Phosphate Concentrations and Modifying Factors in Healthy Children From 12 to 24 Months of Age

Laura Koljonen, Maria Enlund-Cerullo, Helena Hauta-Alus, Elisa Holmlund-Suila, Saara Valkama, Jenni Rosendahl, Sture Andersson, Minna Pekkinen, Outi Mäkitie, Laura Koljonen, Maria Enlund-Cerullo, Helena Hauta-Alus, Elisa Holmlund-Suila, Saara Valkama, Jenni Rosendahl, Sture Andersson, Minna Pekkinen, Outi Mäkitie

Abstract

Context: Phosphate homeostasis and its modifiers in early childhood are inadequately characterized.

Objective: To determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age.

Design: This study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age 2 weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months.

Main outcome measures: Plasma phosphate concentrations at 12 and 24 months of age.

Results: Mean (SD) phosphate concentration decreased from 12 months (1.9 ± 0.15 mmol/L) to 24 months (1.6 ± 0.17 mmol/L) of age (P < 0.001 for repeated measurements). When adjusted by covariates, such as body size, creatinine, serum 25-hydroxyvitamin D, intact and C-terminal fibroblast growth factor 23, mean plasma phosphate was higher in boys than girls during follow-up (P = 0.019). Phosphate concentrations were similar in the vitamin D intervention groups (P > 0.472 for all). Plasma iron was associated positively with plasma phosphate at both time points (B, 0.006 and 0.005; 95% CI, 0.004-0.009 and 0.002-0.008; P < 0.001 at both time points, respectively). At 24 months of age, the main modifier of phosphate concentration was plasma creatinine (B, 0.007; 95% CI 0.003-0.011, P < 0.001).

Conclusion: Plasma phosphate concentration decreased from age 12 to 24 months. In infants and toddlers, the strongest plasma phosphate modifiers were sex, iron, and creatinine, whereas vitamin D supplementation did not modify phosphate concentrations.

Trial registration: ClinicalTrials.gov NCT01723852.

Keywords: clinical trial; hypophosphatemia; mineral homeostasis; phosphate; vitamin D.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
(A) Phosphate concentrations in children 12 and 24 months of age according to study identification number (ID). (B) Mean of phosphate concentrations in children at 12 and 24 months of age (unadjusted: mean ± SD; adjusted: estimates mean ± SE). Unadjusted mixed model with repeated measurements without covariates (Pinteraction < 0.001) and adjusted mixed model with repeated measurements with covariates (Pinteraction < 0.001): season, iron, length, weight, creatinine, ionized calcium, 25OHD, C-terminal FGF23, and intact FGF23. Pinteraction indicates repeated measurements of covariance.
Figure 2.
Figure 2.
Differences in mean phosphate concentrations (mmol/L) between sexes and intervention groups (mean ± SD, estimates mean ± SE [adj]). (A) Phosphate concentrations (mmol/L) at 12 months of age between girls and boys (t test P = 0.416) and at 24 months (t test P = 0.150). (B) Phosphate concentrations (mmol/L) at 12 months of age between intervention groups (t test P = 0.702) and at 24 months (t test P = 0.472). (C) Phosphate concentrations (estimates) at 12 months and 24 months of age between girls and boys (mixed model, Bonferroni P = 0.019). (D) Phosphate concentrations (estimates) at 12 and 24 months of age between the vitamin D intervention groups (mixed model, Bonferroni P = 0.706). Adjusted values were obtained by the analysis of mixed model with time-dependent covariates. The covariates were season (1 = winter, 2 = others), iron (µmol/L), length (cm), weight (kg), creatinine (µmol/L), ionized calcium (mmol/L), 25OHD (nmol/L), C-terminal FGF23 (pmol/L), and intact FGF23 (pg/mL).

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