**3. Results**

Table 1 shows the participant characteristics at each study visit. Just over half of the children were male, and the age ranged from 12.2 ± 0.28 months at the 1-year visit to 116 ± 8.2 months at the 9 year visit. Most of the children were of normal weight between 1 and 6 years; however, at 9 years, almost half of the children were overweight (24.8%) or obese (22.0%). Physical activity at 4 and 6 years was 65.8 ± 30.0 and 69.73 ± 29.3 min/day on average, respectively, and decreased to 21.0 ± 7.10 min/day at 9 years. The majority of children (more than 80% at 4, 6, and 9 years) were not exposed to secondhand tobacco smoke and were of middle or lower socioeconomic status.


**Table 1.** Participant characteristics at follow-up study visits.

a: Classification according to BMI/age z-score (Underweight <sup>&</sup>lt;−2SD, normal >−2SD to ≤+1SD, overweight >+1SD to +2SD, obesity >+2SD); b: Aerobic activities: Play in the park, run, walk, ride a bike, dance, stage 48−*<sup>n</sup>* = 7 missing observations; c: Classification according to the minutes that children expend with smokers, stage 48−*<sup>n</sup>* = 7 missing observations, stage 72−*n* = 12 missing observations, stage 96−*<sup>n</sup>* = 4 missing observations; d: Classification according to the AMAI index; data from the enrollment.

Table 2 shows kidney function parameters measured at 9 years; the mean cystatin C was 0.730 ± 0.17 mg/dL, while the mean BUN was 12.20 ± 3.09 mg/dL. Using the eGFRCystatinC formula, there were two children below 60 mL/min/1.73 m<sup>2</sup> and 75 children in the 60–90 mL/min/1.73 m<sup>2</sup> range, while for the eGFRSchwartz, a single child was between 60 and 90 and the rest had and eGFR ≥ 90 mL/min/1.73 m2. We note that while fewer children had SCr measures, this observation is in line with evidence that SCr-based equations may overestimate eGFR [26].


**Table 2.** Kidney function parameters from 9-year-old children.

Figure 1 shows the primary foods contributing to the estimated dietary intake of Cd from 1 to 9 years of age. At 1 and 2 years, the top contributors were leafy greens (1 year: 16.0%, 2 years: 9.0%), milk (1 year: 10.1%, 2 years: 9.8%), and carrots (1 year: 8.8%, 2 years: 7.9%); at 4 years, the top contributors were sweets (6.8%), milk (6.1%), and carrots (4.8%); at 6 years, the top contributors were lettuce (6.8%), sandwich (6.6%), and sweets (6.4%); and at 9 years, the top contributors were lettuce (6.0%), pasta soup (5.7%), and sweets (5.5%). Total dietary Cd intake was 4.43 ± 2.53 μg/d

at 1 year; 4.65 ± 2.45 μg/d at 2 years; 6.00 ± 3.45 μg/d at 4 years; 6.83 ± 3.15 μg/d at 6 years; and 8.09 ± 4.33 μg/d at 9 years. According to the TWI, Cd intakes were exceeded by children at all study visits (study visit, % children): 1 year, 64%; 2 years, 49%; 4 years, 35%; 6 years, 28%; and 9 years, 16%. For the cumulative Cd score (*n* = 175 children with information on dietary Cd in all study visits), we saw that 23 children had low Cd across all study visits; 38 children had high Cd in one study visit; 57 children had high Cd in two study visits; 31 children had high Cd in three study visits; 16 children had high Cd in four study visits; and 10 children had high Cd intake in all five study visits.

**Figure 1.** Primary foods contributing to estimated dietary Cd intake in 1–9-year-old children.

For the cross-sectional associations between higher 9-year dietary Cd and kidney parameters (Table 3), we observed an inverse association between dietary Cd and BUN (β = −0.077 (95% CI: [−0.151, −0.003])) and, marginally, with eGFRCystatinC (β = −0.046 (95% CI: [−0.107, 0.014])).

**Table 3.** Association between tolerable weekly intake (TWI) a dietary cadmium exposure at 9 years and concurrent kidney function parameters in children.


a Tolerable Weekly Intake: High ≥2.5 μg/kg body weight, low: <2.5 μg/kg body weight. b adjusted for sex, age, z-score BMI, physical activity, secondhand smoke, and socioeconomic status. c Serum creatinine.

We observed no significant associations between 1-year dietary Cd and subsequent children's kidney function (Table 4).


**Table 4.** Association between TWI dietary cadmium exposure (high vs. low) a at 1-year and kidney function parameters in 9-year-old children.

a Tolerable Weekly Intake: High ≥2.5 μg/kg body weight, low: <2.5 μg/kg body weight. b adjusted for sex, age, z-score BMI, physical activity, secondhand smoke, and socioeconomic status. c Serum creatinine.

Finally, we assessed associations with cumulative Cd intake using an ordinal score, analyzed as discrete and categorical (Table 5). We again identified an inverse association with BUN when using the score as a discrete variable; however, no associations with the other parameters were observed. Using the score as categorical, we observed an inverted "U-shaped" relationship with cystatin C where estimates decreased with an increasing cumulative Cd score to 3 and then increased with the cumulative Cd score from 4 and 5; and a negative dose-response for BUN where, as the score increased, the model estimates decreased progressively from −0.006 to −0.187 (Table 5).

**Table 5.** Association between estimated cumulative dietary Cd score (as a discrete and categorical variable) and 9-year kidney function parameters a.


a adjusted for sex, age, z-score BMI, physical activity, secondhand smoke, and socioeconomic status. b Serum creatinine.
