consensus report on nutrition for pediatric.4

8/12/2019 Consensus Report on Nutrition for Pediatric.4

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Consensus Report on Nutrition for Pediatric Patients With

Cystic Fibrosis

*Drucy Borowitz, *Robert D. Baker, and Virginia Stallings

*Childrens Hospital of Buffalo, Buffalo, New York, U.S.A.; Childrens Hospital of Philadelphia For the Consensus Committee,

Philadelphia, Pennsylvania, U.S.A.

2001 CONSENSUS COMMITTEE MEMBERS

Laura K. Bachrach, M.D.Robert J. Beall, Ph.D.Preston W. Campbell, III, M.D.Susan C. Casey, B.S., R.D.

Mitchell B. Cohen, M.D.Mary Corey, Ph.D.W. Hobart Davies, Ph.D.Judy A. Fulton, R.D.Richard J. Grand, M.D.John E. Grunow, M.D.Dana S. Hardin, M.D.Lesles Hendeles, Pharm.D.James E. Heubi, M.D.Van S. Hubbard, M.D.Hui-Chuan Kai, Ph.D.Sheila Innis, Ph.D.Elisabeth Luder, Ph.D., R.D.

Karen MacGuiness, R.D.Richard K. Mathis, M.D.Annie McKenna, M.S., R.D., C.N.S.Antoinette Moran, M.D.Laurie Moyer-Mileur, Ph.D., R.D.Kimberly O. OBrien, Ph.D.Hebe Quinton, M.S.Lynne M. Quittell, M.D.Ross W. Shepherd, M.D., FRACPRonald J. Sokol, M.D.Lori J. Stark, Ph.D.John N. Udall, Jr., M.D., Ph.D.Babette Zemel, Ph.D.

INTRODUCTION

Patients with cystic fibrosis should have normalgrowth. Growth requires appropriate energy and nutrientintake, but gastrointestinal and pulmonary function andgenetic potential are also important. Poor clinical out-

comes are associated with undernutrition in patients withCF (16). The Cystic Fibrosis Foundation recognizesthat attention to nutrition is an integral part of CF care. InMarch 2001 a Consensus Committee, co-sponsored bythe Cystic Fibrosis Foundation and the North AmericanSociety for Pediatric Gastroenterology, Hepatology andNutrition, met to review the literature and update a Con-sensus Conference Statement published in 1992 address-ing these issues (7).

The CF care team should monitor growth, provideanticipatory counseling, and plan intervention strategieswhen patients are at risk for undernutrition or are diag-nosed with nutritional failure. A registered dietitian mustbe a part of the team to provide the discipline-specific

expertise needed for optimal nutritional management andmay, along with other team members such as the physi-cian, nurse, social worker or a psychologist, provide ex-pertise concerning developmental and behavioral aspectsof eating. Prevention and early intervention are most suc-cessful in combating nutritional failure. This documentoutlines the current recommendations of the ConsensusCommittee on how best to monitor growth and nutrition,strategies to prevent undernutrition, and interventions forpatients with nutritional failure. It is based on the limitedevidence available in the literature and also representsexpert opinion. As with all such documents, these rec-ommendations are likely to change as new data becomesavailable.

MONITORING GROWTH, BODY

COMPOSITION, PUBERTAL AND

BONE STATUS

Early detection of suboptimal growth allows for ap-propriate intervention and timely rehabilitation. Present

Address correspondence and requests for reprints to Robert D.Baker, MD, PhD, Digestive Disease and Nutrition Center, ChildrensHospital of Buffalo, 219 Bryant St., Buffalo, NY 14222, U.S.A.(e-mail: [email protected]).

The Consensus Conference was co-sponsored by the Cystic FibrosisFoundation and by the North American Society for Pediatric Gastro-enterology, Hepatology and Nutrition.

Journal of Pediatric Gastroenterology and Nutrition35:246259 September 2002 Lippincott Williams & Wilkins, Inc., Philadelphia

246 DOI: 10.1097/01.MPG.0000025580.85615.14


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Cystic Fibrosis Foundation (CFF) guidelines suggest thatpatients be seen on a routine basis, every 3 months (8).Growth and nutritional status should be monitored atthese intervals (Table 1).

There are three specific times when special attentionshould be focused on growth and nutritional status withinthe scope of usual clinical care. These are: (1) the first 12months after the diagnosis of CF for each patient; (2)birth to 12 months of age for infants diagnosed prenatallyor at birth, until a normal pattern of growth (head cir-cumference, weight, and length) is clearly established;and (3) the peripubertal growth period (girls about 9 to16, and boys about 12 to 18 years of age). By establish-ing a pattern of normal growth and development after thediagnosis of CF, patients enter mid-childhood and pu-bertal growth well nourished, and are more likely to con-tinue this pattern of normal growth.

Surveillance of Growth and Body Composition

Accurate, sequential measurement, plotting and inter-pretation of head circumference, weight, length, andheight are essential to the care of children with CF. Stan-dard anthropometric measurement techniques are welldescribed in the literature (911). Mid-arm circumfer-ence and triceps skinfold thickness measurements pro-vide clinical information about lean body mass (muscleand organ) development and subcutaneous fat (energy)stores, respectively. Each center should select and main-tain anthropometric instruments, establish a detailedmeasurement protocol, and train those responsible for

obtaining anthropometric measurements. Each clinicshould also have standard protocols for cleaning the in-struments between patient assessments to protect againstthe spread of infectious agents.

Clinical Evaluation of Measures of Growth and

Body Composition

Evaluation of Growth Measurements

Weight and length (measured supine) or height (mea-sured standing), as well as head circumference in infants,should be monitored and analyzed as growth parameters.In 2000, new NCHS/CDC growth charts were distributedfor plotting weight, head circumference, length, andheight (CDC web site, http://www.cdc.gov/growthchartsto download charts). The percentiles for all growth mea-sures are expanded, compared to the 1977 charts, withtwo new percentile curves (97th and 3rd) for more pre-cise evaluation at the extremes of the growth distribution.

In addition, charts are provided for body mass index(BMI(weight in kg)/(height in meters)2) with percen-tiles for boys and girls, age 2 to 20 years. Referencevalues are available for tracking head circumference inchildren beyond 36 months of age (12).

The 2000 edition growth charts should be used for allCF clinical care, and have been used in calculation of theCFF Patient Registry data beginning with the 1999 an-nual report. For optimal care, it is suggested that patientsless than 24 months of age have all previously collectedgrowth data (weight, length, head circumference) com-

TABLE 1. Nutritional assessment in routine CF center care

Atdiagnosis

Every 3 months birthto 24 months

Everythree mont hs Annually

Head circumference xa xWeight (to 0.1 kg) x x xLength (to 0.1 cm) x xHeight (to 0.1 cm) x xMid-arm circumference (to 0.1 cm) x xTriceps skinfold (to 1.0 mm) xb xMid-arm muscle area, mm2 (calcula ted from MAC and TSF) xb xMid-arm fat area, mm2 (calculated from MAC and TSF) xb xBiological parents heightc xPubertal status, female xd

Pubertal status, male xe

24 hour diet recall xNutritional supplement intakef xAnticipatory dietary and feeding behavior guidance x xg x

a If less than 24 months of age at diagnosis;b Only in patients over one year of age;c Record in cm and gender-specific height percentile; note patients target height percentile on all growth charts;d Starting at age 9 years, annual pubertal self-assessment form (patients, or parent and patient) (Reference 25) or physician examination for breast

and pubic hair Tanner stage determination; annual question as to menarchal status. Record month and year of menarche on all growth charts;e Starting at age 10 years, annual pubertal self-assessment form (patients, or parent and patient) (Reference 25) or physician examination for genital

development and pubic hair Tanner stage determination;fA review of enzymes, vitamins, minerals, oral or enteral formulas, herbal, botanical and other CAM products;g Routine surveillance may be done informally by other team members, but the annual assessment and q 3 monthly visits in the first two years of

life and q3 monthly visits for patients at nutritional risk should be done by the Center Dietician.

NUTRITION AND CYSTIC FIBROSIS 247

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pletely transferred to a 2000 edition growth chart. Forpatients older than 24 months, it is suggested that previ-ously collected growth data be transferred to the 2000growth charts for each six-month interval. Based uponclinical judgment of the pattern of growth and relatedclinical events (i.e., prolonged illness, use of a feedingtube, lung transplantation), more extensive growth datashould be transferred to the 2000 edition growth chart.

One strong indicator of global nutritional sufficiencyis if patients are growing in height to their full geneticpotential (13). The genetic potential for height of eachpatient can be estimated by a variety of methods (1416).This should be determined for each patient and the targetheight range (genetic potential related to biologic paren-tal height) should be noted on the growth chart. Catch-uplinear growth may take up to four years in children withCF diagnosed in infancy (17). A steady increase in per-centile height towards the target height range indicatesadequate nutritional status.

Evaluation of Weight for Height Proportion

Assessment of the weight for height proportion for anindividual patient is of clinical importance. The 1992CFF Consensus Report (7) contained some inconsisten-cies in how to use the recommended weight-for-heightindex. In practice, some CF Centers adopted the Mooremodification (18) while others used the originalMcLaren and Read method (19). To standardize the ap-proach to assessing relative proportion of weight forheight, the committee now recommends that the termpercent ideal body weight (abbreviated as %IBW)and the modification of Moore et al. be used. This rec-

ommendation will be followed in subsequent discussions(Fig. 1). Users of software that calculates %IBW mustknow what method the program employs, since not allprograms use the Moore method. Although somewhatcumbersome to calculate, %IBW remains a very sensi-tive index of body weight allowing for gender, age, andheight. Weight-for-height percentile from NCHS/CDC

growth charts is less valuable because the age of the childis ignored.

BMI is an estimate of adiposity, which should remainrelatively constant throughout adulthood. However, BMIis not constant across the pediatric age range; therefore,BMI percentiles available on the 2000 CDC growthcharts, rather than BMI, should be used to evaluate thepediatric patient. Guidelines for classifying underweightby BMI have been reported in the general population foradults but have not been validated in children with CF(20,21). Although the cut-off values for BMI percentilesthat relate to health status are not yet well established,low BMI has been shown to be associated with increasedmortality (22). Since children are growing in weight andstature, the Consensus Committee recommends that BMIpercentile should be used for clinical evaluation. Just aswith percentile height and weight charts, an individualBMI percentile value reflects genetic as well as healthfactors. Plotted sequential values indicate problems whenthe pattern varies from a consistent percentile. For now,it is suggested that both %IBW and BMI percentile becalculated and used for clinical care decisions. BMI per-centiles are not available for children under age 2 years,so weight-for-length percentile should be used.

Evaluation of %IBW, BMI percentiles, and weight-for-length percentiles permits the identification of pa-tients at risk for nutritional failure (Table 2). However,not all patients in the at risk category will have nutri-tional insufficiency. Use of percentiles, by definition,only describes the distribution of growth in a population.Expertise will need to be used to determine who requirescloser evaluation and follow-up to prevent nutritionalfailure. Patients who meet the definition of nutritionalfailure, as outlined in Table 2, should be evaluated andtreated (see below).

Evaluation of Body Composition Measurements

The two body composition measurements, mid-armcircumference and triceps skinfold thickness, are trans-lated to age- and gender-specific percentiles using refer-ence data from Frisancho (23). Two additional values arecalculated from the mid-arm circumference and tricepsmeasurements, and provide more accurate assessmentsof muscle and fat stores. These are the mid-arm musclearea (mm2) and mid-arm fat area (mm2) with age andgender reference data also provided by Frisancho (23).

Clinical Evaluation of Pubertal Development

Pubertal development is often delayed in patients withCF. This delay is usually related to growth failure andpoor nutritional status, rather than to a rare primary en-docrine disorder. Progressing through pubertal develop-ment is an important component of physical growth aswell as psychosocial health of the child and family. InFIG. 1. Calculation of percent ideal body weight (% IBW).

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function must be lost before symptoms of PI are apparent(35). PI leads to malabsorption of dietary fat, protein, andother nutrients. Pancreatic functional status is a strongpredictor of long-term outcome (36) and has a directinfluence on nutritional status; therefore, knowing thepancreatic phenotype is useful not only in nutritionalmanagement but as a prognosticator. Specific CFTR mu-tations are associated with pancreatic sufficiency in adominant fashion (see Table 3). Possessing an allelefrom this group offers protection even in combinationwith an allele normally associated with PI (37).

When the diagnosis of CF has been established, PI isoften inferred by clinical signs and symptoms such as:frequent, malodorous, greasy stools, the presence of me-conium ileus, or distal intestinal obstruction syndrome.Tests to document PI include: (1) duodenal intubationwith stimulation; (2) 72-hour fecal fat balance study; (3)immunoreactive trypsinogen after 8 years of age; and (4)other markers as they become more widely available,such as fecal elastase-1 and fecal chymotrypsin determi-nations (38). Indirect tests to infer PI include low serumfat-soluble vitamins and/or low serum beta-carotene (af-ter the introduction of fruits and vegetables). It is impor-tant to assess the pancreatic function of patients as soonas the diagnosis of CF is made. Steatorrhea may be theresult of other conditions. When PI is present, enzyme,and vitamin therapy (Table 4) as well as proactive nu-tritional management should be started.

Some patients whose tests initially indicate that theyare pancreatic sufficient (PS) become PI. PS patientsshould be reevaluated annually for the conversion to PI,especially if genetic testing reveals two mutations thatare generally associated with PI. This evaluation canconsist of monitoring growth, nutrition, and stool pat-tern; one or more of the tests listed above for assessingpancreatic function may be needed for more objectiveevidence.

Recommendation for Pancreatic Enzyme

Replacement Therapy

Pancreatic enzyme replacement therapy is initiatedonce PI has been identified. Enzymes are given with allfoods and milk products including predigested formulasand breast milk. Medium chain triglycerides (MCT) re-

quire less lipase activity than long-chain fats for efficientabsorption, although lipase is still needed (39). Micro-sphere or microtablet preparations are preferable to pow-ders because the acid-resistant enteric coating preventsacid-inactivation of the enzymes, and are not associatedwith mouth and/or perianal excoriation. Decreased pan-creatic bicarbonate secretion combined with gastric acidmay cause the duodenum and proximal jejunum to re-main acidic, preventing dissolution of the protectivecoating until the capsules have bypassed a significantamount of intestinal absorptive surface. This can betreated by the administration of a histamine-2 receptorblocker or a proton pump inhibitor (40,41). Enzymeswork best when taken before each meal and snack. Forprolonged meal events, such as at a buffet or party, theenzymes may be more effective if distributed throughoutthe meal. Parents and adolescent should learn to adjustenzyme dosage according to the anticipated amount offat in the meal or snack based on guidance from their CFteam. Schools and caretakers should be aware of the needfor enzymes with all meals and snacks.

Generic enzymes are not bio-equivalent to proprietaryenzymes (42). Therefore it is recommended that onlyproprietary enzymes be prescribed and that the prescrip-tion be marked no substitution, or an equivalent state-ment.

The adequacy of enzyme therapy can be assessed sub-jectively by following growth parameters and stool pat-terns. At present the best objective test available is a72-hour fecal fat collection with calculation of a coeffi-cient of fat absorption. Infants taking MCT-enriched for-mulas or patients receiving MCT-containing enteral for-mulas must have stool analyzed for fat using the Jeejeeb-hoy method (43) to avoid false negative results. A varietyof newer methods are being developed to determine theadequacy of enzyme therapy, but are not yet available forclinical use (44). This is an important research area.Tests such as fecal elastase-1 and stool chymotrypsin aremeasures of pancreatic function but do not establish theadequacy of enzyme replacement.

A more complete discussion of pancreatic enzyme re-placement therapy can be found in the report of the Con-sensus Conference on Enzyme Therapy and FibrosingColonopathy (45). To avoid fibrosing colonopathy, it isrecommended that enzyme doses should be less than2500 lipase units/kg per meal or less than 4000 lipaseunits/gram fat per day (46).

Developmental Approach to Nutritional

Anticipatory Guidance

Infants (First Year of Life)

Breast-feeding is recommended for most infants as theprimary source of nutrition for the first year of life. Pro-prietary formulas can also be used. Intolerance to cows

TABLE 3. Pancreatic function and mutations

Pancreatic-sufficientdominant CF mutations

Variable pancreatic-sufficientCF mutations

G551S G85EP574H R347PR117H 3849 + 10kb C TR334W A455ER347H 2789 5G AR352QT3381




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milk, either from allergy or lactose intolerance, is nomore common in patients with CF than in the general

population. Often, a caloric density greater than the stan-dard 20 kcal/ounce may be needed and can be achievedby fortifying breast milk, by concentrating formula, or bythe addition of fat and/or carbohydrate. Breast or formulafeeding should continue for the first 12 months of life.Thereafter, whole milk can be used in the thriving child.Solid foods should be added at 4 to 6 months develop-mental age according to the recommendations of theAmerican Academy of Pediatrics. Infant cereal should beprepared with formula or breast milk, not water or juice.

Sources of fluoride and iron should be identifiedwithin the first year, in addition to the vitamin supple-mentation recommended for children with CF (Table 4).Supplemental fluoride and iron need to be given if the

dietary intake is inadequate (47,48). Hyponatremic alka-losis may occur in the breast or formula fed infant withCF. Supplementation with sodium chloride, especiallyduring the summer is necessary (see below).

For infants who are taking solids but not achievingtheir expected rate of growth, additional calories can beadded to infant cereal with the addition of carbohydratepolymers (e.g., Polycose, Ross Laboratories Division,Abbott Labs, Columbus, OH)) and/or fats such as veg-etable oil, Microlipid, (Mead Johnson, Evansville, IN)or MCT oil. As infants are introduced to table foods, it isimportant that families understand the concept that chil-dren with CF should eat a balanced diet that is moderateto high in fat and protein. Parents and caregivers should

be aware that this advice is counter to the usual nutri-tional advice for children without CF.

Toddlers to Preschool Age (14 Years)

At this age, dietary intake and degree of physical ac-tivity vary from day to day. Routinely adding calories totable foods may help with maintaining growth at this

stage. The family should buy whole milk for the childwith CF and lower fat milk for other family membersover two years of age. Parents should avoid giving theirchildren with CF low fat or low calorie foods. During thesecond year of life children establish self-feeding skills,food preferences, and dietary habits. Mealtime is a socialevent as well as a nutritional one. Dietitians caring forpatients with CF should inquire about feeding behaviorsto promote positive interactions and to prevent negativebehaviors before they become entrenched. Grazing be-havior should be discouraged.

School Age (510 Years)

This is a high-risk period for decreased rate of growthin children with CF (49,50). Participation in activitiesleading to limited time for snacks and enzyme adherence,taste fatigue, and progression of disease may be respon-sible for this decrease in growth rate. Behavioral inter-ventions should be considered in this age group if prob-

lematic mealtime behaviors are identified. School-agechildren must have a basic knowledge of physiology andpractical aspects of enzyme therapy.

Adolescence (1118 Years)

This stage is associated with high nutrient require-ments due to accelerated growth, pubertal development,and high levels of physical activity. CF adolescent de-velopment and behavior reflect the general population.Pulmonary infections are more common in this period,also increasing nutritional needs. Females are at greaterrisk for nutritional failure (51). This is an age when con-founding factors, such as CF-related diabetes or liver

disease, may complicate nutrition management. Growthfailure and pubertal delays may occur and come at a timeof social pressure and psychosocial stress. Nutritionalcounseling will be more effective if directed toward thepatient as well as toward the parent. Teenagers may bemore receptive to efforts to improve muscular strengthand body image as a justification for better nutrition thanstressing weight gain and improved disease status.

Recommendations for Energy Intake and

Specific Nutrients

Energy Intake

Optimal dietary intake is an essential component ofnutritional care of the patient with CF especially in thepresence of pancreatic insufficiency. Patients with CFoften require a greater fat intake (35 to 40% of calories)than that recommended for the general population(30%). Energy intake should be evaluated based on thepattern of weight gain and of fat stores. There is noperfect method to estimate the caloric needs of an indi-

TABLE 4. Recommendations for vitamin supplementationIn addition to a standard, age appropriate dose of

non-fat-soluble multivitamins, the following should be given:

Individual vitamin daily supplementation

Vitamin A(IU)

Vitamin E(IU)

Vitamin D(IU)

Vitamin K(mg)

012 months 1500 4050 400 0.30.5*13 years 5000 80150 400800 0.30.5*48 years 5,00010,0000 100200 400800 0.30.5*>8 years 10,000 200400 400800 0.30.5*

* Currently, commercially available products do not have ideal dosesfor supplementation. In a recent review, no adverse effects have beenreported at any dosage level of Vitamin K (Reference 110). Cliniciansshould try to follow these recommendations as closely as possible untilbetter dosage forms are available. Prothrombin time or, ideally,PIVKA-II levels should be checked in patients with liver disease, andvitamin K dose titrated as indicated.




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vidual with CF. The desired clinical outcome is a steadyrate of weight gain in growing children.

Fat-Soluble Vitamins and Beta Carotene

Fat malabsorption can lead to the loss of vitamins that

are aggregated with fat. Patients with CF who are ad-equately treated with pancreatic enzymes continue tomalabsorb fat-soluble vitamins. Bile acids also are nec-essary for absorption of fat and fat-soluble vitamins; pa-tients with CF have malabsorption of bile acids as well aspancreatic dysfunction (52). Patients with CF who haveliver disease or interruption of the enterohepatic bile acidcirculation thus are at even higher risk for fat-solublevitamin malabsorption. There is ample evidence that pa-tients with CF become depleted of fatty substances (5357). Recommendations for surveillance and replacementof these substances are given in Tables 5 and 4.

Beta-CaroteneBeta-carotene is a precursor of vita-min A and may also function as an antioxidant. It is

uncertain whether a beta-carotene deficiency state existsin patients with CF or not. A number of studies havedocumented low serum levels of beta-carotene in pa-tients with CF that, with oral supplementation, can becorrected (53,58,59). One randomized study showed adecreased number of days on antibiotics for patients tak-ing beta-carotene, suggesting that it may play a physi-ologic role (59). Further evidence for a clinical defi-ciency state is lacking.

Vitamin AVitamin A is important for vision, epithe-lial cell integrity, epithelial proliferation, and immunity.Pancreatic lipase is required to digest retinyl esters be-fore absorption. In cross-sectional studies between 15and 40% of CF patients have been found to be vitamin A

deficient (54,60,61). In one study, 18% of adult CF pa-tients were found to have deficits in dark field adaptation(62). The combination of these studies suggests that Vi-tamin A deficiency in CF is common. Vitamin A is anegative acute phase reactant, so levels measured duringacute illnesses may yield misleadingly low results (63).Thus, surveillance levels should not be drawn at the timeof admission to the hospital for illness.

Vitamin DVitamin D functions to increase calciumabsorption. Vitamin D nutriture takes on added impor-tance because of the prevalence of osteoporosis and bonefractures among patients with CF (64). Ten to forty per-cent of patients with CF have been demonstrated to bedeficient in vitamin D (55). Older children and adults andthose residing in northern latitudes are more likely tohave inadequate 25-hydroxy vitamin D levels, because oflimited exposure to sunlight.

Vitamin E Vitamin E (alpha tocopherol) is an anti-oxidant. Deficiency states lead to hemolytic anemia, neu-romuscular degeneration, as well as retinal and cognitive

deficits. Vitamin E has been reported to be low in pa-tients with CF, even in those taking pancreatic enzymesand multivitamins, and symptomatic deficiency stateshave been reported (65,66). Five to ten percent of CFpatients continue to have low serum vitamin E levelsdespite supplementation (56).

Vitamin K (Phylloquinone, Menaquinone)VitaminK functions in the biosynthesis of clotting factors andwith osteocalcin as well as in GLA protein hydroxyl-ation. Since measurement of serum vitamin K levels isnot practical, plasma prothrombin concentration (PT) hasbeen used as a surrogate. Although it is not widely avail-able, PIVKA-II (Proteins Induced by Vitamin K Absenceor Antagonism) is a more sensitive measure of vitamin K

TABLE 5. Laboratory monitoring of nutritional status

How often to monitor

At diagnosis Annually Other Tests

Beta carotene At physicians discretion Serum levelsVitamin A x* x Vitamin A (retinol)Vitamin D x* x 25-OH-DVitamin E x* x -tocopherolVitamin K x* If patient has hemoptysis or hematemesis;

in patients with liver diseasePIVKA-II (preferably) or prothromin time

Essential fatty acids Consider checking in infants or those withFTT

Triene:tetraene

Calcium/bone status >age 8 years if risk factors are present (seetext)

Calcium, Phosphorus, Ionized PTH, DEXAscan

Iron x x Consider in-depth evaluation for patientswith poor appetite

Hemoglobin, hematocrit

Zinc Consider 6 month supplementation trial andfollow growth

No acceptable measurement

Sodium Consider checking if exposed to heat stressand becomes dehydrated

Serum sodium; spot urine sodium if totalbody sodium depletion suspected

Protein stores x x Check in patients with nutritional failure orthose at risk

albumin

* Patients diagnosed by neonatal screening do not need these measured.




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adequacy. Insufficiency of vitamin K leads to the forma-tion of under -carboxylated vitamin K-dependent clot-ting factors. PIVKA-II will detect changes of a fewng/ml while PT detects changes of 100 g/ml. Someauthors suggested that vitamin K deficiency was uncom-mon, while others, using the more sensitive PIVKA-II,found it to be very common, even if enzymes and mul-tivitamins are given (55,57,66,67). Colonic bacteria are asource of vitamin K. Disruption of the enteric flora byantibiotic use can reduce vitamin K levels. In a study ofadults with CF who were taking oral antibiotics, vitaminK at doses of 5mg four times a week was not sufficientto correct PIVKA-II levels. This study suggests that pre-vious recommendations for vitamin K replacement dur-ing antibiotic therapy may be inadequate (66).

Essential Fatty Acids and DHA

Biochemical essential fatty acid deficiency (EFAD) is

common in patients with CF, and can occasionally beseen in PS patients as well as in those who are PI (6871). However, clinical signs and symptoms are rare, al-though EFAD should be considered in young infantswith failure to thrive. The triene:tetraene ratio falls inpatients with EFAD. Essential fatty acids are polyunsatu-rated fats that can be metabolized to linoleic (n-6 series)and alpha-linolenic acid (n-3 series). Linoleic acid is fur-ther metabolized to arachidonic acid (AA), and alpha-linoleinic acid is metabolized to docosohexaenoic acid(DHA). DHA downregulates AA incorporation intophospholipid membranes. Failure of DHA to limit AAincorporation may be a factor in the increased AA seenin bronchoalveolar lavage fluid in patients with CF.

There has been speculation that abnormal fatty acid me-tabolism is a primary problem in CF (i.e., is not second-ary to fat malabsorption) (72). Whether DHA supple-mentation is warranted in patients with CF is the subjectof careful research; no recommendations can be made atthe present time. Vegetable oils such as flax, canola andsoy, and cold-water marine fish are rich in linolenic acid,are a good source of energy and can be recommended.Human breast milk contains DHA and should be encour-aged for infants.

Minerals and Electrolytes

CalciumRecently, dietary calcium recommendationsfor the general population have been revised upward(33). There has also been an increased awareness of thehigh prevalence of osteopenia, osteoporosis, and an in-creased fracture risk in children and adults with CF. Sev-eral studies have indicated that calcium insufficiency andlow bone mass are major issues of concern even in thepediatric CF population (28,7375). To maximize skel-etal accretion of calcium in children and adolescents,

intake should, at a minimum, achieve levels specified bythe 1997 IOM recommendations.

IronIron deficiency is an issue of concern for childrenwith CF (7678). Ferritin is frequently used as an indexof iron status. However, ferritin is an acute phase reac-tant and may be artificially elevated in patients with CFdue to concurrent inflammation. Serum transferrin recep-tors are a more sensitive indicator of iron deficiencybecause they are not affected by inflammation, but atpresent, this test is not available commercially (79). Untilbetter tests are available, it is recommended that ironstatus be monitored yearly in children and adolescentswith CF by checking hemoglobin and hematocrit.

ZincRecent stable isotope studies have reported in-creased endogenous fecal zinc losses and decreased zincabsorption in children and infants with CF (80,81). Zincdeficiency in CF is difficult to characterize because zincdeficiency may be present when plasma zinc is in thenormal range. Empiric zinc supplementation as a treat-ment trial for a period of six months can be consideredfor CF patients who are failing to thrive or have shortstature. Zinc deficiency is known to affect vitamin Astatus, so zinc supplementation is also reasonable in CFpatients with suboptimal vitamin A status or in thosewho report night blindness that does not respond to vi-tamin A therapy alone (54).

Sodium Infants and children with CF are at risk ofhyponatremia because of salt loss through the skin. Theevidence in infants is limited to case reports (82,83),while sodium loss in older patients with CF has beenstudied in more detail (84). Patients with CF are advisedto take in a high salt diet. This recommendation shouldbe emphasized during the summer months and for thosewho live in hot climates. Infants without CF require 24mEq/kg/d of sodium; infants with CF likely are at theupper end of this range when not exposed to heat stress.Before the introduction of complementary foods or whenexposed to heat stress, babies with CF should havesupplemental sodium. Historically, sodium supplementshave been given using 1/8 tsp table salt (which containsapproximately 11 mEq sodium). This method has thedisadvantage of being imprecise and has the potential formistakes. Sodium chloride solutions are availablethrough pharmacies and can be dispensed more accu-rately.

Complementary and Alternative Medicine (CAM)

It is estimated that between 33 and 66% of CF patientshave used non-traditional medicine (85,86). Interest-ingly, 33 to 100% of these patients report achieving ben-efit from these therapies. Use of herbal or dietary thera-pies is lower, in the range of 11 to 28%. CAM productsare problematic for two reasons. First, no proof of safetyor efficacy is required by U.S. law and second, there isno assurance of purity, potency, or quality.




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Patients with CF and their parents may be reluctant todiscuss non-traditional therapies with medical team. TheAmerican Academy of Pediatrics Committee on Chil-dren with Disabilities published guidelines on CAMtherapy that state:To best serve the interest of children,it is important to maintain a scientific perspective, pro-vide balanced advice about treatment options, guardagainst bias, and to establish and maintain a trustingrelationship with families (87). It is important to askpatients with CF and their parents about CAM in a non-judgmental way.

EVALUATION OF PATIENTS WITH

NUTRITIONAL FAILURE AND THOSE AT RISK

Definition of Nutritional Failure and

Patients at Risk

Criteria for considering patients to have nutritionalfailure and to be at risk for nutritional failure are given in

Table 2. When poor growth is identified, patients shouldbe seen more frequently than the every three-month Cen-ter visits outlined in the Practice Guidelines for routinesurveillance. Infants should be seen every two to fourweeks, and children over age two years should be seenevery four to six weeks. These visits should includemedical, behavioral, and nutritional assessment, educa-tion and intervention as outlined in Figure 2. Nutritionintervention should aim at achieving the patients targetgoal for both weight-for-height proportion and geneticheight potential.

Evaluation of Co-Morbid Medical Conditions

Medical as well as nutritional and behavioral factorsshould always be considered in the patient who fails togain weight. If pulmonary or sinus disease are active,these should be treated. Gastroesophageal reflux disease(GERD) occurs with increased frequency in patients withCF of all ages, and can cause both pulmonary symptomsand poor growth (88,89). An extensive review of theliterature and recommendations for diagnosis and treat-ment of GERD in infants and children has recently beenpublished (90). CF related diabetes (CFRD) with or with-out fasting hyperglycemia can cause poor growth. Insu-linopenia causes protein catabolism (91). An oral glucosetolerance test should be considered strongly in all pa-

tients with poor growth. The reader is referred to therecent Consensus Conference for management of CFRD(92). Non-pancreatic causes of malabsorption may alsocontribute to poor growth. These include CF-relatedhepatobiliary disease (93), infectious enteritis, bacterialovergrowth of the small intestine, or intestinal mucosalproblems such as Crohns or celiac disease. Intestinalresection with short bowel syndrome, which may occurfollowing surgery for meconium ileus, can worsen fat

malabsorption and result in poor essential fatty acid sta-tus and poor growth (94). Fibrosing colonopathy shouldbe considered in patients who have received pancreaticenzyme supplements at doses greater than 2,500 lipaseunits/kg/meal (45). Referral to a gastroenterologist may

be warranted for patients with persistent poor growth.An important and easily treatable cause of poor

growth and nutritional status in the patient with PI isineffective pancreatic enzyme replacement therapy. Inaddition, inactivation of enzymes by an acidic duodenalenvironment may render even an appropriate dose inef-fective.

Behavioral Evaluation

Presence of ineffective feeding behaviors and parent-ing strategies should be assessed early in the evaluationof patients with nutritional failure. The Behavioral Pedi-

atrics Feeding Assessment Scale is a self-reported mea-sure of mealtime problems (95). It is easy to use andappears to have adequate psychometric properties to beused clinically to identify problem behaviors that can beaddressed to improve caloric intake. Research on eatingin adolescents with CF has primarily focused on assess-ment of eating disorders or disturbances of body image,and no excess of these problems has been identified.However, concomitant anorexia nervosa should be con-

FIG. 2. Algorithm for CF patients with weight loss or lack ofweight gain.




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sidered in the adolescent with CF with very low bodyweight.

Dietary Evaluation

Dietary intake can be difficult to assess if patients are

eating breakfast and/or lunch at school, meals are beingserved by daycare centers, sitters or relatives, or if theparents are working alternate shifts and meals are noteaten together. Specific questions should be asked aboutthe volume of juice, flavored sugar drinks and carbon-ated beverages ingested, as well as the fat content andvolume of milk. Parents should be questioned about fat-free or low-fat foods, which may be used on the runwhen enzymes are unavailable. Meals may be skippedaltogether if the child is too rushed to eat breakfast, dis-likes school lunches, or has an activity schedule whichinterferes with dinner. A 24-hour dietary recall providesa qualitative assessment of dietary patterns and is easilyobtained in the office setting. A prospective 3 to 5 day

diet record must be collected for any quantitative assess-ment of energy and nutrient intake. Medical factors suchas iron deficiency or constipation should be consideredin children with poor appetites.

Interventions for Patients With Nutritional Failure

Behavioral Intervention

If problematic mealtime behaviors as described underbehavioral assessment are identified, behavioral inter-vention may be used in conjunction with nutritional in-tervention to improve oral intake. Behavioral interven-tions have been demonstrated to be effective in changing

feeding dynamics for children ages 3 to 12 years andtheir parents in a research setting (96) and can be used inthe clinical setting. The first behavioral strategy is tograduallyincrease calories by working on one meal at atime. A second strategy involves teaching parents alter-native ways of responding to their child who eats slowlyor negotiates what he or she will eat. A third strategy isto identify appropriate rewards for eating the expectedamount of food at each meal. Referral for more in-depthbehavioral therapy should be considered.

Dietary Interventions

Oral SupplementsGenerally, nutritional interven-tions start with addition of high-calorie foods to the pa-tients regular diet and use of nutritional energy supple-ments. Positive weight gain was demonstrated by onerandomized study and one case-controlled study of nu-tritional counseling and homemade high-calorie foods(97,98). Two studies using commercially availablesupplements failed to improve nutritional status(99,100). Use of energy supplements is warranted, but

surveillance is necessary to assure that they are not usedas substitutes for normal food intake. The convenience ofpre-packaged supplements may be useful for patientswith busy schedules.

Enteral FeedingsIntroduction to Family and Initiation Supplemental

enteral feedings should be started when oral supplemen-tation fails to result in weight gain. The purpose andgoals of enteral feedings should be explained to the pa-tient and family, and their acceptance and commitment tothis intervention should be realistically assessed. Enteralfeedings should be presented as a positive treatment, notas a threat or the beginning of the end. Likewise, en-teral feedings should be presented as a supportivetherapy to improve quality of life and outcome. A pos-sible way of assuring that families and patients under-stand this concept is to introduce the idea of enteral feedsat diagnosis or early in the course of CF, before nutri-tional failure is present. Enteral feeds should be pre-sented as one of many treatment modalities to improvenutritional status and quality of life. The family shouldbe provided with concrete information on the types offeeding tubes and formulas and how feeding systemswork.

Since no good data exist to demonstrate the superiorityof one type of enteral access over another, the choice oftube and technique for its placement (nasogastric, oro-gastric, gastrostomy, or jejunostomy) should be based onthe experience of the Center. Some clinicians believe thatthe presence and/or severity of GERD should be assessedbefore initiation of enteral feedings, and if severe GERDis present, an antireflux procedure should be performedat the time of gastrostomy placement. Further research isneeded to clarify the risks and benefits of this approach.Pulmonary health should be maximized before place-ment of all permanent tubes, and a plan for managementof postoperative pain should be made before the proce-dure.

Formulas and Caloric GoalsStandard (complete pro-tein, long-chain fat) formulas typically are well tolerated.Calorically dense formulas (1.52.0 kcal/cc) usually arenecessary for provision of adequate calories. The data areunclear as to whether formulas with medium-chain tri-glycerides are beneficial. Some practitioners find semi-elemental formulas helpful in patients who have exces-sive anorexia, bloating or nausea. Nocturnal infusion isencouraged to promote normal eating patterns during theday. Initially, 30 to 50% of estimated energy require-

ments should be provided overnight. Anecdotally, a totaldaily caloric goal of 120 to 150 kcal/kg/d may be neededin infants to achieve catch-up growth and promote opti-mal lung growth. The amount of calories deliveredshould then be titrated based on the rate of weight gain,fat stores, and growth. Very low-fat, elemental formulasmay be used without enzyme supplements for patientwho have endotracheal tubes in place and should begiven by continuous infusion to maximize absorption.




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Use of Enzymes With Enteral FeedingsThere are in-adequate data on the appropriate dosing of pancreaticenzymes with overnight enteral feedings. One studyfound that complete formula with enzymes given beforeand after feedings and semi-elemental (hydrolyzed pro-tein, medium chain triglyceride-enriched) formula givenwithout enzymes, were equally well absorbed, althoughthere was a trend towards less absorption of long chainfat and protein in the semi-elemental formula group(101). One study indicated that enzyme replacement im-proved fat absorption in infants receiving semi-elementalformulas (102). Another study of three formulas contain-ing 0, 32, and 58% of calories as fat demonstrated 82 to85% fat absorption when the usual mealtime dose ofenzymes was given orally both before and mid-waythrough 8-hour nocturnal enteral feedings (103). TheConsensus Committee recommends that pancreatic en-zyme supplements be taken orally in the usual pre-mealdose before all nocturnal enteral feedings (with the ex-ception of very low-fat, elemental formulas, as above).Additional doses may need to be given mid-way throughor at the end of a feeding. Further research is needed todefine the optimal method to provide pancreatic enzymesupplementation with enteral feedings.

ComplicationsComplications may be associated withenteral feedings. Patients on enteral feedings should bemonitored for carbohydrate intolerance. Once the fullcaloric goal has been achieved, blood sugars should bechecked two to three hours into the feeding and at the endof the feeding on two separate nights. Insulin should beadded if these blood sugars are greater than 180 mg/dl.This schedule of blood sugar monitoring should be re-peated when a patient is ill, receiving steroids, or if thepatient is not gaining weight. Patients with permanentfeeding tubes should have their skin evaluated for localbreakdown. Patients with excessive bloating may benefitfrom the addition of pro-kinetic agents or use of a semi-elemental formula.

Anabolic Agents

Insulin promotes anabolism as well as lowering bloodsugar. Proteolysis is higher in patients with CF than con-trols, but those with CF exhibit resistance to the anaboliceffects of insulin (104). Insulin therapy improves weightin patients with CFRD and fasting hyperglycemia (105).It is unknown whether insulin therapy improves weight

and muscle mass in malnourished patients who haveCFRD without fasting hyperglycemia, but treatment ofthese patients with insulin should be considered on acase-by-case basis. One group of children treated withgrowth hormone had increased height and weight veloc-ity, lean body mass, and pulmonary function and haddecreased hospitalizations (106). However, since heightand weight increased proportionately, treated patients re-mained significantly underweight at the end of one year

of treatment, suggesting that this expensive interventionis not a replacement for nutritional intervention. Growthhormone can also reverse protein catabolism and de-crease circulating inflammatory cytokines (107). Longi-tudinal studies are needed to determine if the improve-ments are sustained. There may be a role for growthhormone therapy in selected children with CF. Severalsmall studies have demonstrated increased appetite andweight gain in patients treated with megestrol acetate(108110), although side effects such as adrenal suppres-sion, insulin resistance, development of Cushingoid fa-cies, insomnia, hyperactivity, and hypertension havebeen noted. Improvements do not appear to be sustainedafter the drug is discontinued. Until more data becomeavailable that show the benefits outweigh the risks, ana-bolic agents cannot be recommended for routine use in CF.

CONCLUSION

Our aim is to have every child with CF achieve normal

growth and development. This requires regular and ac-curate surveillance, adequate calories and nutrients, anda plan for prompt intervention when growth is subopti-mal. This is best accomplished with a multidisciplinaryteam approach at an accredited CF Center. This docu-ment is intended to present our best recommendationsbased on current knowledge. However, cystic fibrosisand nutrition research is needed in many areas beforeguidelines can be made based on evidence and not con-sensus opinion.

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