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School of Health Sciences and Priority Research Centre in Physical Activity and Nutrition, Faculty of Health and Medicine, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia
Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales, Sydney, NSW 2052, AustraliamiCF Research Centre, Sydney Children's Hospital, High Street, Randwick, NSW 2031, AustraliaDepartment of Gastroenterology, Sydney Children's Hospital, High Street, Randwick, NSW 2031, Australia
CF children consumed significantly more total energy than controls.
•
CF children had significantly higher intake in most micronutrients than controls.
•
Energy-adjusted micronutrient intake decreased as CF children reached school age.
•
CF children failed to meet RDIs for key micronutrients such as folate and iron.
•
High school CF children are most at risk of overall inadequate micronutrient intake.
Abstract
Background
Children with CF have been reported to consume significantly more energy-dense, nutrient-poor foods than controls where there are now concerns of inadequate micronutrient intake. There are no current or comprehensive dietary studies assessing micronutrient intake in CF children.
Objectives
To evaluate micronutrient intake in children with CF compared to recommended dietary intakes (RDIs).
Methods
Dietary intake of 13 micronutrients was measured in CF children aged 2–18 years and age- and sex-matched controls using a validated food frequency questionnaire (The Australian Child and Adolescent Eating Survey).
Results
CF children (n = 82) consumed significantly more energy than controls (n = 82) [3142(2531–3822) kcal vs 2216(1660–2941) kcal; p < .001]. Absolute intake in CF children was significantly higher in all micronutrients except vitamin C and folate, however energy-adjusted intake was significantly lower for all micronutrients except vitamin A, sodium, calcium and phosphorous. Energy-adjusted intake in primary school CF children was significantly less than controls in 8/13 micronutrients. Overall, median intakes exceeded the RDIs for all micronutrients however CF children fell short of the RDIs for folate (26.8%), iron (15.9%) and calcium (9.8%). In pre-school, 50% of CF children and 91.7% of controls did not meet the iron RDI. High school CF and control children failed to meet RDIs for 7/13 and 9/13 micronutrients respectively.
Conclusion
Increased intake of most micronutrients in CF children was largely attributed to higher energy consumption. However, micronutrient density of the diet declined with increasing age, where high school children failed to meet RDIs for most key micronutrients.
Cystic fibrosis (CF) is an autosomal, recessive disorder prominent in Caucasians, which arises from defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene [
]. This defect results in the accumulation of thick, sticky mucus which leads to chronically altered microbial ecology and secondary inflammation within affected organ systems such as the respiratory and gastrointestinal tracts [
]. In the pancreas, inspissated pancreatic secretions lead to the obstruction of pancreatic ducts, and inflammation and destruction of the exocrine pancreas [
It has been well established that people with CF have increased energy requirements compared to the healthy population due to recurrent pulmonary infections, higher resting energy expenditure from increased work of breathing, and malabsorption [
]. Nutrition Guidelines for CF in Australia and New Zealand have advocated for an energy consumption of 110–200% of the general population target with up to 40% energy from fat [
Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review.
Australian and New Zealand guidelines advise that recommended dietary intakes (RDIs) of micronutrients for people with CF coincide with those of the healthy population apart from sodium, being approximately five times the general RDI [
]. This will also vary depending on latitude. International recommendations provide little guidance on ensuring nutritional adequacy of the CF diet in terms of micronutrients. Energy and macronutrient intakes (particularly fat) in patients with CF have been extensively explored however micronutrient intake in CF has not been as frequently or comprehensively investigated. A contemporary study by this group has previously reported that children with CF, especially those of school age, consume significantly more energy-dense, nutrient-poor foods than their age-matched controls [
]. This dietary pattern together with impaired digestion, malabsorption and increased nutrient utilization, highlights the potential difficulty children with CF may have in achieving optimal micronutrient status. Adequate micronutrient intake is critical during childhood and adolescence for growth and development [
]. As individuals with CF are now living longer, they have been accompanied with nutrition-related complications such as stunted growth and decreased bone mineral density [
]. These studies focused on vitamin A, B vitamins, calcium and phosphorous, and/or iron. Dietary data was mostly collected through three-day food records. Sample sizes ranged between 51 and 221 subjects, with one study including age- and sex-matched controls [
]. No studies provided a comprehensive evaluation of micronutrient intake in children with CF. Therefore, this study aims to provide a contemporary, comprehensive evaluation of the dietary intake of 13 micronutrients in children with CF compared to age- and sex-matched controls; and recommended dietary intakes (RDIs) [
This is a cross-sectional study (the Dietary Intake Study in cHildren (DISH)) of 102 children with CF who attended the Cystic Fibrosis Clinic at Sydney Children's Hospital Randwick, Australia, between January 2015 and December 2016. Included subjects were children between 2 and 18 years of age who had a confirmed diagnosis of CF (sweat chloride ≥60 mmol/L and/or 2 CF-causing genetic mutations). Age- and sex-matched controls (age-matched within 12 months) were recruited through nomination from the CF child, direct invitations during orthopaedic clinic appointments (healthy children with fractures) or internal advertisements to hospital staff via email. For both CF and control groups, any child receiving enteral nutrition, following a prescribed diet for existing medical conditions other than CF (e.g. coeliac disease) or children who were vegetarian were excluded. Parental written consent was obtained at the time of recruitment. Ethics approval was obtained by the Sydney Children's Hospital Network Ethics Committee (LNR/14/SCHN/561). Majority of subjects in this study were previously reported in a separate study [
Weight and height, in all participants, were measured using electronic scales (accurate to 0.01 kg) and a stadiometer (accurate to 0.1 cm) respectively. Body mass index (BMI) was calculated as kg/m2. Height and weight were then compared to growth data from the Centers for Disease Control and Prevention 2000 to establish weight-for age (WAZ), height-for-age (HAZ) and BMI-for-age (BMIZ) z-scores [
Dietary intake data for energy and 13 micronutrients was evaluated via The Australian Children and Adolescent Eating Survey (ACAES), a 120-item semi-quantitative, validated food frequency questionnaire (FFQ) [
]. Intake from supplements was not included. Subjects and parents/guardians were provided with detailed instructions on how to complete the FFQ, with an emphasis on providing the subjects' usual food and beverage intake. For children under 9 years of age, the FFQ was to be filled out by the parent or guardian. Children between 9 and 18 years of age were given the option to complete the FFQ themselves. Food items within the FFQ were organised by food group or meal type (e.g. fruits, main meals) with varying frequency categories for each. These ranged from “never” to “4 or more a day” for most food items and up to “7 or more glasses per day” for beverages. Each question included typical portion sizes (e.g. 1 slice of bread, 1 glass of milk) derived from the 1995 Australian National Nutrition Survey (NNS) [
]. Respondents were asked to consider portion sizes when entering intake frequency. FFQ's were scanned for completeness before collecting, and then computer-scanned and analysed by the University of Newcastle. Analysis was conducted through FoodWorks (Version 3.02.581), and the Australian AusNut 1999 (All Food) Revision 14 and AusFoods (Brands) Revision 5 (Xyris Software (Australia) Pty Ltd., FoodWorks Professional Version 3.02.581. 2004: Brisbane, Australia) databases. This produced individual mean daily intake of macro- and micronutrients. However only micronutrient intake data was included in this study.
2.4 Statistical analyses
Micronutrient intakes for all children were quantified as absolute intake and energy-adjusted intake (amount of the micronutrient per 1000 kcals). Individual consumption of each nutrient was calculated as a percentage of age- and sex-appropriate RDIs or adequate intakes (AIs) where RDIs did not exist. Mean percentage RDI or AI and the proportion of children not meeting their recommendations were calculated for each group. Age group analyses were conducted by dividing CF and control children into three groups: pre-school (2–4 years), primary school (5–12 years) and high school (13–18 years). Dietary intake data was presented as median (interquartile range) unless otherwise stated. Overall intakes between CF and controls were compared using student t-tests and Mann-Whitney tests for parametric and non-parametric data respectively. Comparisons of age groups within CF and between CF and controls were assessed using Mann-Whitney tests. All statistical analyses were performed through the IBM SPSS Statistics Software (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, New York: IBM Corp). A p-value of <0.05 was considered statistically significant.
3. Results
Based on the aforementioned inclusion and exclusion criteria, 91 children with CF and 91 age- and sex-matched controls were recruited for this study. However, children with CF who failed to return completed FFQs were excluded (n = 9). Therefore, a total of 82 children with CF and 82 age- and sex-matched controls were included for analysis.
3.1 Anthropometric measures
Anthropometric data of all children and across age groups are presented in Table 1. There were no significant differences between CF and controls for median (IQR) weight-for-age z-score, height-for-age z-score, and BMI z-score.
Table 1Anthropometric characteristics of children with cystic fibrosis and controls by age groups.
All Children
Pre-School (2–4 years)
Primary School (5–12 years)
High School (13–18 years)
CF (n = 82)
Control (n = 82)
p
CF (n = 12)
Control (n = 12)
p
CF (n = 46)
Control (n = 46)
p
CF (n = 24)
Control (n = 24)
p
Age (years)
9.52 (6.23–13.5)
10.3 (6.12–14.0)
0.75
2.83 (2.00–3.67)
2.79 (2.43–3.65)
0.80
8.22 (6.61–10.4)
8.81 (6.55–10.9)
0.64
15.8 (14.8–16.7)
15.6 (14.7–16.7)
0.84
Weight (kg)
31.8 (21.3–47.1)
32.9 (21.8–50.2)
0.49
14.1 (13.1–14.5)
14.6 (13.5–15.1)
0.31
26.6 (22.1–33.9)
30.0 (23.0–39.4)
0.35
54.8 (49.0–64.0)
57.6 (49.9–68.5)
0.43
Height (cm)
137 (116–159)
138 (120–163)
0.53
94.3 (88.8–96.8)
93.3 (91.2–99.0)
1.00
130 (120–141)
136 (122–142)
0.43
165 (160–169)
169 (162–174)
0.24
BMI (kg/m2)
16.9 (15.8–19.3)
17.4 (15.7–20.1)
0.50
16.1 (15.5–16.4)
16.7 (15.7–17.6)
0.40
16.3 (15.3–17.5)
16.1 (15.2–18.3)
0.93
20.4 (19.2–22.2)
19.9 (19.2–23.0)
0.67
WAZ
0.060 (−0.478–0.578)
0.280 (−0.275–0.865)
0.15
0.140 (−0.420–0.614)
0.670 (−0.787–0.936)
0.40
0.060 (−0.370–0.563)
0.370 (−0.186–0.795)
0.22
−0.080 (−0.506–0.544)
0.080 (−0.288–0.969)
0.46
HAZ
0.035 (−0.500–0.645)
0.350 (−0.513–1.33)
0.12
0.030 (−0.234–0.514)
0.050 (−0.604–0.929)
0.93
0.030 (−0.503–0.609)
0.050 (−0.281–1.25)
0.15
0.020 (−0.524–0.751)
0.370 (−0.451–1.41)
0.20
BMIZ
−0.030 (−0.440–0.050)
−0.030 (−0.465–0.830)
0.63
−0.280 (−0.627–0.263)
0.450 (−0.014–0.856)
0.15
−0.02 (−0.362–0.340)
0.010 (−0.438–0.786)
0.95
−0.020 (−0.325–0.532)
−0.120 (−0.435–0.840)
0.94
BMI: body mass index; WAZ: weight-for-age z-score; HAZ: height-for-age z score;
BMIZ: BMI-for-age z-score.
Results presented as median (interquartile range).
CF children consumed significantly more total energy than controls [3142 (2531–3822) kcal/day vs. 2216 (1660–2941) kcal/day; p < .001] (Table 2). Absolute consumption of all micronutrients apart from vitamin C and folate were significantly higher in CF children. However, energy-adjusted intakes showed that CF children consumed significantly less per 1000 kcal in all micronutrients apart from vitamin A, sodium, calcium and phosphorous.
Table 2Energy and micronutrient intake of children with cystic fibrosis and controls.
Table 3 shows CF children consumed significantly more energy than controls in all age groups. In pre-school, absolute intake of niacin equivalents, sodium and potassium was significantly higher in CF children than controls. For primary school, CF children consumed significantly more in all micronutrients than controls apart from thiamin, vitamin C and folate. For high school, CF children only consumed significantly more sodium than controls. Energy-adjusted intakes however, showed that in pre-school, CF children consumed less folate, magnesium and phosphorous per 1000 kcal than controls (Fig. 1). In primary school, CF children consumed significantly less per 1000 kcal than controls in all micronutrients apart from riboflavin, vitamin A, potassium, calcium and phosphorous. In high school, CF children consumed significantly less per 1000 kcal than controls for thiamin, vitamin C, folate, magnesium and iron.
Table 3Absolute micronutrient intake for children with cystic fibrosis and controls by age groups.
Within CF, pre-school children consumed significantly more per 1000 kcal for thiamin, riboflavin, folate, potassium, magnesium, calcium and phosphorous than both primary and high school. There were no significant differences in energy-adjusted intake between primary and high school apart from calcium.
3.4 Meeting the RDIs
When considering group medians, CF children and controls met or exceeded their age- and sex-appropriate RDIs or AIs for all micronutrients. At an individual level, there were substantial proportions of individuals in both groups who were not meeting the RDIs for key micronutrients. High school children, both CF and control were much more likely than primary school and preschool children to fall short of meeting the RDIs, in 7/13 and 9/13 micronutrients respectively (Table 4). There was a greater percentage of control children not meeting the RDI for a given micronutrient (apart from magnesium in high school students); this held true regardless of age groupings. The most at-risk nutrients in CF children were as follows: iron in preschool children; folate in primary school children; and folate, calcium, magnesium and iron in high school children.
Table 4Proportion of children with CF and controls not meeting the RDIs or AIs for micronutrients by age group.
Nutritional management has been recognised as an important contributor to the prognosis and long-term survival in patients with CF. This paediatric, cross-sectional study utilising age- and sex-matched controls indicates that children with CF consume significantly more of most micronutrients than their counterparts, owing to the fact that they consume significantly more energy. However, the micronutrient density of their diet was in general significantly lower and there was a strong relationship with age, with a stepwise reduction in micronutrient density from pre-school to primary school and then to high school. As a result, we have highlighted that age is a risk factor for suboptimal micronutrient intake, with high school children most likely to fall short of RDIs for key micronutrients.
This is the first study within the last decade to comprehensively evaluate micronutrient intake in children with CF. Infants and toddlers (7–35 months) with CF have been reported to consume adequate micronutrient intakes from food and beverages alone [
]. However this study suggests that there is difficulty in achieving micronutrient intake targets solely from the diet throughout childhood and adolescence in CF.
Children with CF were consuming significantly more of most micronutrients which could be attributed to their increased intake of total energy compared to controls. Sutherland et al. reported that children with CF were achieving elevated energy requirements through significantly higher intakes of energy-dense, nutrient-poor foods than controls which also contributed a significantly greater proportion to total energy intake [
]. This is a plausible explanation as to why children with CF were consuming a diet significantly less dense in all micronutrients apart from vitamin A, sodium, calcium and phosphorous.
The divergence in micronutrient density between CF and control children became more apparent as children started school. The diet of pre-school CF children was significantly less dense than controls in 3/13 micronutrients, which increased to 8/13 in primary school and 5/13 in high school. The school environment may have influenced intake as structured mealtimes are introduced and parental control over intake is limited. Nutritional quality may be compromised by increased availability and convenience of energy-dense, nutrient-poor foods in school canteens alongside social pressures and taste preference changes.
Adolescence is a time of increased independence where types of foods eaten become an individual choice. While micronutrient density was lower in CF children, it was poor overall with high school children failing to meet RDIs or AIs for 7/13 micronutrients in CF and 9/13 in controls suggesting current dietary patterns were suboptimal. RDIs for key micronutrients such as folate, calcium and iron were not met.
Folate aids in cell division and is required for growth and development, making it critical during periods of rapid growth such as early childhood and adolescence [
]. In this study, the proportion of CF children not meeting folate RDIs increased from pre-school (16.7%) to high school (50%). This may have resulted from poor intake of folate-rich food sources (e.g. vegetables). According to the 2011–12 Australian Health Survey (AHS), Australian children 2–18 years old were not meeting their daily serves of vegetables where children 4–18 years of age were consuming less than half their recommended serves [
]. Calcium intake was significantly reduced with increasing age groups. This coincided with findings of White et al. however their study showed all age groups (5–16 years) remained above recommended targets [
]. In this study, 29.2% of high school CF children were not meeting their RDIs which may have resulted from poor intake of dairy foods. Low bone mineral density is prevalent in patients with CF which has appeared to evolve throughout adolescence and into adulthood [
]. Despite 20.8% of high school CF children not meeting the RDI, 50% of pre-school CF children were also falling short, along with 91.7% of controls. This may have arisen from poor intake of red meats. Australian Dietary Guidelines recommend children aged 2–4 years to consume 1–1.5 serves daily from the meat and alternatives food group, half of which is sourced from red meat [
]. However, the 2011–12 AHS reported children aged 2–3 years were consuming <20 g/day (approximately one third of a serve) of unprocessed, lean red meat [
It is important to note that RDIs account for almost all of the general healthy population in a particular age and sex group and thus often exceed individual needs [
]. Despite this, patients with CF are likely to require intakes toward the upper end of the spectrum due to reduced nutrient absorption and retention [
]. However, for the general population, comparison of intake against Estimated Adequate Intakes (EARs) may have been more appropriate. Considering this, only 1 control child (8.3%) was not meeting the EAR for iron.
This study had both strengths and limitations. Strengths of this study included the use of a large sample of children with CF with age- and sex-matched controls who were recruited over a wider age range than dietary studies conducted within the last decade [
]. However, this study represented a single centre with one of the highest rankings for growth outcomes in Australia. It could be hypothesized that micronutrient intake is therefore higher than other centres which raises the clinically relevant question as to whether centres with poorer growth outcomes have a larger deficit in micronutrient intakes. A future multicentre study would be useful to corroborate our findings. Further testing for serum micronutrient levels, where able, may have been beneficial to assess micronutrient status in relation to dietary intake. However, as serum levels reflect intakes from both diet and supplements, data on the latter would be needed to interpret findings. Collecting data on medication adherence being notoriously difficult.
Intake data was obtained through a validated FFQ which has been vigorously tested in Australian children aged 2–18 years [
]. However FFQs are limited by frequent overestimation of nutrient intake. Reliance on memory makes distortion of the diet possible, and periodically consumed foods are often missed. However, self-administration and short completion time (20–30 min) enabled lower respondent burden.
Furthermore, portion sizes used in the ACAES were derived from the 1995 NNS [
]. This may contribute to over- or underestimation of intake where further investigation is needed to address current portion sizes in relation to micronutrient intake in CF.
5. Conclusion
Long-term nutrition-related complications are becoming increasingly important as survival improves in CF. Despite children with CF consuming more total energy and micronutrients than controls apart from vitamin C and folate, a concerning proportion failed to meet requirements for key micronutrients such as folate, iron and calcium. Age appears to be a major factor contributing to micronutrient density where relative intake decreased as CF children started school. Pre-school children were most at risk of inadequate iron intake, and high school children were most at risk of overall inadequate intake. This emphasises the importance of not only quantity, but also quality of the CF diet, especially at a time where nutritional status is pivotal in achieving optimal growth and development. Clinicians and dietitians are encouraged to communicate the importance of consuming a healthful diet alongside high-energy and high-fat. Future directions should include representative samples from Australia and abroad to further corroborate these results.
Declaration of Competing Interest
None.
Acknowledgments
The authors would like to thank all the children and their parents/carers who took the time to take part in the study as well as Dr. Michael Coffey for his statistical support.
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Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review.
Significant (p < .05).
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