Nutritional management after necrotizing enterocolitis and focal intestinal perforation in preterm infants.

Nutritional management of preterm infants recovering from necrotizing enterocolitis (NEC) or focal intestinal perforation (FIP) is challenging, especially in infants managed surgically. The logistics of how, when, and what to feed are unclear and current nutritional practices are primarily based on physiological principles and consensus opinion in individual units, rather than high-quality evidence. The aim of this narrative review is to summarize the literature on nutritional management after NEC or FIP in preterm infants: when to restart enteral nutrition, type of enteral nutrition to use, and how to advance nutrition. We also discuss treatment of micronutrient deficiencies, cholestasis, replacement of stoma losses, and optimal time of stoma closure. In conclusion, there are in sufficient high-quality studies available to provide evidence-based recommendations on the best nutritional practice after NEC or FIP in preterm infants. A local or national consensus based early nutrition guideline agreed upon by a multidisciplinary team including pediatric surgeons, pediatricians/neonatologists, nurses, and nutritionists is recommended. Further studies are urgently needed. IMPACT: There is no good quality evidence or nutritional standard across neonatal units treating infants after medical or surgical NEC or FIP. With this review we hope to start providing some consistency across patients and between providers treating patients with NEC and FIP. Mother's own milk is recommended when restarting enteral nutrition after NEC or FIP. In the absence of high-quality evidence, a consensus based early nutrition guideline agreed upon by a multidisciplinary team is recommended. Nutritional research projects are urgently needed in NEC and FIP patients.

Correction: Investigating Father or Partner Involvement in Family Integrated Care in Neonatal Units: Protocol for a Prospective, Multicenter, Multiphase Study.

[This corrects the article DOI: 10.2196/53160.].

The role of nutritional interventions in the prevention and treatment of chronic lung disease of prematurity.

Chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Nutrition may affect incidence and severity of BPD. In this context, the Section on Nutrition, Gastroenterology and Metabolism, the Pulmonary Section of the European Society for Paediatric Research (ESPR) and SPR have joined forces to review the current knowledge on nutritional issues related to BPD. The aim of this narrative review is to discuss the clinical implications for nutritional practice. Nutrient deficiencies may influence pathogenesis of BPD. Adequate nutrition and growth can play a crucial role in the prevention of and recovery from BPD. Optimal nutrition strategy is an important principle, especially in the early postnatal period. As optimal energy intake in infants at risk of BPD or with evolving BPD is not yet defined, further research with well-designed studies on nutritional strategies for preterm infants with BPD is urgently needed. IMPACT: Based on current evidence it seems reasonable to recommend that BPD diagnosed infants should receive an energy supply ranging from 120 to 150 Kcal/kg/d. Exclusive MOM feed with adequate fortification should be encouraged as this is associated with a significant reduction in the risk of BPD. Suboptimal nutritional delivery is often seen in preterm infants with BPD compared to controls.

Investigating Father or Partner Involvement in Family Integrated Care in Neonatal Units: Protocol for a Prospective, Multicenter, Multiphase Study

BACKGROUND: Neonatal unit (NU) admissions for premature babies can last for months, which can significantly impact parental mental health (MH) with symptoms of depression, stress, and anxiety. Literature suggests fathers experience comparable MH symptoms to mothers. Family integrated care (FICare) is a culture where parents are collaborators and partners in caring for their hospitalized newborns. FICare improves infant outcomes and maternal MH. Similar reports on fathers are limited. OBJECTIVE: The primary aim of this study is to investigate the impact of supporting father or partner engagement in FICare of preterm infants on their MH up to 6 weeks postdischarge. The secondary aim is to investigate the impact on maternal MH. METHODS: This is a 2-phase study: phase 1 to gather baseline information and phase 2 to assess the impact of enhanced father or partner engagement in FICare on their MH, involving 2 NUs (tertiary and level 2). Enhanced FICare will be developed and introduced (eg, information booklet, workbook, classes, and a father peer-support group) alongside standard FICare practices. Father or partner MH will be assessed with semistructured qualitative interviews and validated questionnaires: Generalized Anxiety Disorder Assessment, Patient Health Questionnaire, and Parental Stressor Scale: Neonatal Intensive Care Unit from NU admission to 6 weeks postdischarge. Mothers will be assessed by focus groups and the same questionnaires. Descriptive statistics and appropriate comparative tests, such as the 2-tailed t test, will be used to analyze and compare phase 1 and 2 data. Qualitative data will be coded line by line with the use of NVivo (Lumivero) and thematically analyzed. Simultaneously, systematic reviews (SRs) of fathers' experiences of FICare and their MH outcomes will be conducted. The study was approved by the National Research Ethics Committee (22/EM/0140) in August 2022. A parent advisory group was formed to advise on the study methodology, materials, involvement of participant parents, and dissemination of study findings. RESULTS: A recent SR demonstrated that data saturation is likely to be achieved by interviewing 9 to 17 participants. We will study a maximum of 20 parents of infants born at less than 33 weeks' gestation in each phase. As of October 2023, the study was ongoing. The SR studies are registered with the PROSPERO database (324275 and 306760). The projected end date for data collection is July 2024; data analysis will be conducted in November 2024 and publication will occur in 2025. CONCLUSIONS: The study aims to demonstrate the feasibility of using a father or partner-sensitive FICare model for parents of premature babies with a positive impact on their MH. It will demonstrate the feasibility of providing FICare to extremely premature babies receiving intensive care. This study may support the development of inclusive FICare guidelines for nonbirthing parents and their extremely premature infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06022991; https://classic.clinicaltrials.gov/ct2/show/NCT06022991. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53160.

Current Understanding of Transfusion-associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence.

Introduction: The association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC), so-called transfusion-associated NEC (ta-NEC), was first described in 1987. However, further work is needed to confirm a causal relationship, elucidate underlying mechanisms, and develop possible strategies for prevention. We performed an extensive literature search in the databases PubMed, EMBASE, and Scopus. Areas covered: Although multiple retrospective human studies have strongly suggested an association between blood transfusions and subsequent occurrence of NEC, meta-analyses of randomized controlled trials (RCTs) testing RBC transfusion thresholds or the use of recombinant erythropoiesis-stimulating growth factors did not confirm an association of anemia with ta-NEC. These conflicting data necessitated the development of an animal model to elucidate mechanisms and causal factors. Data from this recent mouse model of ta-NEC highlighted the importance of sequential exposure to severe anemia followed by transfusion for development of ta-NEC. Expert opinion: This review summarizes current human and experimental data, highlights open questions, and suggests avenues for further research aimed at preventing ta-NEC in preterm infants. Further studies are required to delineate whether there is a tipping point, in terms of the level and duration of anemia, and to develop an effective strategy for blood management and the quality of RBC transfusions.

COVID-19 restrictions and psychological well-being of fathers with infants admitted to NICU-An exploratory cross-sectional study.

AIM: To describe the impact of the COVID-19 restrictions on the caregiving activities and psychological well-being of fathers with infants admitted to neonatal units. METHODS: Cross-sectional study using adapted COPE-IS and COPE-IU tools. Participants' recruitment occurred online via social media and parents' associations. Online survey in English, French and Italian were distributed and promoted via websites and social media platforms of parent's associations. The study was undertaken across 12 countries in Asia, Australia, Africa and Europe. RESULTS: A total of 108 fathers of NICU infants completed the survey. COVID-19 related restrictions were categorised into 3 types: no restrictions, partial and severe restrictions. Fathers who experienced partial restrictions reported more involvement in caregiving activities but high levels of emotional difficulties and sleeping problems compared to those who experienced full or no restrictions. CONCLUSION: Given the impact on the psychological well-being of fathers, restrictions should be avoided as much as possible in the neonatal unit and fathers given free access to their infants if they follow appropriate infection control precautions.

Single Nucleotide Polymorphisms in Neonatal Necrotizing Enterocolitis.

The etiopathogenesis of necrotizing enterocolitis (NEC) remains unclear, but increasing information suggests that the risk and severity of NEC may be influenced by single nucleotide polymorphisms in many genes. In this article, we have reviewed gene variations that have either been specifically identified in NEC or have been noted in other inflammatory bowel disorders with similar histopathological abnormalities. We present evidence from our own peer-reviewed laboratory studies and data from an extensive literature search in the databases PubMed, EMBASE, and Scopus. To avoid bias in the identification of existing studies, search keywords were short-listed both from our own studies and from PubMed's Medical Subject Heading (MeSH) thesaurus.

Racial Disparities in Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a serious disease of the intestinal tract affecting 5-10% of pre-term infants with up to 50% mortality in those that require surgery. There is wide variation in the rates and outcomes of NEC by race and ethnicity, and the reasons for this disparity are poorly understood. In this article, we review the epidemiology and discuss possible explanations for racial and ethnic differences in NEC. Most of the current evidence investigating the role of race in NEC comes from North America and suggests that Hispanic ethnicity and non-Hispanic Black race are associated with higher risk of NEC compared to non-Hispanic White populations. Differences in pre-term births, breastfeeding rates, and various sociodemographic factors does not fully account for the observed disparities in NEC incidence and outcomes. While genetic studies are beginning to identify candidate genes that may increase or decrease risk for NEC among racial populations, current data remain limited by small sample sizes and lack of validation. Complex interactions between social and biological determinants likely underly the differences in NEC outcomes among racial groups. Larger datasets with detailed social, phenotypic, and genotypic information, coupled with advanced bioinformatics techniques are needed to comprehensively understand racial disparities in NEC.

Implementation of bowel ultrasound practice for the diagnosis and management of necrotising enterocolitis.

Necrotising enterocolitis (NEC) is a serious inflammatory bowel disease of prematurity with potentially devastating complications and remains a leading cause of morbidity and mortality among premature infants. In recent years, there has been accumulating data regarding benefits of using bowel ultrasound (BUS) in the diagnosis and management of NEC. Despite this, adoption of robust BUS programmes into clinical practice has been slow. As BUS is a relatively new technique, many barriers to implementation exist, namely lack of education and training for sonographers and radiologists, low case volume and unfamiliarity by clinicians regarding how to use the information provided. The aim of this manuscript is to provide a framework and a roadmap for units to implement BUS in day-to-day practice for NEC diagnosis and management.

Defining necrotizing enterocolitis: current difficulties and future opportunities.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in hospitalized infants. First classified through Bell staging in 1978, a number of additional definitions of NEC have been proposed in the subsequent decades. In this review, we summarize eight current definitions of NEC, and explore similarities and differences in clinical signs and radiographic features included within these definitions, as well as their limitations. We highlight the importance of a global consensus on defining NEC to improve NEC research and outcomes, incorporating input from participants at an international NEC conference. We also highlight the important role of patient-families in helping to redefine NEC.

Low serum albumin concentration predicts the need for surgical intervention in neonates with necrotizing enterocolitis.

PURPOSE: To investigate whether serum albumin (SA) concentration can predict the need for surgical intervention in neonates with necrotizing enterocolitis (NEC). METHODS: Retrospective review of all cases with NEC Bell's stage 2 and 3 that were treated in a single center between 2009 and 2015. Data on patient demographics, clinical parameters, laboratory findings and surgical status were recorded. Receiver operating characteristics analysis was used to evaluate optimal cutoffs and predictive values. RESULTS: Overall, 151 neonates with NEC were identified. Of these, 132 (87.4%) had confirmed NEC Bell's stage 2. The median gestational age was 28.4 (range, 23.1-39.0) weeks and 69 (52.3%) had a birth weight of ≤1000 g. Sixty-eight (51.5%) underwent surgery, showing a sustained reduction in SA over time with significantly lower median SA levels compared to 64 (48.5%) cases that responded well to medical treatment (18.3 ±â€¯3.7 g/L vs. 26.0 ±â€¯2.0 g/L; P < 0.001). SA concentration of ≤20 g/L on day 2 of NEC diagnosis was a significant predictor for surgery (OR 3.41; P = 0.019) with a positive predictive value of 71.4%. CONCLUSIONS: An SA concentration of ≤20 g/L on day 2 of the NEC disease process is associated with a higher likelihood for surgical intervention in neonates with NEC Bell's stage 2. SA, in combination with other clinical parameters and serological markers, may be a useful predictive tool for surgery in NEC. LEVEL OF EVIDENCE: II.

Long-Chain Polyunsaturated Fatty Acids and Lipid Peroxidation Products in Donor Human Milk in the United Kingdom: Results From the LIMIT 2-Centre Cross-Sectional Study.

BACKGROUND: Donor human milk (DHM) is used as alternative to maternal milk to feed preterm infants; however, it may provide less long-chain (LC) polyunsaturated fatty acids (PUFAs) and more oxidized lipids, which may be detrimental to preterm infant health and development. Levels have not been reported for DHM in the United Kingdom. METHODS: DHM (n = 19) from 2 neonatal units, preterm milk from a neonatal unit (n = 10), and term milk from the community (n = 11) were analyzed for fatty acids, malondialdehyde, 4-hydroxy-2-nonenal, and hexanal. STUDY REGISTRATION: NCT03573531. RESULTS: DHM had significantly lower absolute LCPUFA content than term (P < .001) and significantly lower ω-3 PUFAs than preterm milk (P < .05), although relative LCPUFA composition did not differ. Exclusive DHM feeding leads to significantly lower fat (3.7 vs 6.7 g/d) and LCPUFA (docosahexaenoic acid [DHA]: 10.6 vs 16.8 mg/d; arachidonic acid [ARA]: 17.4 vs 25.2 mg/d) intake than recommended by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, and provides 17.3% and 43.1% of the in utero accreted ARA and DHA. DHM had the highest proportion of lipid peroxidation. CONCLUSIONS: This study confirms that DHM in the United Kingdom has insufficient LCPUFAs for preterm infants. It demonstrates for the first time that DHM has the highest level of lipid peroxidation, compared with preterm or term milk. This has important implications for preterm infant nutrition, as exclusive DHM feeding might not be suitable long term and may contribute to the development of major preterm neonatal morbidities.

The effects of storage conditions on long-chain polyunsaturated fatty acids, lipid mediators, and antioxidants in donor human milk - A review.

Donor human milk (DHM) is the recommended alternative, if maternal milk is unavailable. However, current human milk banking practices may negatively affect the nutritional quality of DHM. This review summarises the effects of these practices on polyunsaturated fatty acids, lipid mediators and antioxidants of human milk. Overall, there is considerable variation in the reported effects, and further research is needed, particularly with lipid mediators and antioxidants. However, to preserve nutritional quality, DHM should be protected from light exposure and storage at 4 °C minimised, to prevent decreases in vitamin C and endocannabinoids and increases in free fatty acids and lipid peroxidation products. Storage at -20 °C prior to pasteurisation should also be minimised, to prevent free fatty increases and total fat and endocannabinoid decreases. Storage ≤-70 °C is preferable wherever possible, although post-pasteurisation storage at -20 °C for three months appears safe for free fatty acids, lipid peroxidation products, and total fat content.

Abdominal ultrasound should become part of standard care for early diagnosis and management of necrotising enterocolitis: a narrative review.

Necrotising enterocolitis (NEC) is a leading cause of death and disability in preterm newborns. Early diagnosis through non-invasive investigations is a crucial strategy that can significantly improve outcomes. Hence, this review gives particular attention to the emerging role of abdominal ultrasound (AUS) in the early diagnosis of NEC, its performance against abdominal radiograph and the benefits of AUS use in daily practice. AUS has been used in the diagnosis and management of NEC for a couple of decades. However, its first-line use has been minimal, despite growing evidence demonstrating AUS can be a critical tool in the early diagnosis and management of NEC. In 2018, the NEC group of the International Neonatal Consortium recommended using AUS to detect pneumatosis and/or portal air in preterm NEC as part of the 'Two out of three' model. To facilitate widespread adoption, and future improvement in practice and outcomes, collaboration between neonatologists, surgeons and radiologists is needed to generate standard operating procedures and indications for use for AUS. The pace and scale of the benefit generated by use of AUS can be amplified through use of computer-aided detection and artificial intelligence.