Clinical usefulness of splanchnic oxygenation in predicting necrotizing enterocolitis in extremely preterm infants: a cohort study.

BACKGROUND: Impaired intestinal microcirculation seems to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). A previous study showed that a SrSO2 < 30% is associated with an increased risk of developing of NEC. We aimed to determine the clinical usefulness of the cut off < 30% for SrSO2 in predicting NEC in extremely preterm neonates. METHODS: This is a combined cohort observational study. We added a second cohort from another university hospital to the previous cohort of extremely preterm infants. SrSO2 was measured for 1-2 h at days 2-6 after birth. To determine clinical usefulness we assessed sensitivity, specificity, positive and negative predictive values for mean SrSO2 < 30. Odds ratio to develop NEC was assessed with generalized linear model analysis, adjusting for center. RESULTS: We included 86 extremely preterm infants, median gestational age 26.3 weeks (range 23.0-27.9). Seventeen infants developed NEC. A mean SrSO2 < 30% was found in 70.5% of infants who developed NEC compared to 33.3% of those who did not (p = 0.01). Positive and negative predictive values were 0.33 CI (0.24-0.44) and 0.90 CI (0.83-0.96), respectively. The odds of developing NEC were 4.5 (95% CI 1.4-14.3) times higher in infants with SrSO2 < 30% compared to those with SrSO2 ≥ 30%. CONCLUSIONS: A mean SrSO2 cut off ≥ 30% in extremely preterm infants between days 2-6 after birth may be useful in identifying infants who will not develop NEC.

Time to full enteral feeding after necrotizing enterocolitis in preterm-born children is related to neurodevelopment at 2-3 years of age.

BACKGROUND: Necrotizing enterocolitis (NEC) is associated with poorer neurodevelopment. It is, however, unclear which factors besides surgery affect neurodevelopment in preterm-born children surviving NEC. AIMS: We determined whether time to full enteral feeding (FEFt) and post-NEC complications after NEC were associated with neurodevelopment. STUDY DESIGN: Prospective observational cohort study. SUBJECTS: Two to three year old preterm-born children who survived NEC (Bells stage ≥ 2). We categorized children in two groups, one group shorter and equal and one group longer than the group's median FEFt. Post-NEC complications included recurrent NEC and/or post-NEC stricture. OUTCOME MEASURES: Bayley Scales of Infants and Toddler Development III (Bayley-III) and Child Behavior Checklist (CBCL). Associations between Bayley-III and CBCL scores with FEFt and Post-NEC complications were determined using linear regression analyses, adjusted for severity of illness and potential confounders. RESULTS: We included 44 children, median gestational age of 27.9 [IQR: 26.7-29.3] weeks, birth weight 1148 [IQR: 810-1461] grams. Median FEFt after NEC was 20 [IQR: 16-30] days. Median follow-up age was 25.7 [IQR: 24.8-33.5] months. FEFt > 20 days was associated with lower cognitive and lower motor composite scores of the Bayley-III (B: -8.6, 95% CI -16.7 to -0.4, and B: -9.0, 95% CI, -16.7 to -1.4). FEFt was not associated with CBCL scores. Post-NEC complications (n = 11) were not associated with Bayley-III scores nor with CBCL scores. CONCLUSIONS: Prolonged FEFt after NEC in preterm-born children surviving NEC is associated with lower cognitive and lower motor composite scores at the age of 2-3 years. These results show the importance of limiting the duration of the nil per mouth regimen if and when possible.

Necrotizing Enterocolitis Associated with Congenital Heart Disease: a Different Entity?

BACKGROUND: Necrotizing enterocolitis (NEC) predominantly occurs in preterm infants (PT-NEC). In term neonates, NEC occurs more frequently when a congenital heart disease is present (CHDNEC). Our aim was to evaluate differences and similarities in disease characteristics of PT-NEC versus CHD-NEC. METHODS: In this retrospective case-control study we identified all CHD infants who developed NEC Bell's stage ≥2 in our center from 2004 to 2014. We randomly selected (1:2 ratio) PT-NEC infants from the same period. Biochemical and clinical variables were retrieved from patient files. RESULTS: We found 18 CHD-NEC infants and selected 36 PT-NEC infants (gestational age 28.3 [25-35.6] weeks vs. 38.6 [31.7-40.7] weeks). Postnatal age at onset was significantly lower in CHD-NEC patients (4 [2-24] vs. 11 [4-41] days, p < 0.001). Lowest pH levels were lower (7.21 [7.01-7.47] vs. 7.27 [6.68-7.39], p = 0.02), and highest CRP levels were higher (112.5 mg/L [5.0-425.0] vs. 66.0 [5.2-189.0], p = 0.05) in PT-NEC vs. CHD-NEC. Anatomic localisation of the disease differed: the colon was significantly more often involved in CHD-NEC versus PT-NEC (86% vs. 33%, p = 0.03). Mortality caused by NEC was not different (22% vs. 11%, p = 0.47). CONCLUSION: While outcome of NEC in both groups is similar, the predominant NEC localisation differed between CHD-NEC and PT-NEC patients. This suggests that both variants of the disease have a different underlying pathophysiological mechanism that predisposes different intestinal regions to develop NEC. TYPE OF STUDY: Retrospective Case-Control Study. LEVEL OF EVIDENCE: Level III.

Growth patterns and cerebroplacental hemodynamics in fetuses with congenital heart disease.

OBJECTIVES: Congenital heart disease (CHD) has been associated with reduced fetal head circumference (HC), although the underlying pathophysiology remains undetermined. We aimed to define trends in fetal growth and cerebroplacental Doppler flow, and to investigate their relationship, in fetuses with CHD. METHODS: This was a retrospective study in two fetal medicine units in The Netherlands. We included all fetuses with CHD in whom Doppler flow patterns (middle cerebral artery (MCA) pulsatility index (PI), umbilical artery (UA) PI and cerebroplacental ratio (CPR)) and biometry (HC and abdominal circumference (AC)) had been measured serially after 19 weeks' gestation between January 2010 and November 2016. Fetuses were categorized into three groups based on the expected cerebral arterial oxygen saturation of their particular type of CHD: normal; mild to moderately reduced; severely reduced. Trends over time in Z-scores were analyzed using a linear mixed-effects model. RESULTS: A total of 181 fetuses fulfilled the inclusion criteria. Expected cerebral arterial oxygen saturation in CHD was classified as normal in 44 cases, mild to moderately reduced in 84 and severely reduced in 53. In the cohort overall, average trends over time were significant for both HC and AC Z-scores. HC Z-scores showed a tendency to decrease until 23 weeks, then to increase until 33 weeks, followed by another decrease in the late third trimester. AC Z-scores increased progressively with advancing gestation. MCA-PI and UA-PI Z-scores showed significant trends throughout pregnancy, but CPR Z-scores did not. There were no associations between expected cerebral arterial oxygen saturation and fetal growth. Average trends in MCA-PI Z-scores were significantly different between the three subgroups, whereas those in UA-PI Z-scores and in CPR Z-scores were similar between the subgroups. There was no significant association between MCA-PI and HC Z-scores. CONCLUSIONS: Fetal biometry and Doppler flow patterns are within normal range in fetuses with CHD, but show trends over time. Head growth in fetuses with CHD is not associated with cerebral blood flow pattern or placental function and HC is not influenced by the cerebral arterial oxygen saturation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Identification of bacterial invasion in necrotizing enterocolitis specimens using fluorescent in situ hybridization.

OBJECTIVE: Investigation of bacterial invasion into the intestinal wall in necrotizing enterocolitis (NEC) specimens. STUDY DESIGN: We compared 43 surgical NEC specimens with 43 age-matched controls. We used fluorescent in situ hybridization (FISH), a universal bacterial probe together with species-specific probes for Clostridium spp., Enterobacteriaceae, bacteroides and enterococci/lactobacilli. We used a FISH scoring system to reveal invasion of the intestinal wall, in which 1 represented no colonies and 4 invasion of the intestinal wall. RESULTS: We observed invasion of the intestinal wall in 22/43 of the most affected NEC tissue samples as compared with 16/43 in the least affected NEC tissue samples (P=0.03). A FISH score of 4 was reached in 7/43 control cases. Enterobacteriaceae dominated the NEC specimens. Clostridium spp. were detected occasionally in NEC samples. CONCLUSION: Bacterial invasion of the intestinal wall is more present in most affected NEC tissue samples compared with least affected NEC tissue samples or controls. Enterobacteriaceae are prevalent in advanced NEC.

Risk factors associated with postnecrotizing enterocolitis strictures in infants.

INTRODUCTION: Survivors of necrotizing enterocolitis (NEC) often develop a post-NEC intestinal stricture, causing severe and prolonged morbidity. OBJECTIVES: We first aimed to determine the incidence of post-NEC strictures. Second, we aimed to determine risk factors associated with intestinal post-NEC strictures. MATERIALS AND METHODS: A total of 441 patients diagnosed with NEC Bell's stage ≥2 were retrospectively included in three academic pediatric surgical centers between January 2005 and January 2013. Clinical data were related to the occurrence of intestinal post-NEC strictures. Post-NEC strictures were defined as clinically relevant strictures with a radiological and/or surgical confirmation of this post-NEC stricture. RESULTS: The median gestational age of the 337 survivors of the acute phase of NEC was 29weeks (range 24-41) and median birth weight was 1130g (range 410-4130). Of the survivors, 37 (17%) medically treated NEC patients developed a post-NEC strictures versus 27 surgically treated NEC patients (24%; p=0.001). Highest C-reactive protein (CRP) level measured during the NEC episode was associated with the development of post-NEC strictures (OR 1.20, 95% confidence interval 1.11-1.32; p=0.03). No post-NEC strictures were detected in patients with CRP levels <46mg/L. CONCLUSION: This multicenter retrospective cohort study demonstrates an overall incidence of clinical relevant post-NEC strictures of 19%, with a higher rate (24%) in NEC cases treated surgically. Increased CRP levels during the NEC episode were associated with the development of post-NEC strictures.

Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC.

INTRODUCTION: Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question. OBJECTIVE: We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome. MATERIAL AND METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included. RESULTS: BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell's stage (p=0.85), mortality was higher in patients with a BSI (p=0.005). CONCLUSION: The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC.

Intestinal fatty acid-binding protein levels in Necrotizing Enterocolitis correlate with extent of necrotic bowel: results from a multicenter study.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) is considered as a specific marker for enterocyte damage in necrotizing enterocolitis (NEC). OBJECTIVE: The purpose of this study was to evaluate the association of plasma and urinary I-FABP levels with the extent of macroscopic intestinal necrosis in surgical NEC. METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Nine and 10 infants with surgical NEC were included, respectively. Plasma and urinary of I-FABP at disease onset were correlated with the length of intestinal resection during laparotomy. RESULTS: Median length of bowel resection was 10cm (range 2.5-50) and 17cm (range 0-51), respectively. Median I-FABP levels were 53ng/mL (range 6.3-370) and 4.2ng/mL (range 1.1-15.4) in plasma in cohort 1 respectively cohort 2 and 611ng/mL (range 3-23,336) in urine. The length of bowel resection significantly correlated with I-FABP levels in plasma (Rho 0.68; p=0.04 and Rho 0.66;p=0.04) and in urine (Rho 0.92; p=0.001). CONCLUSION: This 'proof of concept' study demonstrates that plasma and urine I-FABP levels at disease onset was strongly associated with the length of intestinal resection in surgical NEC. This offers further evidence that I-FABP levels are a promising biomarker for assessing intestinal necrosis in infants with advanced NEC.

Airway resistance measurements in pre-school children with asthmatic symptoms: the interrupter technique.

Measuring airway resistance in pre-school children with the interrupter technique has proven to be feasible and reliable in daily clinical practice and research settings. Whether it contributes to diagnosing asthma in pre-school children still remains uncertain. From the results of previous studies a need for standardisation of the technique has emerged. In this overview we will elaborate on research concerning the position of the interrupter technique in the difficult process of diagnosing asthma in pre-school children.