Clinical correlates of cerebellar injury in preterm infants with surgical necrotizing enterocolitis.

BACKGROUND: The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood. AIM: Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). METHODS: Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss. RESULTS: Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury.On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. CONCLUSION: Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury.

Risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis and associated outcomes.

BACKGROUND: We aim to determine clinical risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). METHODS: A retrospective cohort study of preterm infants with surgical NEC or SIP to compare clinical factors between those with and without postoperative complications. RESULTS: 78/109 (71.5%) infants had any complication following surgical NEC. Adhesions (20/35, 57.1%) and wound infection (6/35, 17.1%) were the most common single surgical complications. Patients with a single surgical complication (35/66, 53%) were significantly less likely to be exposed to antenatal steroids, more frequently had a jejunostomy, needed a central line longer, and had a longer length of stay than those without any surgical complication. Infants with > 1 surgical complication (43/71, 60.5%) included mainly females, and had AKI more frequently at NEC onset, lower weight z-scores and lower weight for length z- scores at 36 weeks PMA than those without any complications.On multinomial logistic regression, antenatal steroids exposure (OR 0.23 [CI 0.06, 0.84]; p = 0.027) was independently associated with lower risk and jejunostomy 4.81 (1.29, 17.9) was independently associated with higher risk of developing a single complication. AKI following disease onset (OR 5.33 (1.38, 20.6), P = 0.015) was independently associated with > 1 complication in surgical NEC/SIP infants. CONCLUSION: Infants with postoperative complications following surgical NEC were more likely to be female, have additional morbidities, and demonstrate growth failure at 36 weeks PMA than those without surgical complications. There was no difference in mortality between those with and without surgical complications.

Clinical determinants of intestinal failure and death in preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B.On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15-0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02-3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26-6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death.

Clinical impact of analgesic-sedative agents and peri-operative clinical status on white matter brain injury in preterm infants following surgical NEC.

BACKGROUND: The potential influence of exposure to analgesic-sedative agents (ASA) before, during, and after surgical NEC and peri-operative clinical status on white matter injury (WMI) in preterm infants has not been fully defined, and a comprehensive evaluation may inform future research and clinical interventions. METHODS: A retrospective study comparing ASA exposure before/during /after surgical NEC and peri-operative clinical status in neonates with and without WMI. RESULTS: Infants with any WMI (grade 2-4, n = 36/67, 53.7%) had a higher number of surgical procedures receiving ASA (5 [IQR: 3, 8] vs. 3 [2, 4]; p = 0.002) and had a longer duration of hypotension during their first (48.0 hours [26.0, 48.0] vs. 15.5 [6, 48]; p = 0.009) and second surgery (20 hours [0, 48h] vs. 0 [0, 22]; p = 0.017), received more hydrocortisone (35% vs.13.3%,p = 0.04) than those without any WMI. There were no differences in fentanyl/morphine/midazolam exposure before/during/after the NEC onset in the two groups.Infants with severe WMI (19/67, 28.3%, grade 3/4) had a higher incidence of AKI (P = 0.004), surgical morbidity (p = 0.047), more surgical procedures (6.5 [3, 10] vs. 4 [2, 5]; p = 0.012), and received higher mean fentanyl doses(p = 0.03) from birth until NEC onset than those without severe WMI. The univariate associations between these factors and severe WMI remained insignificant after multivariable logistic regression. CONCLUSION: Infants with WMI had more surgical procedures receiving ASA and had a longer duration of hypotension during surgeries. A large multicenter prospective study is needed to understand the full impact of ASA.

Correlation of placental pathology with the postoperative outcomes and white matter injury in preterm infants following necrotizing enterocolitis.

BACKGROUND: To determine the association of placental pathologic lesions with postoperative outcomes, survival, and white matter injury (WMI) in preterm infants with NEC. METHODS: A retrospective chart review of 107 neonates with NEC (Bell stage > IIa) from Jan 2013- June 2020 was completed. Demographic, clinical, and outcome data were compared between infants with or without placental pathologic lesions. RESULTS: In this cohort, 59/107 (55%) infants had medical NEC, and 48 (45%) had surgical NEC. The infants had a mean gestational age of 28.1±3.7 weeks and a birth weight of 1103±647 g. Maternal vascular malperfusion (82/107, 76.6%) and acute histological chorioamnionitis (42, 39.3%) were the most common pathological placental lesions. Acute histologic chorioamnionitis with fetal inflammatory response was more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). The NEC Infants with WMI on brain MRI scans had a significantly higher incidence of acute histological chorioamnionitis (52% vs. 27.8%; P = 0.04). No significant differences in mortality, length of stay and postoperative outcomes in neonates with and without acute histologic chorioamnionitis with fetal inflammatory response were noted. On unadjusted logistic regression, acute histologic chorioamnionitis without fetal inflammatory response was also associated with higher odds of WMI (OR 2.81; 95% CI 1.05-7.54; p = 0.039). CONCLUSION: Acute histological chorioamnionitis without fetal inflammatory response was associated with higher odds of WMI in infants with NEC, with no significant impact on mortality and other postoperative outcomes.

Clinical determinants and impact of hemorrhagic lesions on intestinal pathology in preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: We sought to determine the clinical and histopathological factors associated with intestinal hemorrhage and its correlation with clinical outcomes in neonates with surgical necrotizing enterocolitis (NEC). METHODS: A retrospective study compared clinical and histopathology information in neonates following surgical NEC with severe hemorrhage and those with mild/moderate hemorrhagic lesions seen on resected intestine pathology. RESULTS: The infants with severe hemorrhage (Grade 3-4, 81/148, 54.7%) had significantly lower exposure to antenatal steroids (52.5 % vs 76.9 %; p = 0.004), had higher gestational age (28.5 weeks [7.14] vs. 26.58 [2.90]; p = 0.034), lost more bowel length (p = 0.045), had higher CRP levels at 2 weeks (p = 0.035), and had less intestinal failure ([30.3 % vs 52.5 %]; p = 0.014) than mild/moderate (Grade 0-2, 67/148, 45.2%) hemorrhage group. Those with severe hemorrhage had significantly higher mean inflammation score (2.67 [0.94] vs. 1.63 [0.92]; p = <0.001), higher necrosis scores (1.95 [1.28] vs. 1.49 [1.35]; p = 0.037), higher neovascularization (p = 0.01), higher fibroblasts (p = 0.023) and higher lymphocyte percentages up to 48 hours (p < 0.05) following NEC than mild/ moderate hemorrhage group.On multivariable regression, less exposure to antenatal steroids (OR 0.18 [95% CI 0.05-0.58]; p = 0.005), higher inflammation (OR 3.7 [95% CI 2.09-7.32]; p = 0.001), and lymphocyte count on the day of onset/24 hours following NEC (OR 1.06 [95% CI 1.02-1.11]; p = 0.005) were independently associated with a higher odd of severe intestinal hemorrhage. CONCLUSION: The surgical NEC infants with intestinal hemorrhage were less likely to have antenatal steroid exposure but had higher inflammation grade and lymphocyte counts following NEC onset on multivariable regression modeling.

Clinical outcomes and gestational age based prediction of pneumatosis intestinalis in preterm infants with necrotizing enterocolitis.

BACKGROUND: To determine the clinical implications and gestation age-specific diagnostic predictability of pneumatosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A retrospective study on abdominal radiographs comparing clinical and radiological information in infants with and without pneumatosis. RESULT: Our findings disproved our hypothesis. Pneumatosis was seen more frequently in infants with higher gestational age [28.4 (26.1-32.4) vs. 26.4 (24.3-29) weeks; p < 0.001] and birth weight [1110 (762-1768) vs. 770 (645-1022) grams; p < 0.001] and were more likely delivered vaginally (39.1% vs. 21.7%, p = 0.01). Portal venous gas was seen frequently on radiographs (10.3% vs. 0%, p < 0.001), but not pneumoperitoneum (20.7% vs. 36.7%, p = 0.02). Infants with pneumatosis frequently developed acute kidney injury, with higher serum creatinine (16.5% vs. 4.5%, p = 0.02) and frequent oliguria (12.9% vs. 2.7 %; p = 0.043) and had higher C-reactive protein levels at 24 and 96 hours (p < 0.002). Receiver operating curves for pneumatosis showed GA >28 weeks and birth weight > 1000 gm to have a sensitivity of 58.6% and specificity of 72.5%. CONCLUSION: Contrary to our hypothesis, infants who developed pneumatosis during NEC were more mature with a higher gestational age and birth weight than those who did not.