children

Univariate analysis found that history of cardiac surgery, STS risk grade, delayed sternal closure, BMI (<P5 percentile), CPB time, aortic clamping time, lymphocyte counts, lymphocyte/WBC ratio, high neutrophil count, high neutrophil/WBC ratio, high ALT and AST of nosocomial infection CHD children were all significantly different with non-nosocomial infection CHD children.

Multivariate analysis found that history of cardiac surgery (OR 1.476, 95%CI: 1.03-2.116; P=0.034), STS risk grade (OR 1.555, 95%CI: 1.328-1.82; P<0.001), BMI (<P5 percentile) (OR 1.956, 95%CI: 1.412-2.71; P<0.001), CPB time (OR 1.012, 95%CI: 1.009-1.015; P<0.001), low lymphocyte/WBC ratio (OR 3.321, 95%CI: 1.479-7.454; P=0.004) and high AST (OR 1.748, 95%CI: 1.285-2.379; P0.001) were significantly associated with nosocomial infection in CHD children (table 5).

Nomograms predicting nosocomial infection risk of CHD children after cardiac surgery

Nosocomial infection probability of CHD children after cardiac surgery can also be estimated with the nomograms, and calculation method is similar with that of CHD infant (figure 3).

CHD has become the most common congenital defect in China. Due to China’s large population base, the number of new cases of CHD per year is huge. Surgery is the main treatment for most heart defects[13]. But pediatric cardiac surgery reduces the patient's immunity and increases the risk of postoperative infection[14]. The study found that nosocomial infection was one of the main complications in the postoperative period in children with CHD, and are major causes of morbidity and mortality after cardiac surgery[15]. Nosocomial infections are also associated with longer intensive care unit (ICU) stay and greater antibiotic usage[16-18]. Analysis and identification of risk factors for nosocomial infections is important for identifying the highest risk population and developing strategies to prevent nosocomial infections. There have been few previous studies on the risk of nosocomial infection after cardiac surgery in children with congenital heart disease, and most of the studies were small size studies. This study investigated the risk factors for infection in 11937 CHD children after cardiac surgery, the results have important clinical significance for the prevention and treatment of nosocomial infection in CHD children.

In present study, nosocomial infection rate was 11.10%, and nosocomial infection rates of newborns, infant and child were 25.41%, 15.78%, and 5.31%, respectively. Overall nosocomial infection rate is slightly lower than previous studies[19, 20].

Nosocomial infection rate of CHD newborn was higher than infant and child in our study, age may be one of the main reasons for this difference. We also found that age was significantly associated with nosocomial infection of infant and child after cardiac surgery. Previous studies found that younger age was associated with higher incidence of postoperative infectious complications[21, 22]. Younger age was independently associated with acquisition of bacterial infection post-heart transplantation in children[8]. A matched case-control study found that age younger than 1 year was an independent risk factors for any type of SSI after cardiac surgery in children[23]. Sen et al. assessed the risk factors for postoperative infection after congenital heart surgery using data from the International Quality Improvement Collaborative for Congenital Heart Surgery in Developing World Countries, they found younger age was one of independent risk factors for infection[15].

Surgery itself is the risk of postoperative infection[24]. In our study, STS risk grade and history of cardiac surgery were significantly associated with post-operative nosocomial infection in CHD infant and child. The complexity of surgery is related to the operation time. The more complicated the operation, the longer the operation time, and the worse the outcome of the patient[25]. Duration of surgery and surgical complexity score are all risk factors of nosocomial infections in infants and children undergoing open heart surgery[19, 26]. The possible cause is that the risk of bacterial contamination and cell damage increases at the surgical site as the operation time increases. Retrospective study confirmed high complexity and previous cardiothoracic operation were associated with major infection after pediatric cardiac surgery[24, 27]. A cross-sectional prospective study found that duration of operation ≥ 3 hours significantly predicted surgical site infection[28]. Previous case-control studies showed longer duration of surgery were independently associated with hospitalized surgical site infections after cardiovascular surgery in children[23, 29]. Higher surgical complexity was an independent risk factor for nosocomial infection after congenital heart surgery[15].

Obesity and BMI is associated with an increased number of ventilator days, as well as increased ICU and hospital lengths of stay, which increase the risk of nosocomial infections[30, 31]. Previous study showed that a higher BMI is directly related to longer hospital and ICU stay[32], which increases the risk of nosocomial infections[11, 33]. In a two-center prospective randomized controlled study, multiple regression analysis demonstrated a preoperative BMI of >30 kg/m2 was an independent predictor for an increased surgical site infection rate after cardiac surgery in adult patients[34]. Higher BMI patients have a higher risk of community acquired and nosocomial infections in the ICU[32, 35, 36]. However, in this study, BMI <P5 percentile was significantly associated with increased odds of nosocomial infection after cardiac surgery in CHD infant and child. But BMI ＞P95 percentile was a protective factor for postoperative infection in CHD infant. This correlation is different from that of adults. The possible reason is that the BMI of children with CHD in our study is smaller than general population, and the patients with BMI >P95 percentile have not reached the standard of obesity. And BMI <P5 may result from CHD and bad nutrition. It also suggested that the better nutrition condition may be helpful to prevent nosocomial infection after cardiac surgery in children. In addition, among the adult population, people with high BMI are prone to diabetes, high blood pressure and other diseases, which are risk factors for postoperative infection[37, 38]. However, children with high BMI have a low risk of developing these diseases. This may also be one of the reasons why higher BMI was associated with decreased odds of postoperative infection risk in CHD children.

During cardiac surgery, CBP induces a systemic inflammatory response that causes immune disorders and significant pulmonary dysfunction[39, 40]. CPB time is closely related to aortic clamping time. Interestingly, we found through multivariate analysis that CPB time was significantly associated with the risk of nosocomial infection after cardiac surgery in children, but there was no significant association with the risk of postoperative infection in infants. The aortic clamping time is just the opposite, and there is only a significant correlation with the risk of postoperative nosocomial infection in infants. Aortic cross-clamp time greater than 85 minutes was an independent risk factor for surgical site infections in children undergoing cardiac surgery[23]. Lomtadze et al. confirmed that long CPB and cross-clamp time are major risk factors for nosocomial infection after cardiac surgery in a retrospective case study[41].

Neutrophils, the most abundant human immune cells, are rapidly recruited to sites of infection, where they fulfill their life-saving antimicrobial functions[42]. Neutrophils are responsible for nonspecific inflammation through secretion of many inflammatory mediators[43]. This study found neutrophils are involved in the activation of non-specific inflammation, and lymphopenia is associated with adverse outcomes[43]. In our study, high neutrophils/WBC ratio was significantly associated with nosocomial infection in CHD infants, low lymphocyte/WBC ratio was significantly associated with nosocomial infection in child after surgery.

AST is one of the commonly used enzyme indicators for clinical evaluation of myocardial injury, and myocardial damage leads to an increase in AST levels[44]. The patients included in this study were children with congenital heart disease and had varying degrees of myocardial cell damage. These patients have lower immunity than normal people, and the risk of inflammatory reactions and infections increases. This may explain the association between increased AST levels in CHD children and postoperative infection, but further clinical studies are needed.

Several limitations should be considered to interpret this study. First, this is a retrospective single-center study. Second, some biomarkers of infection or inflammatory, such as CRP, as well as PCT, was not measured and analyzed. Third, the type of infection such as bacteria or virus, the grams positive of negative bacteria was not analyzed in this study.

STS risk grade, BMI, CPB duration, low lymphocyte/WBC ratio or high neutrophil/WBC ratio were independently associated with nosocomial infection in CHD infant and children after cardiac surgery. Additional preventive strategies, including controlling weight (such as nutrition support), optimizing the surgical procedure may reduce risk of postoperative infection, but further research is needed.

Acknowledgments

Thanks to all the staff of Shanghai Children’s Medical Center who have contributed to the study. Thanks to Shanghai Synyi Medical Technology Co., Ltd for providing a data analysis and statistical platform.

Sources of Funding: The research was funded by National Science Foundation of China (No: 81670372)

Conflict of Interest Statement

The authors declare no competing interests.

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Table 1. Baseline characteristics of postoperative infection and non-postoperative infected neonates

Parameter		Postoperative infection group (n=31)	Non- postoperative infection group (n=91)	Total (n=122)	P value
Age (days)	Median (Range)	20 (7,30)	13 (2,30)	14 (2,30)	0.002^
CPB time	Median (Range)	85 (14,228)	109 (23,473)	101 (14,473)	0.006^
Gender	MALE	19 (61.29%)	60 (65.93%)	79 (64.75%)	0.64#
	FEMALE	12 (38.71%)	31 (34.07%)	43 (35.25%)
Preterm birth	NO	30 (96.77%)	84 (92.31%)	114 (93.44%)	0.678##
	YES	1 (3.23%)	7 (7.69%)	8 (6.56%)
History of cardiac surgery	NO	30 (96.77%)	88 (96.7%)	118 (96.72%)	>0.999##
	YES	1 (3.23%)	3 (3.3%)	4 (3.28%)
BMI	<P5 percentile	4 (13.79%)	10 (12.05%)	14 (12.5%)	0.723#
	P5~P95 percentile	18 (62.07%)	58 (69.88%)	76 (67.86%)
	>P95 percentile	7 (24.14%)	15 (18.07%)	22 (19.64%)
STS risk grade	1	0 (0%)	3 (3.3%)	3 (2.46%)	0.352^
	2	9 (29.03%)	10 (10.99%)	19 (15.57%)
	3	12 (38.71%)	47 (51.65%)	59 (48.36%)
	4	10 (32.26%)	31 (34.07%)	41 (33.61%)
Delayed sternal closure	NO	27 (87.1%)	71 (78.02%)	98 (80.33%)	0.272#
	YES	4 (12.9%)	20 (21.98%)	24 (19.67%)
ALT	Low	2 (9.09%)	13 (17.57%)	15 (15.63%)	0.409##
	Normal	18 (81.82%)	58 (78.38%)	76 (79.17%)
	High	2 (9.09%)	3 (4.05%)	5 (5.21%)
AST	Normal	13 (59.09%)	37 (50%)	50 (52.08%)	0.454#
	High	9 (40.91%)	37 (50%)	46 (47.92%)
ALP	Normal	22 (100%)	74 (100%)	96 (100%)
Serum creatinine	Normal	20 (95.24%)	61 (92.42%)	81 (93.1%)	>0.999##
	High	1 (4.76%)	5 (7.58%)	6 (6.9%)
WBC counts	Normal	29 (93.55%)	88 (96.7%)	117 (95.9%)	0.6##
	High	2 (6.45%)	3 (3.3%)	5 (4.1%)
Lymphocyte count	Low	7 (22.58%)	18 (19.78%)	25 (20.49%)	0.235#
	Normal	5 (16.13%)	29 (31.87%)	34 (27.87%)
	High	19 (61.29%)	44 (48.35%)	63 (51.64%)
Neutrophil count	Low	3 (9.68%)	4 (4.4%)	7 (5.74%)	0.074#
	Normal	20 (64.52%)	43 (47.25%)	63 (51.64%)
	High	8 (25.81%)	44 (48.35%)	52 (42.62%)
Lymphocytes/WBC	Low	14 (45.16%)	52 (57.14%)	66 (54.1%)	0.512#
	Normal	13 (41.94%)	30 (32.97%)	43 (35.25%)
	High	4 (12.9%)	9 (9.89%)	13 (10.66%)
Neutrophils/WBC	Low	7 (22.58%)	13 (14.29%)	20 (16.39%)	0.465#
	Normal	5 (16.13%)	12 (13.19%)	17 (13.93%)
	High	19 (61.29%)	66 (72.53%)	85 (69.67%)

Table 2. Baseline characteristics of postoperative infection and non-postoperative infected infants

Parameter		Postoperative infection group (n=1005)	Non- postoperative infection group (n=5363)	Total (n=6368)	P value
Age (days)	Median (Range)	137 (30,361)	195 (30,365)	187 (30,365)	<0.001^
CPB time	Median (Range)	68 (14,332)	52 (10,493)	54 (10,493)	<0.001^
Gender	MALE	597 (59.4%)	3059 (57.04%)	3656 (57.41%)	0.164#
	FEMALE	408 (40.6%)	2304 (42.96%)	2712 (42.59%)
Preterm birth	NO	995 (99%)	5315 (99.1%)	6310 (99.09%)	0.759#
	YES	10 (1%)	48 (0.9%)	58 (0.91%)
History of cardiac surgery	NO	984 (97.91%)	5291 (98.66%)	6275 (98.54%)	0.07#
	YES	21 (2.09%)	72 (1.34%)	93 (1.46%)
BMI	<P5 percentile	161 (17.44%)	1073 (21.37%)	1234 (20.76%)	0.019#
	P5~P95 percentile	532 (57.64%)	2811 (55.98%)	3343 (56.24%)
	>P95 percentile	230 (24.92%)	1137 (22.64%)	1367 (23%)
STS risk grade	1	401 (39.9%)	3178 (59.26%)	3579 (56.2%)	<0.001^
	2	319 (31.74%)	1484 (27.67%)	1803 (28.31%)
	3	163 (16.22%)	365 (6.81%)	528 (8.29%)
	4	120 (11.94%)	330 (6.15%)	450 (7.07%)
	5	2 (0.2%)	6 (0.11%)	8 (0.13%)
Delayed sternal closure	NO	995 (99%)	5338 (99.53%)	6333 (99.45%)	0.037#
	YES	10 (1%)	25 (0.47%)	35 (0.55%)
ALT	Low	19 (2.24%)	81 (1.61%)	100 (1.7%)	0.233#
	Normal	758 (89.18%)	4571 (90.84%)	5329 (90.6%)
	High	73 (8.59%)	380 (7.55%)	453 (7.7%)
AST	Normal	329 (38.66%)	1920 (38.02%)	2249 (38.11%)	0.722#
	High	522 (61.34%)	3130 (61.98%)	3652 (61.89%)
ALP	Normal	840 (99.17%)	5014 (99.37%)	5854 (99.34%)	0.523#
	High	7 (0.83%)	32 (0.63%)	39 (0.66%)
Serum creatinine	Low	8 (0.95%)	38 (0.76%)	46 (0.78%)	0.01##
	Normal	835 (98.7%)	4993 (99.22%)	5828 (99.15%)
	High	3 (0.35%)	1 (0.02%)	4 (0.07%)
WBC counts	Low	18 (1.79%)	59 (1.1%)	77 (1.21%)	0.183#
	Normal	944 (93.93%)	5077 (94.67%)	6021 (94.55%)
	High	43 (4.28%)	227 (4.23%)	270 (4.24%)
Lymphocyte count	Low	43 (4.28%)	161 (3%)	204 (3.2%)	<0.001#
	Normal	275 (27.36%)	1198 (22.34%)	1473 (23.13%)
	High	687 (68.36%)	4004 (74.66%)	4691 (73.67%)
Neutrophil count	Low	230 (22.89%)	1379 (25.71%)	1609 (25.27%)	<0.001#
	Normal	705 (70.15%)	3796 (70.78%)	4501 (70.68%)
	High	70 (6.97%)	188 (3.51%)	258 (4.05%)
Lymphocytes/WBC	Low	106 (10.55%)	187 (3.49%)	293 (4.6%)	<0.001#
	Normal	348 (34.63%)	1484 (27.67%)	1832 (28.77%)
	High	551 (54.83%)	3692 (68.84%)	4243 (66.63%)
Neutrophils/WBC	Low	608 (60.5%)	3906 (72.83%)	4514 (70.89%)	<0.001#
	Normal	191 (19%)	928 (17.3%)	1119 (17.57%)
	High	206 (20.5%)	529 (9.86%)	735 (11.54%)

Table 3. Univariate and multivariate logistic regression analysis of risk factors for postoperative infection in infants with congenital heart disease

		Unadjusted		Adjusted
Parameter		OR (95% CI)	P-value	OR (95% CI)	P value
Age (days)	Unit=30	0.808 (0.786,0.831)	<0.001	0.804 (0.776,0.834)	<0.001
Gender	Female	1.000
	Male	1.102 (0.961,1.264)	0.164
Preterm birth	No	1.000
	Yes	1.113 (0.561,2.207)	0.76
History of cardiac surgery	No	1.000
	Yes	1.57 (0.961,2.565)	0.071
STS risk grade	Unit=1	1.535 (1.437,1.64)	<0.001	1.308 (1.203,1.423)	<0.001
Delayed sternal closure	No	1.000
	Yes	2.146 (1.027,4.482)	0.042
BMI	P5~P95 percentile	1.000
	<P5 percentile	0.793 (0.656,0.959)	0.017	1.287 (1.026,1.615)	0.029
	>P95 percentile	1.069 (0.902,1.266)	0.441	0.802 (0.661,0.974)	0.026
CPB time	Unit=1	1.011 (1.009,1.013)	<0.001	1.007 (1.005,1.009)	<0.001
Lymphocyte count	Normal	1.000
	Low	1.164 (0.811,1.67)	0.41
	High	0.747 (0.641,0.872)	<0.001
Lymphocytes /WBC	Normal	1.000
	Low	2.417 (1.854,3.152)	<0.001
	High	0.636 (0.549,0.737)	<0.001
Neutrophil count	Normal	1.000
	Low	0.898 (0.764,1.055)	0.191
	High	2.005 (1.506,2.669)	<0.001
Neutrophil /WBC	Normal	1.000
	Low	0.756 (0.633,0.903)	0.002	0.842 (0.683,1.037)	0.106
	High	1.892 (1.512,2.367)	<0.001	1.456 (1.103,1.923)	0.008
ALT	Normal	1.000
	Low	1.415 (0.854,2.346)	0.178
	High	1.158 (0.891,1.505)	0.271
AST	Normal	1.000
	High	0.973 (0.838,1.13)	0.721
ALP	Normal	1.000
	High	1.306 (0.575,2.968)	0.524
Serum creatinine	Normal	1.000
	Low	1.259 (0.585,2.708)	0.556
	High	17.923 (1.863,172.419)	0.012

Table 4. Baseline characteristics of postoperative infection and non-postoperative infected children

Parameter		Postoperative infection group (n=289)	Non-postoperative infection group (n=5158)	Total (n=5447)	P value
Age (days)	Median (Range)	824 (368,3650)	934 (365,3647)	930 (365,3650)	0.027^
CPB time	Median (Range)	88 (18,318)	48 (11,479)	50 (11,479)	<0.001^
Gender	MALE	157 (54.33%)	2854 (55.33%)	3011 (55.28%)	0.738#
	FEMALE	132 (45.67%)	2304 (44.67%)	2436 (44.72%)
Preterm birth	NO	287 (99.31%)	5119 (99.24%)	5406 (99.25%)	>0.999##
	YES	2 (0.69%)	39 (0.76%)	41 (0.75%)
History of cardiac surgery	NO	201 (69.55%)	4455 (86.37%)	4656 (85.48%)	<0.001#
	YES	88 (30.45%)	703 (13.63%)	791 (14.52%)
BMI	<P5 percentile	82 (30.83%)	760 (15.91%)	842 (16.7%)	<0.001#
	P5~P95 percentile	175 (65.79%)	3771 (78.94%)	3946 (78.25%)
	>P95 percentile	9 (3.38%)	246 (5.15%)	255 (5.06%)
STS risk grade	1	61 (21.11%)	3078 (59.67%)	3139 (57.63%)	<0.001^
	2	148 (51.21%)	1526 (29.59%)	1674 (30.73%)
	3	39 (13.49%)	362 (7.02%)	401 (7.36%)
	4	38 (13.15%)	185 (3.59%)	223 (4.09%)
	5	3 (1.04%)	7 (0.14%)	10 (0.18%)
Delayed sternal closure	NO	284 (98.27%)	5138 (99.61%)	5422 (99.54%)	0.009##
	YES	5 (1.73%)	20 (0.39%)	25 (0.46%)
ALT	Low	20 (8.47%)	320 (6.57%)	340 (6.66%)	<0.001#
	Normal	203 (86.02%)	4477 (91.93%)	4680 (91.66%)
	High	13 (5.51%)	73 (1.5%)	86 (1.68%)
AST	Normal	157 (63.82%)	3865 (78.16%)	4022 (77.48%)	<0.001##
	High	89 (36.18%)	1080 (21.84%)	1169 (22.52%)
ALP	Normal	245 (99.59%)	4909 (99.31%)	5154 (99.33%)	>0.999##
	High	1 (0.41%)	34 (0.69%)	35 (0.67%)
Serum creatinine	Low	0 (0%)	4 (0.08%)	4 (0.08%)	0.321##
	Normal	244 (99.59%)	4933 (99.86%)	5177 (99.85%)
	High	1 (0.41%)	3 (0.06%)	4 (0.08%)
WBC counts	Low	4 (1.38%)	31 (0.6%)	35 (0.64%)	<0.001#
	Normal	269 (93.08%)	5021 (97.34%)	5290 (97.12%)
	High	16 (5.54%)	106 (2.06%)	122 (2.24%)
Lymphocyte count	Low	7 (2.42%)	26 (0.5%)	33 (0.61%)	<0.001#
	Normal	107 (37.02%)	1559 (30.22%)	1666 (30.59%)
	High	175 (60.55%)	3573 (69.27%)	3748 (68.81%)
Neutrophil count	Low	22 (7.61%)	449 (8.7%)	471 (8.65%)	<0.001#
	Normal	228 (78.89%)	4353 (84.39%)	4581 (84.1%)
	High	39 (13.49%)	356 (6.9%)	395 (7.25%)
Lymphocytes/WBC	Low	15 (5.19%)	51 (0.99%)	66 (1.21%)	<0.001#
	Normal	67 (23.18%)	921 (17.86%)	988 (18.14%)
	High	207 (71.63%)	4186 (81.16%)	4393 (80.65%)
Neutrophils/WBC	Low	211 (73.01%)	4091 (79.31%)	4302 (78.98%)	<0.001#
	Normal	64 (22.15%)	990 (19.19%)	1054 (19.35%)
	High	14 (4.84%)	77 (1.49%)	91 (1.67%)

Table 5. Univariate and multivariate logistic regression analysis of risk factors for postoperative infection in children with congenital heart disease

		Unadjusted		Adjusted
Parameter		OR (95% CI)	P-value	OR (95% CI)	P value
Age (days)	Unit=30	0.997 (0.992,1.002)	0.307
Gender	Female	1.000
	Male	0.96 (0.757,1.218)	0.737
Preterm birth	No	1.000
	Yes	0.915 (0.22,3.807)	0.902
History of cardiac surgery	No	1.000
	Yes	2.774 (2.133,3.609)	<0.001	1.476 (1.03,2.116)	0.034
STS risk grade	Unit=1	2.097 (1.872,2.35)	<0.001	1.555 (1.328,1.82)	<0.001
Delayed sternal closure	No	1.000
	Yes	4.523 (1.685,12.139)	0.003
BMI	P5~P95 percentile	1.000
	<P5 percentile	2.325 (1.769,3.057)	<0.001	1.956 (1.412,2.71)	<0.001
	>P95 percentile	0.788 (0.399,1.56)	0.494	0.768 (0.339,1.74)	0.527
CPB time	Unit=1	1.015 (1.013,1.018)	<0.001	1.012 (1.009,1.015)	<0.001
Lymphocyte count	Normal	1.000
	Low	3.923 (1.665,9.245)	0.002
	High	0.714 (0.557,0.914)	0.008
Lymphocytes/WBC	Normal	1.000
	Low	4.043 (2.16,7.567)	<0.001	3.321 (1.479,7.454)	0.004
	High	0.68 (0.511,0.904)	0.008	0.861 (0.6,1.236)	0.417
Neutrophil count	Normal	1.000
	Low	0.935 (0.598,1.464)	0.771
	High	2.092 (1.465,2.988)	<0.001
Neutrophil /WBC	Normal	1.000
	Low	0.798 (0.598,1.064)	0.125
	High	2.813 (1.508,5.244)	0.001
ALT	Normal	1.000
	Low	1.378 (0.859,2.212)	0.184
	High	3.928 (2.142,7.204)	<0.001
AST	Normal	1.000
	High	2.029 (1.551,2.654)	<0.001	1.748 (1.285,2.379)	<0.001
ALP	Normal	1.000
	High	0.589 (0.08,4.323)	0.603
Serum creatinine	Normal	1.000
	Low	0 (0,.)	0.983
	High	6.739 (0.698,65.023)	0.099

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Editorial decision: Major revision
10 Oct, 2019
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Reviewer #1 agreed at journal
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Risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease

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