Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Exposure Biomarker Assessment
2.3. Effect Biomarker Assessment: Urinary and Serum BDNF Levels
2.4. Behavioral Assessment in the NACII-IT Cohort
2.5. Covariates
2.6. Statistical Analysis
2.6.1. Phthalate Exposure Biomarkers
2.6.2. Urinary and Serum BDNF Protein Levels
2.6.3. Covariates and Confounding Factors
2.6.4. Cross-Sectional Associations between Phthalates, BDNF Concentrations and Children’s Behavior
2.6.5. Phthalate’s Mixture Models
2.6.6. Sensitivity Analysis
2.6.7. Interpretation and Software
3. Results
3.1. Study Population Characteristics
3.2. Phthalate–BDNF–Behavior Associations in the NACII-IT Cohort
3.3. Phthalate–Urinary BDNF Associations in NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO Cohorts (N = 1148)
3.4. Phthalate–Serum BDNF Associations in the CRP-SLO Cohort (N = 124)
3.5. Phthalate’s Mixture Associations
3.6. Sensitivity Analysis
4. Discussion
4.1. Phthalate–CBCL Associations
4.2. Urinary Phthalates and Serum BDNF Levels
4.3. Urinary Phthalate–Urinary BDNF Associations—Possible “Urine Concentration Bias”?
4.4. BDNF Biomarkers in Relation to CBCL
4.5. Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | NACII-IT | PCB-SK | InAirQ-HU | NEBII-NO | CRP-SLO | Combined b |
---|---|---|---|---|---|---|
Cohort characteristics [Mean (SD) or frequency (percentage)] | ||||||
Country | Italy | Slovakia | Hungary | Norway | Slovenia | - |
Initial sample size | 300 | 294 | 257 | 297 | 124 | 1148 |
Age | 7.0 (0.2) | 11.1 (0.4) | 9.3 (0.7) | 9.83 (1.17) | 8.85 (0.97) | 9.32 (1.68) |
BMI (Kg/m2) | 16.9 (2.26) | 20.2 (4.3) | 17.4 (3.3) | 17.4 (2.46) | 17.2 (3.09) | 18.0 (3.50) |
BMI z-score | 0.49 (1.15) | 0.92 (1.22) | 0.27 (1.35) | 0.32 (0.81) | 0.34 (1.44) | 0.51 (1.17) |
Child sex = boys | 150 (50%) | 130 (44%) | 130 (51%) | 160 (54%) | 55 (44%) | 570 (50%) |
Maternal education | ||||||
Low | 42 (14%) | 33 (11%) | 9 (4%) | 0 (0%) | 11 (9%) | 84 (8%) |
Medium | 139 (46%) | 235 (80%) | 122 (52%) | 39 (13%) | 30 (24%) | 535 (47%) |
High | 119 (40%) | 25 (9%) | 103 (44%) | 258 (87%) | 83 (67%) | 505 (45%) |
Maternal IQ | 120 (10.7) [68–128] | 108 (15.1) [63–132] | - | - | - | 114.1 (14.5) [63–132] |
Behavior CBCL assessment (Mean (SD)/[range] and BDNF levels (Median, P25, P75; μg/g creatinine) | ||||||
Total CBCL score | 23.2 (15.0) [0–87] | - | - | - | - | - |
Externalizing score | 5.4 (4.6) [0–27] | - | - | - | - | - |
Internalizing score | 6.3 (5.4) [0–34] | - | - | - | - | - |
Urinary BDNF a | 2.87 (1.98, 4.21) | 2.65 (1.85, 3.83) | 2.52 (1.70, 3.54) | 1.52 (1.08, 1.98) | - | 2.31 (1.52, 3.46) |
Serum BDNF | - | - | - | - | 45.1 (38.9, 52.6) | - |
Phthalate concentrations (Median, P25, P75; μg/g creatinine) | ||||||
MEP | 63.5 (33.3, 131.9) | 23.9 (12.9, 54.9) | 9.64 (5.82, 18.1) | 14.3 (9.70, 25.6) | 25.3 (15.7, 51.2) | 21.8 (10.4, 54.4) |
MnBP | 21.9 (14.5, 33.0) | 58.8 (35.9, 102.8) | 18.6 (11.5, 30.0) | 23.9 (15.1, 35.2) | 19.9 (14.0, 26.9) | 26.3 (15.5, 47.2) |
MiBP | 34.2 (24.6, 50.2) | 48.3 (25.9, 81.0) | 34.0 (19.9, 51.7) | 26.7 (16.1, 41.3) | 27.0 (17.5, 43.5) | 33.9 (21.5, 57.7) |
MBzP | 6.69 (3.89, 11.1) | 3.94 (0.77, 7.58) | 1.59 (0.93, 2.84) | 4.88 (2.95, 8.61) | 3.47 (2.12, 5.52) | 4.14 (1.80, 7.99) |
∑DEHP | 69.4 (51.8, 108.1) | 88.2 (57.8, 136.6) | 36.9 (23.8, 56.3) | 40.8 (29.3, 62.3) | 55.4 (38.4, 87.4) | 56.4 (35.6, 93.4) |
MEHHP | 19.2 (14.3, 28.8) | 20.3 (14.0, 31.8) | 10.8 (6.85, 16.6) | 9.29 (6.35, 14.5) | 14.6 (9.11, 21.9) | 14.8 (8.56, 23.5) |
MEOHP | 9.82 (6.89, 15.0) | 18.1 (12.2, 25.6) | 5.23 (3.43, 8.42) | 5.74 (3.89, 8.66) | 11.1 (7.27, 17.4) | 8.62 (4.91, 15.4) |
MECPP | 24.2 (16.8, 37.3) | 28.2 (18.0, 46.8) | 11.4 (7.32, 18.3) | 17.2 (12.3, 24.8) | 17.7 (11.7, 25.8) | 19.6 (12.5, 31.6) |
∑DINCH c | 6.17 (3.40, 10.5) | 2.52 (1.43, 4.97) | 1.97 (1.25, 4.11) | - | 4.27 (2.43, 7.05) | 3.30 (1.68, 6.68) |
MHINCH | 3.65 (2.03, 6.68) | 1.65 (0.90, 3.35) | 1.20 (0.74, 2.42) | 2.94 (1.91, 5.52) | 2.61 (1.41, 4.52) | 2.28 (1.23, 4.54) |
MCOCH c | 2.24 (1.26, 4.13) | 0.86 (0.46, 1.62) | 0.90 (0.49, 1.68) | - | 1.55 (0.89, 2.70) | 1.21 (0.58, 2.49) |
Outcome | All | Boys | Girls |
---|---|---|---|
IRR or PC (95% CI) | IRR or PC (95% CI) | IRR or PC (95% CI) | |
Total CBCL score | 1.09 (0.96, 1.23) | 1.07 (0.91, 1.25) | 1.11 (0.90, 1.35) |
Externalizing score | 1.15 (0.97, 1.36) | 1.20 (0.96, 1.49) | 1.11 (0.88, 1.39) |
Internalizing score | 1.03 (0.90, 1.17) | 1.04 (0.85, 1.29) | 1.00 (0.76, 1.30) |
Urinary BDNF levels | 25.9 (17.6, 34.7) | 36.0 (24.3, 48.9) | 18.6 (7.92, 30.5) |
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Salamanca-Fernández, E.; Espín-Moreno, L.; Olivas-Martínez, A.; Pérez-Cantero, A.; Martín-Rodríguez, J.L.; Poyatos, R.M.; Barbone, F.; Rosolen, V.; Mariuz, M.; Ronfani, L.; et al. Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies. Toxics 2024, 12, 642. https://doi.org/10.3390/toxics12090642
Salamanca-Fernández E, Espín-Moreno L, Olivas-Martínez A, Pérez-Cantero A, Martín-Rodríguez JL, Poyatos RM, Barbone F, Rosolen V, Mariuz M, Ronfani L, et al. Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies. Toxics. 2024; 12(9):642. https://doi.org/10.3390/toxics12090642
Chicago/Turabian StyleSalamanca-Fernández, Elena, Lydia Espín-Moreno, Alicia Olivas-Martínez, Ainhoa Pérez-Cantero, José L. Martín-Rodríguez, Rafael M. Poyatos, Fabio Barbone, Valentina Rosolen, Marika Mariuz, Luca Ronfani, and et al. 2024. "Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies" Toxics 12, no. 9: 642. https://doi.org/10.3390/toxics12090642