Nutrient Intake and Obesity in Prepubescent Children with Down Syndrome
   
Amy Luke, Ph.D.
Marjorie Sutton, MS, RD
Dale A. Schoeller, Ph.D.
Nancy J. M. Roizen, M.D.
J Am Diet Assoc 96 (12): 1262-7 (1996 Dec)
Reprinted with the permission of Saudia Muhammad, Permissions Editor
Journal of the American Dietetic Association
Copyright © 1996 by The American Dietetic Association

Abstract
Objective The aim of this study was to measure nutrient intake and body composition in prepubescent children with Down syndrome to understand dietary barriers involved in the prevention and treatment of obesity.
Design Dietary intake was determined from parent-reported 3-day diet records for children with Down syndrome and control subjects. Energy intake was compared with energy expenditure measured by the doubly labeled water method. Body composition was determined by deuterium dilution, bioelectrical impedance analysis, and skinfold thickness measurements.
Subjects/Setting Ten prepubescent children with Down syndrome and 10 control subjects were recruited from the hospital community. The study was conducted in the Clinical Research Center of the University of Chicago Medical Center.
Main outcome measures Nutrient intakes were compared with the Recommended Dietary Allowances (RDAs) to estimate risk for nutrient deficiency. Fat-free mass values determined by bioelectrical impedance analysis and measurement of skinfold thicknesses were compared with values determined using the deuterium dilution method.
Statistical analysis performed Unpaired t tests were used for comparisons between subjects groups and the Wilcoxon signed-rank test was used for comparison of nutrient intakes with RDAs.
Results The subjects with Down syndrome were significantly shorter (P < .01) than control subjects; however, body composition did not differ between the groups. Reported energy intake was lower in subjects with Down syndrome. In addition, several micronutrients were consumed, especially among nonobese subjects with Down syndrome, at less than 80% of the RDA.
Applications To avoid lowering already inadequate intakes of several vitamins and minerals, we suggest that treatment of obesity in children with Down syndrome combine a balanced diet without energy restriction, vitamin and mineral supplementation, and increased physical activity.
   Obesity in children with Down syndrome has long been recognized by parents and health professionals1. Using a definition of overweight as a body mass index (kg/[m.sup.2]) above the 85th percentile of the second National Health and Nutrition Examination Survey (NHANES II), researchers found that 50% of children with Down syndrome between the ages of 1 month and 18 years were overweight1-4. The prevalence of children with Down syndrome whose body mass index was greater than the 85th percentile was always more than 30%, although this value fluctuated with age. This finding is similar to more recent estimates of 20% to 25% for children in the general population, according to the NHANES II criterion5,6.
   Obesity in all children is of concern for a variety of reasons. Studies indicate that there is a growing incidence of obesity in the United States and confirm that obese children and adolescents are more likely to become obese adults than nonobese children7. Obesity in adulthood is associated with an increased risk for hypertension; hyperlipidemia; diabetes mellitus; surgical morbidity; and renal, pulmonary, and orthopedic problems8-12. In addition to medical risks, a study by Gortmaker et al.13 documented significantly increased discrimination toward obese women in the workplace and in social situations. Also, psychosocial dysfunction resulting from perceived or actual discrimination tends to make the obese state self-perpetuating12,13. In persons with Down syndrome, where the syndrome itself may stigmatize the person, obesity can further limit the capacity to participate in social, recreational, and athletic activities that are so important for physical and emotional development1,3,14,15.
   The high prevalence of and the risks associated with obesity in children with Down syndrome necessitate the development of treatments. Nonpharmacologic treatment of obesity in adults typically includes energy restriction and increased physical activity. The use of energy restriction is limited in children because of potential effects on growth. In children with Down syndrome, however, dietary treatment of obesity is complicated by feeding difficulties and inappropriate energy and nutrient intakes15-17. Inactivity is a known risk factor for obesity in all people and an emphasis on physical fitness in childhood is a recognized treatment measure5,15,18. Unfortunately, developmental and physical limitations place children with Down syndrome at greater risk for inactivity than the average child14,19.
   Our study was designed to examine the body composition and energy and nutrient intakes of prepubescent children with Down syndrome compared with that of control children to understand dietary barriers in the treatment or prevention of obesity in this population.

SUBJECTS AND METHODS
The study subjects included 10 prepubertal boys and girls with Down syndrome, 5 to 11 years old, recruited from the University of Chicago Wyler Children's Hospital and LaRabida Children's Hospital (Chicago, Ill) and through the National Association for Down Syndrome (Oak Brook, Ill). The subjects were selected to represent a range of body sizes from 95% to 200% of ideal body weight. Ten healthy control subjects were recruited from within the University of Chicago hospital community. The age and weight ranges of the control group were comparable to those in the group with Down syndrome. Subject characteristics are listed in Table 1. The protocol was approved by the Institutional Review Board of the University of Chicago and signed parental consent was obtained before subject participation.

Table 1 Characteristics of study subjects (mean ± standard deviation)
Characteristic  Subjects with Down syndrome (n=10)   Control subjects (n=10) 
Gender
Chronologic age (y)
6 girls, 4 boys
8.8 ± 2.5
5 girls, 5 boys
9.1 ± 2.9
Height agea (y)
Height (cm)
6.9 ± 2.6
120.0 ± 15.0
9.3 ± 3.8
130.8 ± 18.0
Height (percentile NCHSb)
Height (percentile Down syndromec)
10.8 ± 12.0**
58.5 ± 22.7
57.2 ± 27.4
NAd
Weight (kg)
Weight (percentile NCHSb)
33.8 ± 17.3
58.4 ± 34.1
35.1 ± 14.2
58.3 ± 32.0
Weight (percentile Down syndromec
Weight height index
67.7 ± 25.4
1.39 ± 0.31
NA
1.19 ± 0.27
Body mass index 22.1 ± 6.0 19.8 ± 4.7
1Fomon et al.26.
bNational Center for Health Statistics (NCHS) tables4.
cGrowth tables for children with Down syndrome2.
dNA = not applicable.
**Significantly different from controls (P < .01).

   Subjects were admitted to the Clinical Research Center at the University of Chicago Hospitals between 7:30 and 8:30 AM on the study day, having fasted since 8 PM the night before. Height was measured to the nearest 0.1 cm using a Harpenden Stadiometer (San Francisco, Calif). Subjects were weighed without shoes and dressed in light clothing on an electronic balance (Digitron Corp, Chicago, Ill), accurate to 0.1 kg. Heights and weights were compared with National Center for Health Statistics (NCHS) and Down syndrome growth charts2,4.
   After the collection of a baseline urine sample, subjects were given an oral dose of 18O- and deuterium-labeled water for measurement of total body water and energy expenditure. The energy expenditure measurement period covered 2 weeks starting at the clinic visit. Parents were instructed to collect the first urine void of day 8 and of day 14. On day 14, the subjects returned to the Clinical Research Center for a final weight measurement and to turn in the collected urine samples. A complete description of the doubly labeled water method for measurement of energy expenditure is presented elsewhere20. Mean daily energy expenditure data for these study participants were published previously and are presented here for validation of dietary intake records21.
   Dietary assessment was obtained by 3-day written diet records kept by parents during the 2-week energy expenditure period. Parents were instructed in measuring techniques and portion estimation and kept records for 3 consecutive days, which included 1 weekend day and 2 week days. Incomplete dietary data were provided for two of the control subjects, so they were omitted from all dietary analyses. Diet records were analyzed using the Food Processor II program (version 2.1, 1989, ESHA Research, Portland, Ore) and compared with the 1989 Recommended Dietary Allowances (RDAs) for both chronologic and height ages22. No significant differences were found between RDAs for chronologic and height age; therefore, only data for chronologic age are reported in the Results section. Dietary intake data were then used as the basis for individual nutrition counseling.
   In addition to dietary assessment, body composition data were collected by means of three methods: deuterium dilution, bioelectrical impedance analysis (BIA) (model BIA 101, RJL Systems, Detroit, Mich), and four-site skinfold thickness measurements. Deuterium dilution was used as the reference method for the calculation of total body water and fat-free mass. With this technique, the subject ingests a small, known volume of the stable isotope deuterium in the form of deuterium oxide. After the deuterium oxide equilibrates with body water, approximately 6 hours after isotope administration, a sample is collected and analyzed for deuterium content (urine was used in this study). Using the dilution principle, total body water can then be calculated after comparing deuterium levels in urine before and after administration of the isotope. Further description of the principle and technique has been reported elsewhere23.
   Total body water was also measured by BIA, a technique based on the electrical properties of living organisms. In brief, an electrical current is applied across electrodes placed on the hand and foot in the standard tetrapolar positioning; the electrolyte-containing compartment of the body (i.e., fat-free mass) will conduct the small current whereas the nonelectrolyte-containing compartment (i.e., fat mass) provides resistance to current flow. Total body water was calculated using an equation developed by Kushner et al.24: TBW = 0.593 (height(2)/resistance) + 0.065 (weight) + 0.04, where TBW is total body water in kilograms, height is in centimeters, resistance is in ohms, and weight is in kilograms. Complete descriptions of the BIA principle and technique have been published25.
   Fat-free mass was calculated by dividing total body water, derived from either deuterium dilution or BIA, by age-specific hydration constants based on the subject's height age26. Fat mass was obtained by subtracting fat-free mass from body weight.
   Fat-free mass and fat mass levels were also determined from skinfold thickness measurements. All anthropometric measurements were performed by a single dietitian. Skinfold thickness was measured in triplicate at the biceps, triceps, sub-scapular, and suprailiac sites to the nearest 0.2 mm using Lange calipers (Cambridge, NJ). Body density was calculated using the age- and sex-appropriate equations of Brook27 for children aged 4 to 10 years and of Durnin and Rahaman28 for children older than 10 years. Percentage body fat was then calculated using the Siri equation29. The determination of body fat content from skinfold measurements is based on the assumption that the volume of subcutaneous fat comprises a constant proportion of total body fat. This technique is commonly used for determination of body composition in clinical settings, but its validity has been questioned30.
   Data herein are presented as means ± standard deviation. The Wilcoxon signed-rank test was used for comparisons between the subject groups. The statistical software package used was Minitab (release 10 for Windows, 1994, Minitab Inc, State College, PA).

RESULTS
As listed in Table 1, subjects with Down syndrome were significantly shorter than control subjects when height was expressed as percentile of NCHS growth charts (P < .001), although the two groups were of comparable weight, weight percentile of NCHS charts, and body mass index (all P > .10). Albeit the subjects with Down syndrome were shorter than control subjects, the average height of the subjects with Down syndrome fell near the median height of the Down syndrome growth charts (range=16th to 95th percentile). The mean weight:height index (defined as weight/mean relative weight for height provided in gender-specific standard tables) for the group with Down syndrome was 1.39 based on NCHS tables, as presented in Table 1, yet only 1.20 if based on Down syndrome growth tables. The mean index for ratio of weight to height for the control group was 1.19 based on NCHS tables. When obesity is defined as an index for ratio of weight to height greater than 1.2, 50% of those with Down syndrome were obese, regardless of the growth charts used, compared with 30% of the control subjects2,4.
   Fat-free mass levels measured using BIA and four-site skinfold thickness were compared with fat-free mass calculated from deuterium dilution; results are presented in Table 2. No significant difference in body composition was noted between the subject groups (P > .20). The three methods of determining body composition provided comparably accurate results (P > .50).

Table 2 Fat-free mass as measured by three methods (mean ± standard deviation)
Method  Subjects with Down syndrome (n=10)   Control subjectsa (n=10) 
kg % Referenceb kg % Reference
Deuterium dilution 21.2 ± 7.7   23.6 ± 7.3  
Bioelectrical impedance analysis  22.5 ± 7.9 103.2 ± 6.1 23.2 ± 7.8 97.4 ± 4.7
Skinfold thickness measurement 21.8 ± 7.4 103.3 ± 5.2 24.0 ± 6.8 103.0 ± 6.0
aNo statiscally significant differences betweeen methods.
bReference=deuterium dilution.

   Mean daily energy intakes calculated from the 3-day diet. records and energy expenditure as measured by the doubly labeled water method are compared in Table 3. No significant differences were found in reported energy intakes (P = .13) or energy expenditures as measured by the doubly labeled water method (P = .35) between subject groups. The reported energy intake, expressed as percentage of RDA, of the group with Down syndrome was significantly less than that of control subjects (P < .05).

Table 3 Daily energy intake (mean ± standard deviation)
Energy intake  Subjects with Down syndrome (n=10)   Control subjects (n=8) 
Reported intake (kcal/d) 1,861 ± 488 2,393 ± 781
Measured expenditurea (kcal/d) 1,680 ± 477 1,957 ± 613
Reported intake (% of expenditure)  114.0 ± 24.8 122.1 ± 14.6
Reported intake (% of RDAb) 86.5 ± 28.6* 111.3 ± 21.6
aDaily expenditure as measured by doubly labeled water.
bRecommended Dietary Allowance22 for energy by age group.
*Significantly less than control subjects (P < .05).

   The macronutrient composition and cholesterol content of the diets did not differ between groups (P > .25 and P = .45, respectively) and compared favorably with the recommendations of the National Cholesterol Education Program, the American Academy of Pediatrics, and the American Heart Association (Table 4)31-33). Both subject groups, however, ate less than recommended amounts of dietary fiber: 75% of those with Down syndrome and 63% of control subjects consumed less than 80% of the recommended 1 g/100 kcal22.

Table 4 Daily macronutrient, fiber, and cholesterol intake (mean ± standard deviation)
Intake  Subjects with Down syndrome (n=10)   Control subjects (n=8)   Recommended intakesa 
Protein (% of energy)b 17.4 ± 2.8 16.9 ± 1.2 15
Carbohydrate (% of energy) 53.0 ± 7.9 50.9 ± 4.6 55
Fat (% of energy) 30.3 ± 6.8 33.3 ± 3.6 30
Fiber (g/100 kcal) 0.69 ± 0.37 0.80 ± 0.26 1.00
Cholesterol (mg) 298 ± 186 362 ± 181 300
aAmerican Heart Association, American Academy of Pediatrics, National Cholesterol Education Program31-33.
bPercents do not equal 100% because of roundingRecommended Dietary Allowance.

   Compared with the control group, the subjects with Down syndrome had significantly lower intakes of riboflavin, pyridoxine, iron, and calcium (P > .05) (Table 5). In addition, the intake of several micronutrients was less than 80% of the RDA for individual subjects in both groups (Table 6). Fifty percent of the subjects with Down syndrome consumed less than 80% of the RDA for calcium and/or zinc. Eighty percent of those with Down syndrome and 38% of control subjects had similarly low intakes of copper. When the subjects with Down syndrome were separated into nonobese (index for ratio of weight to height <= 1.2) and obese (index for ratio of weight to height > 1.2) groups, the disparity in micronutrient intake increased. Compared with obese subjects with Down syndrome and control subjects, more nonobese subjects with Down syndrome had intakes below 80% of recommended levels for all nutrients except vitamin C and calcium.

DISCUSSION
This study of the dietary intake and body composition of prepubescent children with Down syndrome provides insight on the difficulties of treating obesity in this population, as well as validation of two clinically useful tools for the determination of body composition. The subjects with Down syndrome had significantly lower reported intakes of energy and several micronutrients than control subjects, levels that may put individuals at risk for vitamin or mineral deficiencies. As reported previously, measured total energy expenditure was also lower in the subjects with Down syndrome and, compared with the control subjects, they had a 10% to 15% lower resting metabolic rate but equivalent expenditure above resting, that is, as physical activity and thermic effect of food21. Therefore, children with Down syndrome may have an inherent metabolic risk factor for expending less total energy because of their lower resting metabolic rate, which places them at risk for developing obesity. In contrast to the energy intake and expenditure differences, the subject groups were comparable in terms of body composition; in other words, the subjects with Down syndrome did not exhibit abnormal levels of body fat for their weight and age. These results may influence the choice of obesity treatment modalities for children with Down syndrome; for example, increase energy expended as physical activity rather than restrict diet.
   In light of concern about the validity of self-reported dietary intake measurements, we compared the parent-recorded intakes with objectively measured expenditures. We accepted the assumption that in weight-stable children intake will approximate expenditure plus a very small increment for growth26,34. Parent-recorded dietary intakes in our study were quite accurate for total energy, as was the case in a report by Livingstone et al.35. The fact that parents recorded energy intake accurately during the same period for which energy expenditure was measured suggests that reported intakes of other nutrients are also likely to be relatively accurate. This validation of parent-reported energy intake strengthens the contention that persons with Down syndrome are consuming less than recommended levels of several micronutrients.
   Dietary treatment of obesity in all children is complicated by their energy and nutrient requirements for growth and development. Energy restriction during childhood can result in stunted linear growth and immunologic impairment36-38. Although children with Down syndrome are typically shorter than healthy children, as they were in this study, the stunting is thought to be due to factors associated with the chromosomal abnormalities and possibly, in part, to defects in growth hormone and insulin-like growth factor rather than nutritional deficits39. For the subjects with Down syndrome in our study, intake of several micronutrients, even though lower than recommended, were not likely to be a cause of their short stature. The concern over obesity exhibited by parental enthusiasm for participating in this study, however, could result in harmful dietary restriction that affects linear growth in the long term36.
   Although energy intake was lower in the subjects with Down syndrome than in control subjects, both groups conformed fairly well to the guidelines for macronutrient distribution set up by the American Heart Association: 30% and 33% of total energy, respectively, from fat in the diets of those with Down syndrome and control subjects32. In both groups cholesterol intakes were close to the recommended levels for adults33. The slightly higher cholesterol intake of control subjects was due to their greater consumption of meat, as some parents of the children with Down syndrome reported that their children had problems chewing meats. Fiber intake, however, was low in both subject groups: 75% of subjects with Down syndrome and 63% of control subjects consumed less than 80% of the recommended 1 g/100 kcal22. Low fiber intake may be a contributing factor to the constipation often reported in persons with Down syndrome40. An increase of fiber was recommended for almost all of the subjects during individual nutrition counseling.
   The macronutrient distribution of the diets conformed well to recommended levels, but micronutrient intakes did not consistently meet the RDAs. Vitamin and mineral intakes were lower overall in subjects with Down syndrome than in control subjects, except for vitamin C. This finding may be related to the feeding difficulties in patients with Down syndrome discussed by Pipes and Holm16, which included refusal to eat from specific food groups, such as milk or vegetables. For example, the intake of fruits and vegetables was less than the recommended five servings per day in both groups and was reflected in low intakes of vitamins A and C, especially in the subjects with Down syndrome41. In addition to lower than recommended intakes, it has been reported that absorption of vitamin A is decreased and plasma levels of retinol are low in those with Down syndrome42-44. Inadequate vitamin A nutriture in this population has been implicated in abnormalities in immune response and dentition development43-44. With risk for deficiency defined as less than 80% of the RDA, 20% of subjects with Down syndrome were at risk for vitamin A and C deficiencies and 50% for vitamin E deficiency. Few control subjects had similarly low intakes. Although simple carbohydrate intake was not quantified, examination of diet records showed a lower consumption of high-sugar snacks among the group with Down syndrome than the control group. In the group with Down syndrome most consumption of simple carbohydrate resulted from the intake of fruit juices. Thus, an increased consumption of "empty calorie" simple sugars is not likely the cause of lower than recommended micronutrient intakes.
   Mineral intake was also low in the group with Down syndrome. Half of these subjects had deficient calcium intakes — a finding similar to that of Pipes and Holm16 — whereas intake was sufficient in all of the control subjects. Calcium insufficiency in the subjects with Down syndrome, combined with the relative lack of weight-bearing exercise, raises concern abut bone density later in life3,15. In addition, the low intakes of the trace minerals zinc (in the group with Down syndrome) and copper (in both groups) support the suggestion that the intake of such trace minerals may be marginal in the US population as a whole45. Zinc and copper are vital for proper growth and development, and zinc nutriture has been especially examined for its potential role in the immune function in Down syndrome46-48.

APPLICATIONS
To our knowledge, this investigation is the first attempt to compare body composition measurement by BIA, an indirect measure of fat-free mass, and skinfold thickness, an indirect indicator of fat mass, with a reference method such as deuterium dilution in children with Down syndrome. Deuterium dilution is also an indirect measure of fat-free mass. Fat-free mass values calculated from four-site skinfold measurements and BIA were comparable to within about 5% of the values determined by deuterium dilution in both subject groups. These easy-to-use, clinical tools allow periodic measurement of body fat in children so that body compositional changes during growth and weight gain can be monitored. Because problems with overweight and obesity in children with Down syndrome often appear in prepubescence, accurate measurements at regular intervals make early detection of changes in linear growth and weight parameters possible, thereby allowing prompt intervention where needed.
   With respect to the prevention of obesity, the low micronutrient intake was more pronounced in those subjects with Down syndrome who were not obese and, therefore, not receiving energy in excess of their needs. Treatment of obesity in children with Down syndrome is likely more problematic than in children without Down syndrome, even though levels of body fat and degrees of obesity are similar in children with Down syndrome and control subjects of the same age and weight range. The relatively low intake of children with Down syndrome would make it difficult to decrease energy intake further without increasing the risk of deficiencies of several vitamins and minerals. Fat restriction is one avenue, but our subjects already conformed to guidelines for dietary fat. We suggest that any weight management program tailored to children with Down syndrome include a balanced diet, individually prescribed, that incorporates nutrient-rich, natural food sources of nutrients and a daily vitamin/mineral supplement. Increasing physical activity adapted to the individual child's age and ability is also important, because it provides an increase in energy expenditure without necessitating a decrease in energy intake.

This research was supported by the Down Syndrome Research Foundation and National Institutes of Health grants RR00055 and DK26678.

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A. Luke is a research associate in the Department of Preventive Medicine and Epidemiology, Loyola University Chicago, Maywood, Ill. At the time of this study, she was a PhD candidate at the University of Chicago, Committee on Human Nutrition and Nutritional Biology, Chicago, Ill, where M. Sutton is a nutrition specialist and N. J. M. Roizen is an assistant professor of clinical pediatrics in the Department of Pediatrics, and D. A. Schoeller is a professor in the Department of Medicine.
Revised: November 21, 1999.