Determining an upper reference value for the urinary fluoride-creatinine ratio in healthy children younger than 7 years

The urinary fluoride/creatinine ratio (U&lt;sub&gt;F/Cr&lt;/sub&gt;) in a spot urine sample could be a useful systemic F exposure monitoring tool. No reference value for U&lt;sub&gt;F/Cr&lt;/sub&gt; currently exists, therefore this study aimed to establish an upper reference value for a U&lt;sub&gt;F/Cr&lt;/sub&gt;, corresponding to excessive systemic F exposure, i.e., &gt;0.07 mg F/kg body weight (b.w.)/day, in children. Subsidiary aims were to examine the relationship between (i) total daily F intake (TDFI) and 24-h urinary F excretion (DUFE); (ii) DUFE and U&lt;sub&gt;F/Cr&lt;/sub&gt;, and (iii) TDFI and U&lt;sub&gt;F/Cr&lt;/sub&gt;. Simultaneously collected TDFI, DUFE, and urinary creatinine (U&lt;sub&gt;Cr&lt;/sub&gt;) data in children &lt;7 years were taken from UK studies conducted from 2002 to 2014 in order to calculate U&lt;sub&gt;F/Cr&lt;/sub&gt; (mg/g) for each child. For the 158 children (mean age 5.8 years) included in the data analysis, mean TDFI and DUFE were 0.049 (SD 0.033) and 0.016 (SD 0.008) mg/kg b.w./day, respectively, and the mean U&lt;sub&gt;F/Cr&lt;/sub&gt; was 1.21 (SD 0.61) mg/g. Significant (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) positive linear correlations were found between TDFI and DUFE, DUFE and U&lt;sub&gt;F/Cr&lt;/sub&gt;, and TDFI and U&lt;sub&gt;F/Cr&lt;/sub&gt;. The estimated upper reference value for U&lt;sub&gt;F/Cr&lt;/sub&gt; was 1.69 mg/g; this was significantly (&lt;i&gt;p&lt;/i&gt; = 0.019) higher than the U&lt;sub&gt;F/Cr&lt;/sub&gt; (1.29) associated with optimal F exposure (0.05-0.07 mg/kg b.w./day). In conclusion, the strong positive correlation between TDFI and U&lt;sub&gt;F/Cr&lt;/sub&gt; confirms the strong association of these 2 F exposure variables and the value of a spot urine sample for prediction of TDFI (i.e., the most important risk factor in determining fluorosis occurrence and severity) in young children. Establishing an estimation of an upper reference value of 1.69 mg/g for U&lt;sub&gt;F/Cr&lt;/sub&gt; in spot urine samples could simplify and facilitate their use as a valuable tool in large epidemiological studies.</jats:p