The Incidence of Necrotizing Enterocolitis and Late-Onset Sepsis during the COVID-19 Pandemic in Sweden: A Population-Based Cohort Study.

INTRODUCTION: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. METHODS: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98-99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. RESULTS: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55-0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). CONCLUSION: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged.

Transition of Extremely Preterm Infants from Birth to Stable Breathing: A Secondary Analysis of the CORSAD Trial.

OBJECTIVE: Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period. METHODS: This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups. RESULTS: Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD -16.5, 95% CI [-31.7 to -1.1], p 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD -15.6, 95% CI [-30.7 to -0.8], p 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups. CONCLUSION: In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation.

Respiratory outcomes after delivery room stabilisation with a new respiratory support system using nasal prongs.

AIM: To study if stabilisation using a new respiratory support system with nasal prongs compared to T-piece with a face mask is associated with less need for mechanical ventilation and bronchopulmonary dysplasia. METHODS: A single-centre follow-up study of neonates born <28 weeks gestation at Karolinska University Hospital, Stockholm included in the multicentre Comparison of Respiratory Support after Delivery (CORSAD) trial and randomised to initial respiratory support with the new system versus T-piece. Data on respiratory support, neonatal morbidities and mortality were collected up to 36 weeks post-menstrual age. RESULTS: Ninety-four infants, 51 female, with a median (range) gestational age of 25 + 2 (23 + 0, 27 + 6) weeks and days, were included. Significantly fewer infants in the new system group received mechanical ventilation during the first 72 h, 24 (52.2%) compared with 35 (72.9%) (p = 0.034) and during the first 7 days, 29 (63.0%) compared with 39 (81.3%) (p = 0.045) in the T-piece group. At 36 weeks post-menstrual age, 13 (28.3%) in the new system and 13 (27.1%) in the T-piece group were diagnosed with bronchopulmonary dysplasia. CONCLUSION: Stabilisation with the new system was associated with less need for mechanical ventilation during the first week of life. No significant difference was seen in the outcome of bronchopulmonary dysplasia.

Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility randomized controlled trial.

PURPOSE: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual's limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. METHODS: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. RESULTS: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. CONCLUSIONS: The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.

Hyponatremia at the onset of necrotizing enterocolitis is associated with intestinal surgery and higher mortality.

It has previously been shown that hyponatremia reflects the severity of inflammation in pediatric gastrointestinal diseases. Interpretation of electrolyte disorders is a common, but not well studied challenge in neonatology, especially in the context of early detection of necrotizing enterocolitis and bowel necrosis. The aim of this study was to assess if hyponatremia, or a decrease in plasma sodium level, at the onset of necrotizing enterocolitis (NEC) is associated with intestinal ischemia/necrosis requiring bowel resection and/or NEC-related deaths. This was a retrospective cohort study including patients with verified NEC (Bell's stage ≥ 2) during the period 2009-2014. Data on plasma sodium 1-3 days before and at the onset of NEC were collected. The exposure was hyponatremia, defined as plasma sodium < 135 mmol/L and a decrease in plasma sodium. Primary outcome was severe NEC, defined as need for intestinal resection due to intestinal ischemia/necrosis and/or NEC-related death within 2 weeks of the onset of NEC. Generalized linear models were applied to analyze the primary outcome and presented as odds ratio. A total of 88 patients with verified NEC were included. Fifty-four (60%) of them had severe NEC. Hyponatremia and a decrease in plasma sodium at onset of NEC were associated with increased odds of severe NEC (OR crude 3.91, 95% CI (1.52-10.04) and 1.19, 95% CI (1.07-1.33), respectively). Also, a sub-analysis, excluding infants with pneumoperitoneum during the NEC episode, showed an increased odds ratio for severe NEC in infants with hyponatremia (OR 23.0, 95% CI (2.78-190.08)). CONCLUSIONS: The findings of hyponatremia and/or a sudden decrease in plasma sodium at the onset of NEC are associated with intestinal surgery or death within 2 weeks. WHAT IS KNOWN: • Clinical deterioration, despite optimal medical treatment, is a relative indication for surgery in infants with necrotizing enterocolitis. • Hyponatremia is a common condition in preterm infants from the second week of life. WHAT IS NEW: • Hyponatremia and a decrease in plasma sodium level at the onset of necrotizing enterocolitis are positively associated with need of surgery or death within 2 weeks. • In infants with necrotizing enterocolitis, without pneumoperitoneum, where clinical deterioration despite optimal medical treatment is the only indication for surgery, hyponatremia, or a decrease in plasma sodium level can predict the severity of the disease.

Low Splanchnic Oxygenation and Risk for Necrotizing Enterocolitis in Extremely Preterm Newborns.

OBJECTIVE: The aim of the study was to investigate whether splanchnic oxygenation (SrSO2), measured with near-infrared spectroscopy (NIRS), during the first week of life is associated with the risk of developing necrotizing enterocolitis (NEC) in extremely preterm infants. METHODS: This was a prospective observational cohort study including extremely preterm infants (<28 weeks of gestation) born at Karolinska University Hospital from September 2014 to December 2016. Using 1-hour NIRS monitoring during enteral feeding, mainly continuous enteral feeding, in the first week of life we measured both cerebral and splanchnic oxygenation. Primary outcome was risk of developing NEC (Bell stage ≥ II). Secondary outcome was the association between low mean SrSO2 during the first week of life and postnatal age at full enteral nutrition. RESULTS: We enrolled 52 extremely preterm newborns, but only 45 infants had complete NIRS data. One infant developed NEC within 1 day of NIRS monitoring and was excluded from the study. Median gestational age was 25.6 weeks (range 23.0-27.9) and median birth weight 698 g (range 485-1353). Eight infants developed NEC at the median postnatal age of 15 days (range 6-35). Median postnatal age at full enteral nutrition was 10 days (range 6-23). Infants with mean SrSO2 <30% had a higher risk for developing NEC compared with those with SrSO2 >30% (crude risk ratio 5.25; 95% CI [1.19-23.01]). Small for gestational age, gestational age, birth weight, postnatal age did not affect the results. We found no association between SrSO2 and age at full enteral nutrition. CONCLUSIONS: Low mean SrSO2 (<30%) during the first week of life is associated with an increased risk for developing NEC in extremely preterm infants on mainly continuous enteral nutrition.

The effect of gestational age on clinical and radiological presentation of necrotizing enterocolitis.

BACKGROUND/PURPOSE: To test the hypothesis that clinical and radiological features of necrotizing enterocolitis vary with gestational age in all neonates with NEC and in subgroup of surgically treated patients. METHODS: This was a retrospective study case series. NEC cases treated in Stockholm County from 2009 to 2014 were identified in the National Quality Register. Patients were included in the study if they had a verified NEC diagnosis and they were divided into 2 groups according to the gestational age. RESULTS: A total of 89 patients were included. Of these 60 (67.4%) neonates had a gestational age <28 and 29 (32.6%) infants ≥28weeks. Surgical NEC patients were 57 (64%). Pneumatosis intestinalis at the abdominal radiographs was noted significantly more often in neonates born at ≥28weeks of gestation (86.2%) compared to extremely preterm newborns (60.0%). Neonates born at ≥28weeks of gestation presented more often bloody stools (58.6%) compared to extremely preterm newborns (20.0%). In surgical NEC patients gasless abdomen was detected in 35.6% of the neonates born <28weeks compared to 6.7% of the more mature neonates. CONCLUSIONS: Extremely preterm neonates with NEC show less specific clinical and radiological signs of NEC compared to more mature neonates. This suggests that Bell's classification is not adequate for the diagnosis and staging of NEC in extremely preterm neonates. LEVEL OF EVIDENCE: III.

Complex Fluid Collection on Abdominal Ultrasound Indicates Need for Surgery in Neonates with Necrotizing Enterocolitis.

Aim The aim of this study was to determine whether a correlation exists between the sonographic findings and the clinical outcomes, defined as surgery or death, in neonates with radiographically and/or histopathologically confirmed necrotizing enterocolitis (NEC). Material and Methods In this retrospective study, the case notes of 58 patients admitted to Karolinska University Hospital, Stockholm, Sweden, with radiographically confirmed NEC from September 2010 to August 2013, were reviewed. We included all newborns who underwent both plain abdominal radiographs and an abdominal ultrasound on the same day. The images were reviewed retrospectively. Patients' characteristics, clinical data, and histopathological data were recorded from the case notes. We excluded newborns who developed free gas before surgery. Abdominal ultrasound images were reviewed for free intraperitoneal gas, peritoneal fluid, pneumatosis intestinalis, portal gas, bowel vascularity, bowel wall thickness, and peristalsis. We correlated the sonographic features with the clinical outcomes; defined as the need for surgery or death. Results Overall, 25 neonates were included. Out of these, 11 patients underwent surgery and 5 patients died. The sonographic finding of complex fluid collection was statistically significant, predicting severe NEC that needed surgery. No other sonographic features were related to the need for surgery or death. Conclusion Complex fluid collection shown with abdominal ultrasound appears to be strongly correlated to the need for surgery in newborn infants with severe NEC.