0061 Nutritional Support (2) (2)

Nutritional Support - Medical Clinical Policy Bulletins | Aetna Page 1 of 58

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Nutritional Support

Policy History

Last Review

03/19/2021

Effective: 10/20/1995

Next

Review: 01/13/2022

Review History

Definitions

Additional Information

Clinical Policy Bulletin

Notes

Number: 0061

(Replaces CPB 144)

Policy *Please see amendment for PennsylvaniaMedicaid at the end of this CPB.

Notes: I. For members with such a plan benefit, specific

nutritional support is considered to be a medical item

only when it is administered enterally (i.e., by feeding

tube) or parenterally (i.e., by intravenous

administration) where the member has either (a) a

permanent * non-function or disease of the structures that normally permit food to reach the small bowel; or

(b) disease of the small bowel that impairs digestion and

absorption of an oral diet, either of which requires

enteral or parenteral feedings to provide sufficient

nutrients to maintain weight and strength

commensurate with the member's overall health status.

Note: Not all benefit plans cover nutritional support

even in the circumstances stated above. Please check

benefit plan descriptions.

https://aetnet.aetna.com/mpa/cpb/1_99/0061.html

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II. Aetna does not cover nutritional support that is taken

orally (i.e., by mouth), unless mandated by state law.

Oral nutrition is not considered a medical item. See

section on Special Medical Foods below.

III. Regular food products are not considered medical

items. Regular food products include food thickeners,

baby food, gluten-free food products, high protein

powders and mixes, low carbohydrate diets, normal

grocery items, nutritional supplement puddings, weight-

loss foods and formula (products to aid weight loss), or

other regular grocery products that can be mixed in

blenders and used with an enteral system regardless of

whether these regular food products are taken orally or

parenterally.

Determinants of the route of administration of nutritional

support include the functional status of the gastrointestinal

tract and the anticipated duration of therapy.

I. Enteral Tube Feedings

Enteral nutrition is the provision of nutritional requirements

through a tube into the stomach or small intestine.

The short-term methods of enteral tube feedings include

nasogastric, nasoduodenal and, less frequently, nasojejunal

tubes. Long-term enteral feedings are best administered by a

percutaneous gastrostomy or jejunostomy tube.

Aetna considers enteral tube feedings medically

necessary when the member has either (a) permanent *

non-function or disease of the structures that normally

permit food to reach the small bowel; or (b) disease of

the small bowel that impairs digestion and absorption

of an oral diet, either of which requires tube feedings to

provide sufficient nutrients to maintain weight and




strength commensurate with the member's overall

health status.

The member's condition could be either an anatomic abnormality

(e.g., obstruction due to head and neck cancer or reconstructive

surgery, etc.) or a motility disorder (e.g., severe dysphagia

following a stroke, neuromuscular or disease of the central

nervous system that interferes with the ability to chew or

swallow, etc.). Enteral nutrition is not considered medically

necessary for members with a functioning gastrointestinal tract

whose need for enteral nutrition is due to reasons such as

anorexia or nausea associated with mood disorder, end-stage

disease, etc.

The member must require tube feedings to maintain weight and

strength commensurate with the member's overall health status.

Adequate nutrition must not be possible by dietary adjustment

and/or oral supplements. Enteral nutrition may be considered

medically necessary for members with partial impairments (e.g.,

a member with dysphagia who can swallow small amounts of

food or a member with Crohn's disease who requires prolonged

infusion of enteral nutrients to overcome a problem with

absorption).

Note: Enteral nutrition products that are administered

orally and related supplies are not covered.

* Note: The member must have a permanent

impairment. Permanence does not require a

determination that there is no possibility that the

member's condition may improve sometime in the

future. If the judgment of the doctor, substantiated in

the medical record, is that the impairment can

reasonably be expected to exceed 3 months (90 days),

the test of permanence is considered met. This is

consistent with Center for Medicare and Medicaid

Services (CMS) guidelines.




Formulas consisting of semi-synthetic intact proteins or protein

isolates (e.g., Enrich, Ensure, Ensure HN, Ensure Powder, Isocal,

Lonalac Powder, Meritene, Meritene Powder, Osmolite,

Osmolite HN, Portagen Powder, Renu, Sustacal, Sustagen

Powder, Travasorb) are considered medically necessary for

enteral feeding of the majority of older members who meet

criteria for enteral feeding. Formulas consisting of natural intact

proteins or protein isolates (e.g., Compleat B, Compleat B

Modified, Vitaneed) are considered medically necessary for

enteral feeding of members with an allergy or intolerance to semi-

synthetic formulas. Calorically dense formulas are also

considered medically necessary for enteral feedings if they are

indicated. The medical necessity for special formulas for enteral

feedings must be justified in each member.

Infant Formula

Note: Infant formulas are only covered if administered

via the tube-feeding route and the criteria for coverage

of enteral feedings are met. Infant formulas given orally

are not covered. In addition, breast milk additive to

prevent necrotizing enterocolitis in premature infants is

only covered if administered via the tube-feeding route

and the criteria for coverage of enteral feedings are

met.

Equipment

Appropriate nutrients, administration supplies, and equipment are

considered medically necessary for persons who meet criteria for

enteral feedings. Tube feedings are usually given by gravity

feedings or syringe. Pumps are considered medically necessary

durable medical equipment (DME) only where gravity feedings

or syringe feedings have caused complications or are otherwise

not indicated (e.g., gravity feeding is not satisfactory due to

reflux and/or aspiration, severe diarrhea, dumping syndrome,

administration rate less than 100 ml/hr, blood glucose

fluctuations, circulatory overload, gastrostomy/jejunostomy tube




used for feeding). More than 3 nasogastric tubes or 1

gastrostomy/jejunostomy tube every 3 months is rarely

considered medically necessary.

Note: Some Aetna plans exclude coverage of DME and

supplies. Please check benefit plan descriptions.

II. Relizorb

Aetna considers digestive enzyme cartridges (e.g. Relizorb,

Alcresta Pharmaceuticals) which connect to enteral feeding tubes

for hydrolysis (digestion) of fats in enteral formula, medically

necessary for persons with cystic fibrosis on enteral feedings.

III. Parenteral Nutrition/Total Parenteral Nutrition (TPN)

Parenteral nutrition involves the delivery of micronutrients and

macronutrients through catheters in central or peripheral veins.

In most instances, the central venous route is utilized; for long-

term total parenteral nutrition (TPN), a central catheter (e.g.,

Hickman, Broviac, PIC) is burrowed through a subcutaneous

tunnel on the anterior chest.

Generally, the parenteral approach is considered medically

necessary only if adequate nutritional intake is not possible via

the oral or tube-feeding route.

Aetna considers parenteral nutrition medically necessary for

members who meet any of the following criteria:

A. Documentation of a failure of enteral (i.e., oral or

tube feeding) nutrition, as defined by either of the

following:

1. A non-edematous or post-dialysis documented loss

of greater than 10 % of body weight over a 3-month

period; or

2. Total protein less than 6 g/dL or serum albumin




less than 3.4 g/dL;

B. A condition in which it is necessary for the

gastrointestinal tract to be totally non-functioning for a

period of time;

C. Evidence of structural or functional bowel disease that

makes oral and tube feedings inappropriate;

D. Hyperemesis gravidarum (only in cases of failed

medical management or when used in a step-therapy

program);

E. Member is peri-operative (regardless of disease

state) and unable to tolerate oral or tube feedings.

Parenteral nutrition may be either “self-mixed” (i.e., the member

or family caregiver is taught to prepare the nutrient solution

aseptically) or “pre-mixed”. The doctor must justify the need for

pre-mixed parenteral nutritional solutions.

Parenteral nutrition is not considered medically necessary for

members with a functioning gastrointestinal tract whose need for

parenteral nutrition is only due to:

A. A physical disorder impairing food intake such as the

dyspnea of severe pulmonary or cardiac disease;

B. A psychological disorder impairing food intake such as

depression;

C. A side effect of a medication;

D. A swallowing disorder;

E. A temporary defect in gastric emptying such as a

metabolic or electrolyte disorder;

F. Disorders inducing anorexia such as cancer;

G. Renal failure and/or dialysis. *

*Members receiving intra-dialytic parenteral nutrition

must meet the criteria for total parenteral nutrition set

forth above.




Aetna considers intra-peritoneal nutrition experimental

and investigational. Aetna considers intra-peritoneal

amino acid (IPAA) supplementation medically necessary

for members on peritoneal dialysis when all of the

following criteria are met:

A. Inability to administer or tolerate adequate oral

protein nutrition, including food supplements, or

enteral tube feeding; and

B. The combination of some oral or enteral intake that,

when combined with IPAA, will meet the individual's

nutritional goals; and

C. There is evidence of inadequate dietary protein

intake and protein malnutrition.

Equipment

If the criteria for parenteral nutrition are met, medically

necessary nutrients, administration supplies, and equipment are

considered medically necessary.

IV. Special Medical Foods Taken Orally

Note: Aetna covers special medical foods only when

mandated by state law.

Special medical foods are used for the treatment of inborn errors

of metabolism (histidinemia, homocystinuria, maple syrup urine

disease [MSUD], phenylketonuria [PKU], and tyrosinemia). The

special oral formulas are designed to restrict intake of one or

more amino acids. Some states now have mandates requiring

coverage of these dietary formulas.

Aetna does not cover banked breast milk, food

supplements, specialized infant formulas, vitamins

and/or minerals taken orally (i.e., by mouth).




Food supplements, specialized infant formulas (e.g., Alimentum,

Elecare, Neocate, and Nutramigen), lactose-free foods, vitamins

and/or minerals may be used to replace intolerable foods, for

lactose intolerance, to supplement a deficient diet, or to provide

alternative nutrition in the presence of such conditions as

allergies, gastrointestinal disorders, hypoglycemia, and obesity.

Food supplements, lactose-free foods, specialized infant

formulas, vitamins and/or minerals taken orally are not covered,

even if they are required to maintain weight or strength and

regardless of whether these are prescribed by a physician.

Most Aetna plans do not specifically include coverage of infant

formulas when taken orally. In the absence of a specific

inclusion or state mandate, specialized infant formulas are not

covered.

V. Enteral Nutrition/Enteral Feeding

Aetna considers enteral nutrition for induction and maintenance

of remission in adults with Crohn's disease experimental and

investigational because of insufficient evidence in the peer-

reviewed literature.

Aetna considers enteral nutrition for the treatment of eating

disorders (except in life-saving cases of severe cases of anorexia

nervosa) experimental and investigational because of insufficient

evidence in the peer-reviewed literature.

Aetna considers enteral lactoferrin supplementation for

prevention of sepsis and necrotizing enterocolitis in preterm

infants experimental and investigational because of insufficient

evidence in the peer-reviewed literature.

Background




Parenteral nutrition involves the delivery of micronutrients and

macronutrients through catheters in central or peripheral

veins. In most instances, the central venous route is utilized,

and for long-term total parenteral nutrition a central catheter

(e.g., Hickman, Broviac, PIC) is burrowed through a

subcutaneous tunnel on the anterior chest.

Enteral nutrition can be administered via a small catheter

placed through the nose into the stomach or by a surgically

placed catheter into the stomach or intestines. Enteral

nutrition therapy may supplement protein and calories in a

variety of situations where oral nutrition is not adequate, with

the intention of providing part or all of the daily requirements.

Specialized diets for specific diseases or pathophysiologic

situations may be administered via enteral nutrition. These

specialized diets may involve restricting a particular element of

the diet (e.g., fat, lactose), adding a particular nutrient that may

be required in larger amounts than are available from a regular

diet (e.g., calcium, potassium), or altering the consistency of

the diet (e.g., high-fiber, full-liquid).

The need for specialized foods is very common, and for most

conditions, the specialized food is needed for the person's

entire lifetime. For example, in Europe and the United States,

the prevalence of lactose intolerance is 7 to 20 % in

Caucasians, and is as high as 80 to 95 % among Native

Americans, 65 to 75 % among Africans and African

Americans, and 50 % in Hispanics (Scrimshaw et al, 1988).

The prevalence exceeds 90 % in some populations in eastern

Asia.

Another example of a common medical condition requiring a

specialized diet is celiac disease (also called gluten-sensitive

enteropathy and non-tropical sprue), with a prevalence of

almost 1 % of the population (Fasano et al, 2003). There are

many other examples where specialized diets are prescribed,

which could extend to specialized diets for hypertension,

diabetes, or cardiovascular disease.




Aetna's policy on parenteral and enteral nutrition is similar to

Medicare policy. Medicare provides reimbursement under the

part-B prosthetic-device benefit for parenteral and enteral

nutrition. Consistent with its policy of covering supplies

necessary for use of prosthetics, Medicare will generally cover

medically necessary supplies, equipment, and nutrients

associated with parenteral and enteral nutrition if the coverage

requirements for enteral or parenteral nutritional therapy are

met under the prosthetic device benefit provision.

Sullivan et al (2010) evaluated the health benefits of an

exclusively human milk-based diet compared with a diet of

both human milk and bovine milk-based products in extremely

premature infants. Infants fed their own mothers' milk were

randomized to 1 of 3 study groups. Groups HM100 and HM40

received pasteurized donor human milk-based human milk

fortifier (HMF) when the enteral intake was 100 and 40

ml/kg/day, respectively, and both groups received pasteurized

donor human milk if no mother's milk was available. Group

BOV received bovine milk-based HMF when the enteral intake

was 100 ml/kg/day and preterm formula if no mother's milk

was available. Outcomes included duration of parenteral

nutrition, morbidity, and growth. The 3 groups (total n = 207

infants) had similar baseline demographic variables, duration

of parenteral nutrition, rates of late-onset sepsis, and growth.

The groups receiving an exclusively human milk diet had

significantly lower rates of necrotizing enterocolitis (NEC; p =

0.02) and NEC requiring surgical intervention (p = 0.007). The

authors concluded that for extremely premature infants, an

exclusively human milk-based diet is associated with

significantly lower rates of NEC and surgical NEC when

compared with a mother's milk-based diet that also includes

bovine milk-based products.

Ganapathy et al (2012) evaluated the cost-effectiveness of a

100 % human milk-based diet composed of mother's milk

fortified with a donor human milk-based HMF versus mother's




milk fortified with bovine milk-based HMF to initiate enteral

nutrition among extremely premature infants in the neonatal

intensive care unit (NICU). A net expected costs calculator

was developed to compare the total NICU costs among

extremely premature infants who were fed either a bovine milk-

based HMF-fortified diet or a 100 % human milk-based diet,

based on the previously observed risks of overall NEC and

surgical NEC in a randomized controlled study that compared

outcomes of these 2 feeding strategies among 207 very low

birth-weight infants. The average NICU costs for an extremely

premature infant without NEC and the incremental costs due

to medical and surgical NEC were derived from a separate

analysis of hospital discharges in the state of California in

2007. The sensitivity of cost-effectiveness results to the risks

and costs of NEC and to prices of milk supplements was

studied. The adjusted incremental costs of medical NEC and

surgical NEC over and above the average costs incurred for

extremely premature infants without NEC, in 2011 US$, were

$74,004 (95 % confidence interval [CI]: $47,051 to $100,957)

and $198,040 (95 % CI: $159,261 to $236,819) per infant,

respectively. Extremely premature infants fed with 100 %

human-milk based products had lower expected NICU length

of stay and total expected costs of hospitalization, resulting in

net direct savings of 3.9 NICU days and $8,167.17 (95 % CI:

$4,405 to $11,930) per extremely premature infant (p <

0.0001). Costs savings from the donor HMF strategy were

sensitive to price and quantity of donor HMF, percentage

reduction in risk of overall NEC and surgical NEC achieved,

and incremental costs of surgical NEC. The authors

concluded that compared with feeding extremely premature

infants with mother's milk fortified with bovine milk-based

supplements, a 100 % human milk-based diet that includes

mother's milk fortified with donor human milk-based HMF may

result in potential net savings on medical care resources by

preventing NEC.

Relizorb




Fat malabsorption is most common in individuals who cannot

produce or secrete adequate amounts of digestive enzymes

because of compromised pancreatic function. According to

current United European Gastroenterology guidelines (Lohr, et

al., 2018), "enteral nutrition is indicated with PERT [pancreatic

enzyme replacement therapy] administered alongside where

necessary (GRADE 2C, strong agreement)" in persons with

pancreatic insufficiency who are unable to achieve adequate

intake with oral nutrition.

There is little evidence to support how PERT is best

administered and optimised in people with CF receiving

enteral nutrition (van der Haak & Kench, 2017). In the absence

of sufficient evidence, a number of techniques have been

described including oral administration, PERT suspended in

juice, PERT dissolved in bicarbonate and administered via an

enteral feeding tube, and administration of crushed

microspheres via an enteral feeding tube.

According to the manufacturer, Relizorb is considered a first of

it's kind enzyme cartridge. It is designed to mimic the action of

pancreatic lipase for use in adults receiving enteral tube

feedings (Medscape, 2015). Relizorb is an enzyme packed

cartridge indicated for use in adults to hydrolyze fats in entral

formula. The cartridge fits in line with enteral feeding systems,

and is connected between the infusion pump and the feeding

tube. The active ingredient is the digestive enzyme lipase,

attached to polymetric carriers together called iLipase. As the

formula passes through Relizorb, it makes contact with the

iLipase, and fats in the formula are modified to more

absorbable forms prior to ingestion. It was cleared for

marketing by the Food and Drug Administration (FDA) for this

indication. However, efficacy data are limited and Relizorb has

not been compared to other methods of administration of

PERT. Therefore, there is an insufficient evidence base to

support its use at this time.




Schwarzenberg and associates (2016) stated that nutrition is

integral to the care of individuals with cystic fibrosis (CF).

Better nutritional status is associated with improved pulmonary

function. In some individuals with CF, enteral tube feeding can

be useful in achieving optimal nutritional status. Current

nutrition guidelines do not include detailed recommendations

for enteral tube feeding. The Cystic Fibrosis Foundation

convened an expert panel to develop enteral tube feeding

recommendations based on a systematic review of the

evidence and expert opinion. These guidelines addressed

when to consider enteral tube feeding, assessment of

confounding causes of poor nutrition in CF, preparation of the

patient for placement of the enteral feeding tube, management

of the tube after placement and education about enteral

feeding. These recommendations are intended to guide the

CF care team, individuals with CF, and their families through

the enteral tube feeding process. The guideline stated that an

inline cartridge enzyme (lipase) delivery system for enteral

feeds was approved by the FDA for adults during the

development of these guidelines; evaluation of its benefits and

limits should be considered before use.

In a multi-center, randomized, double-blind, cross-over, open-

label clinical trial, Freedman and colleagues (2017) evaluated

the safety, tolerability, and fat absorption of a new in-line

digestive cartridge (Relizorb) that hydrolyzes fat in enteral

formula provided to patients with CF. Plasma omega-3 fatty

acid (FA) concentrations were measured and used as markers

of fat absorption. Gastro-intestinal symptoms were recorded

to evaluate safety and tolerability. Information regarding the

effect of enteral nutrition (EN) on appetite and breakfast

consumption was also collected. Before study entry,

participants had received EN for a mean of 6.6 years at a

mean volume of approximately 800ml, yet had a mean body

mass index (BMI) of only 17.5kg/m and omega-3 FA plasma

concentrations were only 60 % of levels found in normal

healthy subjects. Compared with placebo, cartridge use

resulted in a statistically significant 2.8-fold increase in plasma




omega-3 FA concentrations. There were no adverse

experiences associated with cartridge use, and a decrease in

the frequency and severity of most symptoms of malabsorption

was observed with cartridge use. Participants reported

increased preservation of appetite and breakfast consumption

with cartridge use compared with their pre-study regimen. The

authors concluded that the use of this in-line digestive

cartridge was safe and well-tolerated, and resulted in

significantly increased levels of plasma omega-3 FA used with

enteral formula, suggesting an overall increased fat

absorption.

The authors of this manufacturer-sponsored study stated that

the main drawback of this study was the small sample size (n

= 34). Despite the relatively small sample size, the study,

however, included approximately 1 % of the population of

patients with CF who receive EN. In addition, the age range of

the study population is representative of the population of

patients with CF in the United States. The authors stated that

these study results should be generalizable to the larger

population of patients with CF and exocrine pancreatic

insufficiency who receive supplemental EN. Only 1 feeding

through digestive cartridge was, however, used to measure its

effect on fat absorption, and only 7 days of digestive cartridge

use were used to measure its safety. They stated that a longer-

term study is currently ongoing to assess the effects of

sustained digestive cartridge use, particularly without

concomitant pancreatic enzyme replacement therapy.

Alkaade and Vareedayah (2017) stated that exocrine

pancreatic insufficiency (EPI) is characterized by a deficiency

of exocrine pancreatic enzymes, resulting in deficits in

digestion of all macronutrients, with deficiencies in digestion of

fats being the most clinically relevant. The leading cause of

EPI is chronic pancreatitis. However, many other causes and

conditions may be implicated, including CF, pancreatic duct

obstruction, gastric and pancreatic surgery, diabetes mellitus

and other conditions. Physical and biochemical causes of EPI




include decreased production and secretion of lipase,

increased lipase destruction, pancreatic duct obstruction,

decreased lipase stimulation and degradation, as well as

gastro-intestinal (GI) motility disorders. Exocrine pancreatic

insufficiency is largely diagnosed clinically, and is often

identified by symptoms such as steatorrhea, weight loss,

abdominal discomfort, and abdominal bloating. Lifestyle

modifications (e.g., smoking cessation, limiting or avoiding

alcoholic drinks, and reducing dietary fat intake) and

exogenous pancreatic enzyme supplements are commonly

used to help restore normal digestion and absorption of dietary

nutrients in patients with EPI. The authors noted that

approximately 44 % of patients with CF require oral

supplemental nutrition, and 11 % require enteral tube feeding.

Nutrient utilization may be improved using semi-elemental or

elemental enteral products or dosing pancreatic enzyme

replacement therapy (PERT) with enteral feedings.

Additionally, a recently approved in-line medical device with

immobilized lipase (Relizorb) has been developed to hydrolyze

fats in enteral formula.

Nguyen (2017) noted that EN is preferred over parenteral

nutrition (PN) as a result of the greater safety of EN therapy

and comparative convenience. A wide variety of EN products

have been developed, including disease-specific products to

help manage the nutritional needs of patients with kidney

failure, liver failure, lung disease, diabetes, and other

conditions. An assessment of each patient's nutritional needs

and digestive function should be conducted prior to initiation of

EN therapy. Other considerations in determining the

appropriate route and method of EN administration include the

time and nursing involvement required for administration,

potential complications of medication administration, and

concerns related to pancreatic dysfunction in certain groups.

The author noted that (i) a recently approved in-line medical

cartridge with immobilized lipase (Relizorb) hydrolyzes fats in

enteral formulas just prior to delivery into the patient with an

enteral feeding tube; and (ii) to eliminate the challenges of




PERT administration, the Cystic Fibrosis Foundation indicates

Relizorb may be used to deliver enteral formula in this

population.

Freedman (2017) stated that patients with EPI have

suboptimal secretion of pancreatic digestive enzymes and

experience a range of clinical symptoms related to the

malabsorption of fat. In patients with EPI unable to meet their

nutritional requirements, EN support is used to augment

nutritional status. In addition to protein and carbohydrate, EN

formulas contain fats as a calorie source, as well as vitamins

and minerals to help prevent nutritional deficiencies related to

malabsorption. Semi-elemental EN formulas are

advantageous as they contain hydrolyzed protein, shorter

chain carbohydrates, and may contain medium chain

triglycerides as a fat source. However, severely pancreatic

insufficient patients may be unable to absorb complex long-

chain triglycerides provided by EN formulas due to insufficient

pancreatic lipase; replacement pancreatic enzyme products

are recommended for these patients. The author stated that

currently, none of the FDA-approved PERT products are

indicated for use in patients receiving EN and administration of

enzymes by mixing into EN formula is not supported by

guidelines as this route is associated with risks. Relizorb

(immobilized lipase) is a novel in-line digestive cartridge that

has been designed to address the unmet need for PERT in

patients receiving EN. Relizorb efficacy and compatibility with

a range of commercially available polymeric and semi-

elemental formulas with varying nutrient, caloric content, and

triglyceride chain lengths have been demonstrated. In most

formulas, Relizorb efficiently hydrolyzed greater than 90 % of

fats within the formula into absorbable FAs and

monoglycerides.

Freedman and colleagues (2018) noted that PI and

malabsorption of fats lead to reduced caloric intake, inability to

maintain weight, and increased GI symptoms; thus, EN is used

in patients with CF and poor nutritional status. In an industry-




sponsored study, these researchers evaluated safety,

tolerability and improvement of FA status in red blood cell

(RBC) membranes, a marker of long-term FA absorption, with

an in-line digestive cartridge (Relizorb) that hydrolyzes fat in

enteral formula. Patients with CF receiving EN participated in

a multi-center, 90-day open-label study during which Relizorb

was used with overnight EN. The primary end-point was

change over time in RBC uptake of docosahexaenoic acid

(DHA) and eicosapentaenoic acid (EPA); GI symptoms were

collected to evaluate safety and tolerability. Several clinical

and anthropometric parameters were also assessed

throughout the study. A total of 36 subjects completed the

study with a mean age of 13.6 years, BMI of 17.7 and 6.2

years mean use of over-night EN. Fat absorption significantly

improved as shown by increased RBC levels of DHA+EPA,

improved ω-6/ω-3 ratio, and increased plasma levels of

DHA+EPA; Relizorb use was not associated with any

unanticipated adverse events (AEs). The authors concluded

that this study established the safety and tolerability of

Relizorb and showed its potential to normalize fat absorption,

improve symptoms commonly associated with fat mal-

absorption and enhance nutritional status in patients with CF

receiving EN feedings. They stated that this was the 1st

prospective study to show EN can improve FA abnormalities in

CF. Since improvement in omega-3 levels has been shown to

help pulmonary and inflammatory status as well as

anthropometric parameters in CF, Relizorb may have

important long-term therapeutic benefits in patients with CF.

Moreover, these investigators stated that it is not possible to

draw definitive conclusions from the current and previous

Relizorb studies regarding the influence of Relizorb use on

changes in patient anthropometric measurements.

The authors stated that this study had several drawbacks. It

was a relatively small study (n = 36). In addition, the study

was strictly open-label and was not intended to compare

outcomes between participants who did and did not use

Relizorb. Furthermore, other than enteral nutrition, dietary




intake was not recorded during the study, limiting the ability to

determine if oral caloric intake was adequate to lead to weight

gain. Additionally, the study may not have been long enough

to observe an increase in body weight or BMI for patients in a

relatively fat-starved condition. Furthermore, because the

current study did not measure body tissue composition, it is

unknown whether subjects improved their tissue composition

without changing body weight or size. It may turn out that

nutritional health may be more accurately measured using

biomarkers other than the traditional body weight and BMI.

Body tissue composition, including fat mass, fat-free mass,

and lean body mass may be more important to overall health

than body size or mass. It is likely that body tissue

composition is an indirect measure of important cellular and

molecular processes that may be directly measured using

molecules such as long-chain polyunsaturated FAs

(LCPUFAs), which are essential building blocks of cell

membranes and play important roles in cell and tissue function

throughout the body.

Formula versus Donor Breast Milk for Feeding Preterm or Low Birth Weight Infants

Quigley and colleagues (2018) noted that when sufficient

maternal breast milk is not available, alternative forms of EN

for preterm or low birth weight (LBW) infants are donor breast

milk or artificial formula. Donor breast milk may retain some of

the non-nutritive benefits of maternal breast milk for preterm or

LBW infants. However, feeding with artificial formula may

ensure more consistent delivery of greater amounts of

nutrients. Uncertainty exists about the balance of risks and

benefits of feeding formula versus donor breast milk for

preterm or LBW infants. In a Cochrane review, these

investigators determined the effect of feeding with formula

compared with donor breast milk on growth and development

in preterm or LBW infants. They used the Cochrane Neonatal

search strategy, including electronic searches of the Cochrane

Central Register of Controlled Trials (CENTRAL; 2017, Issue




6), Ovid Medline, Embase, and the Cumulative Index to

Nursing and Allied Health Literature (until June 8, 2017), as

well as conference proceedings and previous reviews.

Randomized or quasi-randomized controlled trials (RCTs)

comparing feeding with formula versus donor breast milk in

preterm or LBW infants were selected for analysis. Two

review authors assessed trial eligibility and risk of bias and

extracted data independently. They analyzed treatment

effects as described in the individual trials and reported risk

ratios (RRs) and risk differences (RDs) for dichotomous data,

and mean differences (MDs) for continuous data, with

respective 95 % CIs. These researchers used a fixed-effect

model in meta-analyses and explored potential causes of

heterogeneity in subgroup analyses. They assessed the

quality of evidence for the main comparison at the outcome

level using "Grading of Recommendations Assessment,

Development and Evaluation" (GRADE) methods. A total of

11 trials, in which 1,809 infants participated in total, fulfilled the

inclusion criteria; 4 trials compared standard term formula

versus donor breast milk; and 7 compared nutrient-enriched

preterm formula versus donor breast milk. Only the 4 most

recent trials used nutrient-fortified donor breast milk. The trials

contain various weaknesses in methodological quality,

specifically concerns about allocation concealment in 4 trials

and lack of blinding in most of the trials. Formula-fed infants

had higher in-hospital rates of weight gain (MD 2.51, 95 % CI:

1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95 % CI: 0.77

to 1.65 mm/week) and head growth (MD 0.85, 95 % CI: 0.47 to

1.23 mm/week). These researchers did not find evidence of

an effect on long-term growth or neurodevelopment. Formula

feeding increased the risk of necrotizing enterocolitis (typical

RR 1.87, 95 % CI: 1.23 to 2.85; RD 0.03, 95 % CI: 0.01 to

0.06). The GRADE quality of evidence was moderate for rates

of weight gain, linear growth, and head growth (down-graded

for high levels of heterogeneity) and was moderate for

neurodevelopmental disability, all-cause mortality, and

necrotizing enterocolitis (down-graded for imprecision). The

authors concluded that in preterm and LBW infants, feeding




with formula compared with donor breast milk, either as a

supplement to maternal expressed breast milk or as a sole

diet, resulted in higher rates of weight gain, linear growth, and

head growth and a higher risk of developing necrotizing

enterocolitis. The trial data did not show an effect on all-cause

mortality, or on long-term growth or neurodevelopment.

Enteral Nutrition for Induction / Maintenance of Remission in Crohn's Disease

Narula and associates (2018) noted that corticosteroids are

often preferred over EN as induction therapy for Crohn's

disease (CD). Prior meta-analyses suggested that

corticosteroids are superior to EN for induction of remission in

CD. Treatment failures in EN trials are often due to poor

compliance, with drop-outs frequently due to poor acceptance

of a naso-gastric (NG) tube and unpalatable formulations.

This systematic review was an update of a previously

published Cochrane review. These investigators evaluated

the safety and effectiveness of exclusive EN as primary

therapy to induce remission in CD and examined the

importance of formula composition on effectiveness. They

searched Medline, Embase and CENTRAL from inception to

July 5, 2017. They also searched references of retrieved

articles and conference abstracts; RCTs involving patients with

active CD were considered for inclusion. Studies comparing

one type of EN to another type of EN or conventional

corticosteroids were selected for review. Data were extracted

independently by at least 2 authors. The primary outcome

was clinical remission; secondary outcomes included adverse

events (AEs), serious adverse events (SAEs) and withdrawal

due to AEs. For dichotomous outcomes, these researchers

calculated the RR and 95 % CI. A random-effects model was

used to pool data. They performed intention-to-treat (ITT) and

per-protocol analyses for the primary outcome. Heterogeneity

was explored using the Chi-2 and I2 statistics. The studies

were separated into 2 comparisons: one EN formulation

compared to another EN formulation; and EN compared to




corticosteroids. Subgroup analyses were based on formula

composition and age. Sensitivity analyses included abstract

publications and poor quality studies. These investigators

used the Cochrane risk of bias tool to assess study quality.

They used the GRADE criteria to assess the overall quality of

the evidence supporting the primary outcome and selected

secondary outcomes. A total of 27 studies (1,011 participants)

were included; 3 studies were rated as low risk of bias; 7

studies were rated as high risk of bias, and 17 were rated as

unclear risk of bias due to insufficient information; 17 trials

compared different formulations of EN, 13 studies compared 1

or more elemental formulas to a non-elemental formula, 3

studies compared EN diets of similar protein composition but

different fat composition, and 1 study compared non-elemental

diets differing in glutamine enrichment. Meta-analysis of 11

trials (378 subjects) demonstrated no difference in remission

rates; 64 % (134/210) of patients in the elemental group

achieved remission compared to 62 % (105/168) of patients in

the non-elemental group (RR 1.02, 95 % CI: 0.88 to 1.18;

GRADE very low quality). A per-protocol analysis (346

participants) produced similar results (RR 1.04, 95 % CI: 0.91

to 1.18). Subgroup analyses performed to evaluate the

different types of elemental and non-elemental diets

(elemental, semi-elemental and polymeric) showed no

differences in remission rates. An analysis of 7 trials including

209 patients treated with EN formulas of differing fat content

(low fat: less than 20 g/1,000 kCal versus high fat: greater than

20 g/1,000 kCal) demonstrated no difference in remission

rates (RR 1.03; 95 % CI: 0.85 to 1.26). Very low fat content

(less than 3 g/1,000 kCal) and very low long chain triglycerides

demonstrated higher remission rates than higher content EN

formulas. There was no difference between elemental and non-

elemental diets in AEs rates (RR 1.00, 95 % CI: 0.63 to 1.60;

GRADE very low quality), or withdrawals due to AEs (RR 1.29,

95 % CI: 0.80 to 2.09; GRADE very low quality).

Common AEs included nausea, vomiting, diarrhea and

bloating. A total of 10 trials compared EN to steroid therapy.

Meta-analysis of 8 trials (223 participants) demonstrated no




difference in remission rates between EN and steroids; 50 %

(111/223) of patients in the EN group achieved remission

compared to 72 % (133/186) of patients in the steroid group

(RR 0.77, 95 % CI: 0.58 to 1.03; GRADE very low quality).

Subgroup analysis by age showed a difference in remission

rates for adults but not for children. In adults, 45 % (87/194) of

EN patients achieved remission compared to 73 % (116/158)

of steroid patients (RR 0.65, 95 % CI: 0.52 to 0.82; GRADE

very low quality). In children, 83 % (24/29) of EN patients

achieved remission compared to 61 % (17/28) of steroid

patients (RR 1.35, 95 % CI: 0.92 to 1.97; GRADE very low

quality). A per-protocol analysis produced similar results (RR

0.93, 95 % CI: 0.75 to 1.14). The per-protocol subgroup

analysis showed a difference in remission rates for both adults

(RR 0.82, 95 % CI: 0.70 to 0.95) and children (RR 1.43, 95 %

CI: 1.03 to 1.97). There was no difference in AEs rates (RR

1.39, 95 % CI: 0.62 to 3.11; GRADE very low quality).

However, patients on EN were more likely to withdraw due to

AEs than those on steroid therapy (RR 2.95, 95 % CI: 1.02 to

8.48; GRADE very low quality). Common AEs reported in the

EN group included heartburn, flatulence, diarrhea and

vomiting, and for steroid therapy acne, moon facies,

hyperglycemia, muscle weakness and hypoglycemia. The

most common reason for withdrawal was inability to tolerate

the EN diet.

The authors concluded that very low quality evidence

suggested that corticosteroid therapy may be more effective

than EN for induction of clinical remission in adults with active

CD. Very low quality evidence also suggested that EN may be

more effective than steroids for induction of remission in

children with active CD. Protein composition did not appear to

influence the effectiveness of EN for the treatment of active

CD. EN should be considered in pediatric CD patients or in

adult patients who can comply with NG tube feeding or

perceive the formulations to be palatable, or when steroid side

effects are not tolerated or better avoided. These researchers

stated that further research is needed to confirm the




superiority of corticosteroids over EN in adults; and further

research is needed to confirm the benefit of EN in children.

Furthermore, they stated that more effort from industry should

be taken to develop palatable polymeric formulations that can

be delivered without use of a NG tube as this may lead to

increased patient adherence with this therapy.

Akobeng and colleagues (2018) stated that prevention of

relapse is a major issue in the management of quiescent CD.

Current therapies (e.g., methotrexate, biologics,

6-mercaptopurine and azathioprine) may be effective for

maintaining remission in CD, but these drugs may cause

significant AEs. Interventions that are safe and effective for

maintenance of remission in CD are desirable. These

investigators evaluated the safety and efficacy of EN for the

maintenance of remission in CD and examined the impact of

formula composition on effectiveness. They searched

Medline, Embase, CENTRAL, the Cochrane IBD Group

Specialized Register and clinicaltrials.gov from inception to

July 27, 2018. They also searched references of retrieved

studies and reviews; RCTs including participants of any age

with quiescent CD were considered for inclusion. Studies that

compared EN with no intervention, placebo or any other

intervention were selected for review. Two authors

independently screened studies for inclusion, extracted data

and assessed methodologic al quality using the Cochrane risk

of bias tool. The primary outcome was clinical or endoscopic

relapse as defined by the primary studies. Secondary

outcomes included anthropometric measures (i.e., height and

weight), quality of life (QOL), AEs, serious AEs (SAEs) and

withdrawal due to AEs. These researchers calculated the RR

and 95 % CI for dichotomous outcomes. For continuous

outcomes, they calculated the MD and 95 % CI. A random-

effects model was used for the statistical analysis. These

researchers used the GRADE criteria to assess the overall

certainty of the evidence supporting the primary outcome and

selected secondary outcomes. A total of 4 RCTs (262 adult

participants) met the inclusion criteria; 1 study (n = 33)


http://clinicaltrials.gov



compared an elemental diet to a non-elemental (polymeric)

diet; 1 study (n = 51) compared a half elemental diet to a

regular free diet. Another study (n = 95) compared an

elemental diet to 6-mercaptopurine (6-MP) or a no treatment

control group; 1 study (n = 83) compared a polymeric diet to

mesalamine; 2 studies were rated as high risk of bias due to

lack of blinding or incomplete outcome data. The other 2

studies were judged to have an unclear risk of bias. The

studies were not pooled due to differences in control

interventions and the way outcomes were assessed. The

effect of an elemental diet compared to a polymeric diet on

remission rates or withdrawal due to AEs was uncertain; 58 %

(11/19) of participants in the elemental diet group relapsed at

12 months compared to 57 % (8/14) of participants in the

polymeric diet group (RR 1.01, 95 % CI: 0.56 to 1.84; very low

certainty evidence); 32 % (6/19) of participants in the

elemental diet group were intolerant to the enteral nutritional

formula because of taste or smell and were withdrawn from the

study in the first 2 weeks compared to zero participants (0/14)

in the polymeric diet group (RR 9.75, 95 % CI: 0.59 to 159.93;

low certainty evidence). Anthropometric measures, QOL, AEs

and SAEs were not reported as outcomes. The effect of an

elemental diet (half of total daily calorie requirements)

compared to a normal free diet on relapse rates was uncertain;

35 % (9/26) of participants in the elemental diet group

relapsed at 12 months compared to 64 % (16/25) of

participants in the free diet group (RR 0.54, 95 % CI: 0.30 to

0.99; very low certainty evidence). No AEs were reported.

This study reported no differences in weight change between

the 2 diet groups. Height and QOL were not reported as

outcomes. The effect of an elemental diet compared to 6-MP

on relapse rates or AEs was uncertain; 38 % (12/32) of

participants in the elemental diet group relapsed at 12 months

compared to 23 % (7/30) of participants in the 6-MP group (RR

1.61; 95 % CI: 0.73 to 3.53; very low certainty evidence); 3 %

(1/32) of participants in the elemental diet group had an AE

compared to 13 % (4/30) of participants in the 6-MP group (RR

0.23, 95 % CI: 0.03 to 1.98; low certainty evidence); AEs in the




elemental diet group included surgery due to worsening CD;

AEs in the 6-MP group included liver injury (n = 2), hair loss (n

= 1) and surgery due to an abscess (n = 1). No SAEs or

withdrawals due to AEs were reported. Weight, height and

QOL were not reported as outcomes. The effect of a

polymeric diet compared to mesalamine on relapse rates and

weight was uncertain; 42 % (18/43) of participants in the

polymeric diet group relapsed at 6 months compared to 55 %

(22/40) of participants in the mesalamine group (RR 0.76; 95

% CI: 0.49 to 1.19; low certainty evidence). The MD in weight

gain over the study period was 1.9 kg higher in the polymeric

diet group compared to mesalamine (95 % CI: -4.62 to 8.42;

low certainty evidence); 2 participants in the polymeric diet

group experienced nausea and 4 had diarrhea. It was unclear

if any participants in the mesalamine group had an AE.

Height, QOL, SAEs and withdrawal due to AEs were not

reported as outcomes.

The authors concluded that the findings of this review were

uncertain and no firm conclusions regarding the safety and

efficacy of EN in quiescent CD could be drawn. They stated

that more research is needed to determine the safety and

efficacy of using EN as maintenance therapy in CD. Currently,

there are 4 ongoing studies (estimated enrolment of 280

participants). This review will be updated when the results of

these studies are available.

Guidelines on clinical nutrition in inflammatory bowel disease

from the European Society for Parentaral and Enteral Nutrition

(Forbes, et al., 2017) state that "there is no 'IBD diet' that can

be generally recommended to promote remission in IBD

patients with active disease." The guidelines noted that, due to

strong concerns over corticosteroid use and aiming for optimal

growth in children, enteral nutrition is often first-line therapy for

pediatric patients with active Crohn's disease. The guidelines

noted that, although enteral nutrition as primary therapy in

adults with Crohn's disease has also repeatedly been

considered to be effective "the data are not robust." The




guidelines note that "meta-analyses do not support the use of

EN as primary treatment for acute exacerbations of CD in

adults. Patchy clinical conviction and the data, which appear

better than might be expected with placebo, ensure continuing

controversy over its role in adults."

Early Enteral Nutrition for Individuals Who Have Severe Head Injury

Yi and colleagues (2019) noted that the role of early enteral

nutrition (EEN) supplemented with probiotics (less than 48

hours) in improving clinical outcomes of patients with severe

head injury (SHI) remains controversial. In a meta-analysis,

these investigators examined the efficacy of EEN

supplemented with probiotics on clinical outcomes in these

patients. Systematic searches were performed in PubMed,

Cochrane Central Register of Controlled Trials, China National

Knowledge Infrastructure, Wanfang database, and Chinese

Biomedical Literature to identify potential studies; 2

investigators checked citations, extracted data, appraised risk

of bias, and then STATA 12.0 was used to perform statistical

analysis. A total of 18 trials were eventually included in the

present study. Meta-analysis indicated that EEN

supplemented with probiotics was associated with decreased

risk of infection (RR, 0.53; 95 % CI: 0.44 to 0.65), decreased

risk of mortality (RR, 0.56; 95 % CI: 0.38 to 0.82), decreased

risk of GI complications (RR, 0.19; 95 % CI: 0.13 to 0.25), and

shortened stays in ICU (MD, -4.55; 96 % CI: -5.91 to -3.19).

The authors concluded that EEN supplemented with probiotics

may be a promising alternative for patients with SHI because it

decreased the risk of infection, mortality, and GI complications,

as well as shortened the stays in ICU. These researches

stated that further large-scale and well-designed studies are

needed to establish this conclusion.



Enteral Nutrition in the Treatment of Eating Disorders


Hale and Logomarsino (2019) stated that EN is frequently

used in the treatment of anorexia nervosa (AN), and less

commonly, bulimia nervosa (BN); yet, no standardized

guidelines for treatment exist at this time. These investigators

examined the efficacy of EN in the treatment of eating

disorders and made recommendations for clinical practice and

future research. They carried out a literature search of 7

databases. The search strategy combined key terms anorexia

nervosa, bulimia, and eating disorders with terms associated

with EN. There were no restrictions on publication date or

language. Studies that assessed the effect of EN on weight

restoration, refeeding syndrome, and binge/purge behaviors in

the treatment of AN and BN were included. Of 73 full-text

articles reviewed, 22 met inclusion criteria; 19 studies reported

that significant short-term weight gain was achieved when EN

was used for re-feeding malnourished AN patients; however,

results varied for the 6 studies reporting on long-term weight

gain, maintenance, and recovery. In studies with a

comparator, no significant differences were found between the

EN and oral re-feeding cohorts regarding GI disturbance, re-

feeding syndrome, or electrolyte abnormalities; 5 studies

examined the effect of EN on binge/purge behaviors,

suggesting that temporary exclusive EN decreased the

frequency and severity of binge/purge episodes. The authors

concluded that although EN is an essential life-saving

treatment in severe cases of AN, it does not guarantee long-

term success or recovery. The results of this systematic

review highlighted the need for prospective controlled trials

with adequate sample sizes to make comparisons between

specific feeding methods, formulations, and defined short- and

long-term outcomes. These researchers stated that evidence-

based standards for clinical practice are needed with specific

guidelines for best results for AN and BN treatment. Level of

Evidence = I.



Early Enteral Nutrition Following Gastrointestinal Surgery


In a Cochrane review, Herbert and colleagues (2019)

examined if early commencement of post-operative enteral

nutrition (within 24 hours), oral intake and any kind of tube

feeding (gastric, duodenal or jejunal), compared with

traditional management (delayed nutritional supply) is

associated with a shorter length of hospital stay (LOS), fewer

complications, mortality and AEs in patients undergoing lower

gastro-intestinal (GI) surgery (distal to the ligament of Treitz).

These investigators searched the Cochrane Central Register

of Controlled Trials (CENTRAL, the Cochrane Library 2017,

issue 10), Ovid Medline (1950 to November 15, 2017), Ovid

Embase (1974 to November 15, 2017). They also searched

for ongoing trials in ClinicalTrials.gov and World Health

Organization International Clinical Trials Registry Platform

(November 15, 2017), and hand-searched reference lists of

identified studies and previous systematic reviews. These

researchers included RCTs comparing early commencement

of enteral nutrition (within 24 hours) with no feeding in adult

patients undergoing lower GI surgery. Two review authors

independently assessed study quality using the Cochrane

'Risk of bias' tool tailored to this review and extracted data.

Data analyses were conducted according to the Cochrane

recommendations. They rated the quality of evidence

according to GRADE. Primary outcomes were LOS and post-

operative complications (wound infections, intra-abdominal

abscesses, anastomotic dehiscence, pneumonia). Secondary

outcomes were: mortality, AEs (nausea, vomiting), and QOL;

LOS was estimated using MD (presented as mean +/- SD).

For other outcomes, these researchers estimated the common

RR and calculated the associated 95 % CIs. For analysis,

these investigators used an inverse-variance random-effects

model for the primary outcome (LOS) and Mantel-Haenszel

random-effects models for the secondary outcomes. They

also performed Trial Sequential Analyses (TSA). These

researchers identified 17 RCTs with 1,437 patients undergoing

lower GI surgery. Most studies were at high or unclear risk of


http://clinicaltrials.gov



bias in 2 or more domains; 6 studies were judged as having

low risk of selection bias for random sequence generation and

insufficient details were provided for judgement on allocation

concealment in all 17 studies. With regards to performance

and deception bias; 14 studies reported no attempt to blind

subjects and blinding of personnel was not discussed either.

Only 1 study was judged as low risk of bias for blinding of

outcome assessor. With regards to incomplete outcome data,

3 studies were judged to be at high risk because they had

more than 10 % difference in missing data between groups.

For selective reporting, 9 studies were judged as unclear as

protocols were not provided and 8 studies had issues with

either missing data or incomplete reporting of results. LOS

was reported in 16 studies (1,346 subjects). The mean LOS

ranged from 4 to 16 days in the early feeding groups and from

6.6 to 23.5 days in the control groups. Mean difference in LOS

was 1.95 (95 % CI: -2.99 to -0.91, p < 0.001) days shorter in

the early feeding group. However, there was substantial

heterogeneity between included studies (I2 = 81 %, Chi2 =

78.98, p < 0.00001), thus the overall quality of evidence for

LOS was low. These results were confirmed by the TSA

showing that the cumulative Z-curve crossed the trial

sequential monitoring boundary for benefit. These

investigators found no differences in the incidence of post-

operative complications: wound infection (12 studies, 1,181

subjects, RR 0.99, 95 % CI: 0.64 to 1.52, very low-quality

evidence), intra-abdominal abscesses (6 studies, 554

subjects, RR 1.00, 95 % CI: 0.26 to 3.80, low-quality

evidence), anastomotic leakage/dehiscence (13 studies, 1,232

subjects, RR 0.78, 95 % CI: 0.38 to 1.61, low-quality e vidence;

number needed to treat for an additional beneficial outcome

(NNTB) = 100), and pneumonia (10 studies, 954 subjects, RR

0.88, 95 % CI: 0.32 to 2.42, low-quality evidence; NNTB =

333). Mortality was reported in 12 studies (1,179 subjects),

and showed no between-group differences (RR = 0.56, 95 %

CI: 0.21 to 1.52, p = 0.26, I2 = 0 %, Chi2 = 3.08, p = 0.96, low-

quality evidence). The most commonly reported cause of

death was anastomotic leakage, sepsis and acute myocardial




infarction (MI); 7 studies (613 subjects) reported vomiting (RR

1.23, 95 % CI: 0.96 to 1.58, p = 0.10, I2 = 0 %, Chi2 = 4.98, p

= 0.55, low-quality evidence; number needed to treat for an

additional harmful outcome (NNTH) = 19), and 2 studies (118

subjects) reported nausea (RR 0.95, 0.71 to 1.26, low-quality

evidence); 4 studies reported combined nausea and vomiting

(RR 0.94, 95 % CI: 0.51 to 1.74, very low-quality evidence); 1

study reported QOL assessment; the scores did not differ

between groups at 30 days after discharge on either QOL

scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-

quality evidence). The authors concluded that the findings of

this review suggested that early enteral feeding may lead to a

reduced post-operative LOS, however cautious interpretation

must be taken due to substantial heterogeneity and low-quality

evidence. For all other outcomes (post-operative

complications, mortality, AEs, and QOL) the findings were

inconclusive, and further studies are needed to enhance the

understanding of early feeding for these. In this updated

review, only a few additional studies have been included, and

these were small and of poor quality. To improve the

evidence, future trials should address quality issues and focus

on clearly defining and measuring post-operative

complications to allow for better comparison between studies.

However due to the introduction of fast track protocols that

already include an early feeding component, future trials may

be challenging. A more feasible trial may be to examine the

effect of differing post-operative energy intake regimens on

relevant outcomes.

Braungart and Siminas (2020) noted that prolonged post-

operative fasting has been the traditional model of care

following pediatric GI surgery. In contrast, early feeding has

become well established in the adult population, where meta-

analyses have shown early introduction of enteral feeding to

be beneficial to hospital stay and patient outcomes. In a

systematic review, these researchers examined the safety and

effectiveness of early enteral feeding versus traditional enteral

feeding after GI anastomosis in children in the pediatric




literature. They carried out a comprehensive literature search

of the English literature (PubMed, Ovid, Embase data-bases)

from inception to present according to the PRISMA guidelines.

Included studies were evaluated according to the MINORS

criteria. Outcomes for time to 1st feed and full feeds, and

discharge, and risk of major complications were synthesized.

A total of 10 studies comprising 451 patients were included in

the analysis. All studies aimed at examining the safety of early

feeding in pediatric GI surgery, with or without a fast-track

program. Only 4 studies compared the study group to a

control group in which patients were fed in a traditional way

(traditional feeding). Most studies defined early feeding as

feeds commenced less than or equal to 24 hours post-

operatively (range of 2 to 72 hours). Mean time to 1st feed

was significantly lower in the early feeding group, but not

significantly lower for the mean time to full feeds and mean

hospital stay. Bowel obstruction and anastomotic breakdown

were classed as major complications. There was no

significant difference in their occurrence in both groups. The

authors concluded that although the studies identified were

few and heterogeneous, they showed that there was no clear

advantage of keeping children "nil by mouth" and no clear

disadvantage of providing early enteral nutrition following

elective GI surgery. Moreover, these researchers stated that

larger RCTs are needed to examine the true impact on post-

operative complications, healthcare-associated costs, and to

examine patient-reported outcome measures.

Enteral Lactoferrin Supplementation for Prevention of Sepsis and Necrotizing Enterocolitis in Preterm Infants

Pammi and Suresh (2020) stated that lactoferrin could

enhance host defenses and may be effective for prevention of

sepsis and necrotizing enterocolitis (NEC) in preterm

neonates. In a Cochrane review, these researchers examined

the safety and effectiveness of lactoferrin supplementation to

enteral feeds for prevention of sepsis and NEC in preterm

neonates. In addition, they evaluated the effects of lactoferrin




supplementation to enteral feeds on the duration of positive-

pressure ventilation, development of chronic lung disease

(CLD) or peri-ventricular leukomalacia (PVL), length of hospital

stay to discharge among survivors, and adverse neurological

outcomes at 2 years of age or later. These investigators used

the standard search strategy of Cochrane Neonatal to update

their search. They searched the Cochrane Central Register of

Controlled Trials (CENTRAL 2019, Issue 9), Medline via

PubMed (1966 to January 20, 2020), PREMEDLINE (1996 to

January 20, 2020), Embase (1980 to January 20, 2020), and

CINAHL (1982 to January 20, 2020). These researchers also

searched clinical trials data-bases, conference proceedings,

and the reference lists of retrieved articles for RCTs and quasi-

randomized trials. They included RCTs evaluating enteral

lactoferrin supplementation at any dose or duration to prevent

sepsis or NEC in preterm neonates; and used the standard

methods of Cochrane Neonatal and the GRADE approach to

examine the certainty of evidence. Meta-analysis of data from

12 RCTs showed that lactoferrin supplementation to enteral

feeds decreased late-onset sepsis (typical RR 0.82, 95 % CI:

0.74 to 0.91; typical RD -0.04, 95 % CI: -0.06, -0.02; NNTB 25,

95 % CI: 17 to 50; 12 studies, 5,425 participants, low-certainty

evidence) and decreased LOS (MD -2.38, 95 % CI: -4.67,

-0.09; 3 studies, 1,079 participants, low-certainty evidence).

Sensitivity analysis including only good methodological

certainty studies suggested a decrease in late-onset sepsis

with enteral lactoferrin supplementation (typical RR 0.87, 95 %

CI: 0.78 to 0.97; typical RD -0.03, 95 % CI: -0.05 to -0.0; 9

studies, 4,702 participants, low-certainty evidence). There

were no differences in NEC stage II or III (typical RR 1.10, 95

% CI: 0.86 to 1.41; typical RD -0.00, 95 % CI: -0.02 to 0.01; 7

studies, 4,874 participants; low-certainty evidence) or “all-

cause mortality” (typical RR 0.90, 95 % CI: 0.69 to 1.17; typical

RD -0.00, 95 % CI: -0.01 to 0.01; 11 studies, 5,510

participants; moderate-certainty evidence). One study

reported no differences in neurodevelopmental testing by

Mullen's or Bayley III at 24 months of age after enteral

lactoferrin supplementation (1 study, 292 participants, low-




certainty evidence). Lactoferrin supplementation to enteral

feeds with probiotics decreased late-onset sepsis (RR 0.25, 95

% CI: 0.14 to 0.46; RD -0.13, 95 % CI: -0.18 to -0.08; NNTB 8,

95 % CI: 6 to 13; 3 studies, 564 participants; low-certainty

evidence) and NEC stage II or III (RR 0.04, 95 % CI: 0.00 to

0.62; RD -0.05, 95 % CI: -0.08 to -0.03; NNTB 20, 95 % CI:

12.5 to 33.3; 1 study, 496 participants; very low-certainty

evidence), but not “all-cause mortality” (very low-certainty

evidence). Lactoferrin supplementation to enteral feeds with

or without probiotics had no effect on CLD, duration of

mechanical ventilation or threshold retinopathy of prematurity

(low-certainty evidence). Investigators reported no adverse

effects in the included studies. The authors found low-

certainty evidence from studies of good methodological quality

that lactoferrin supplementation of enteral feeds decreased

late-onset sepsis but not NEC of greater than or equal to stage

II or “all-cause mortality” or neurodevelopmental outcomes at

24 months of age in preterm infants without adverse effects.

Low-to-very low certainty evidence suggested that lactoferrin

supplementation of enteral feeds in combination with

probiotics decreased late-onset sepsis and NEC of greater

than or equal to stage II in preterm infants without adverse

effects, however, there were few included studies of poor

methodological quality. These researchers stated that the

presence of publication bias and small studies of poor

methodology that may inflate the effect size made

recommendations for clinical practice difficult.

In a RCT, Pehlevan and colleagues (2020) examined the

effect of Lactobacillus and Bifidobacterium together with

oligosaccharides and lactoferrin on the development of NEC or

sepsis in very low birth weight neonates. Neonates with a

gestational age of less than or equal to 32 weeks and birth

weight of less than or equal to 1,500 g were enrolled. The

study group received a combination of synbiotics and

lactoferrin, whereas the control group received 1 ml of distilled

water as placebo starting with the 1st feed until discharge.

The outcome measures were the incidence of NEC stage of




greater than or equal to 2 or late-onset culture-proven sepsis

and NEC stage of greater than or equal to 2 or death. Mean

birth weight and gestational age of the study (n = 104) and the

control (n = 104) groups were 1,197 ± 235 g versus 1,151 ±

269 g and 29 ± 1.9 versus 28 ± 2.2 weeks, respectively (p >

0.05). Neither the incidence of NEC stage greater than or

equal to 2 or death, nor the incidence of NEC stage greater

than or equal to 2 or late-onset culture-proven sepsis differed

between the study and control groups (5.8 % versus 5.9 %, p

= 1; 26 % versus 21.2 %, p = 0.51). The only significant

difference was the incidence of all stages of NEC (1.9 %

versus 10.6 %, p = 0.019). The authors concluded that the

combination of synbiotics and lactoferrin did not reduce NEC

severity, sepsis, or mortality.

Home Enteral Nutrition After Esophagectomy for Esophageal Cancer

Liu and colleagues (2020) stated that not only has the

placement rate of enteral feeding tubes during operations for

esophageal cancer increased, but also has number of patients

who choose to continue enteral feeding at home instead of

removing the feeding tube at discharge. In a systematic

review, these researchers examined the impacts of home

enteral nutrition (HEN) after esophagectomy in esophageal

cancer patients. This systematic review was carried out in

accordance with PRISMA and Cochrane guidelines. English

and Chinese data-bases, including PubMed, Embase, Web of

Science, the Cochrane Library, Scopus, CBM, CNKI, and Wan

Fang were searched from inception to December 7, 2019;

RCTs evaluating the short-term outcomes of HEN following

esophagectomy in cancer patients were included. The risk of

bias of the included studies was appraised according to the

Cochrane risk of bias tool. The summary of relative risk (RR) /

weighted mean difference (WMD) estimates and

corresponding 95 % CI were calculated using fixed- and

random-effects models. A total of 9 RCTs involving 757

patients were included in the meta-analysis. Compared with




oral diet, HEN was associated with significantly increased

body weight (WMD 3 kg, 95 % CI: 2.36 to 3.63, p < 0.001),

BMI (WMD 0.97 kg/m, 95 % CI: 0.74 to 1.21, p < 0.001),

albumin (WMD 3.43 g/L, 95 % CI: 2.35 to 4.52, p < 0.001),

hemoglobin (WMD 7.23 g/L, 95 % CI: 5.87 to 8.59, p < 0.001),

and total protein (WMD 5.13 g/L, 95 % CI: 3.7 to 6.56, p <

0.001). No significant differences were observed in pre-

albumin and GI adverse reactions. Physical (WMD 8.82, 95 %

CI: 6.69 to 10.95, p < 0.001) and role function (WMD 12.23, 95

% CI: 2.72 to 21.74, p = 0.01) were also significantly better in

the HEN group. The nausea/vomiting (WMD -5.43, 95 % CI:

-8.29 to -2.57, p = 0.002) and fatigue symptoms (WMD -11.76,

95 % CI: -16.21 to -7.32, p < 0.001) were significantly

reduced. Appetite loss (WMD -8.48, 95 % CI: -14.27 to -4.88,

p = 0.001), diarrhea (WMD -3.9, 95 % CI: -7.37 to -0.43, p =

0.03) , and sleep disturbance (WMD -7.64, 95 % CI: -12.79 to

-2.5, p = 0.004) in the HEN group were also significantly less

than the control group. The authors concluded that HEN

improved nutrition status, physical and role function, and

reduced nausea/vomiting, fatigue, appetite loss, diarrhea, and

sleep disturbance compared with an oral diet in esophageal

cancer patients post-surgery; and HEN did not increase

adverse reactions.

The authors stated that a major drawback of this study was

that HEN after an esophagectomy for cancer is mainly used in

China; thus, the current evidence is mainly based on studies

performed in Chinese populations, so it is unclear how

applicable these findings are to other regions. These

researchers stated that multi-center studies with better

methodological quality are needed to examine the effects of

long-term HEN and provide more data and evidence to

reinforce these findings.

CPT Codes / HCPCS Codes / ICD-10 Codes


4/12/2021https://aetnet.aetna.com/mpa/cpb/1_99/0061.html

Code Code Description

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

CPT codes covered if selection criteria are met:

99507 Home visit for care and maintenance of

catheter(s) (e.g., urinary, drainage, and enteral)

99601 Home infusion/specialty drug administration,

per visit (up to 2 hours)

+ 99602 each additional hour (List separately in

addition to code for primary procedure)

Other CPT codes related to the CPB:

36555 -

36571

Insertion of central venous catheter

43246 Upper gastrointestinal endoscopy including

esophagus, stomach, and either the duodenum

and/or jejunum as appropriate; with directed

placement of percutaneous gastrostomy tube

43510 Gastrotomy; with esophageal dilation and

insertion of permanent intraluminal tube (e.g.,

Celestin or Mousseaux-Barbin)

43653 Laparoscopy, surgical; gastrostomy, without

construction of gastric tube (e.g., Stamm

procedure) (separate procedure)

43752 Naso- or oro-gastric tube placement, requiring

physician's skill and fluoroscopic guidance

(includes fluoroscopy, image documentation

and report)

43762 -

43763

Replacement of gastrostomy tube,

percutaneous, includes removal, when

performed, without imaging or endoscopic

guidance






43761 Repositioning of the gastric feeding tube,

through the duodenum for enteric nutrition

43810 -

43832

Gastroduodenostomy, gastrojejunostomy;

without vagotomy, with vagotomy, any type,

gastrostomy, open; without construction of

gastric tube (e.g., Stamm procedure) (separate

procedure), neonatal, for feeding, or with

construction of gastric tube (e.g., Janeway

procedure)

+ 44015 Tube or needle catheter jejunostomy for enteral

alimentation, intraoperative, any method (List

separately in addition to primary procedure)

44372 Small intestinal endoscopy, enteroscopy

beyond second portion of duodenum, not

including ileum; with placement of

percutaneous jejunostomy tube

44373 with conversion of percutaneous gastrostomy

tube to percutaneous jejunostomy tube

44500 Introduction of long gastrointestinal tube (e.g.,

Miller-Abbott) (separate procedure)

49440 Insertion of gastrostomy tube, percutaneous,

under fluoroscopic guidance including contrast

injection(s), image documentation and report

49441 Insertion of duodenostomy or jejunostomy tube,

percutaneous, under fluoroscopic guidance

including contrast injection(s), image

documentation and report

49446 Conversion of gastrostomy tube to gastro-

jejunostomy tube, percutaneous, under

fluoroscopic guidance including contrast






49450 Replacement of gastrostomy or cecostomy (or

other colonic) tube, percutaneous, under

fluoroscopic guidance including contrast


49451 Replacement of duodenostomy or jejunostomy

tube, percutaneous, under fluoroscopic

guidance including contrast injection(s), image


49452 Replacement of gastro-jejunostomy tube,

percutaneous, under fluoroscopic guidance

including contrast injection(s), image


74340 Introduction of long gastrointestinal tube (eg,

Miller-Abbott), including multiple fluoroscopies

and images, radiological supervision and

interpretation

HCPCS codes covered if selection criteria are met:

Enteral lactoferrin supplementation – no specific code:

B4034 -

B4083,

B4102 -

B9999

Enteral and Parenteral Therapy (except food

thickener)

B4087 Gastrostomy/jejunostomy tube, standard, any

material, any type, each

B4088 Gastrostomy/jejunostomy tube, low-profile, any

material, any type, each

B4102 Enteral formula, for adults, used to replace

fluids and electrolytes (e.g., clear liquids), 500

ml= 1 unit





B4103 Enteral formula, for pediatrics, used to replace

fluids and electrolytes (e.g., clear liquids), 500

ml = 1 unit

B4104 Additive for enteral formula (e.g., fiber)

B4105 In-line cartridge containing digestive enzyme(s)

for enteral feeding, each

B4149 Enteral formula, manufactured blenderized

natural foods with intact nutrients, includes

proteins, fats, carbohydrates, vitamins and

minerals, may include fiber, administered

through an enteral feeding tube, 100 calories =

1 unit

S5497 Home infusion therapy, catheter care/

maintenance, not otherwise classified; includes

administrative services, professional pharmacy

services, care coordination, and all necessary

supplies and equipment (drugs and nursing

visits coded separately), per diem


maintenance, simple (single lumen), includes



supplies and equipment (drugs and nursing



maintenance, complex (more than one lumen),

includes administrative services, professional

pharmacy services, care coordination, and all

necessary supplies and equipment (drugs and

nursing visits coded separately), per diem






maintenance, implanted access device,

includes administrative services, professional


necessary supplies and equipment (drugs and

nursing visits coded separately), per diem (use

this code for interim maintenance of vascular

access not currently in use)

S5517 Home infusion therapy, all supplies necessary

for restoration of catheter patency or declotting

S5518 Home infusion therapy, all supplies necessary

for catheter repair

S5520 Home infusion therapy, all supplies (including

catheter) necessary for a peripherally inserted

central venous catheter (PICC) line insertion

S5521 Home infusion therapy, all supplies (including

catheter) necessary for a midline catheter

insertion

S5522 Home infusion therapy, insertion of peripherally

inserted central venous catheter (PICC),

nursing services only (no supplies or catheter

included)

S5523 Home infusion therapy, insertion of midline

central catheter, nursing services only (no

supplies or catheter included)

S9342 Home therapy; enteral nutrition via pump;



supplies and equipment (enteral formula and






S9343 Home therapy; enteral nutrition via bolus;



supplies and equipment (enteral formula and


S9364 Home infusion therapy, total parenteral nutrition

(TPN); administrative services, professional


necessary supplies and equipment including

standard TPN formula (lipids, specialty amino

acid formulas, drugs other than in standard

formula and nursing visits coded separately),

per diem


(TPN); 1 liter per day, administrative services,

professional pharmacy services, care

coordination, and all necessary supplies and

equipment including standard TPN formula

(lipids, specialty amino acid formulas, drugs

other than in standard formula and nursing



(TPN); more than 1 liter but no more than 2

liters per day, administrative services,












(TPN); more than 2 liters but no more than 3

liters per day, administrative services,








(TPN); more than 3 liters per day,



supplies and equipment including standard

TPN formula (lipids, specialty amino acid

formulas, drugs other than in standard formula

and nursing visits coded separately), per diem

HCPCS codes not covered for indications listed in the CPB:

A9152 Single vitamin/mineral/trace element, oral, per

dose, not otherwise specified

A9153 Multiple vitamins, with or without minerals and

trace elements, oral, per dose, not otherwise

specified

B4100 Food thickener, administered orally, per oz

Other HCPCS codes related to the CPB:

S9123 Nursing care, in the home; by registered nurse,

per hour (use for general nursing care only, not

to be used when CPT codes 99500-99600 can

be used)

S9124 Nursing care, in the home; by licensed practical

nurse, per hour





S9433 Medical food nutritionally complete,

administered orally, providing 100% of

nutritional intake

S9434 Modified solid food supplements for inborn

errors of metabolism

S9435 Medical foods for inborn errors of metabolism

S9810 Home therapy; professional pharmacy services

for provision of infusion, specialty drug

administration, and / or disease state

management, not otherwise classified, per hour

(do not use this code with any per diem code)

ICD-10 codes covered if selection criteria are met (not all inclusive):

C00.0 -

C21.8

Malignant neoplasm of lip, oral cavity, pharynx,

esophagus, stomach, small intestine, colon,

rectosigmoid junction, rectum, anus and anal

canal

C76.0 Malignant neoplasm of head, face and neck

E40, E41,

E42, E43

Kwashiorkor, nutritional marasmus, marasmic

kwashiokor and unspecified severe protein-

calorie malnutrition

E44.0 -

E44.1

Protein-calorie malnutrition of moderate and

mild degree

E45 Retarded development following protein-calorie

malnutrition

E46 Unspecified protein-calorie malnutrition

E84.0 -

E84.9

Cystic fibrosis




I69.091

I69.191

I69.291

I69.391

I69.891

I69.991

Sequelae of cerebrovascular disease

[dysphagia]

K22.4 Dyskinesia of esophagus

O21.0 Mild hyperemesis gravidarum

O21.1 Hyperemesis gravidarum with metabolic

disturbance

O21.2 Late vomiting of pregnancy

O21.8 Other vomiting complicating pregnancy

O21.9 Vomiting of pregnancy, unspecified

R13.0 -

R13.19

Aphagia and dysphagia

Z93.1 Gastrostomy status

Z93.4 Other artificial openings of gastrointestinal tract

status

ICD-10 codes not covered for indications listed in the CPB:

A40.0 -

A40.9

Streptococcal sepsis [prevention of sepsis]

A41.9 Sepsis, unspecified organism [prevention of

sepsis]

F01.50 -

F80.2

F80.4 -

F84.0

F84.3 -

F99

Mental and behavioral disorders






K50.00 -

K50.919

Crohn's disease

K55.30 Necrotizing enterocolitis, unspecified

[prevention of necrotizing enterocolitis]

K55.31 Stage 1 necrotizing enterocolitis [prevention of

necrotizing enterocolitis]





N17.0 -

N19

Acute kidney failure and chronic kidney disease

Z99.2 Dependence on renal dialysis

Enteral lactoferrin supplementation:

HCPCS codes covered if selection criteria are met:

Enteral lactoferrin supplementation - no specific code:

ICD-10 codes not covered for indications listed in the CPB:

A40.0 -

A40.9

Streptococcal sepsis [prevention of sepsis]

A41.9 Sepsis, unspecified organism [prevention of

sepsis]

K55.30 Necrotizing enterocolitis, unspecified

[prevention of necrotizing enterocolitis]











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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan

benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial,

general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care

services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors

in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely

responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is

subject to change.

Copyright © 2001-2021 Aetna Inc.

https://aetnet.aetna.com/mpa/cpb/1_99/0061.html 4/12/2021


AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical Policy Bulletin Number: 0061 Nutritional

Support

Special medical foods are used for the treatment of inborn errors of metabolism (histidinemia, homocystinuria, maple syrup urine disease [MSUD], phenylketonuria [PKU], and tyrosinemia). The special oral formulas are designed to restrict intake of one or more amino acids. These are covered under the Pennsylvania Medical assistance plan.

Breast milk additive to prevent necrotizing enterocolitis in premature infants is covered under the Pennsylvania Medical assistance plan if administered via the tube‐feeding route or by mouth. Human donor breast milk is covered for the Pennsylvania Medical assistance plan. The following benefit information does not apply to Medicaid. Regular food products are not considered medical items. Regular food products include food thickeners, baby food, gluten‐free food products, high protein powders and mixes, low carbohydrate diets, normal grocery items, nutritional supplement puddings, weight‐loss foods and formula (products to aid weight loss), or other regular grocery products that can be mixed in blenders and used with an enteral system regardless of whether these regular food products are taken orally or parenterally.

The Pennsylvania Medical Assistance Program covers most medically necessary services. Please contact Aetna Better Health Member Service at 1‐866‐638‐1232 to determine the member’s benefit plan.

revised 03/19/2021

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