Preterm Nutrition Hot Topic Consensus Statement (2023)

Reviewed by Sarvin Ghavam, MD

Preterm Nutrition Consensus, Hot Topic 2022
Date of Initial Publication: August 2022
Revision Date:
Contact Author: Sarvin Ghavam
Contributing Authors: Danielle Callaway, Lori Christ, Molly May, Lauren Slivka, Traci Fauerbach, Elizabeth Salazar, Meg Begany, Kristin Spaide, Maureen Dowling

Abstract

Preterm nutritional care is multifaceted, in this Hot Topic section the use of supplements including sodium chloride and probiotics were investigated. Probiotics is becoming more commonly used in the term or near-term population, given the latest AAP guidance, there is not sufficient evidence to make a strong recommendation for Probiotic use in preterm neonates. Evidence surrounding the use of probiotics is discussed along with sample formats of current probiotics use in US Neonatal units. Blood transfusions and feeds is a hotly debated topic in preterm nutrition, in this review there is not strong evidence to recommend withholding feeds during a blood transfusion of preterm neonate. The use of modular in order to help growth of the preterm neonate is discussed including dosing for Liquid protein and Medium Chain Triglycerides. Recommendations for Vitamin D and Ferrous Sulfate for discharge of premature neonates is given below.

Consensus Goals

Sodium Chloride requirements and dosing for preterm nutrition
Probiotic recommendations for preterm neonates
Discussion of blood transfusions and feeding for preterm neonates
Use of Modulars for growth in preterm neonates

Background

Sodium chloride is an essential component for preterm neonatal growth, and maternal milk and fortifiers may not provide enough sodium chloride to promote appropriate growth. Probiotics is become a hot national topic in neonatal care, dysbiosis is associated with many disease states including Necrotizing enterocolitis and late onset sepsis; a healthy intestinal biome can help in forming a protective mucosal barrier. In comparison to term infants, preterm infants are higher risk for dysbiosis with fewer probiotic microorganisms. The Cochrane meta-analysis shows weak support in favor of probiotics. Given the no FDA approved pharma and conflicting data at this time Probiotics is not recommended in the preterm neonate. Transfusion related NEC has been reported in observation studies but a causal pathway has yet to be determined versus presumed severe anemia causing intestinal injury. It continues to remain controversial whether continuing to feed during blood transfusions increases the likelihood of NEC. Given the current literature review there is not strong evidence to recommend holding pRBC transfusion during feeds of preterm neonates. Adding modular should be considered if faltering growth in a premature neonate and after multi-nutritional source has been adjusted. Modulars include MCT oil, cream, Liquigen and liquid protein.

Previous Consensus Statement or Data from Division of Neonatology (if applicable)

None

Literature Search

Title	Author	Level of Evidence	Primary Outcome & Results	Key Findings / Conclusions
Impact of Early Sodium Supplementation on Hyponatremia and Growth in Premature Infants: An RCT	Isemann et Al J Parenteral Enteral Nutrition 2014	I	Infants <32w and supplemented DOL 7-35 with Na 4 mEq/kg/d given when at 100 ml/kg/d feeds	Improved % infants maintaining BW at 6 wks and increased velocity of weight gain Significantly increased velocity of wt gain, and percentage increase in wt gain from birth to 6 wks in subgroup analysis of <28w
Effects of Salt Supplementation on Premature Infants on Neurodevelopment at 10- 13 years of age	Al-Dahhan et al Arch Dis Child Fetal Neonatal Ed 2002	II	Recalled infants from a prior study in the group that had received sodium supplementation (4mmol/kg/d if 31-34w and 5 mmol/kg/d if <31w) on DOL 4-14	NaCl supplementation resulted in improved scores on some developmental testing
Physiologic Approach to Sodium Supplementation in Preterm Infants	Segar et al American J of Perinatology 2018	II	Developed a urine sodium algorithm to guide supplementation starting at DOL 14 Infants 23w-29+6 compared to historical cohort	Urine sodium decreased with time and does not correlate with serum sodium Weight Z-score between 2-8 wks significantly improved with supplementation
Probiotics for the prevention of Necrotizing Enterocolitis in very preterm or very low birthweight infants	Cochrane Review 2020 Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W	I	Combined analyses showed that giving very preterm and very low birth weight infants probiotics may reduce the risk of necrotizing enterocolitis, and probably reduces the risk of death and serious infection. There is no evidence of an effect on disability or developmental outcomes. Few trials provided data for extremely preterm infants (born more than 12 weeks' early) and extremely low birth weight (less than 1.0 kg), and these analyses did not show effects on necrotising enterocolitis, death and serious infection.	The evidence for an effect on necrotizing enterocolitis is "low-certainty" because of concerns that the effect could have been biased by small trials with unreliable methods.
Blood transfusion alters the superior mesenteric artery blood flow velocity response to feeding in premature infants.	Krimmel GA et al. 2009	Level II - RCT	- Mean, peak systolic, and end diastolic Doppler mesenteric blood flow velocity 30 minutes before and after feedings at baseline (anemic) and with the first feeding posttransfusion. -22 infants -Anemic infants >1250g had increase in mean and peak systolic MBFV after feeding	- We speculate that the lack of response to feeding in the immediate posttransfusion state may contribute to the development of transfusionassociated necrotizing enterocolitis.
FEEding DURing red cell transfusion (FEEDUR RCT): a multi-arm randomised controlled trial	Schindler et al., 2020	Level II - RCT -Compared 1) Withhold feeds 12 h prior 2) Continue feeds 3) Restrict to 120 kcal/kg/day	- Mean splanchniccerebral oxygenation ratio (SCOR) and mean splanchnic fractional oxygen extraction (FOE) before (1 h prior), during (1 h into transfusion) and after (end of transfusion; 12 and 24 h post) transfusion. -60 transfusion episodes, 41 infant -There were no differences in mean SCOR and mean splanchnic FOE -3 groups with similar baseline characteristics -No differences in NEC among group	- There were no differences in splanchnic oxygenation when enteral feeds were either withheld,continued or restricted during a transfusion -Larger scale clinical trial needed for clinical outcomes
The WHEAT pilot trial— WithHolding Enteral feeds Around packed red cell Transfusion to prevent necrotising enterocolitis in preterm neonates: a multicentre, electronic patient record (EPR), randomised controlled point-ofcare pilot trial	Gale et al., 2019	Level II - RCT, Pilot trial	-Comparing continued feeds vs. holding feeds for 4 hrs prior during and 4 hrs afterwards - Primary feasibility outcomes: recruitment, opt-out, retention, compliance, data completeness and data accuracy -clinical outcomes: mortality and NEC. -Ongoing	-To be determined
Effect of withholding feeds on transfusion-related acute gut injury in preterm infants: a pilot randomized controlled trial.	Sahin et al., 2020	Level II - RCT pilot trial	-NEC rate -154 transfusion episodes (74 NPO, 80Fed) -Similar demographics -No significant difference in NEC rates -Statistically insignificant higher rates of feeding intolerance	-Does not support holding feedings, but is not adequately powered to suggest that NPO decreases NEC rates
Withholding feeds and transfusionassociated necrotizing enterocolitis in preterm infants: a systematic review.	Jasani et al., 2017	Level V - Meta synthesis of 7 non-RCT	-Transfusion associated NEC rates - n = 7492 - withholding feeds during PRBC transfusion significantly reduced the incidence of TANEC (RR: 0.47; 95% CI: 0.28, 0.80; P = 0.005; I 2 = 11%). -Moderate GRADE evidence	-Adequately powered RCTs needed
Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants	Patel et al., 2016	Level III - Observational Cohort Study	-NEC, Stage 2 -Mortality -600 infants enrolled -pRBC not significantly related to NEC in adjusted analyses -NEC rate was significantly increased among VLBW infants with severe anemia	-Severe anemia associated with NEC

Literature Summary

As per above, sodium supplementations helps promote growth in premature neonates and may help with long term neurodevelopment. With regards to probiotics, a large Cochrane Review noted “low-certainty” of evidence an effect on necrotizing enterocolitis given the concerns that the effect could have been biased by small trails with unreliable methods. The AAP recently published a statement not recommending probiotics in premature neonates. With regards to feeding during blood transfusions and incidence of necrotizing enterocolitis, there is not strong evidence to support NPO during blood transfusions at this time.

Delphi Survey Round Results (if applicable)

None

Disclaimer

Use of this site is subject to the Terms of Use.

The Neonatology Consensus Statements (“Statements”) are based on a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These Statements are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

Accordingly, these Statements are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among CHOP, its physicians and the individual patients in question. CHOP does not represent or warrant that the Statements are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. CHOP is not responsible for any errors or omissions in the Statements, or for any outcomes a patient might experience where a clinician consulted one or more such Statements in connection with providing care for that patient. If you use a printed version of a Statement, please ensure that you are using the most current version.