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Purpose: The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2 years' corrected age (CA) in infants born before 32 weeks' gestation (WG). Methods: We studied neurodevelopment at 2 years' CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire. Results: At 2 years' CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability (p < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2 years' CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0–9.1) but not NEC as compared with controls. Conclusion: NEC and SIP significantly increased the risk of death or sensorimotor disability at 2 years' CA. SIP was also associated with risk of developmental delay at 2 years' CA. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) affect 6–8% of extremely low birth weight (ELBW) infants. SIP has lower mortality than NEC, but with similar short-term morbidity in length of stay, growth failure, and supplemental oxygen requirements. Comparative long-term neurodevelopmental outcomes have not been clarified. Data were prospectively collected from 59 North American neonatal units, regarding ELBW infants (401–1000 g or 22–27 weeks gestational age) born between 2011 and 2018 and evaluated again at 16–26 months corrected age. Outcomes were collected from infants with laparotomy-confirmed NEC, laparotomy-confirmed SIP, and those without NEC or SIP. The primary outcome was severe neurodevelopmental disability. Secondary outcomes were weight <10th percentile, medical readmission, post-discharge surgery and medical support at home. Adjusted risk ratios (ARR) were calculated. Of 13,673 ELBW infants, 6391 (47%) were followed including 93 of 232 (40%) with NEC and 100 of 235 (42%) with SIP. There were no statistically significant differences in adjusted risk of any outcomes when directly comparing NEC to SIP (ARR 2.35; 95% CI 0.89, 6.26). However, infants with NEC had greater risk of severe neurodevelopmental disability (ARR 1.43; 1.09–1.86), rehospitalization (ARR 1.46; 1.17–1.82), and post-discharge surgery (ARR 1.82; 1.48–2.23) compared to infants without NEC or SIP. Infants with SIP only had greater risk of post-discharge surgery (ARR 1.64; 1.34–2.00) compared to infants without NEC or SIP. ELBW infants with NEC had significantly increased risk of severe neurodevelopmental disability and post-discharge healthcare needs, consistent with prior literature. We now know infants with SIP also have increased healthcare needs. Level II. • What is currently known about this topic? SIP has decreased risk of mortality compared to NEC, with similar short-term morbidity. NEC has increased risk of long-term morbidity. Limited data exists in SIP. • What new information is contained in this article? ELBW NEC infants had increased risk of neurodevelopmental disability and post-discharge healthcare needs. SIP infants also have increased healthcare needs. [ABSTRACT FROM AUTHOR]

Reduction–oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates. [ABSTRACT FROM AUTHOR]

White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysiology distinctive, thus requiring a tailored approach to treatment. Neonates present a unique opportunity to repair WMIs due to a transient abundance of neural stem/progenitor cells (NSPCs) present in the germinal matrix with oligodendrogenic potential. We identified an endogenous oxysterol, 20-αHydroxycholesterol (20HC), in human maternal breast milk that induces oligodendrogenesis through a sonic hedgehog (shh), Gli-dependent mechanism. Following WMI in neonatal mice, injection of 20HC induced subventricular zone-derived oligodendrogenesis and improved myelination in the periventricular white matter, resulting in improved motor outcomes. Targeting the oligodendrogenic potential of postnatal NSPCs in neonates with WMIs may be further developed into a novel approach to mitigate this devastating complication of preterm birth.

Introduction: Necrotizing enterocolitis (NEC) poses a significant threat to preterm infants, with nonspecific early manifestations complicating timely diagnosis. Therefore, this study aimed to develop a novel scoring system for early diagnosis of NEC, incorporating clinical and laboratory data with urinary caveolin-1 levels. Material and methods: A single-center prospective cohort study was conducted at a tertiary hospital in East Java, Indonesia. NEC diagnosis was established by Bell's criteria and proven gut dysbiosis. Urinary levels of claudin-2, caveolin-1, and epidermal growth factor (EGF) were assessed as potential indicators of tight junction disruption. The selected urine biomarker cutoff value was determined using symbolic classification analysis and combined with clinical and laboratory parameters from Bell's criteria to create an NEC scoring system, validated with the Aiken index. Sensitivity and specificity analyses were performed. Results: Thirty-four neonates, comprising NEC, preterm non-NEC, and term infants, were included. qPCR analysis highlighted elevated Klebsiella, Lactobacillus, Clostridium, and Bacteroides levels in NEC patients, indicating a gut dysbiosis trend. Among 3 biomarkers, caveolin-1 ≥ 17.81 ng/dl on day 3 demonstrated 72.86% negative predictive value and 87.50% positive predictive value. The combined scoring system which comprised abdominal cellulitis, distension, radiology, advanced resuscitation at birth, prematurity or low birthweight, platelet count, sepsis, orogastric retention, metabolic acidosis and caveolin-1 findings exhibited an AUC of 0.922 (95% CI: 0.81-1.00, p < 0.001), with ≥ 1.81 as the cutoff, offering 93% sensitivity and 94% specificity. Conclusions: Urine caveolin-1 on day 3 signifies enterocyte tight junction damage and the acute phase of NEC in premature infants. The proposed scoring system demonstrates good performance in predicting NEC incidence in preterm infants. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a devastating disease of the neonatal intestine, causing widespread intestinal necrosis as well systemic illness that frequently results in death. Because the clinical onset of NEC is sudden and difficult to predict, NEC is considered an acute event. However, NEC does not occur in utero, meaning that postnatal exposures are required, and it does not typically occur right after birth, suggesting that longitudinal changes may be occurring before NEC can develop. In this perspective, the author considers whether NEC should be re-considered as a problem of disordered intestinal epithelial development, with required maladaptation over time prior to the onset of the necrotic event. This framework is similar to how bronchopulmonary dysplasia is currently conceptualized. They also advocate that NEC researchers incorporate this possibility into future studies on NEC susceptibility and pathogenesis.

BackgroundPrematurity and congenital heart disease (CHD) are the leading causes of neonatal mortality and morbidity. Limited data are available about the outcomes of premature infants with severe CHD.MethodsWe queried The National Inpatient Database using ICD-10 codes for premature patients (

Introduction Necrotizing enterocolitis (NEC) poses a significant threat to preterm infants, with nonspecific early manifestations complicating timely diagnosis. Therefore, this study aimed to develop a novel scoring system for early diagnosis of NEC, incorporating clinical and laboratory data with urinary caveolin-1 levels. Material and methods A single-center prospective cohort study was conducted at a tertiary hospital in East Java, Indonesia. NEC diagnosis was established by Bell’s criteria and proven gut dysbiosis. Urinary levels of claudin-2, caveolin-1, and epidermal growth factor (EGF) were assessed as potential indicators of tight junction disruption. The selected urine biomarker cutoff value was determined using symbolic classification analysis and combined with clinical and laboratory parameters from Bell’s criteria to create an NEC scoring system, validated with the Aiken index. Sensitivity and specificity analyses were performed. Results Thirty-four neonates, comprising NEC, preterm non-NEC, and term infants, were included. qPCR analysis highlighted elevated Klebsiella, Lactobacillus, Clostridium, and Bacteroides levels in NEC patients, indicating a gut dysbiosis trend. Among 3 biomarkers, caveolin-1 ≥ 17.81 ng/dl on day 3 demonstrated 72.86% negative predictive value and 87.50% positive predictive value. The combined scoring system which comprised abdominal cellulitis, distension, radiology, advanced resuscitation at birth, prematurity or low birthweight, platelet count, sepsis, orogastric retention, metabolic acidosis and caveolin-1 findings exhibited an AUC of 0.922 (95% CI: 0.81–1.00, p < 0.001), with ≥ 1.81 as the cutoff, offering 93% sensitivity and 94% specificity. Conclusions Urine caveolin-1 on day 3 signifies enterocyte tight junction damage and the acute phase of NEC in premature infants. The proposed scoring system demonstrates good performance in predicting NEC incidence in preterm infants.

Reduction–oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates.

Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (−21%, p = 0.002) and Candida spp. (−16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon's and Simpson's indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC), an inflammatory disease of the intestine, is a common gastrointestinal emergency among preterm infants. Intestinal barrier dysfunction, hyperactivation of the premature immune system, and dysbiosis are thought to play major roles in the disease. Human milk (HM) is protective, but the mechanisms underpinning formula feeding as a risk factor in the development of NEC are incompletely understood. Hyaluronic acid 35 kDa (HA35), a bioactive glycosaminoglycan of HM, accelerates intestinal development in murine pups during homeostasis. In addition, HA35 prevents inflammation-induced tissue damage in pups subjected to murine NEC, incorporating Paneth cell dysfunction and dysbiosis. We hypothesized HA35 treatment would reduce histological injury and mortality in a secondary mouse model of NEC incorporating formula feeding. NEC-like injury was induced in 14-day mice by dithizone-induced disruption of Paneth cells and oral gavage of rodent milk substitute. Mortality and histological injury, serum and tissue cytokine levels, stool bacterial sequencing, and bulk RNA-Seq comparisons were analyzed. HA35 significantly reduced the severity of illness in this model, with a trend toward reduced mortality, while RNA-Seq analysis demonstrated HA35 upregulated genes associated with goblet cell function and innate immunity. Activation of these critical protective and reparative mechanisms of the small intestine likely play a role in the reduced pathology and enhanced survival trends of HA-treated pups subjected to intestinal inflammation in this secondary model of NEC, providing potentially interesting translational targets for the human preterm disease.

Objective: Acute kidney injury (AKI) in the neonatal period is associated with worst outcomes as increased mortality and increased length of hospital stay. Very low birth weight (VLBW) newborns are at higher risk for developing several other conditions that are associated with worst outcomes. Understanding the risk factors for AKI may help to prevent this condition and improve neonatal care for this population. Methods: This retrospective cohort study included 155 very low birth weight newborns admitted between 2015 and 2017. The authors compared the newborns who developed neonatal AKI with the non-AKI group and analyzed the main risk factors for developing AKI in the population. The authors also performed an analysis of the main outcomes defined as the duration of mechanical ventilation, length of stay, and death. Results: From the cohort, a total of 61 (39.4%) patients had AKI. The main risk factors associated with Neonatal AKI were necrotizing enterocolitis (aOR 7.61 [1.69 – 34.37]; p = 0.008), neonatal sepsis (aOR 2.91 [1.17 – 7.24], p = 0.021), and hemodynamic instability (aOR 2.99 [1.35 – 6.64]; p = 0.007). Neonatal AKI was also associated with an increase in the duration of mechanical ventilation in 9.4 days (p = 0.026) and in an increase in mortality 4 times (p = 0.009), after adjusting for the other variables. Conclusion: The present results highlight the importance of minimizing sepsis and necrotizing enterocolitis, as well as the importance of identifying hemodynamic instability, to prevent AKI and diminish the burden of morbimortality in VLBW newborns.

Objective Antenatal steroids are commonly used to stimulate fetal lung maturation, particularly in pregnancies at risk of early preterm labor. This study aimed to compare the effects of administering betamethasone at a 12- versus 24-hour interval on perinatal outcomes. Study Design This retrospective study included 423 early preterm births from 26 +0/7 to 33 +6/7 weeks of gestation. Patients received betamethasone at either a 12- or 24-hour dosing interval. Results When all patients in each group were evaluated together, there was no statistically significant difference between both groups for complications of prematurity, including respiratory distress syndrome (RDS). When the two groups were divided by gestational age (GA), the 32 +0/7 to 33 +6/7 -week group that received betamethasone at a 24-hour interval had statistically lower 1- and 5-minute APGAR scores (p = 0.06 and p = 0.02, respectively). They also had a greater need for neonatal intensive care unit (NICU), NICU length of stay, RDS, and need for surfactant (p = 0.20, p = 0.09, p = 0.27, and p = 0.23, respectively) than did the infants at 32 +0/7 to 33 +6/7 weeks, who received betamethasone at a 12-hour interval. In the group with GA between 28 +0/7 and 29 +6/7 weeks, the 1-minute APGAR score was lower (p = 0.22), and the durations of hospital stay, and mechanical ventilation were longer (p = 0.048, p = 0.21, respectively) in the 24-hour interval group. No statistically significant difference was observed for all parameters in other GA groups. Conclusion A 12-hour dosing interval for betamethasone appears to be more appropriate, as it results in a reduction in some neonatal complications and provides a short dose interval. Key Points RDS is reduced when betamethasone is used 12 hours apart. When betamethasone is used 12 hours apart, the need for surfactant is reduced. The use of betamethasone 12 hours apart is advantageous with its short dose interval. [ABSTRACT FROM AUTHOR]

Objective The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity (ROP). Study Design This was a secondary data analysis of 7,483 preterm infants from the Postnatal Growth and Retinopathy of Prematurity Study. Associations between infants with surgical NEC, early-onset surgical NEC (8–28 days), and late-onset surgical NEC (over 28 days) with ROP were evaluated by using multivariable logistic regression models, controlling for birth weight, gestational age, small for gestational age status, chronic lung disease, intraventricular hemorrhage, hydrocephalus, patent ductus arteriosus, and periventricular leukomalacia. Results Three hundred fifty-six (4.8%) infants had surgical NEC, with 56% having early surgical NEC. Infants with surgical NEC had a higher risk of any ROP and severe ROP (adjusted odds ratio [OR]: 2.7; 95% CI: 1.9–3.7) and 2.5 (95% CI: 1.9–3.3), respectively; p < 0.001) compared with infants without surgical NEC. Infants with early surgical NEC were at the highest risk of developing ROP and severe ROP (adjusted OR: 3.1 [95% CI: 2.1–4.8], and 3.3 [95% CI: 2.3–4.7] respectively, p < 0.001). Infants with late surgical NEC were also at increased risk of developing ROP and severe ROP (adjusted OR: 2.1 [95% CI: 1.3–3.4], and 1.9 [95% CI: 1.3–2.8] respectively, p < 0.001) compared with infants without surgical NEC. Conclusion Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP. Key Points Infants with surgical NEC are at higher risk of ROP and severe ROP than those without surgical NEC. Increased ROP risk is seen in infants with both early- or later onset surgical NEC. Early-onset surgical NEC is associated with a higher ROP risk compared with later onset surgical NEC. [ABSTRACT FROM AUTHOR]

Objective Compare delivery room practices and outcomes of infants born at less than 32 weeks' gestation or less than 1,500 g who have plastic wrap/bag placement simultaneously during placental transfusion to those receiving plastic wrap/bag placement sequentially following placental transfusion. Study Design Retrospective analysis of data from a multisite quality improvement initiative to refine stabilization procedures pertaining to placental transfusion and thermoregulation using a plastic wrap/bag. Delivery room practices and outcome data in 590 total cases receiving placental transfusion were controlled for propensity score matching and hospital of birth. Results The simultaneous and sequential groups were similar in demographic and most outcome metrics. The simultaneous group had longer duration of delayed cord clamping compared with the sequential group (42.3 ± 14.8 vs. 34.1 ± 10.3 seconds, p < 0.001), and fewer number of times cord milking was performed (0.41 ± 1.26 vs. 0.86 ± 1.92 seconds, p < 0.001). The time to initiate respiratory support was also significantly shorter in the simultaneous group (97.2 ± 100.6 vs. 125.2 ± 177.6 seconds, p = 0.02). The combined outcome of death or necrotizing enterocolitis in the simultaneous group was more frequent than in the sequential group (15.3 vs. 9.3%, p = 0.038); all other outcomes measured were similar. Conclusion Timing of plastic wrap/bag placement during placental transfusion did affect duration of delayed cord clamping, number of times cord milking was performed, and time to initiate respiratory support in the delivery room but did not alter birth hospital outcomes or respiratory care practices other than the combined outcome of death or necrotizing enterocolitis. Key Points Plastic bag placement during placental transfusion is effective in stabilization of preterms. Plastic bag placement after placental transfusion is effective in stabilization of preterms. Plastic bag placement during placental transfusion and risk of death or necrotizing enterocolitis needs additional study. [ABSTRACT FROM AUTHOR]

In 2015, a protocol including early laparoscopy-assisted surgery in the treatment of necrotizing enterocolitis (NEC) was implemented at our institution. Carbon dioxide insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to compare post-operative outcome after early laparoscopy-assisted surgery and classical laparotomy for NEC. Charts of premature infants undergoing surgery for NEC (2012–2021) were reviewed. Cases operated by early laparoscopy-assisted surgery (2015–2021) were compared to infants operated for NEC between 2012 and 2015 (laparotomy-NEC). Outcomes were post-operative CRP, need for reintervention, mortality, and the occurrence of post-NEC intestinal strictures. CRP was measured on the day of surgery (POD-0), 2 days (POD-2), and 7 days after surgery (POD-7). Data were compared using contingency tables for categorical variables and Student t-test or Mann–Whitney test for continuous variables. Infants with NEC operated by early laparoscopy (n = 48) and laparotomy (n = 29) were similar in terms of perforation (60% vs 58%, p = 0.99) and POD-0 CRP (139 vs 124 mg/L, p = 0.94). Delay between first signs of NEC and surgery was shorter in the laparoscopy group (3 vs 6 days, p = 0.004). Early laparoscopy was associated with a lower CRP on POD-2 (108 vs 170, p = 0.005) and POD-7 (37 vs 68, p = 0.002), as well as a lower rate of post-operative intestinal stricture (34% vs 61%, p = 0.04). In addition to being safe and feasible in premature infants, early laparoscopic-assisted surgery was associated with decreased NEC-related post-operative inflammation and strictures. A prospective, randomized study is needed in order to evaluate short and long-term effects of laparoscopy in infants with NEC. Level III. [ABSTRACT FROM AUTHOR]

The intestinal microbiome is frequently implicated in necrotizing enterocolitis (NEC) pathogenesis. While no particular organism has been associated with NEC development, a general reduction in bacterial diversity and increase in pathobiont abundance has been noted preceding disease onset. However, nearly all evaluations of the preterm infant microbiome focus exclusively on the bacterial constituents, completely ignoring any fungi, protozoa, archaea, and viruses present. The abundance, diversity, and function of these nonbacterial microbes within the preterm intestinal ecosystem are largely unknown. Here, we review findings on the role of fungi and viruses, including bacteriophages, in preterm intestinal development and neonatal intestinal inflammation, with potential roles in NEC pathogenesis yet to be determined. In addition, we highlight the importance of host and environmental influences, interkingdom interactions, and the role of human milk in shaping fungal and viral abundance, diversity, and function within the preterm intestinal ecosystem. [ABSTRACT FROM AUTHOR]

Objective Scores to predict sepsis or define sepsis severity could improve care for very low birth weight (VLBW) infants. The heart rate characteristics (HRC) index (HeRO score) was developed as an early warning system for late-onset sepsis (LOS), and also rises before necrotizing enterocolitis (NEC). The neonatal sequential organ failure assessment (nSOFA) was developed to predict sepsis-associated mortality using respiratory, hemodynamic, and hematologic data. The aim of this study was to analyze the HRC index and nSOFA near blood cultures in VLBW infants relative to diagnosis and sepsis-associated mortality. Study Design Retrospective, single-center study of VLBW infants from 2011 to 2019. We analyzed HRC index and nSOFA around blood cultures diagnosed as LOS/NEC. In a subgroup of the cohort, we analyzed HRC and nSOFA near the first sepsis-like illness (SLI) or sepsis ruled-out (SRO) compared with LOS/NEC. We compared scores by diagnosis and mortality during treatment. Results We analyzed 179 LOS/NEC, 93 SLI, and 96 SRO blood culture events. In LOS/NEC, the HRC index increased before the blood culture, while nSOFA increased at the time of culture. Both scores were higher in nonsurvivors compared with survivors and in LOS/NEC compared with SRO. The nSOFA 12 hours after the time of blood culture predicted mortality during treatment better than any other time point analyzed (area under the curve 0.91). Conclusion The HRC index provides earlier warning of imminent sepsis, whereas nSOFA after blood culture provides better prediction of mortality. Key Points The HRC index and nSOFA provide complementary information on sepsis risk and sepsis-related mortality risk. This study adds to existing literature evaluating these risk scores independently by analyzing them together and in cases of not only proven but also suspected infections. The impact of combining risk models could be improved outcomes for premature infants. [ABSTRACT FROM AUTHOR]

Preterm birth is a major contributor to neonatal morbidity and mortality. Complications of prematurity such as bronchopulmonary dysplasia (BPD, affecting the lung), pulmonary hypertension associated with BPD (BPD-PH, heart), white matter injury (WMI, brain), retinopathy of prematurity (ROP, eyes), necrotizing enterocolitis (NEC, gut) and sepsis are among the major causes of long-term morbidity in infants born prematurely. Though the origins are multifactorial, inflammation and in particular the imbalance of pro- and anti-inflammatory mediators is now recognized as a key driver of the pathophysiology underlying these illnesses. Here, we review the involvement of the interleukin (IL)-1 family in perinatal inflammation and its clinical implications, with a focus on the potential of these cytokines as therapeutic targets for the development of safe and effective treatments for early life inflammatory diseases. [ABSTRACT FROM AUTHOR]

Neonates born prematurely (<37 weeks of gestation) are at a significantly increased risk of developing inflammatory conditions associated with high mortality rates, including necrotizing enterocolitis, bronchopulmonary dysplasia, and hypoxic-ischemic brain damage. Recently, research has focused on characterizing the content of extracellular vesicles (EVs), particularly microRNAs (miRNAs), for diagnostic use. Here, we describe the most recent work on EVs-miRNAs biomarkers discovery for conditions that commonly affect premature neonates. [ABSTRACT FROM AUTHOR]

Background: Neonatal intraventricular hemorrhage prevention bundles for preterm infants commonly defer daily weighing for the first 72 h, with reweighing occurring on day 4. Clinicians rely on maintaining stable sodium values as a proxy of fluid status to inform fluid management decisions over the first 96 h after birth. Yet, there exists a paucity of research evaluating whether serum sodium or osmolality are appropriate proxies for weight loss and whether increasing variability in sodium or osmolality during this early transitional period is associated with adverse in-hospital outcomes. Objectives: To evaluate whether serum sodium or osmolality change in the first 96 h after birth was associated with percent weight change from birth weight, and to assess potential associations between serum sodium and osmolality variability with in-hospital outcomes. Methods: This retrospective, cross-sectional study included neonates born at ≤30 gestational weeks or ≤1250 g. We evaluated associations between serum sodium coefficient of variation (CoV), osmolality CoV, and maximal weight loss percentage in the first 96 h after birth with in-hospital neonatal outcomes. Results: Among 205 infants, serum sodium and osmolality were poorly correlated with percent weight change in individual 24-h increments (R² = 0.01-0.14). For every 1% increase in sodium CoV, there was an associated 2-fold increased odds of surgical necrotizing enterocolitis and 2-fold increased odds of in-hospital mortality (odds ratio, 2.07; 95% CI: 1.02, 4.54; odds ratio, 1.95; 95% CI: 1.10, 3.64, respectively). Sodium CoV was more strongly associated with outcomes than absolute sodium maximal change. Conclusions: In the first 96 h, serum sodium and osmolality are poor proxies for assessing percent weight change. Increasing variability of serum sodium is associated with later development of surgical necrotizing enterocolitis and all-cause in-hospital mortality. Prospective research is needed to evaluate whether reducing sodium variability in the first 96 h after birth, as assessed by CoV, improves newborn health outcomes. [ABSTRACT FROM AUTHOR]

IntroductionNecrotizing enterocolitis (NEC) is a potentially fatal intestinal disease primarily affecting preterm infants. Early diagnosis of neonates with NEC is crucial to improving outcomes; however, traditional diagnostic tools remain inadequate. Biomarkers represent an opportunity to improve the speed and accuracy of diagnosis, but they are not routinely used in clinical practice.MethodsIn this study, we utilized an aptamer-based proteomic discovery assay to identify new serum biomarkers of NEC. We compared levels of serum proteins in neonates with and without NEC and identified ten differentially expressed serum proteins between these groups.ResultsWe detected two proteins, C-C motif chemokine ligand 16 (CCL16) and immunoglobulin heavy constant alpha 1 and 2 heterodimer (IGHA1 IGHA2), that were significantly increased during NEC and eight that were significantly decreased. Generation of receiver operating characteristic (ROC) curves revealed that alpha-fetoprotein (AUC = 0.926), glucagon (AUC = 0.860), and IGHA1 IGHA2 (AUC = 0.826) were the proteins that best differentiated patients with and without NEC.DiscussionThese findings indicate that further investigation into these serum proteins as a biomarker for NEC is warranted. In the future, laboratory tests incorporating these differentially expressed proteins may improve the ability of clinicians to diagnose infants with NEC rapidly and accurately.

Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (−21%, p = 0.002) and Candida spp. (−16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon’s and Simpson’s indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery.

Abstract Background Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2–3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants. Methods The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants’ index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity. Discussion The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery. Trial registration Trial registration data: June 25, 2019 NCT03997266 .

Necrotizing enterocolitis (NEC) is a devastating, multifactorial disease mainly affecting the intestine of premature infants. Recent discoveries have significantly enhanced our understanding of risk factors, as well as, cellular and genetic mechanisms of this complex disease. Despite these advancements, no essential, single risk factor, nor the mechanism by which each risk factor affects NEC has been elucidated. Nonetheless, recent research indicates that maternal factors, antibiotic exposure, feeding, hypoxia, and altered gut microbiota pose a threat to the underdeveloped immunity of preterm infants. Here we review predisposing factors, status of unwarranted immune responses, and microbial pathogenesis in NEC based on currently available scientific evidence. We additionally discuss novel techniques and models used to study NEC and how this research translates from the bench to the bedside into potential treatment strategies.

Background: Development of necrotizing enterocolitis is multifactorial, with contributing factors that are unique to the preterm infant in the neonatal intensive care unit (NICU). The use of probiotics may reduce these risk factors.Purpose: To evaluate evidence of biologic plausibility for probiotic supplementation to mitigate key risk factors implicated in the development of disease and show recent evidence of safety and effectiveness.Data Sources: A literature survey of electronic databases, including PubMed, Cochrane Database of Systematic Reviews, and CINAHL, was conducted.Study Selection: Selection terms included "necrotizing enterocolitis," "probiotics," and "prematurity." Reviews that were included were full text, in English, and published in the last 5 years. Ten systematic reviews of randomized controlled trials were extracted from 749 records. Excluded were studies that used adjuncts to probiotics, such as lactoferrin or prebiotics, and studies of probiotics given antenatally.Data Extraction: Two independent reviewers extracted data to AMSTAR 2, a critical appraisal tool for systematic reviews of randomized or nonrandomized studies of healthcare interventions.Results: All the reviews found statistically significant reductions in necrotizing enterocolitis rates after supplementation with probiotics. None of the reviews reported adverse effects.Implication For Practice and Research: Probiotic supplementation with specific strains reduces risk for necrotizing enterocolitis. To advance probiotic use in the NICU, additional high-quality trials are needed to focus on specific strains or combinations of strains and to evaluate dosing and duration of treatment.Video Abstract available athttps://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx . [ABSTRACT FROM AUTHOR]

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Abstract Background Necrotizing enterocolitis (NEC) is a common, potentially catastrophic intestinal disease among very low birthweight premature infants. Affecting up to 15% of neonates born weighing less than 1500 g, NEC causes sudden-onset, progressive intestinal inflammation and necrosis, which can lead to significant bowel loss, multi-organ injury, or death. No unifying cause of NEC has been identified, nor is there any reliable biomarker that indicates an individual patient’s risk of the disease. Without a way to predict NEC in advance, the current medical strategy involves close clinical monitoring in an effort to treat babies with NEC as quickly as possible before irrecoverable intestinal damage occurs. In this report, we describe a novel machine learning application for generating dynamic, individualized NEC risk scores based on intestinal microbiota data, which can be determined from sequencing bacterial DNA from otherwise discarded infant stool. A central insight that differentiates our work from past efforts was the recognition that disease prediction from stool microbiota represents a specific subtype of machine learning problem known as multiple instance learning (MIL). Results We used a neural network-based MIL architecture, which we tested on independent datasets from two cohorts encompassing 3595 stool samples from 261 at-risk infants. Our report also introduces a new concept called the “growing bag” analysis, which applies MIL over time, allowing incorporation of past data into each new risk calculation. This approach allowed early, accurate NEC prediction, with a mean sensitivity of 86% and specificity of 90%. True-positive NEC predictions occurred an average of 8 days before disease onset. We also demonstrate that an attention-gated mechanism incorporated into our MIL algorithm permits interpretation of NEC risk, identifying several bacterial taxa that past work has associated with NEC, and potentially pointing the way toward new hypotheses about NEC pathogenesis. Our system is flexible, accepting microbiota data generated from targeted 16S or “shotgun” whole-genome DNA sequencing. It performs well in the setting of common, potentially confounding preterm neonatal clinical events such as perinatal cardiopulmonary depression, antibiotic administration, feeding disruptions, or transitions between breast feeding and formula. Conclusions We have developed and validated a robust MIL-based system for NEC prediction from harmlessly collected premature infant stool. While this system was developed for NEC prediction, our MIL approach may also be applicable to other diseases characterized by changes in the human microbiota.

We conducted a pilot diagnostic randomized clinical trial (RCT) to examine the feasibility, acceptability, and preliminary outcomes of adding bowel ultrasound (BUS) to the diagnostic evaluation for necrotizing enterocolitis (NEC). Infants ≤ 32 weeks' gestational age with NEC concern were randomized to undergo abdominal X-ray (AXR) or AXR + BUS. The primary outcome was study feasibility. Secondary outcomes included rates of NEC diagnosis and duration of treatment with bowel rest and antibiotics. A total of 56 infants were enrolled; 16 developed NEC concern and were randomized. Rates of recruitment (56/82 = 68%), retention (16/16 = 100%), and protocol compliance (126/127 = 99%) met pre-specified thresholds for feasibility. No significant differences in rates of NEC diagnosis were found between the two groups. Durations of bowel rest and antibiotic treatment were also similar. Conclusion: Our study supports the feasibility of conducting a definitive diagnostic RCT to establish safety and efficacy of BUS for NEC. Clinical trial registration: The study was registered at https://clinicaltrials.gov (NCT03963011). What is Known: • Bowel ultrasound (BUS) is increasingly being utilized as an adjunct to abdominal radiographs in evaluating for necrotizing enterocolitis (NEC). • The impact of BUS on patient outcomes is unknown. What is New: • A diagnostic randomized controlled trial study design to determine safety and effectiveness of adding BUS to NEC evaluation is feasible and acceptable. [ABSTRACT FROM AUTHOR]

Neonates with congenital heart disease (CHD) are at an increased risk of developing necrotizing enterocolitis (NEC), an acute inflammatory intestinal injury most commonly associated with preterm infants. The rarity of this complex disease, termed cardiac NEC, has resulted in a dearth of information on its pathophysiology. However, a higher incidence in term infants, effects on more distal regions of the intestine, and potentially a differential immune response may distinguish cardiac NEC as a distinct condition from the more common preterm, classical NEC. In this review, risk factors, differentiated from those of classical NEC, are discussed according to their potential contribution to the disease process, and a general pathogenesis is postulated for cardiac NEC. Additionally, biomarkers specific to cardiac NEC, clinical outcomes, and strategies for achieving enteral feeds are discussed. Working towards an understanding of the mechanisms underlying cardiac NEC may aid in future diagnosis of the condition and provide potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Colonization of the neonatal gut by beneficial bacteria is important for the establishment and maintenance of the mucosal barrier, thus protecting the neonate from enteric pathogens and local and systemic inflammation. The neonatal microbiome is influenced by infant diet, environment, and the maternal microbiome. Dysbiosis in pregnancy increases the risk of pre-eclampsia, diabetes, infection, preterm labor, and later childhood atopy. Dysbiosis of the neonatal gut plays an important role in colic in the term infant, in the disease processes which plague preterm infants, including necrotizing enterocolitis and sepsis, and in the long-term outcomes of neonates. Administration of enteral prebiotics, probiotics, and synbiotics during pregnancy, lactation, and postnatal life appears to be a safe and feasible method to alter the maternal and neonatal microbiome, thus improving pregnancy and neonatal outcomes.

Background: Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants.Methods: The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity.Discussion: The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery.Trial Registration: Trial registration data: June 25, 2019  NCT03997266 . [ABSTRACT FROM AUTHOR]

The intestinal microbiome is frequently implicated in necrotizing enterocolitis (NEC) pathogenesis. While no particular organism has been associated with NEC development, a general reduction in bacterial diversity and increase in pathobiont abundance has been noted preceding disease onset. However, nearly all evaluations of the preterm infant microbiome focus exclusively on the bacterial constituents, completely ignoring any fungi, protozoa, archaea, and viruses present. The abundance, diversity, and function of these nonbacterial microbes within the preterm intestinal ecosystem are largely unknown. Here, we review findings on the role of fungi and viruses, including bacteriophages, in preterm intestinal development and neonatal intestinal inflammation, with potential roles in NEC pathogenesis yet to be determined. In addition, we highlight the importance of host and environmental influences, interkingdom interactions, and the role of human milk in shaping fungal and viral abundance, diversity, and function within the preterm intestinal ecosystem.

Neonates born prematurely (

Background: Necrotizing enterocolitis (NEC) is a common, potentially catastrophic intestinal disease among very low birthweight premature infants. Affecting up to 15% of neonates born weighing less than 1500 g, NEC causes sudden-onset, progressive intestinal inflammation and necrosis, which can lead to significant bowel loss, multi-organ injury, or death. No unifying cause of NEC has been identified, nor is there any reliable biomarker that indicates an individual patient's risk of the disease. Without a way to predict NEC in advance, the current medical strategy involves close clinical monitoring in an effort to treat babies with NEC as quickly as possible before irrecoverable intestinal damage occurs. In this report, we describe a novel machine learning application for generating dynamic, individualized NEC risk scores based on intestinal microbiota data, which can be determined from sequencing bacterial DNA from otherwise discarded infant stool. A central insight that differentiates our work from past efforts was the recognition that disease prediction from stool microbiota represents a specific subtype of machine learning problem known as multiple instance learning (MIL). Results: We used a neural network-based MIL architecture, which we tested on independent datasets from two cohorts encompassing 3595 stool samples from 261 at-risk infants. Our report also introduces a new concept called the "growing bag" analysis, which applies MIL over time, allowing incorporation of past data into each new risk calculation. This approach allowed early, accurate NEC prediction, with a mean sensitivity of 86% and specificity of 90%. True-positive NEC predictions occurred an average of 8 days before disease onset. We also demonstrate that an attention-gated mechanism incorporated into our MIL algorithm permits interpretation of NEC risk, identifying several bacterial taxa that past work has associated with NEC, and potentially pointing the way toward new hypotheses about NEC pathogenesis. Our system is flexible, accepting microbiota data generated from targeted 16S or "shotgun" whole-genome DNA sequencing. It performs well in the setting of common, potentially confounding preterm neonatal clinical events such as perinatal cardiopulmonary depression, antibiotic administration, feeding disruptions, or transitions between breast feeding and formula. Conclusions: We have developed and validated a robust MIL-based system for NEC prediction from harmlessly collected premature infant stool. While this system was developed for NEC prediction, our MIL approach may also be applicable to other diseases characterized by changes in the human microbiota. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal malrotation is life-threatening and often presents during infancy with bilious vomiting. The prevalence and presentation among extremely premature infants are unknown.Methods: We retrospectively reviewed all infants born at less than 28 weeks' gestation diagnosed with symptomatic intestinal malrotation in a tertiary neonatal intensive care unit over a 10-year period (2010-2020).Results: Seven of 514 (1.4%) extremely premature infants developed symptomatic intestinal malrotation during this period. All were non-syndromic. In comparison, the prevalence of symptomatic intestinal malrotation in 7382 infants ≥ 28 weeks' gestation admitted during the same period was 0.2%. Intestinal malrotation was confirmed at laparotomy in all extremely premature infants and six of seven had midgut volvulus. All but one presented with marked abdominal distension; none had bilious vomiting and only three had bilious gastric aspirates. A subacute onset with non-specific features such as recurrent apnoea and bradycardia, feed intolerance, and intermittent abdominal distension was common. All infants underwent a Ladd procedure. Two required extensive bowel resection resulting in short gut syndrome and three underwent further surgery for adhesive small bowel obstruction. One patient died at 10 months of age from respiratory failure but the others were well 1-3 years later.Conclusions: Symptomatic intestinal malrotation in extremely premature infants has a relatively high prevalence. It may present with marked abdominal distension without bilious vomiting, demanding a high index of suspicion. An atypical presentation, potential alternative abdominal pathologies, coexisting comorbidities, and concerns about survival in these fragile babies may deter the surgeon despite the opportunity of a good outcome. [ABSTRACT FROM AUTHOR]

Objective  The aim of this study was to determine whether a regional quality improvement (QI) initiative decreased incidence and severity of surgical necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Study Design  A retrospective review of all VLBW infants who received care at one of the three hospitals involved in a NEC QI initiative from 2011 to 2016. Primary outcome was the number of surgical NEC cases per year. Secondary outcomes included associated outcomes and mortality. Results  Sixty-three infants with either a diagnosis of Stage III NEC (n  = 40) or spontaneous intestinal perforation (SIP) (n  = 23) were included. The incidence of medical and surgical NEC and the mortality rate of infants with surgical NEC decreased over time. Incidence and mortality of SIP did not significantly change. Conclusion  A regional QI bundle to reduce the overall incidence of NEC also significantly decreased the incidence of surgical NEC and all-cause mortality of infants diagnosed with surgical NEC. Key Points QI reduces surgical necrotizing enterocolitis. Reduction in NEC rate improves mortality. Human milk does not change SIP incidence. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development.Purpose: To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions.Methods/search Strategy: Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates.Findings: Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes.Implications For Practice: To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation.Implications For Research: It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes. [ABSTRACT FROM AUTHOR]

Objective  Feeding intolerance (FI) is a common presentation of necrotizing enterocolitis (NEC) and sepsis. NEC and sepsis are associated with hematological changes, but these changes alone are not reliable biomarkers for early diagnosis. This study examined whether the combination of hematological indices and FI can be used as an early diagnostic tool for NEC or sepsis. Study Design  This retrospective cohort study included infants born at <1,500 g or <30 weeks who had symptoms of FI. The exclusion criteria were congenital or chromosomal disorders, thrombocytopenia or platelet transfusion before the onset of FI, and history of bowel resection. We compared the hematological indices from infants with pathologic FI (due to NEC or sepsis) to infants with benign FI. Results  During the study period, 211 infants developed FI; 185 met the inclusion criteria. Infants with pathologic FI (n  = 90, 37 cases with NEC and 53 with sepsis) had lower birth gestational age and weight compared with 95 infants with benign FI (n  = 95). Pathologic FI was associated with lower platelet count (median 152 × 10 3 /μL vs. 285 × 10 3 /μL, p  < 0.001) and higher immature-to-total neutrophil (I/T) ratio (median 0.23 vs. 0.04, p  < 0.001) at the onset of FI. Pathologic FI was also associated with a decrease in baseline platelets compared with an increase in benign FI. For diagnosis of pathologic FI, a decrease ≥10% in platelets from baseline had a sensitivity and specificity of 0.64 and 0.73, respectively, I/T ratio ≥0.1 had a sensitivity and specificity of 0.71 and 0.78, respectively, and the combination of both parameters had a sensitivity and specificity of 0.50 and 0.97, respectively. Conclusion  FI caused by NEC or sepsis was associated with a decrease in platelets from baseline, and a lower platelet level and higher I/T ratio at the onset of FI. These findings can help clinicians in the management of preterm infants with FI. Key Points FI is a common presentation of NEC and sepsis in preterm infants. FI due to NEC or sepsis is associated with changes in platelets and I/T ratio. These changes could be useful as early markers for diagnosis. [ABSTRACT FROM AUTHOR]

Background and objectivesDespite previous studies demonstrating no difference in mortality or morbidity, the various surgical approaches for necrotizing enterocolitis (NEC) in infants have not been evaluated economically. Our goal was to compare total in-hospital cost and mortality by using propensity score-matched infants treated with peritoneal drainage alone, peritoneal drainage followed by laparotomy, or laparotomy alone for surgical NEC.MethodsUtilizing the California OSHPD Linked Birth File Dataset, 1375 infants with surgical NEC between 1999 and 2007 were retrospectively propensity score matched according to intervention type. Total in-hospital costs were converted from longitudinal patient charges. A multivariate mixed effects model compared adjusted costs and mortality between groups.ResultsSuccessful propensity score matching was performed with 699 infants (peritoneal drainage, n = 101; peritoneal drainage followed by laparotomy, n = 172; and laparotomy, n = 426). Average adjusted cost for peritoneal drainage followed by laparotomy was $398,173 (95% confidence interval [CI]: 287,784-550,907), which was more than for peritoneal drainage ($276,076 [95% CI: 196,238-388,394]; P = .004) and similar to laparotomy ($341,911 [95% CI: 251,304-465,186]; P = .08). Adjusted mortality was highest after peritoneal drainage (56% [95% CI: 34-75]) versus peritoneal drainage followed by laparotomy (35% [95% CI: 19-56]; P = .01) and laparotomy (29% [95% CI: 19-56]; P < .001). Mortality for peritoneal drainage was similar to laparotomy.ConclusionsPropensity score-matched analysis of surgical NEC treatment found that peritoneal drainage followed by laparotomy was associated with decreased mortality compared with peritoneal drainage alone but at significantly increased costs.