Carnitine supplementation increases serum concentrations of free carnitine and total acylcarnitine in preterm neonates: A retrospective cohort study.

OBJECTIVE: Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN). STUDY DESIGN: A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds. Univariate analysis was performed, and those factors that were significantly different between the two groups were adjusted for using mixed effects analysis. RESULTS: There were 108 supplemented and 45 unsupplemented neonates in the study. At baseline, free carnitine (19.8 ± 3.3 vs 18.9 ± 3.7 µmol/L, P = 0.53) and total acylcarnitine (26.6 ± 5.1 vs 22.5 ± 7.1 µmol/L, P = 0.11) were similar between the two groups. At full enteral feeds, compared with unsupplemented group, supplemented infants had significantly higher free carnitine (27.1 ± 16.4 vs 17.1 ± 8.5 µmol/L, P < 0.001) and total acylcarnitine (30.3 ± 11.5 vs 20.2 ± 10.1 µmol/L, P < 0.001). None of the supplemented neonates developed biochemical carnitine deficiency as compared with 18% in the unsupplemented group (P < 0.001). No difference was observed in time to reach full lipid provision, and there were no differences in the change in the triglyceride levels from baseline to the time on full PN lipid provision (P = 0.39). CONCLUSION: Preterm neonates routinely supplemented with parenteral carnitine at 5 mg/kg/day demonstrated higher free carnitine and total acylcarnitine levels at full feeds, with none developing biochemical carnitine deficiency.

Plasma Citrulline as a Biomarker for Early Diagnosis of Necrotizing Enterocolitis in Preterm Infants.

OBJECTIVE: Citrulline synthesized by healthy enterocytes and decreases with injury. This work aimed to study plasma citrulline concentrations (CITs) as a biomarker to differentiate among infants presenting with early nonspecific signs and symptoms of necrotizing enterocolitis (NEC) with those who will develop NEC. Further to study the correlation between posttreatment CIT with time to full feeds (TTFF) and length of stay (LOS). STUDY DESIGN: This is a prospective study which included infants < 32 weeks gestational age (GA) with 9 infants each in Group 1 (stage 2/3 NEC), Group 2 (with stage 1 NEC-like presentation), and Group 3 (healthy GA-matched infants). CIT was measured in Groups 1 and 2 within 24 hours of presentation and again in Group 1 after treatment. RESULTS: The three groups were similar in clinical characteristics. Median CIT (µmol/L) in Group 1 (15.4 [interquartile range, IQR: 7.3-18.0]) was lower than Group 2 (22.2 [IQR: 18.3-27.3], p = 0.02) and Group 3 (24.9 [IQR: 19.8-31.9], p = 0.009). Posttreatment CIT in Group 1 did not correlate with TTFF (r = 0.15; p = 0.69) and LOS (r = - 0.33; p = 0.38). CONCLUSION: CIT was lower in infants with NEC as compared with healthy controls and those infants with nonspecific signs of NEC. CIT after treatment does not correlate with TTFF and LOS. KEY POINTS: · Citrulline is produced by enterocytes.. · It is decreased in infants with necrotizing enterocolitis early in disease.. · It can be used as a biomarker for early diagnosis of necrotizing enterocolitis..

Use of serum citrulline concentrations from routine newborn screen as a biomarker for necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC), a leading cause of mortality and morbidity in preterm neonates, lacks a reliable biomarker. Citrulline is primarily produced by enterocytes and correlates with intestinal function. Serum citrulline concentration (CIT) is routinely measured in routine newborn screening (NBS). The purpose of the study is to test if CIT from NBS may predict the occurrence of NEC and whether it correlates with the time to full feeds (TTFF) and length of stay (LOS), serving as a biomarker of NEC and intestinal health. METHODS: In a retrospective case control study conducted on neonates with gestational age of 26-32 weeks, we compared CIT levels between cases (neonates with NEC) and controls (next-born neonate). NBS was collected within first 24 h, at day 5 and when the neonates achieved full feeds and were compared using non-parametric tests. RESULTS: There was no difference in CIT between the controls and cases on day 1 [11.42 (7.42-14.84 vs. 11.93 (6.85-18.8) µmol/L, p = 0.55], on day 5 [11.99 (7.99-16.55) vs. 13.70 (7.42-26.83) µmol/L, p = 0.05], or at full feeds [14.86 (6.85-25.69) vs. 15.7 (7.42-26.26) µmol/L, p = 0.87]. CIT on day 1 did not correlate with TTFF (r = 0.08, p = 0.53) or LOS (r = 0.23, p = 0.06), respectively). CONCLUSIONS: CIT from routine NBS does not serve as a biomarker to predict NEC in preterm neonates.

Transitioning Preterm Infants From Parenteral Nutrition: A Comparison of 2 Protocols.

BACKGROUND: Growth in preterm infants is compromised during the transition phase of nutrition, when parenteral nutrition (PN) volumes are weaned with advancing enteral nutrition (EN) feeds, likely due to suboptimal nutrient intakes during this time. We implemented new PN guidelines designed to maintain optimal nutrient intakes during the transition phase and compared growth outcomes of this cohort with a control group. MATERIALS AND METHODS: A chart review was conducted on infants born <32 weeks' gestation, before (control group) and after (study group) a new transition PN protocol was implemented in the neonatal intensive care unit. Weight parameters and nutrient intakes were calculated for the transition phase and compared between the 2 groups. RESULTS: Demographic and clinical characteristics of the 2 groups were comparable except for higher rates of sepsis in control group. Weight-for-age z scores at birth, at 1 week of life, and at the start of the transition phase were similar. At the end of the transition phase, infants in the study group had significantly higher z scores compared with the control group, even when corrected for sepsis, a difference that persisted at 35 weeks' gestation. During the transition phase, study infants gained 16.1 ± 4.6 g/kg/d compared with 13.2 ± 5.4 g/kg/d in control group ( P < .001). Similar results were observed in the subset of expressed breastmilk-only fed infants (15.9 ± 4.6 g/kg/d in the study group compared with 13.2 ± 5.4 g/kg/d in the control group, P < .004). CONCLUSION: Optimizing nutrition by the use of concentrated PN during the transition phase to maintain appropriate nutrient intakes improves growth rates in preterm infants.

From parenteral to enteral nutrition: a nutrition-based approach for evaluating postnatal growth failure in preterm infants.

BACKGROUND: Nutrition practices for preterm infants include phases of parenteral nutrition (PN), full enteral nutrition (EN), and the transitional phase in between. Our aim was to identify the nutrition phases during which infants are most likely to exhibit poor growth that would affect risk for growth failure (GF) at discharge and to examine factors associated with GF. METHODS: A retrospective chart review was conducted on infants born <32 weeks' gestation. The neonatal intensive care unit stay was divided into 3 nutrition phases: (1) full PN, (2) transitional PN + EN, and (3) full EN. Weekly growth rates were calculated, and for each growth velocity <10 g/kg/d, the coinciding phase was recorded. GF was defined as a discharge weight below the 10th percentile. The nutrition phases during which growth inadequacy predicted GF at discharge were determined, correcting for other clinical factors associated with GF. RESULTS: In total, 156 eligible infants were identified. Seventy-six infants (49%) were discharged with weights <10%. Incidence of poor growth was highest during the transitional phase (46%) and was predictive of GF when adjusted for gestational age, birth weight, and severity of illness. Although energy intakes during the transitional phase were comparable to baseline parenteral provision, protein intakes progressively decreased ( P < .0001), consistently providing 3 g/kg/d as PN was weaned. Serum urea nitrogen also declined and was correlated with protein intake (r = -0.32, P < .001). CONCLUSION: Growth was compromised during the transitional phase, likely related to decreased protein intake. Optimizing protein provision while PN is weaned is an important strategy to prevent postnatal growth failure.

A review of enteral strategies in infant short bowel syndrome: evidence-based or NICU culture?

INTRODUCTION: Short bowel syndrome (SBS) is an increasingly common condition encountered across neonatal intensive care units. Improvements in parenteral nutrition (PN), neonatal intensive care and surgical techniques, in addition to an improved understanding of SBS pathophysiology, have contributed in equal parts to the survival of this fragile subset of infants. Prevention of intestinal failure associated liver disease (IFALD) and promotion of intestinal adaptation are primary goals of all involved in the care of these patients. While enteral nutritional and pharmacological strategies are necessary to achieve these goals, there remains great variability in the application of therapeutic strategies in units that are not necessarily evidence-based. MATERIALS AND METHODS: A search of major English language medical databases (SCOPUS, Index Medicus, Medline, and the Cochrane database) was conducted for the key words short bowel syndrome, medical management, nutritional management and intestinal adaptation. All pharmacological and nutritional agents encountered in the literature search were classified based on their effects on absorptive capacity, intestinal adaptation and bowel motility that are the three major strategies employed in the management of SBS. The Oxford Center for Evidence-Based Medicine (CEBM) classification for levels of evidence was used to develop grades of clinical recommendation for each variable studied. RESULTS: We reviewed various medications used and nutritional strategies included soluble fiber, enteral fat, glutamine, probiotics and sodium supplementation. Most interventions have scientific rationale but little evidence to support their role in the management of infant SBS. While some of these agents symptomatically improve diarrhea, they can adversely influence pancreatico-biliary function or actually impair intestinal adaptation. Surgical anatomy and liver function are two important variables that should determine the selection of pharmacological and nutritional interventions. DISCUSSION: There is a paucity of research investigating optimal clinical practice in infant SBS and the little evidence available is consistently of lower quality, resulting in a wide variation of clinical practices among NICUs. Prospective trials should be encouraged to bridge the evidence gap between research and clinical practice to promote further progress in the field.

Role of trace elements in parenteral nutrition support of the surgical neonate.

BACKGROUND: Parenteral nutrition (PN) has transformed the outcome for neonates with surgical problems in the intensive care unit. Trace element supplementation in PN is a standard practice in many neonatal intensive care units. However, many of these elements are contaminants in PN solutions, and contamination levels may, in themselves, be sufficient for normal metabolic needs. Additional supplementation may actually lead to toxicity in neonates whose requirements are small. METHODS: An electronic search of the MEDLINE, Cochrane Collaboration, and SCOPUS English language medical databases was performed for the key words "trace elements," "micro-nutrients," and "parenteral nutrition additives." Studies were categorized based on levels of evidence offered, with randomized controlled trials and meta-analyses accorded the greatest importance at the apex of the data pool and case reports and animal experiments the least importance. Articles were reviewed with the primary goal of developing uniform recommendations for trace element supplementation in the surgical neonate. The secondary goals were to review the physiologic role, metabolic demands, requirements, losses, deficiency syndromes, and toxicity symptoms associated with zinc, copper, chromium, selenium, manganese, and molybdenum supplementation in PN. RESULTS: Zinc supplementation must begin at initiation of PN. All other trace elements can be added to PN 2 to 4 weeks after initiation. Copper and manganese need to be withheld if the neonate develops PN-associated liver disease. The status of chromium supplementation is currently being actively debated, with contaminant levels in PN being sufficient in most cases to meet neonatal requirements. Selenium is an important component of antioxidant enzymes with a role in the pathogenesis of neonatal surgical conditions such as necrotizing enterocolitis and bronchopulmonary dysplasia. Premature infants are often selenium deficient, and early supplementation has shown a reduction in sepsis events in this age group. CONCLUSION: Appropriate supplementation of trace elements in surgical infants is important, and levels should be monitored. In certain settings, it may be more appropriate to individualize trace element supplementation based on the predetermined physiologic need rather than using bundled packages of trace elements as is the current norm. Balance studies of trace element requirements should be performed to better establish clinical recommendations for optimal trace element dosing in the neonatal surgical population.