Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Time of Onset of Necrotizing Enterocolitis and Focal Perforation in Preterm Infants: Impact on Clinical, Surgical, and Histological Features.

Objective: There is no gold standard test for diagnosis of necrotizing enterocolitis (NEC). Timing of onset is used in some definitions and studies in an attempt to separate NEC from focal intestinal perforation (FIP) with 14 days used as a cutoff. In a large, detailed data set we aimed to compare NEC and FIP in preterm infants born <32 weeks gestation, presenting before 14 days of life in comparison to cases presenting later. Design: Infants with NEC or FIP when parents had consented to enrollment in an observational and sample collection study were included from 2009 to 2019. Clinical, surgical, histological, and outcome data were extracted and reviewed by each author independently. Patients/Episodes: In 785 infants, 174 episodes of NEC or FIP were identified of which 73 (42%) occurred before 14 days, including 54 laparotomies and 19 episodes of medically managed NEC ("early"). There were 56 laparotomies and 45 episodes of medically managed NEC presenting on or after 14 days age ("late"). Results: In early cases, 41% of laparotomies were for NEC (22 cases) and 59% for FIP (32 cases), and in late cases, 91% of laparotomies (51 cases) were for NEC and 9% (five cases) were for FIP. NEC presenting early was more likely to present with an initial septic presentation rather than discrete abdominal pathology and less likely to have clear pneumatosis. Early cases did not otherwise differ clinically, surgically, or histologically or in outcomes compared with later cases. FIP features did not differ by age at presentation. Conclusions: Although most FIP occurred early, 14% occurred later, whereas almost one third (29%) of NEC cases (surgical and medical) presented early. Infant demographics and surgical and histological findings of early- and late-presenting disease did not differ, suggesting that early and late cases are not necessarily different subtypes of the same disease although a common pathway of different pathogenesis cannot be excluded. Timing of onset does not accurately distinguish NEC from FIP, and caution should be exercised in including timing of onset in diagnostic criteria.

ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions 1.

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95% CI = 0.86-1.04; p = 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon.

Congenital epulis: from birth to childhood.

Congenital epulis, a rare benign neonatal tumor, is found more commonly in females and can be a cause of extreme anxiety in parents and health professionals. There is a potential of abnormal dentin development in surgically treated patients. These children should be followed by a pediatric dentist. A watchful approach rather than surgery is justified in small tumors because of the risk of abnormal dentition at the site of surgery. These cases should be followed by dentists if surgical resection is done.

Proportionate reduction in uncertainty of late onset infection in pre-term infants by neutrophil CD64 measurement.

OBJECTIVE: Establish how neutrophil CD64 performs as a marker of definite infection in pre-term infants in comparison to C reactive protein (CRP) and procalcitonin (PCT). METHODS: A total of 38 pre-term infants with suspected late onset infection had CD64 measured by flow cytometry. Proportionate reduction in uncertainty (PRU) curves were generated for CD64 counts at various threshold values. RESULTS: PRU curves reduced the residual uncertainty of the presence of infection by up to 64%. CONCLUSIONS: The CD64 appears to be a useful point of care test (POCT) for further defining the likelihood of infection and performs better than CRP or PCT at helping to rule in infection.

Quality of newborn care: adherence to guidelines for parenteral nutrition in preterm infants in four European countries.

OBJECTIVE: The level of adherence to guidelines should be explored particularly in preterm infants for whom poor nutrition has major effects on outcomes in later life. The objective was to evaluate compliance to international guidelines for parenteral nutrition (PN) in preterm infants across neonatal intensive care units (NICUs) of four European countries. DESIGN: Clinical practice survey by means of a questionnaire addressing routine PN protocols, awareness and implementation of guidelines. SETTING: NICUs in the UK, Italy, Germany and France. PARTICIPANTS: One senior physician per unit; 199 units which represent 74% of the NICUs of the four countries. PRIMARY OUTCOME MEASURE: Adherence of unit protocol to international guidelines. SECONDARY OUTCOME MEASURE: Factors that influence adherence to guidelines. RESULTS: 80% of the respondents stated that they were aware of some PN clinical practice guidelines. For amino acid infusion (AA), 63% of the respondents aimed to initiate AA on D0, 38% aimed to administer an initial dose ≥1.5 g/kg/day and 91% aimed for a target dose of 3 or 4 g/kg/day, as recommended. For parenteral lipids, 90% of the respondents aimed to initiate parenteral lipids during the first 3 days of life, 39% aimed to use an initial dose ≥1.0 g/kg/day and 76% defined the target dose as 3-4 g/kg/day, as recommended. Significant variations in PN protocols were observed among countries, but the type of hospital or the number of admissions per year had only a marginal impact on the PN protocols. CONCLUSIONS: Most respondents indicated that their clinical practice was based on common guidelines. However, the initiation of PN is frequently not compliant with current recommendations, with the main differences being observed during the first days of life. Continuous education focusing on PN practice is needed, and greater efforts are required to disseminate and implement international guidelines.

Deaths in preterm infants: changing pathology over 2 decades.

OBJECTIVE: To establish how cause of death for live-born preterm infants (24-31 weeks gestation) has changed in a single large UK population over 2 decades. STUDY DESIGN: This was an interrogation of a population-based survey of >680, 000 live births (between 1988 and 2008) for deaths in the first postnatal year. We collected cause of death grouped into major etiologies: respiratory, infection, malformation, necrotizing enterocolitis (NEC), and other. Data were analyzed in three 7-year epochs and 2 gestational groups (<27 and 28-31 weeks). Numbers, rates per 1000 live births, and proportional contributions to each epoch were analyzed. RESULTS: A total of 1504 deaths occurred. The infants who died had a median gestational age of 26 weeks (IQR, 25-28 weeks) and a median birth weight of 880 g (IQR, 700-1170 g). The number of deaths decreased with each later epoch (from 671 to 473 and then to 360), as did the proportion of deaths from respiratory causes (64% to 62% and then to 49%). The proportion of deaths occurring after 40 weeks postmenstrual age remained stable across the 3 epochs (8.8%, 8%, and 8%). Deaths from infection and NEC increased with time (from 11% to 13% and then to 21%), as did median time to death (from 2.7 to 3.8 days). CONCLUSION: Infection and NEC are increasingly prevalent causes of death in preterm infants.