Cystic fibrosis

CyStiC fibroSiS in PAediAtriCS

Jacqui Lowden Paediatric Dietitian - Team Leader Critical Care, Therapy & Dietetics, RMCH

Presently team leader for Critical Care and Burns, Jacqueline previously specialised in gastroenterology and cystic fibrosis. Although her career to date has focused on the acute sector, Jacqueline has a great interest in paediatric public health.

important advances in the treatment and management of cystic fibrosis (CF) have resulted in huge improvements in the health of people with CF. individuals born with CF in the 21st century are now expected to live into their mid-50s, even in the absence of developments in the treatment of the underlying genetic defect (1).

One of the advances in CF management that has demonstrated the prevention of severe malnutrition and improvement in long-term growth, is new-born screening (2) which was introduced nationally in 2007. Maximising nutritional status has, however, long been considered a crucial element, being inextricably linked with lung function. The level of malnutrition has been demonstrated to predict survival (3). As the disease progresses, increased nutritional support is normally required. Dietary fortification, oral nutritional supplements and enteral tube feeding are all used.

INfANTS WITH Cf Even with the benefits of infant screening, deficits in weight, length z score, total body fat and lean body mass have all been demonstrated in screened infants with CF at diagnosis (2, 4). A higher than normal intake of protein and energy has also been shown to be required in these infants in order to achieve normal rates of weight gain and growth (5).

It is vital that infants with CF thrive, as achieving optimal nutritional intake and catch-up in weight gain within the first two years of diagnosis in children with CF has been shown to be the single strongest predictor of lung function improvement at six years of age, which is correlated to reduced morbidity and mortality (6).

Most infants with CF thrive on breast milk or normal infant formulae until the commencement of complementary feeding. If the infant is unable to achieve the required amount and/or weight gain is insufficient, a nutrient dense infant formula can be used. There is no evidence for the use of a protein hydrolysate formula in screened infants with CF (7). For infants with CF who have undergone bowel surgery due to meconium ileus, the choice of feed will depend on: 1. the extent of the small intestinal resection; 2. the site of the ileostomy; 3. parental choice to breastfeed.

First choice is expressed breast milk whilst establishing breastfeeding, second a protein hydrolysate with a combination of MCT/LCT and thirdly, a standard infant formula.

Another factor to take into account is sodium depletion, as this can inhibit growth (9). All infants with CF are at risk of sodium depletion. Particularly at risk are those with ileostomies as the sodium content of the output can be high. European Cystic Fibrosis Society guidelines suggest that ‘sodium chloride supplementation (2.0mmol kg/ day) should be considered for all CF infants, and increased during periods of hot weather and with other causes of high salt loss (for example, diarrhoea, fever and ileostomy)’ (8).

oLDER CHILDREN Definitions of nutritional failure The intervention required will be dependent on clear definitions of what is classed as nutritional failure. Presently, there are three sets of national reference standards (Table 1). For children

Uk CF trust 2002 < 5yrs ECFS 2002 < 2yrs 5-18yrs 2-18yrs

> 18yrs > 18yrs

Normal nutritional state - preventative counselling %wt/ht 90-110% %wt/ht 90-110% bMI 19-25 or no recent wt loss

Dietetic referral Consider supplements Any degree of faltering growth* % wt/ht 85-89% wt loss 4-6 months wt plateau >6 months* bMI <18.5(ECfS) bMI <19 (UK Cf Trust) or >5% wt loss over <2 months

Invasive nutritional support faltering growth despite oral supplementation Supplements tried & either %wt/ht <85% or wt fall of 2 centile positions Supplements tried & bMI <18.5 (ECfS) bMI <19 (UK Cf Trust) or >5% wt loss over <2 months

North American C foundation 2008 f <2yrs 2-20yrs > 18yrs

Defined targets to avoid nutritional failure bMI percentile >/= 50th bMI percentile >/= 50th Woman: bMI >/= 22 Man: bMI >/= 23

Table 2

Organisation

UK Cf Trust 2002 200% RNI protein

European Guidelines 2002

North American Cf foundation 2008

recommendations

120-150% EAR energy

Normal energy requirements in presence of good lung function >120% EAR for malnourished individuals No protein recommendations 110-200% energy No protein recommendations

with CF, achievement of a BMI centile equal to or above C 50th is associated with lung function above 90 percent predicted (10).

Dietary recommendations At present, UK standards recommend that we aim for 120 to 150 percent of estimated average requirements for energy and 200 percent of the reference nutrient intake (RNI) of protein. Forty percent of the energy should come from fat (11). Table 2 provides a summary of the present dietary recommendations.

What are children with Cf actually eating? It has been documented that achieving the dietary recommendations is not always possible. In those with mild lung disease, published mean energy intakes have been consistently below the UK recommendations, 99 to 116 percent (12, 13, 14, 15). Also, only 11 to 39 percent have been able to achieve the dietary recommendations , suggesting that there appears to be an upper limit to the amount of food that can be eaten (15, 16). Although the aim is for an increased energy intake, aiming for 40 percent energy from fat, a moderate fat intake has been documented and the children have simply eaten more of all nutrients, compared to children of the same age, without CF (14, 17).

NUTRITIoNAL SUPPoRT IN Cf In undernourished children with CF, oral nutritional supplements and enteral tube feeding have been shown to: 1. increase nutritional intakes; 2. improve growth; 3. improve lung function; 4. positively impact upon life expectancy. (18, 6, 19, 20, 21)

The most recent evidence concludes that enteral tube feeding has the strongest evidence base, with all studies demonstrating significant weight gain and a reduction in the rate of decline of lung function (22). However, it is not without its complications, with gastro-oesophageal reflux and diabetic onset being the most common. Gastro-oesophageal reflux incidence can be as high as 30 percent (23) and diabetic incidence from five percent to 50 percent (8, 23, 24, 25, 26), within one to two years follow up. The treatment and management of CF is dependent upon the use of multiple medications and therapies, which can be complex and time-consuming for the patient and their family.

PANCREATIC INSUffICIENCy (PI) With a direct relationship between pancreatic function and nutritional status in CF, it is essential that maximal absorption of food is attained, with the appropriate use of pancreatic enzyme replacement therapy (PERT). At present, there are no studies determining the optimal dose, or if indeed there is a dose-response association (27, 28). Individual requirements vary, but generally, it should not exceed 10,000 IU lipase/kg body weight/day. Table 3 outlines present recommendations. As there are many factors that affect the efficacy of PERT, doses need to be individually advised and reassessed regularly.

vITAMINS The fat soluble vitamins A, D, E and K should be given from diagnosis onwards in PI patients. Annual monitoring is recommended as a minimum for all patients and doses adjusted individually. Current recommendations do exist and do vary between countries (see Table 4).

ADHERENCE AND MANAGEMENT The treatment and management of CF is dependent upon the use of multiple medications and therapies, which can be complex and time-consuming for the patient and their family. This can result in non-adherence (33, 34) and poor level of competence, resulting in detrimental health outcomes (33). The CF team therefore need to be able to provide treatment that is patient/family centred and holistic that provides a balance between optimum treatment and quality of life (35).

Table 3

European CF Society (8) USA guidelines (27, 28) Australian guidelines (29)

Infants - 2,000 IU lipase/ 100ml feed Not to exceed 10,000 IU lipase/ kg/day Newborn infants - 2,000-5,000 IU lipase/120mls feed Not to exceed 2,500 IU lipase/kg body wt/feed < 4 yrs - 1,000 IU lipase/kg /meal > 4 yrs - 500 IU lipase/kg/meal, max of 2,500 IU lipase/kg/meal Infants - 500-1,000 IU lipase/g fat The lowest effective dose should be used

500-4,000 IU lipase/g fat for a child The lowest effective dose should be used

Table 4: Recommended starting doses per day

vitamin

vitamin A

vitamin E

vitamin D

recommendation

< 1 yr 1,500 IU (455ug) (8) > 1 yr 4,000-10,000 IU (1,200-3,000ug) (31) < 1 yr 10-50mg > 1 yr 50-100mg (31) < 1 yr 1,000-2,000 IU (25-50ug) > 1 yr 1,000-5,000 IU 925-125ug/day) (30) < 2 yrs 300ug/kg to nearest mg > 7 yrs 10mg (32)

SUMMARy It is well established that nutritional status in CF is inextricably linked with lung function and that the level of malnutrition has been demonstrated to predict survival. As the disease progresses, increased nutritional support is normally required, with enteral tube feeding having the strongest evidence base, demonstrating significant weight gain and a reduction in the rate of decline of lung function. Whilst life expectancy and outcomes for CF have made significant advances, it remains a life-limiting condition, placing a huge burden of care onto families and the children as they grow. It is, therefore, essential that the advice provided is specific to that child and their family rather than to the disease itself.

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