In 2017, a monocentric observational retrospective study was undertaken in pediatric surgical patients in neurosurgery, abdominal and orthopedic surgery to determine predictors of postoperative outcome . In this cohort of 594 patients with a mean age of 90.86 ± 71.80 months, there were 25 pre-term infants aged less than 37 weeks. These were all admitted to the neonatal intensive care unit (NICU) and were scheduled for emergency and elective surgery. These pre-term patients were described in detail in this manuscript. The objective of this study was to describe the characteristics and postoperative outcome in these pre-term infants in this cohort.
Secondary analysis and description of pre-term patients included in the initial retrospective observational study from 1 January 2014 to 17 May 2017 . This study was declared to the CNIL, National Commission for Computer Science and Liberties on 21 February 2017 under the registration number 2028257 v0 and received approval from the Ethics Committee of Necker on 21 March 2017 under the registration number 2017-CK-5-R1 .
Inclusion criteria were patients aged less than 37 weeks included in the initial study.
Exclusion criteria were patients aged more than 37 weeks included in the initial study.
Statistics were analyzed with XLSTAT 2020.4.1 software.
Continuous variables were described in means with standard deviation or in medians with interquartile range. Categoric variables were described in proportions. Categoric variables were compared with Fischer’s exact test.
General characteristics are illustrated in Table 1. 25 pre-terms aged <37 weeks were included. Mean weight was 2.43 ± 0.75 kg. There were 20 American Society of Anesthesiologists (ASA) grade III and 5 ASA IV patients.
Surgery concerned 1 intestinal resection for enterocolitis, 1 exploratory laparotomy for volvulus, 3 exploratory laparotomies, 8 gastroschises, 4 omphaloceles and 8 esophageal atresias. 19 patients underwent emergency surgery and 6 underwent elective surgery. 1 patient had a congenital heart disease and 1 had a right atrium thrombus. 4 patients had re-operations. 9 patients presented intraoperative and/or postoperative complications among which 1 had an intra-operative cardiac arrest with favorable outcome, 4 had postoperative respiratory failure, 2 had pulmonary sepsis, 1had surgical wound sepsis, 1 had septicemia, 1 had multi-organ sepsis.
There was no in-hospital mortality.
All were admitted to the NICU, 22 patients were under mechanical ventilation postoperatively and 3 did not require postoperative mechanical ventilation.
Median neonatal intensive care unit stay (LOSICU) was 33 days [20 - 45], median hospital length stay (LOS) was 6 days [0 - 26], median total hospital length
Table 1. General characteristics of preterm infants admitted in NICU after abdominal surgery.
N = total number of patients. n = number of patients with the variable.
stay, TLOS (LOSICU + LOS) was 45 days [32 - 54] and median length of mechanical ventilation (LMV) was 4 days [3 - 8].
None received transfusion.
Median preoperative and postoperative hemoglobin levels were 16.5 g/dL [15 - 17.5] and 15.25 g/dL [14.2 - 18.2] respectively.
Table 2 illustrates complications in each surgical intervention and there was
Table 2. Outcomes per type of surgery.
p > 0.05, Fischer’s exact test.
no difference among different types of surgery.
The rate of patients with postoperative complications in this cohort was comparable to what has been reported in neonatal infants in abdominal major surgery    . There was no significant difference in complication rates among different types of surgery. One patient presented intra-operative cardiac arrest with favorable outcome which represented 4% of the complications. The incidence of intra-operative cardiac arrest was 0.12% according to a recent study in a cohort of 5609 infants aged up to 60 weeks among which 35.7% were pre-terms . According to this same study, the rate of patients with intra-operative critical events was 35.3% among which the majority were commonly due to cardiovascular instability followed by hypoxemia; 16.3% of the patients had one or several postoperative critical events . In our study, intra-operative critical events concerned one patient who presented intra-operative cardiac arrest with favorable outcome representing 4% of the patients. The rate of patients with postoperative complications until discharge from hospital was 36% in our cohort.
Our study of 25 pre-terms in major abdominal surgery revealed that the most common postoperative complications concerned the respiratory system which included respiratory failure and pulmonary sepsis with an overall rate of 24%. According to previous studies in 198 infants with esophageal atresia and 44 pre-terms with gastroschisis, the rate of postoperative respiratory dysfunction varied between 11% and 52.8%  . The second common postoperative complication in our cohort was re-operation (16%) followed by surgical wound sepsis (4%), septicemia (4%) and multi-organ sepsis (4%).
Sepsis after major surgery such as esophageal atresia has been reported to vary between 3.1% - 19.4% . In this cohort, the overall sepsis rate was 20% with pulmonary sepsis being the most common with a rate of 8%. The incidence of early onset sepsis (appearing after less than 3 days of life) in pre-terms varied from 0.5% to 2.5% according to one study  and the rate of late onset sepsis (appearing after 3 days of life) in pre-terms varied from 11% - 32%  . Neonatal sepsis is a major etiology of morbimortality in pre-terms  . Mortality rates due to sepsis in pre-terms can reach 20% - 30% . In our cohort, there was no mortality. Mortality rates reported in the literature in pre-terms scheduled for major neonatal abdominal surgery such as necrotizing enterocolitis, esophageal atresia, gastroschisis and omphalocele varied between 3.4% and 34%       . According to a study in 75 neonates with abdominal wall defects, mortality was higher in patients with associated congenital heart diseases and chromosomic disorders .
In another study of 1554 premature infants in emergency abdominal operations, female gender, inotropic support, mechanical ventilation and ASA score III were predictors of 30 days mortality .
In a study of 566 neonates with gastroschisis, the presence of a complex gastroschisis, pre-term age of <37 weeks, very low birth weight of <1500 grams were factors predicting morbimortality .
According to the multicentric Nectarine study, overall mortality rate was 3.2%, with a 30-day mortality rate in neonates of 4.1% with sepsis and multi-organ failure being major causes of mortality in this subgroup . The Nectarine study which included patients aged up to 60 weeks admitted for different surgical interventions revealed that age, critical events including hypotension, hypoxemia and anemia were predictive of adverse outcome .
In our pre-term cohort, none of the patients were anemic and none received transfusion.
Median total hospital length of stay, TLOS (LOSICU + LOS) was 45 days [32 - 54] and was comparable to what has been reported in the literature . In a study of 442 neonates with gastroschisis of more than 34 weeks of age , median LOS was higher in patients with staged closure than in primary closure, implying that LOS is a variable which depends on multiple factors.
The results of our initial pediatric retrospective study, the results of the Nectarine study, and the results of previous studies in similar neonatal population confirm that outcome in the surgical pediatric population is multifactorial. Identifying these multiple predictors of adverse evolution and applying preventive and improvement measures on each of them can optimize postoperative outcome in children. A meta-analysis in 3290 children aged less than 18 years old evidenced that mortality, organ dysfunction and LOS were lower in children who had optimal intra-operative or postoperative values of regional oxygen saturation, mixed central venous oxygen saturation and lactate levels . Regional oxygen saturation, mixed central venous oxygen saturation and lactate levels reflect tissular perfusion and alterations of these parameters can indicate tissular perfusion impairment which can cause organ dysfunction.
The results of this study confirm that the rate of postoperative complications in critically ill pre-term infants in major abdominal surgery remains high as reported previously. The limit of our study was the sample size.
The strength of our study was the homogeneity of the sample that included critically ill pre-term infants in major abdominal surgery thus a high-risk population.
In this study of 25 critically ill pre-term infants admitted to NICU after abdominal major surgery, the most common postoperative complications concerned the respiratory system which included respiratory failure and pulmonary sepsis; followed by re-surgery, wound sepsis, septicemia and multi-organ sepsis. There was no in-hospital mortality.
Ethics Approval and Informed Consent
This study received approval from the Ethics Committee of Necker on 21 March 2017 under the registration number 2017-CK-5-R1. The Ethics Committee of Necker waived the need for patient consent since this was a retrospective study.
Dr Claudine Kumba conceptualized and designed the study, drafted the initial and final manuscript. She designed the data collection instruments, collected data, carried out initial and final analyses.
Presentation of Preliminary Data
The abstract of this study was accepted for presentation to the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) 15-18 June 2021.
This manuscript has been registered as a preprint on Research Square, a preprint platform under the DOI number https://doi.org/10.21203/rs.3.rs-669064/v1.
 Kumba, C., Cresci, F., Picard, C., et al. (2017) Transfusion and Morbi-Mortality Factors: An Observational Descriptive Retrospective Pediatric Cohort Study. Journal of Anesthesia & Critical Care: Open Access, 8, Article ID: 00315.
 Li, X.W., Jiang, Y.J., Wang, X.Q., et al. (2017) A Scoring System to Predict Mortality in Infants with Esophageal at Resia. A Case-Control Study. Medicine, 96, Article ID: e7755.
 Tsai, M.H., Huang, H.R., Chu, S.M., et al. (2010) Clinical Features of Newborns With Gastroschisis and Outcomes of Different Initial Interventions: Primary Closure Versus Staged Repair. Pediatrics & Neonatology, 51, 320-325.
 Sheng, Q., Lv, Z., Xu, W., et al. (2016) Short-Term Surgical Outcomes of Preterm Infants with Necrotizing Enterocolitis. Medicine, 95, Article ID: e4379.
 Disma, N., Veyckemans, F., Virag, K., Hansen, T.G., et al. (2021) Morbidity and Mortality after Anaesthesia in Early Life: Results of the European Prospective Multicentre Observational Study, Neonate and Children Audit of Anaesthesia Practice in Europe (NECTARINE). British Journal of Anaesthesia, 126, 1157-1172.
 Puopolo, K.M., Mukhopadhay, S., Hansen, N.I., Cotton, C.M., et al. (2017) Identification of Extremely Premature Infants at Low Risk for Early-Onset Sepsis. Pediatrics, 14, Article ID: e20170925.
 Downey, L.C., Smith, P.B. and Benjamin, D.K. (2010) Risk Factors and Prevention of Late Onset Sepsis in Premature Infants. Early Human Development, 86, 7-12.
 Alock, G., Liley, H.G., Cooke, L. and Gray, P.H. (2017) Prevention of Neonatal Late-Onset Sepsis: A Randomized Controlled Trial. BMC Pediatrics, 17, Article No. 98.
 Bauman, B., Stephens, D., Gershone, H., Bongiorno, C., Osterholm, E., Acton, R., et al. (2016) Management of Giant Omphaloceles: A Systematic Review of Methods of Staged Surgical vs. Nonoperative Delayed Closure. Journal of Pediatric Surgery, 51, 1725-1730.
 Cairo, S.B., Tabak, B.D., Berman, L., et al. (2013) Mortality after Emergency Abdominal Operations in Premature Infants. Journal of Pediatric Surgery, 53, 2105-2111.
 Raymond, S.L., Hawkins, R.B., Peter, S.D., et al. (2020) Predicting Morbidity and Mortality in Neonates Born with Gastroschisis. Journal of Surgical Research, 245, 217-224.
 Murthy, K., Evans, J.R., Bhatia, A.M., et al. (2014) The Association of Type of Surgical Closure on Length of Stay among Infants with Gastroschisis Born >34 Weeks Gestation. Journal of Pediatric Surgery, 49, 1220-1225.
 Kumba, C., Willems, A., Querciagrossa, S., et al. (2019) A Systematic Review and Meta-Analysis of Intraoperative Goal Directed Fluid and Haemodynamic Therapy in Children and Postoperative Outcome. Journal of Emergency and Critical Care Medicine, 5, 1-9.