Postoperative Hirschsprung's associated enterocolitis (HAEC): transition zone as putative histopathological predictive factor.

AIMS: Hirschsprung's-associated enterocolitis (HAEC) is the most severe complication of Hirschsprung disease (HD), and its pathogenesis is still unknown. Length of transition zone (TZ) interposed between aganglionic and normal bowel has been poorly explored as predictor for postoperative HAEC (post-HAEC). This study aimed to identify potential predictive factors for post-HAEC, with a particular focus on histopathological findings. METHODS: Data from Hirschsprung patients treated in a single Italian centre between 2010 and 2022 with a follow-up >6 months were collected. Thorough histopathological examination of the resected bowel was conducted, focusing on length of TZ and aganglionic bowel.The degree of inflammatory changes in ganglionic resected bowel was further obtained. Ultra-long HD, total colonic aganglionosis and ultra-short HD were excluded. Bivariate and multivariate regression analysis were performed. RESULTS: Thirty-one patients were included; 5 experienced preoperative HAEC (pre-HAEC) and later post-HAEC (16.1%), further 10 patients developed post-HAEC (total post-HAEC 48.38%). Pre-HAEC-history and a TZ<2.25 cm correlated with an early development of post-HAEC. Multivariate analysis identified a TZ<2.25 cm as an independent post-HAEC predictive factor (p=0.0096). Inflammation within the ganglionic zone and a TZ<2.25 cm correlated with higher risk of post-HAEC (p=0.0074, 0.001, respectively). Severe post-HAEC more frequently occurred in patients with pre-HAEC (p=0.011), histological inflammation (p=0.0009) and short TZ (p=0.0015). CONCLUSIONS: This study suggests that TZ<2.25 cm predicts the risk of post-HAEC. Preoperative clinical and histopathology inflammation may predispose to worst post-HAEC. Readily available histopathological findings might help identifying patients at higher risk for HAEC and implementing prevention strategies.

Enhancing diagnosis of Hirschsprung's disease using deep learning from histological sections of post pull-through specimens: preliminary results.

PURPOSE: Accurate histological diagnosis in Hirschsprung disease (HD) is challenging, due to its complexity and potential for errors. In this study, we present an artificial intelligence (AI)-based method designed to identify ganglionic cells and hypertrophic nerves in HD histology. METHODS: Formalin-fixed samples were used and an expert pathologist and a surgeon annotated these slides on a web-based platform, identifying ganglionic cells and nerves. Images were partitioned into square sections, augmented through data manipulation techniques and used to develop two distinct U-net models: one for detecting ganglionic cells and normal nerves; the other to recognise hypertrophic nerves. RESULTS: The study included 108 annotated samples, resulting in 19,600 images after data augmentation and manually segmentation. Subsequently, 17,655 slides without target elements were excluded. The algorithm was trained using 1945 slides (930 for model 1 and 1015 for model 2) with 1556 slides used for training the supervised network and 389 for validation. The accuracy of model 1 was found to be 92.32%, while model 2 achieved an accuracy of 91.5%. CONCLUSION: The AI-based U-net technique demonstrates robustness in detecting ganglion cells and nerves in HD. The deep learning approach has the potential to standardise and streamline HD diagnosis, benefiting patients and aiding in training of pathologists.

Research Models to Mimic Necrotizing Enterocolitis and Inflammatory Bowel Diseases: Focus on Extracellular Vesicles Action.

This review focuses on the crucial role of the intestinal epithelium in maintaining intestinal homeostasis and its significance in the pathogenesis of necrotizing enterocolitis (NEC) and inflammatory bowel diseases (IBD). NEC is a devastating neonatal disease, while IBD represents a global healthcare problem with increasing incidence. The breakdown of the intestinal barrier in neonates is considered pivotal in the development and progression of both disorders. This review provides an overview of the current state of in vitro, ex vivo, and animal models to study epithelial injury in NEC and IBD, addressing pertinent questions that engage clinicians and researchers alike. Despite significant advancements in early recognition and aggressive treatment, no single therapy has been conclusively proven effective in reducing the severity of these disorders. Although early interventions have improved clinical outcomes, NEC and IBD continue to impose substantial morbidity, mortality, and economic burdens on affected individuals and society. Consequently, exploring alternative therapeutic options capable of preventing and treating the sequelae of NEC and IBD has become a pressing necessity. In recent decades, extracellular vehicles (EVs) have emerged as a potential solution to modulate the pathogenic mechanism in these multifactorial and complex disorders. Despite the diverse array of proposed models, a comprehensive model to investigate and decelerate the progression of NEC and IBD remains to be established. To bridge the translational gap between preclinical studies and clinical applications, enhancements in the technical development of gut-on-a-chip models and EVs hold considerable promise.

Laparoscopic Heller-Dor Is a Persistently Effective Treatment for Achalasia Even in Pediatric Patients: A 25-Year Experience at a Single Tertiary Center.

BACKGROUND: Esophageal achalasia (EA) is a rare primary motility disorder in any age group, and particularly rare in the pediatric population, with a reported incidence of 0.18 per 100,000 children a year. EA in pediatric age is currently treated in the same way as in adults, but this approach is based on only a few studies on small case series. The aim of this retrospective study was to assess the long-term outcome of the laparoscopic Heller-Dor (LHD) procedure when performed in pediatric patients with EA at our university hospital. MATERIALS AND METHODS: We considered children and adolescents younger than 16 years old diagnosed with EA and treated with LHD between 1996 and 2022. Clinical data were prospectively collected in an ongoing database. Symptoms were recorded and their severity was calculated using the Eckardt score. Barium swallow, esophageal manometry (conventional or high-resolution), and endoscopy were performed before and after the surgical procedure. RESULTS: During the study period, 40 children with a median age of 14 years (interquartile range [IQR]: 11-15) underwent LHD. At a median follow-up of 10.5 years (IQR: 4.5-13.9), a good outcome was achieved in 36/40 patients (90%). Two of the four patients whose surgical procedure failed underwent complementary pneumatic dilations successfully, thus increasing the overall success rate to 95%. A previous endoscopic treatment (in five patients) did not affect the final outcome (p = 0.49). An intraoperative mucosal lesion was detected in only one patient (2.5%) and was repaired at the time without further consequences. During the follow-up, 22 patients underwent endoscopy, and 17 had pH monitoring as well: only 2 of these patients showed reflux esophagitis at endoscopy (one of them with abnormal findings on pH monitoring), amounting to a 9.1% rate of instrumentally confirmed postoperative reflux. CONCLUSION: LHD is a safe and persistently effective treatment for EA in pediatric age, with a success rate comparable with what is usually obtained in adults, and better than what has been reported to date in the pediatric literature. Adding a fundoplication certainly helps ensure an optimal long-term control of any gastroesophageal reflux induced by the myotomy.

A survival analysis of cuffed tunneled silicon central venous catheters in children affected by short bowel syndrome: A lesson from the past.

BACKGROUND: Tunneled central venous catheters (CVC) are crucial in the management of children affected by short bowel syndrome (SBS). This work aims to investigate the outcomes of tunneled CVC and to identify factors influencing their survival. METHODS: All the children diagnosed with SBS and undergone a procedure of insertion of a tunneled CVC from 2010 to 2019 were included. Demographic data and surgical information about the procedures were collected. Regression models and Kaplan-Meier analysis were performed to estimate the survival. RESULTS: Eighteen patients, eight males (44%), with a median length of residual bowel measuring 72 cm (IQR 50-102 cm), were enrolled. Thirty-nine Broviac CVCs were inserted with a mean number of 2.2 CVCs per patient and 13365 line-days. The overall incidence of complications was 3.2/1000 line-days, and the incidence of central line associated bloodstream infections (CLABSI) was 1.1/1000 line-days. No episode of catheter thrombosis was reported. The median survival was 269 days (IQR 82-1814 days). The survival was negatively influenced by a younger age at insertion (R2 = 0.29; p < 0.001), 2.7 Fr diameter (median survival 76 days; p < 0.001) and the occurrence of complications (median survival 169 days; p = 0.002). The length of residual bowel was a mild risk factor for anticipated removal (OR 1.1; CI95 1.0-1.1; p = 0.05). CONCLUSION: CVC-related complications negatively influenced the survival of the line. An elder age at insertion together with a larger CVC diameter increased the survival of the line, while a shorter residual bowel was associated with an anticipated removal due to complications.

Anesthesia for fetal operative procedures: A systematic review.

Objective: The anesthetic management of fetal operative procedures (FOP) is a highly debated topic. Literature on fetal pain perception and response to external stimuli is rapidly expanding. Nonetheless, there is no consensus on the fetal consciousness nor on the instruments to measure pain levels. As a result, no guidelines or clinical recommendations on anesthesia modality during FOP are available. This systematic literature review aimed to collect the available knowledge on the most common fetal interventions, and summarize the reported outcomes for each anesthetic approach. Additional aim was to provide an overall evaluation of the most commonly used anesthetic agents. Methods: Two systematic literature searches were performed in Embase, Medline, Web of Science Core Collection and Cochrane Central Register of Controlled Trials up to December 2021. To best cover the available evidence, one literature search was mostly focused on fetal surgical procedures; while anesthesia during FOP was the main target for the second search. The following fetal procedures were included: fetal transfusion, laser ablation of placental anastomosis, twin-reversed arterial perfusion treatment, fetoscopic endoluminal tracheal occlusion, thoraco-amniotic shunt, vesico-amniotic shunt, myelomeningocele repair, resection of sacrococcygeal teratoma, ligation of amniotic bands, balloon valvuloplasty/septoplasty, ex-utero intrapartum treatment, and ovarian cyst resection/aspiration. Yielded articles were screened against the same inclusion criteria. Studies reporting anesthesia details and procedures' outcomes were considered. Descriptive statistical analysis was performed and findings were reported in a narrative manner. Results: The literature searches yielded 1,679 articles, with 429 being selected for full-text evaluation. A total of 168 articles were included. Overall, no significant differences were found among procedures performed under maternal anesthesia or maternal-fetal anesthesia. Procedures requiring invasive fetal manipulation resulted to be more effective when performed under maternal anesthesia only. Based on the available data, a wide range of anesthetic agents are currently deployed and no consistency has been found neither between centers nor procedures. Conclusions: This systematic review shows great variance in the anesthetic management during FOP. Further studies, systematically reporting intraoperative fetal monitoring and fetal hormonal responses to external stimuli, are necessary to identify the best anesthetic approach. Additional investigations on pain pathways and fetal pain perception are advisable.

The Metabolome and the Gut Microbiota for the Prediction of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation: A Systematic Review.

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell's stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3−V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.

Fetal Doppler Evaluation to Predict NEC Development.

Antenatal factors play a role in NEC pathogenesis. This study aimed to investigate the predictive value of fetal ductus venosus doppler (DV) for NEC in fetal growth restriction fetuses (FGRF) and to assess the predictive accuracy of IG21 and Fenton curves in NEC development. Data from FGRF, postnatal findings, and Doppler characteristics were collected between 2010 and 2020 at a single center. Patients were then divided into two groups (i.e., with and without NEC). Bivariate and multivariate analyses were performed. We identified 24 cases and 30 controls. Absent or reversed end-diastolic flow (AREDF) and increased resistance in the DV were more impaired in cases (p < 0.05). Although the median birthweight was not different, the Fenton z-score was lower in NEC (p < 0.05). Fetal cardiopulmonary resuscitation, synchronized intermittent mandatory ventilation, neonatal respiratory distress, persistent patent ductus arteriosus (PDA), and inotropic support were more frequent in the NEC group. Furthermore, NEC patients had lower white blood cells (WBC) (p < 0.05). The predictive model for NEC (model 4), including Fenton z-score, WBC, PDA, and DV had an AUC of 84%. Fetal Doppler findings proved effective in predicting NEC in FGR. The Fenton z-score was the most predictive factor considering the fetal growth assessment showing high sensitivity.

Laparoscopic fundoplication after oesophageal atresia repair.

Background: Esophageal atresia (EA) is a rare congenital malformation. A high incidence of GER unresponsive to medical management is noted with EA. Literature suggests that complications from GER can persist in adulthood. In paediatric age, laparoscopic treatment is a valid option even if recurrence rate is not negligible. Aims and Objectives: To evaluate our experience with gastro-esophageal reflux (GER) treatment after esophageal atresia (EA) repair. Materials and Methods: We retrospectively analysed 29 consecutive patients treated for EA at birth and studied for GER at our Institute in a period of 11 years. Results: 24/29 (82,7%) cases had symptoms of reflux, 17/29 (58,6%) cases were treated with laparoscopic fundoplication (LF). Three infants were younger than 6 months and had apparent life threatening events (ALTE) condition as principal indication for surgery. No intra-operative complications occurred. 3/17 LF had open surgical conversion due to technical problems. 2/17 cases required a second operation. At the last follow-up: (1) 6/17 (35,3%) of patients healed after the last operation, (2) 8/17 (47,1%) have GER improvement (four still in medical treatment), (3) 2/17 (11,8%) have persistent GER, (4) 1/17 (5,9%) died for causes not related to antireflux surgery. Conclusions: According to literature and to our retrospective analysis, LF for GER after EA repair is feasible, even if recurrence risk is not negligible. Infants less than 6 months old with associated conditions (malformations, gastrostomy/jejunostomy) seem to have a higher failure rate with a greater risk of conversion. Longer follow-up and multicenter experiences would guarantee an adequate surveillance for patients with EA.

Risk factors for end stage renal disease in children with anorectal malformation and outcome comparison to children with isolated urological anomalies.

BACKGROUND: End stage renal disease (ESRD) requiring kidney transplant (KT) remains an important cause of morbidity in anorectal malformations (ARM) patients. Current literature is scarce on defining the risk factors for ESRD and the outcomes of KT in ARM patients. OBJECTIVE: This study aimed to identify predisposing factors to ESRD in ARM patients and verify if the long term outcome of KT in these patients differs from pure urological anomalies (UA). STUDY DESIGN: Databases of ARM and KT patients treated at our center between 2000 and 2016 were used for comparing characteristics of ARM cases which developed ESRD and those who did not, and the outcome features of MAR-KT vs UA-KT. RESULTS: Out of 117 ARM patients, 9 developed ESRD. All of them had a complex ARM. Association with UA were significantly higher in ARM-KT compared to other ARM patients (100% vs. 52%, p = 0.001). The most common UA associated to KT in ARM patients was renal dysplasia. During the same period 23 patients underwent KT as a sequelae of pure urological anomalies (UA-KT group). The most represented UA were primary vesico-ureteral reflux (65.2%) and posterior urethral valves (14%) in UA-KT (table 2). ARM-KT patients required more often hemodialysis before KT (50% vs. 8.7%, p = 0.05) and an aorto-caval anastomosis at the transplant (75% vs. 30%, p = 0.04) compared to UA-KT. Moreover ARM-KT patients experienced more often graft failure and and the need for a second KT (50% vs. 8.6%, p = 0.02). DISCUSSION: To our knowledge, this is the first study describing the differences in terms of risk factors and outcomes of KT in ARM patients. We observed a need for KT in 7% of ARM, which is at the higher end of the range reported in the literature. Bilateral dysplasia and cloaca malformation seem the leading cause to ESRD for ARM patients compared to vesico-ureteral reflux and posterior urethral valve in UA-KT. Our experience showed that KT has worst outcome in ARM vs pure UA patients. CONCLUSION: Patients with complex ARM are more frequently associated to renal dysplasia which lead to KT. Graft in ARM patients seems to be the more vulnerable and prone to failure.

Providing the Best Parenteral Nutrition before and after Surgery for NEC: Macro and Micronutrients Intakes.

Necrotizing enterocolitis (NEC) is the main gastrointestinal emergency of preterm infants for whom bowel rest and parenteral nutrition (PN) is essential. Despite the improvements in neonatal care, the incidence of NEC remains high (11% in preterm newborns with a birth weight <1500 g) and up to 20−50% of cases still require surgery. In this narrative review, we report how to optimize PN in severe NEC requiring surgery. PN should begin as soon as possible in the acute phase: close fluid monitoring is advocated to maintain volemia, however fluid overload and electrolytes abnormalities should be prevented. Macronutrients intake (protein, glucose, and lipids) should be adequately guaranteed and is essential in each phase of the disease. Composite lipid emulsion should be the first choice to reduce the risk of parenteral nutrition associated liver disease (PNALD). Vitamin and trace elements deficiency or overload are frequent in long-term PN, therefore careful monitoring should be planned starting from the recovery phase to adjust their parenteral intake. Neonatologists must be aware of the role of nutrition especially in patients requiring long-term PN to sustain growth, limiting possible adverse effects and long-term deficiencies.

Congenital Pouch Colon: Case Series and Review of Evidences for Resection.

BACKGROUND: Congenital pouch colon (CPC) is a rare variant of anorectal malformations (ARM) with its highest reported incidence in India. We aimed to describe five patients affected by CPC, in which the tissue from the terminal dilated colon has been successfully used and to discuss our results on the light of an extended revision of the literature. MATERIALS AND METHODS: The clinical details of five cases treated for CPC in two Italian Centers were retrospectively reviewed assessing the fate of the terminal dilated colon. RESULTS: In all cases, the tissue from dilated colon has been used. The double vascular system of the dilated pouch allowed increasing bladder capacity (case 4), reconstruction of the vagina (case 3, 5), and lengthening of the colon (case 1, 2, 5).In our series, 3/5 have a good bowel control with daily bowel management after ARM correction. In literature, there are not differences in terms of dependence from bowel management in patients with pouch resected and in patients with pouch saved (P = 0.16). CONCLUSIONS: We acknowledge that the analysis of the available literature is limited by the absence of studies with high level of evidence and the removal or the preservation of the abnormal colon tissue seems to follow the surgeon preferences.

Conservative management of anterior located anus: A medium-long term follow up.

BACKGROUND/PURPOSE: The anterior anus (AA) is a condition, almost exclusively present in females, in which the anus is located abnormally anterior along the perineal body, well separated from the vulva. Definition and treatment are still controversial. This study aimed to evaluate the medium-long term follow up of patients with AA conservatively managed, considering the gynaecologic aspects in post-menarchal girls. MATHERIALS/METHODS: This cross-sectional study includes AA patients older than 3 years at time of the study, followed in two referral centres for ARM between January 2000 and May 2017. The API (Anal Position Index) was applied to define AA. A questionnaire regarding the ano-rectal function, occurrence of urinary infection (UTI), familiarity for ARM/AA was administered to parents and patients. Gynecological examination was performed in post-menarchal patients. RESULTS: Fifty-three patients (all females) were retrieved. Three were excluded (2 underwent surgery at another center, 1 was lost at follow-up), 7/50 had major malformations (2 oesophageal atresia, 4 cardiovascular malformations and 1 with Fallot, uretheral duplicity and vertebral anomalies), 5/50 had familiarity for ARM/AA. Only 10% were constipated. Fifteen patients underwent gynecological examination. Their mean API was 0.278 +/- 0.013 DS, they had good buttock tropism, normal resident bacteria, and no UTI. CONCLUSION: AA patients in our centers do not undergo any kind of surgery. At least three quarters of them have a perfectly normal bowel habits and adolescents do not present symptoms related to their condition. These results support the conservative management of this condition.

Optimizing Nutritional Strategies to Prevent Necrotizing Enterocolitis and Growth Failure after Bowel Resection.

Necrotizing enterocolitis (NEC), the first cause of short bowel syndrome (SBS) in the neonate, is a serious neonatal gastrointestinal disease with an incidence of up to 11% in preterm newborns less than 1500 g of birth weight. The rate of severe NEC requiring surgery remains high, and it is estimated between 20-50%. Newborns who develop SBS need prolonged parenteral nutrition (PN), experience nutrient deficiency, failure to thrive and are at risk of neurodevelopmental impairment. Prevention of NEC is therefore mandatory to avoid SBS and its associated morbidities. In this regard, nutritional practices seem to play a key role in early life. Individualized medical and surgical therapies, as well as intestinal rehabilitation programs, are fundamental in the achievement of enteral autonomy in infants with acquired SBS. In this descriptive review, we describe the most recent evidence on nutritional practices to prevent NEC, the available tools to early detect it, the surgical management to limit bowel resection and the best nutrition to sustain growth and intestinal function.

Clinical prognostic factors in pediatric adrenocortical tumors: A meta-analysis.

Pediatric adrenocortical tumors (ACT) are rare and sometimes aggressive malignancies, but there is no consensus on the outcome predictors in children. A systematic search of MEDLINE, SCOPUS, Web of Science, and the Cochrane Library for studies from 1994 to 2020 about pediatric ACT was performed. In 42 studies, 1006 patients, aged 0-18 years, were included. The meta-analyses resulted in the following predictors of better outcome: age <4 years (P < .00001), nonsecreting tumors (P = .004), complete surgical resection (P < .00001), tumor volume (P < .0001), tumor weight (P < .00001), tumor maximum diameter (P = .0009), and Stage I disease (P < .00001). Moreover, patients affected by Cushing syndrome showed a worse outcome (P < .0001). International prospective studies should be implemented to standardize clinical prognostic factors evaluation, together with pathological scores, in the stratification of pediatric ACT.

Urinary Tract Anomalies in Patients With Anorectal Malformations: The Role of Screening and Clinical Follow-Up.

OBJECTIVE: To evaluate the efficacy of the screening protocol and the clinical follow-up to detect urological anomalies (UA) in patients with ARM (ARM-P) in our institution. Secondary aim was to define the prevalence of UA and their relationship with severity of ARM. METHODS: ARM-P were selected from a prospectively maintained database from 2000 to 2016. Exclusion criteria were: incomplete or with less than 3 years of follow-up and absence of surgical correction of the anorectal anomalies. Data from urological screening and follow-up were collected. Patients were divided into complex malformations (Group 1) and less complex malformations (Group 2). RESULTS: One hundred seventeen of 149 were included in the study period (62 group 1, 55 group 2). UA were detected in 36/117 at birth (30.7%) with a difference between groups (P = .0005). VUR was detected in 16 (6 with hydronephrosis, 10 with normal ultrasound at birth). A bladder ultrasound after potty training showed 18 lower urinary tract dysfunction (LUTD; 15 with UA detected at birth, 3 with normal ultrasound). 8 LUTD were found during clinical follow-up, confirmed by ultrasound. Spinal MRI detected spinal cord anomalies (SCA) in 52/117 (44.4%). Considering the subgroups with neurogenic bladder and SCA there was a difference between groups (13/33 vs 1/19). CONCLUSION: This study suggests that ARM-P are at increased risk of UA, most of which were detected on neonatal ultrasound. While screening protocol can show 88% of UA, follow-up can detect 12.9 % of total abnormalities without difference between groups. This data has to be considered when planning follow-up for these patients.

Maternal and placental risk factors associated with the development of necrotizing enterocolitis (NEC) and its severity.

BACKGROUND/PURPOSE: Antenatal factors play an important role in NEC. This study aimed to identify antenatal risk factors associated with the development of NEC, the role of the placental alterations, and the presence of prenatal signs predisposing to a severe NEC. MATERIALS/METHODS: Data of NEC patients including antenatal findings [preeclampsia, diabetes, cholestasis, abnormal antenatal umbilical artery flow (AAUF), clinical chorioamnionitis (CC), and histology of placentas] were compared to unaffected cases between 2002 and 2016 in a single center. Unaffected infants were matched for gestational age. Newborns with cardiovascular diseases were excluded. Bivariate and multivariate analyses were performed. RESULTS: We identified 136 cases and 134 controls. The group of mothers of NEC-neonates had a higher prevalence of preeclampsia, CC, and AAUF. Histology of Placentas from 123/136 cases and 126/133 unaffected newborns was available. Chorioamnionitis was significantly more present in NEC cases vs controls. There weren't differences in vascular anomalies and necrotic alterations. Multivariate analysis identified AAUF, CC and histological chorioamnionitis (HC) as predictors of NEC. Bivariate tests show that preeclampsia and HC occurred more often in severe cases of NEC. CONCLUSION: This study suggests that AAUF, CC, and HC can independently predict the risk of NEC. Preeclampsia and HC seem associated to more severe cases. LEVEL OF EVIDENCE: IIIA.