Participants

Table 1. Table 1. Baseline Characteristics of the Study Participants.

Baseline characteristics were similar in the two study groups, except for a difference in the parents' level of education (Table 1). The mean BMI z score was 0.03, which corresponded with the 51st percentile of Dutch children.23 The SD of 1.02 confirmed that our sample was representative of Dutch children, for whom the SD equals 1.00 by definition. At baseline, the participants consumed a mean (±SD) of 1.02±0.20 sugar-sweetened beverages in the classroom during the 10 a.m. break, Monday through Friday, and 1.50±1.40 sugar-sweetened beverages per day during weekends.

The net duration of the study was a mean of 541±8 days.20 The percentage of participants who consumed the study beverages decreased from 100% at the beginning of the study to 88% at 6 months, 81% at 12 months, and 74% at 18 months (Figure 1). The major reasons for discontinuing the study were dislike of the beverage (accounting for 69% of the children who discontinued the study) and minor adverse events (13%); weight gain accounted for 4% of children who discontinued the study (four in the sugar group and two in the sugar-free group) (Figure 1, and Table S6 in the Supplementary Appendix).

Adherence and Blinding

Table 2. Table 2. Primary and Secondary Outcomes in the Full Cohort, with Imputed Data for Children Who Did Not Complete the Study, and in the Cohort of Children Who Completed the Study.

A total of 26% of the participants stopped consuming the beverages. These children had a slightly higher BMI at baseline, and their parents had completed fewer years of school (Table S7 in the Supplementary Appendix). This difference in educational levels theoretically might have influenced the effect of the beverages on weight loss. During the first 6 months of the study, however, weight loss was the same among children who ultimately completed the study as among children who discontinued the study after 6 months or more (Fig. S1E in the Supplementary Appendix). The proportion of children who were aware of the type of beverage they were consuming was similar among children who did and those who did not complete the study (Table S8 in the Supplementary Appendix). Also, most children who did not complete the study were lean, and few children dropped out because of concern about weight (Tables S6 and S7 in the Supplementary Appendix). Most children who stopped drinking the study beverages did so because they no longer liked the beverages. Analyses in which missing values were imputed (Table 2) also suggested that results for the full cohort would have been similar to those for the children who completed the study.

Figure 2. Figure 2. Urinary Sucralose Concentrations. The sucralose concentration was determined in spot urine samples by means of liquid chromatography with mass spectrometry.21 Samples were obtained from randomly selected children who completed the study. We assigned a value of 0.01 to samples below the detection limit of 0.02 mg per liter. The upper and lower ends of the boxes indicate the 25th and 75th quartiles, the black dots means, the horizontal lines within the boxes medians, the upper whisker the maximum value, and the lower whisker the minimum value. Values for the sugar-free group are based on samples obtained from 116 children at 6 months and from 117 children at 12 and 18 months. Mean (±SD) urinary sucralose concentrations were 6.3±3.7 mg per liter at 6 months, 6.6±4.5 mg per liter at 12 months, and 7.0±5.6 mg per liter at 18 months; sucralose was undetectable in 3% of samples at 6 months, 8% of samples at 12 months, and 10% of samples at 18 months. Values for the sugar group are based on samples obtained from 54 children at 6 months and 36 children at 12 and 18 months. Mean values were 0.04±0.13 mg per liter at 6 months, 0.03±0.14 mg per liter at 12 months, and 0.31±0.56 mg per liter at 18 months; sucralose was undetectable in 93% of samples at 6 months, 97% of samples at 12 months, and 67% of samples at 18 months. We also pooled 543 samples from participants at baseline to produce 20 pools. The mean sucralose concentration in these samples was 0.06±0.07 mg per liter.

The 477 children who completed the study consumed 5.8 cans, or 83% of the assigned 7 cans per week, with no difference according to the type of beverage consumed and no changes over time (Table S2 in the Supplementary Appendix). The mean level of urinary sucralose was 6.7±4.7 mg per liter in the sugar-free group and 0.1±0.3 mg per liter in the sugar group (Figure 2), indicating adherence in the group of children who drank the artificially sweetened beverages.

At 18 months, 609 children were asked which type of beverage they thought they had received (Table S8 in the Supplementary Appendix). Among 474 children who completed the study, 48% in the sugar-free group and 50% in the sugar group answered that they did not know, 36% in the sugar-free group and 27% in the sugar group answered “artificially sweetened,” and the remainder said “sugar-sweetened.” The proportion of participants who correctly responded “artificially sweetened” was 21% (95% confidence interval [CI], 12 to 30) higher (47 more children) than expected by chance, as estimated with the “blinding index” described by Bang et al.27 In the sugar group, the proportion of children who were aware of the type of beverage they had consumed was 3% (95% CI, −12 to 6) lower (7 fewer children) than expected. Among 135 children who did not complete the study, the beverage was correctly identified by 12% more, or 9 more children, than expected, in the sugar-free group, and by 1 less child than expected in the sugar group.

BMI z Score and Other End Points

In the full cohort of 641 children, the mean BMI z score increased by 0.02±0.41 SD units in the sugar-free group and by 0.15±0.42 SD units in the sugar group (Table 2) when missing values were imputed. The mean difference of 0.13 SD units was significant. The sugar-free group gained significantly less body fat, as evidenced by skinfold thickness, waist-to-height ratio, and electrical impedance. The mean weight increased by 6.35±3.07 kg in the sugar-free group and by 7.37±3.35 kg in the sugar group. The mean difference of 1.01 kg (2.2 lb) was significant. The mean difference in weight gain decreased to 0.82 kg (P=0.002) when adjusted for height change. The BMI adjusted for age28 increased 0.36 less in the sugar-free group than in the sugar group (P=0.001). An alternative method for handling missing data — namely, complete case analysis with covariate adjustment29 — yielded very similar results and levels of significance (Table S9 in the Supplementary Appendix).

Figure 3. Figure 3. Body-Mass Index (BMI) z Score in the 477 Children Who Drank the Study Beverages for the Full 18 Months. The z score for BMI is the BMI expressed as the number of standard deviations by which a child differed from the mean in the Netherlands for his or her age and sex. Panel A shows mean z scores for the two study groups over the 18-month study period. Panel B shows the between-group difference in the mean change from baseline (the mean change in the BMI z score in the sugar-free group minus the mean change in the sugar group), as a function of time. T bars in both panels indicate standard errors.

Similar results were also seen in the 477 children who consumed the study beverages for the full 18 months (74% of the children enrolled) (Table 2 and Figure 3). Children in the sugar-free group who completed the study gained 35% less body fat than those in the sugar group, according to impedance measurements,26 and 19% less when fat mass was calculated from the sum of the thicknesses of four skinfolds. According to the changes in skinfold thickness, the sugar-free group gained 1.47 kg of body fat and the sugar group gained 1.82 kg.30 Most of the effect on BMI z score and weight was achieved in the first 6 months (Figure 3B, and Fig. S2B in the Supplementary Appendix). The mean height increased by 10.21±1.85 cm in the sugar-free group and by 10.57±1.93 cm in the sugar group. The mean difference of 0.36 cm (0.14 in) was significant (P=0.04), but the difference in z score for height was not significant (Table 2).

We obtained measurements at 18 months in 136 of the 164 children who did not complete the study. When we combined their measurements with those in the 477 children who completed the study, the mean BMI z score increased by 0.06±0.44 SD units in the sugar-free group and by 0.12±0.44 SD units in the sugar group. The mean difference of 0.07 SD units was not significant (95% CI, −0.134 to 0.002; P=0.06).