Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population.
An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded.
The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided.
Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.

BACKGROUND: Several probiotic species and strains, single or combined, have been evaluated in childhood diarrheal disorders, and recommendations have ever been changing as newer trials are published. Therefore, there is a need to develop a guideline for Indian children describing the current role of probiotics in clinical practice.
OBJECTIVE: To develop a guideline for the use of probiotics in children with diarrhea.
METHODS: A national consultative group (NCG) was constituted by the Indian Academy of Pediatrics (IAP), consisting of subjects experts. Sub-topics were allotted to various experts as paired groups for detailed review. Members reviewed the international and Indian literature for existing guidelines, systematic reviews, meta-analyses and trials. Thereafter, two virtual structured meetings of the group were held on 2nd and 22nd August, 2020. The management guidelines were formulated by the group and circulated to the participants for comments. The final guidelines were approved by all experts, and adopted by the IAP executive board.
CONCLUSIONS: The NCG suggests Lactobacillus GG as a conditional recommendation with low-to-moderate level evidence or Saccharomyces boulardii as a conditional recommendation with very low-to-low level evidence as adjuvant therapy in acute diarrhea. The NCG also recommends the use of combination probiotics in neonatal necrotizing enterocolitis (NEC), as these reduce the risk of NEC stage II and above, late-onset sepsis, mortality and also time to achieve full feeds. The NCG does not recommend the use of any kind of probiotics in the therapy of acute dysentery, persistent diarrhea, Clostridium difficile diarrhea and chronic diarrheal conditions such as celiac disease, diarrhea-predominant irritable bowel syndrome and inflammatory bowel disease in children. Risk of antibiotic-associated diarrhea (AAD) is high with some antibiotics and most of these cases present as mild diarrhea. The NCG recommends probiotics only in special situations of AAD. L. rhamnoses GG or S. boulardii may be used for the prevention of AAD. VSL#3, a combination probiotic, may be used as an adjuvant in active pouchitis, prevention of recurrences and maintenance of remission in pouchitis.

Recent evidence demonstrates that earlier feeding may be beneficial after non-surgical necrotizing enterocolitis (NEC). We aimed to decrease time to reach full enteral feeds by 20% post-NEC by standardizing time to reinitiate feeds.
We implemented a consensus-based guideline for earlier feeding post-NEC. Outcome measures included days to initiate enteral feeds and reach full enteral feeds. Central venous line days and length of stay were also evaluated. Balancing measures were NEC recurrence and post-NEC stricture. Statistical analysis used process control methodology and standard comparison statistical testing.
Average days infants with Stage II NEC began feeding decreased from 9.4 to 5.1 days and average days to reach full feeds was decreased by 35% from 24.0 to 15.7 days. We observed no change in our balancing measures.
A multidisciplinary consensus-based NEC earlier feeding guideline decreased time to reach full enteral feeds and reduced central line days without adverse events.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of neonates, especially of preterm infants, with high morbidity and mortality. The surviving infants may have digestive tract and neurological sequelae. Therefore, the prevention and treatment of NEC are of great significance in improving survival rate and survival quality of neonates. To provide evidence-based recommendations for management of NEC, the guidelines were developed based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the current domestic and overseas studies.

BACKGROUND: Routine measurement of gastric residual volume to guide feeding is widespread in neonatal units but not supported by high-quality evidence. Outcome selection is critical to trial design.
OBJECTIVE: To determine optimal outcome measures for a trial of not routinely measuring gastric residual volume in neonatal care.
METHODS: A focused literature review, parent interviews, modified two-round Delphi survey and stakeholder consensus meeting.
METHODS: Sixty-one neonatal healthcare professionals participated in an eDelphi survey; 17 parents were interviewed. 19 parents and neonatal healthcare professionals took part in the consensus meeting.
RESULTS: Literature review generated 14 outcomes, and parent interviews contributed eight additional outcomes; these 22 outcomes were then ranked by 74 healthcare professionals in the first Delphi round where four further outcomes were proposed; 26 outcomes were ranked in the second round by 61 healthcare professionals. Five outcomes were categorised as \'consensus in\', and no outcomes were voted \'consensus out\'. \'No consensus\' outcomes were discussed and voted on in a face-to-face meeting by 19 participants, where four were voted \'consensus in\'. The final nine consensus outcomes were: mortality, necrotising enterocolitis, time to full enteral feeds, duration of parenteral nutrition, time feeds stopped per 24 hours, healthcare-associated infection; catheter-associated bloodstream infection, change in weight between birth and neonatal discharge and pneumonia due to milk aspiration.
CONCLUSIONS: We have identified outcomes for a trial of no routine measurement of gastric residual volume to guide feeding in neonatal care. This outcome set will ensure outcomes are important to healthcare professionals and parents.

Early introduction of enteral nutrition (EN) in postoperative infants improves intestinal adaptation, reducing the risk of intestinal failure-associated liver disease (IFALD). Our objective was to determine whether guideline use reduces feeding variability and improves outcomes in the neonatal intensive care unit (NICU).
In a cohort study, surgical infants at risk for IFALD were evaluated pre and post implementation of feeding guidelines at 2 NICUs. A total of 167 guideline infants (2013-2018) were compared with 242 historical controls (2007-2013). Adherence was measured with timing and volume of initial postoperative feed. Primary outcomes were IFALD incidence and time to reach 50% and 100% of energy from EN. Secondary outcomes were parenteral nutrition (PN) days, postoperative necrotizing enterocolitis (NEC), central line-associated bloodstream infection (CLABSI), and length of stay (LOS).
Moderate IFALD decreased from 32% to 20% (P = .005) in the guideline group. Time to achieve 50% and 100% energy from EN was decreased from medians of 8 to 5 and 28 to 21 days, respectively (P < .001). There was an overall decrease in PN use from 41 to 29 days (P = .002), CLABSI incidence from 25% to 5% (P < .001), and LOS from 70 to 53 days (P = .030). Once stratified by diagnosis, infants with NEC showed greatest improvement and reduction in IFALD from 67% to 42% (P = .045). With no difference in postoperative NEC (P = .464).
Early standardized postoperative EN guidelines in intestinal-surgery infants was associated with improved outcomes, including faster achievement of feeding goals and reduced IFALD severity, especially in infants with NEC.

BACKGROUND: This study examined clinical outcomes associated with the use of a gastroschisis-specific (GS) feeding advancement guideline.
METHODS: We performed a retrospective study of all simple gastroschisis babies (N = 65) treated between June 2009June 2015. We compared patients treated on a postintestinal surgery guideline using either a 1-day (1D) or 3-day (3D) feeding advancement from August 2009-August 2013 with infants treated on a GS guideline from September 2013-June 2015.
RESULTS: Patients in the 2 groups were similar in sex, race, gestational age, weight, and comorbidities. Median time to full enteral nutrition (EN) was 11 days for the 1D group, 22 days for the 3D group, and 18 days for the GS group (P < .01). However, lengths of stay and estimated weight gain per day were similar among the groups. A total of 3 infants (10%) in the 1D group developed necrotizing enterocolitis compared with none in the 3D or GS groups. Control chart analysis showed reduced variation in median time to full EN in the GS group when compared with the 1D and 3D groups. Guideline adherence was significantly better with the GS guideline when compared with the 1D or 3D guidelines (94% vs 72% vs 90%; P < .01).
CONCLUSIONS: A GS protocol yielded reduced variation in median time to full EN, significant improvement in percent adherence to the guideline, and zero cases of necrotizing enterocolitis. Weight gain and lengths of stay were not adversely affected by slower feeds.

Necrotizing enterocolitis (NEC) is a catastrophic abdominal complication threatening the life of premature infants, but adoption of prevention and early recognition practices differs as do NEC rates in Neonatal Intensive Care Units (NICUs). The purpose of this research was to validate and weight an evidence-based adherence score (aka NEC-Zero Adherence Score) to prevent and foster timely recognition of NEC.
An electronic Delphi (e-Delphi) approach was used to identify consensus. NEC experts were recruited via the NEC Society and surveyed until consensus and stability criteria for the Delphi were met (≥70% consensus and mean responses changed <15% between rounds).
Expert panelists (n=22) were experienced (M=17.6, SD 11years) and predominately physicians (68%) or neonatal nurse practitioners (18%). Consensus (>70% by item) supported a 10 point score. Points were distributed across 1) an exclusive human milk diet (5 points), 2) standardized feeding protocols (3 points), 3) antibiotic stewardship (1 point), and 4) a unit-specified approach to early recognition (1 point). Withholding feeding during transfusion was controversial (M=0.50, SD 0.73) and met consensus criteria to drop from the score.
Holding feeding during transfusion was dropped from the score. Relationships between the score and unit NEC rates as well as its utility for use in audit and feedback should be studied in the future.

Sepsis and necrotizing enterocolitis are major contributors to morbidity and mortality in neonates, especially in those born preterm. While therapeutic interventions are available for both (for e.g. antibiotics), a major dilemma is early diagnosis so that these interventions can be done in a timely manner. As clinical evaluation alone is unreliable in identifying infants in the early stages of neonatal sepsis or necrotizing enterocolitis, there is a need to find specific biomarkers associated with these conditions to improve diagnostic capabilities. Optimal use of biomarkers in the identification and management of affected neonates requires an understanding of the properties of each marker within the timeline of the inflammatory response. We propose that early- and mid-phase markers such as neutrophil CD64 and procalcitonin should be combined with the late-phase biomarker C-reactive protein for maximal diagnostic benefit. Appropriately powered trials evaluating the serial measurements of these markers in decisions related to antibiotic stewardship in the neonatal population are indicated, in addition to more studies investigating other potentially useful biomarkers.

BACKGROUND: Necrotizing enterocolitis or NEC is the most common gastrointestinal emergency in the newborn. The etiology of NEC remains unknown, and treatment consists of antibiotic therapy and supportive care with the addition of surgical intervention as necessary. Unlike most surgical diseases, clear guidelines for the type and duration of peri-operative antibiotic therapy have not been established. Our aim was to review the antibiotic regimen(s) applied to surgical patients with NEC within a single neonatal intensive care unit (NICU) and to evaluate outcomes and help develop guidelines for antibiotic administration in this patient population.
METHODS: A single-center retrospective review was performed of all patients who underwent surgical intervention for NEC from August 1, 2005 through August 1, 2015. Relevant data were extracted including gestational age, age at diagnosis, gender, pre-operative antibiotic treatment, post-operative antibiotic treatment, development of stricture, and mortality. Patients were excluded if there was incomplete data documentation.
RESULTS: A total of 90 patients were identified who met inclusion criteria. There were 56 male patients and 34 female patients. The average gestational age was 30 5/7 wks and average age of diagnosis 16.7 d. A total of 22 different pre-operative antibiotic regimens were identified with an average duration of 10.6 d. The most common pre-operative regimen was ampicillin, gentamicin, and metronidazole for 14 d. A total of 15 different post-operative antibiotic regimens were identified with an average duration of 6.6 d. The most common post-operative regimen was ampicillin, gentamicin, and metronidazole for two days. There were 26 strictures and 15 deaths. No regimen or duration proved superior.
CONCLUSIONS: We found that there is a high degree of variability in the antibiotic regimen for the treatment of NEC, even within a single NICU, with no regimen appearing superior over another. As data emerge that demonstrate the adverse effects of antibiotic overuse, our findings highlight the need for guidelines in the antibiotic treatment of NEC and suggest that an abbreviated course of post-operative antibiotics may be safe.