Cystic fibrosis (CF) is a disease occurring in almost all ethnic groups. In Caucasians it is the most common lethal hereditary disorder with autosomal recessive inheritance. The incidence of clinical disease is approximately 1 in 2500 live births(l). The latest report from Chandigarh comprised of 17 cases over the past 4 years which formed almost 4-5% of the total cases with chronic pulmonary ailments seen at the Advanced Pediatric Centre of PGIMER(2). Delta F-508, which is the commonest mutation identified, has been identified in Asians migrated to U.K., where the incidence is less than 50%(3). Nutri- tional management in children with cystic fibrosis (CF) assumes great importance in view of the associated malabsorption along with respiratory infections leading to failure to thrive and multiple nutritional deficiencies.

This is due to the presence of anorexia especially in respiratory infections/failure or associated vomiting due to chronic cough and negative intrathoracic pressure. In certain cases the problem of gastroesophageal reflux may add to the problem(4). Recurrent abdominal pain due to intestinal obstruction, constipation, cholecystitis, pancreatitis and ascites may also lead to inadequate energy intake(2).

A child born with CF may appear totally normal in size at birth. There is progressive destruction of exocrine pancreas, which leads to impaired intraluminal hydrolysis of dietary lipids and proteins. A child fed on exclusive breast feeds may gradually begin to manifest protein or energy deficit by the age of two months. They may present with malabsorption(5). The common observation that the baby demands larger volume of feeds to compensate for the increased losses, seems to be constantly nursing and is often termed as "always hungry" by the mother(5).

At the time of diagnosis, evidence of protein deficit is usually present in approximately 30-40% of infants, based on their serum albumin and pre albumin levels. In a study by Sokol, et al.(6) those infants who were breast fed prior to diagnosis had a higher frequency of low serum albumin than those receiving formula milk. These babies when put on enzyme therapy, showed a rapid reversal of protein deficit and more gradual reversal of energy expenditure.

Features of kwashiorkor may be observed in exclusively breast fed babies who remain undiagnosed till the age of 6 months.

EFA deficiency can be encountered in patients with CF, due to maldigestion and malabsorption of dietary lipids combined with underweight and negative energy balance with an increased beta oxidation of polyunsaturated fatty acids. The plasma and tissue lipids of such patients tend to have low contents of the precursor EFA, linoleic and µ-linolenic acids. However, the exact possible causative factor of EFA deficiency in patients with CF need further clarification. It has been observed in a controlled trial(7), that ursodeoxycholic acid therapy for 6 months led to an improvement of EFA status. However, there is still insuffi-cient evidence to justify routine use of ursodeoxycholic acid in patients with cystic fibrosis(8). Fish oil preparations being rich in omega-3 series have an anti inflammatory effect. Corn oil also is a good substitute as a source of EFA.

Anti-oxidant protective screen is quite disturbed in patients with CF due to the impaired status of glutathione, vitamin A and carotenoid like b-carotene and lycopene. Glutathione deficiency is known to occur both locally in CF airways and systemically(9). Correction of poor vitamin E and b-carotene status to normal also enhances the resistance against oxidation of plasma lipo-proteins and decreases plasma lipid peroxidation(10,11).

In 85-90% of the cases there is a pancreatic dysfunction leading to pancreatic insuffi-ciency, further causing steatorrhea and azotearrhea(12). Lack of duodenal buffering of gastric acid due to lipase inactivation, caused by deficiency of pancreatic bicarbonate and bile precipitation is another contributory factor leading to malabsorption(13).

Tests using indirect calorimetry have shown that in young adolescents with significant pulmonary involvement, the average daily energy requirement increases to 150% of the usual recommended intake(14). Impaired lung function causes a higher work load for respiratory muscles and increased oxygen cost of breathing in children with cystic fibrosis leading to a resting energy expenditure twice that of controls(15).

A child once diagnosed to have CF needs: (i) nutritional support and rehabilitation and (ii) pancreatic enzyme supplementation.

This is aimed at achieving optimal nutritional status and augmenting growth and development. The main dietary goals therefore would be to provide an energy intake of 120-150% of RDA for age; protein intake of 150-200% of RDA for age; and a fat intake that provides 40% of total energy requirements(16).

Breast feeding should be encouraged due to its high lipase content. However, infant formula too can be used along with the enzyme. In order to mix the enzyme, expressed breast milk can be used.

After 4 months of age, supplements should be initiated as the requirement increases and the child is not satiated by breast feed alone. Baby foods which are cereal based along with pureed vegetables and pulses are ideal weaning foods. To increase the calories, commercial supplements which are dense in calories and proteins can be incorporated along with the formula or cow’s milk.

In older children who may be lactose intolerant or allergic to cows milk-protein, hydrolyzed protein formula (soya based) are good substitutes. Savoury or salt based preparations need to be encouraged to compensate for the electrolyte losses especially during the summer and humid months.

To meet the enhanced caloric requirements of babies with CF on enzyme therapy, extra fats can be incorporated in their feeds e.g., vegetable margarine or coconut oil which is a medium chain triglyceride oil. The deficiency of essential fatty acids can be made up by the vegetable fat rather than butter.

Certain babies might present with perianal soreness, which might be related to the high dose of enzymes passing through the gut undigested. In such cases either a suitable barrier cream may be applied locally or the dosage may be reduced if needed.

By one year of age, the child should be feeding from the family pot. A high fat, high salt, calorie dense diet is stressed upon. This can be achieved by a 5-6 feed pattern, which includes three main meals and 2-3 in between snacks. One bedtime feed or snack can help in tiding over the long gap at nighttime.

Periodic weight record is a helpful guide to assess the adequacy of dietary intake throughout the day. A sub-optimal weight gain is an indicator to check on the enzyme compliance and also the complete diet history or food diary. This gives an idea if the calories from food are optimal before resorting to extra non-enteral supplements. The dietary fat content should ideally provide 35-40% of the total calories; 8.5% of these should be derived from polyunsaturated fats and 10% of the calories from monounsaturated fats(17).

Supplements are not required for children with normal appetite. However, in case of a brief illness leading to suppressed appetite, supplements can prove beneficial, but should be used temporarily, till normal intake is resumed. Various supplements available commercially in India are Protone, Nutrene, Pediasure, B-protin, Spert, etc. However, care should be taken that supplements do not replace a meal. They should be offered always after a meal or at bed time. This may also require increasing the dose of enzyme. A standard age related recommendation for the calorie contribution from supplements to the diet of a patient with CF is 200 Kcals/day (1-2 yr); 400 Kcals/day(3-5 yr), 600 Kcals/day (6-11yr) and 800 Kcals/day (>12yr) (17,18).

Nasogastric feeding has to be resorted to, if oral intake is not adequate. Usually, nocturnal nasogastric feeds are preferred using a pump(19). Commercially available supple-ments in addition to blended home-based preparations, which are calorie and protein dense can be used as nasogastric feeds. Jejunostomy and gastrostomy are the other alternative modes of feeding. Total parenteral nutrition is used as the last resort in more advanced stage of the disease, where oral intake declines drastically and even nasogastric feeds are not tolerated due to coughing, delayed gastric emptying and vomiting.

In hot humid weather, there is excessive fluid and water losses in CF leading to hyponatremia, hypokalemia, hypochloremia and metabolic acidosis. Therefore, routine supplementation of electrolytes is generally practiced in most CF centers in infants above 18 months of age. Liberal amounts of salt and other savoury products for older children are advocated. The following guidelines are suggested for sodium supplements(17).

0- 1 yr 2 mmol/kg (NaCl soulution)

1- 5 yrs l × 600 mg (10 mmol Na tabs)

6-11 yrs 2 × 600 mg (20 mmol Na tabs)

>11 yrs 3 × 600 mg (30-40 mmol Na tabs)

Clinical signs of vitamin A and D deficiency are not common. Vitamin A supplement of 5,000-10,000 IU and 400-800 IU of vitamin D per day are recommended(5). Low serum levels of vitamin E are seen in 40% of infants with CF. Supplements of 5-10 IU/kg/d with meals along with enzyme is advised(19). Vitamin K is not needed with enzyme therapy.

In view of the increased metabolism and increased caloric requirement, generally twice the recommended dietary allowance is advised. This can be met with an unrestricted home based diet along with a multi vitamin tablet. Vitamin B12 needs to be supplemented (100 U/month) if Schilling test is <45% after ileal resection(20).

Iron deficiency is frequently seen in patients with CF, which can be secondary to inadequate dietary intake, malabsorption, blood loss and chronic infections. Pancreatic enzyme may cause impaired oral absorption, so iron should not be supplemented in close proximity to PES(21).

Zinc, an important trace element in many enzymes, may become deficient due to fat malabsorption in patients with CF and is caused by zinc forming complexes with fat and phosphorus. Children need 5-10 mg/day and adults upto 15 mg PES improves zinc absorption(22).

N-acetylcysteine (NAC) is a cysteine amino acid derivative found to have valuable hepatoprotective action against toxic oxygen species. A suggested daily dose of 500 mg 2-3 times a day for adults may decrease hepatotoxin formation and mucus viscosity in CF(23). Lecithin increases cholesterol solubility, emulsifies fats and so plays an important role in fat absorption. A dose of 1200 mg daily or alternate day is suggested in adult patients with CF(24). Coenzyme Q 10 is an immune-enhancing agent given in a dose of 60 mg/day(25).

Carnitine prevents toxic accumulation of long chain fatty acids in the cytoplasm and of acyl CoA in the mitochondria. Fat malabsorption may be corrected by a carnitine rich diet and carnitine supplements. Long term use of medium chain triglycerides is advocated for clinical improvements like weight gain and increased serum albumin level(26). Taurine has been shown to decrease fecal fatty acids and sterol excertion. It is also known to decrease the severity of steatorrhea associated with many CF cases. In a study where CF children were treated with 30 mg/Kg per day of taurine, 92% of them showed decreased fecal fatty acid and sterol excretion(27).

PES is an extract of animal pancreas given with ingested meals. This helps in reversal of protein deficit (as measured by serum albumin), decreases stool fat excretion (72 hours fat estimation) and also reverses energy deficit (as measured by height, weight, triceps skinfold and mid arm circumference)(28).

The doses need to be individualized as per age and weight of the child. The enzyme is available as PH sensitive enteric coated capsules or microspheres. Enzyme supple-mentation helps maintain a reasonable growth rate.

For every 120 mL infant formula or breast milk give 1/4 to 1/3 of a capsule of standard strength pancreatin (10,000 units = 2500-3333 IU lipase; pancrease = 1666 – 2500 IU lipase) as the initial dose. These doses equate to approximately 400-800 IU lipase per gram of dietary fat. Use a microsphere or minimicro-sphere preparation. The enzyme microsphere or minimicrosphere can be mixed with a small amount of infant formula or expressed breast milk or fruit puree and given from spoon directly before the feed. The dose can be increased gradually according to clinical symptoms, appearance of the stools and objective assessment of weight, growth and absorption.

Once solid food is introduced individually, titrate enzyme dose according to the fat intake. Regular advice from a dietician is mandatory for best results. Aim should be to keep the lipase intake below 10,000 IU per Kg body weight per day(17).

Initial dose of 1-2 capsules of standard pancreatin preparation (as Creon 10,000 = 10,000-20,000 IU lipase and Pancrease = 5000-10,000 IU lipase) should be given per meal and ½ to 1 capsule with fat containing snacks. Enzymes should be given with all fat containing foods and supplements. Dose requirements can vary widely between 500-4000 IU lipase per gram of dietary fat(17). The child should be trained to swallow the capsule at as early an age as possible. If removed from the capsule the microsphere should not be sprinkled on or mixed with the whole meal but given from a spoon in one swallow. They should not be chewed or crushed. Enzymes are best given at the beginning or early in the meal e.g., half the dose at the beginning and half in the middle of the meal. The dose is gradually increased until the symptoms are controlled when evidence is sought that absorption has been controlled. Patients and parents should be encouraged to discuss any problems they may have with adherence to enzyme treatment. In tube or gastrostomy fed patients pancreatic enzymes should be given before and after the food.

The pancreatic enzyme being biologically degradable over a period of time, it is important that emergency supplies be kept at specific places and are checked for ‘use by’ dates, or else there is a risk of its being ineffective if kept in a hot case or exposed to heat(16).

If stools are persistently greasy despite a recent increase in enzyme therapy, the use of antacid therapy should be considered. For example, omeprezole or ranitidine. This treatment makes an acidic duodenum more alkaline, therefore encouraging maximum enzyme activity at the appropriate place in the gut(17).

The adverse effects like colonic strictures with use of high strength enzymes have been reported following an epidemiological study in the U.K.(29). Consequently, the Committee on Safety of Medicines (CSM) recommended that Pancrease HL and Nutrizyme 22 are contraindicated for children age 15 years and below and an excess of 10,000 lipase units per kg/day is discouraged(17). Other adverse effects reported are severe acute and chronic gastrointestinal reactions(30) and general allergic reactions may occur by giving powered enzymes to infants with CF(31). In patients when enzyme dose is increased constipation may occur. If administered to breast fed infants, soreness of the infant’s mouth and the mother’s nipple may occur. Perianal irritation may occur from passage of significant enzyme activity in the stools if intestinal transit is rapid or the enzyme dose is excessive.

There are number of pancreatic enzymes now available of various strengths in the Indian market; for example: Pancreaoflat and Pancreaon from Duphar India, Festal N (Hoechst), Enzystal (Torrent), Dispeptal (Nicholas Piramal), Dizec (S. Beecham) and Panzynorm-N (German Remedies).

Some of the CF children may develop diabetes due to a gradual destruction of glucagons and insulin secreting cells in the pancreas. All children above 10 years of age should be screened for diabetes especially when failure to thrive is evident. A CF child with diabetes is managed totally unlike a diabetes child. Some of the dietary guidelines followed in managing a CF child with diabetes are as follows(26).

Some children with CF might also present with celiac disease. In children with failure to thrive and malabsorption, a routine screening for serum antigliadlin can help early detection of the disease. In such cases all gluten containing products have to be eliminated from the diet. A detailed session with the dietician for dietary counseling will help in effective dietary management in such children.

Contributors: MS reviewed and drafted the paper. M Singh provided overall framework and concept. She will act as the guarantor of the article.

Funding: None.

Competing interests: None stated.

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