Table 2.
Summary of the studies included in this review considering a childhood exposure to PFASs. For each study, information about the name of the study, country, year of the first enrolment, and number of subjects included in the statistical analyses were reported. Moreover, the information about PFASs (which ones monitored, when the samples were collected, and measured concentrations) is reported, as well as which outcomes were measured and when. The main associations found are also reported; in particular, each line represents a positive or a negative association between a compound and an outcome: an up arrow before the compound and an up arrow before the outcome indicates a positive association, while an up arrow before the compound and a downward arrow before the outcome indicates a negative association. Marginally significant associations are also reported (m). Finally, in the last column, it is reported if and which estimates were included in the meta-analyses
| Reference | Name of study | Country and region | Years of first enrolment | Number of subjects | Exposure assessment in children | Outcomes measured in children | Significant or marginally significant associations between exposure and outcomes | Data included in the meta-analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| PFASs measured in blood | Sampling time |
PFASs concentrations (ng/mL) |
Type | Time | |||||||
|
Papadopoulou et al., 2021 [65] |
HELIX project | UK, France, Spain, Lithuania, Norway, Greece | from 1999 to 2010, across the 6 cohorts | 1101 | PFOA, PFNA, PFUnDA, PFHxS, PFOS | From mean (SD) age 7 (0.5) to 11 (0.6) years |
Median PFOA: 1.53 PFNA: 0.47 PFUnDA: 0.06 PFHxS: 0.34 PFOS: 1.93 |
WC | 8 years (mean; range: 6 -12 years) |
↑ PFAS mixture—↓ WC ↑ PFOA—↓ WC |
Data not included as for the HELIX project, data from Vrijheid et al., 2020 considered a larger population |
|
Geiger et al., 2021 [96] |
NHANES | U.S | 1999–2000, 2003–2012 | 2473 | PFOA, PFOS | 12–18 years |
Mean PFOA: 3.79 PFOS: 15.66 |
BMI WC |
12–18 years |
↑ PFOA—↑ BMI m ↑ PFOS—↑ BMI (significant in the unadjusted model) ↑ PFOS—↑ WC (significant in the unadjusted model) |
Overweight risk: PFOA, PFOS (both sexes combined) |
|
Averina et al., 2021 [97] |
Fit Futures study | Northern Norway | 2010–2011 | 940 | PFBS, PFPS,PFHxS, PFHpS, PFOS, PFNS, PFDS, PFDoDS, PFOSA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA |
Mean (SD) 16.3 (1.1) – 16.5 (1.4) |
Mean (SD) PFBS: 0.005 (0.002) PFPS: 0.01 (0.007) PFHxS: 0.02 (0.01) PFHxA: 0.04 (0.04) PFHpS: 0.01 (0.01) PFHpS: 0.07 (0.06) PFOS: 0.04 (0.05) PFOA: 0.30 (0.13) PFNS: 0.02 (0.02) PFNA: 0.03 (0.01) PFDS: 0.02 (0.012) PFDA: 0.03 (0.01) PFUnDA: 0.03 (0.02) PFDoDS: 0.03 (0.035) PFDoDA: 0.02 (0.02) PFTrDA: 0.03 (0.030) PFTeDA: 0.08 (0.089) PFOSA: 0.01 (0.010) |
BMI |
Mean (SD) 16.3 (1.1) – 16.5 (1.4) |
↑ PFHxS—↑ obesity ↑ PFHpS—↑ obesity |
Not suitable data (not directly associating with BMI) |
|
Canova et al., 2021 [98] |
Veneto Region Health Surveillance Program | Italy | 2017–2019 |
9362 (6669 adolescents and 2693 children) |
PFOS, PFOA, PFHxS, PFNA, PFHpA, PFBS, PFHxA, PFBA, PFPeA, PFDeA, PFUnA, PFDoA | 14–19 years (adolescents) and 8–11 (children) |
Mean (SD) in adolescents: PFOA: 51.6 (47.2) PFOS: 4.1 (3.5) PFHxS: 3.6 (2.9) PFNA: 0.5 (0.3) Mean (SD) in children: PFOA: 26.2 (21.5) PFOS: 2.6 (2.5) PFHxS: 2.2 (1.5) PFNA: 0.4 (0.2) |
BMI | 14–19 years (adolescents) and 8–11 (children) |
↑ PFOS—↓ BMI (adolescents and children) ↑ PFOA—↓ BMI (children) ↑ PFHxS—↓ BMI (children) ↑ PFNA—↓ BMI (children) |
BMI: PFOS, PFOA, PFHxS (both sexes combined, only boys, and only girls) Included only data about adolescents (and not about children) |
|
Janis et al., 2021 [99] |
Project Viva | eastern Massachusetts, U.S | 1999–2022 | 537 | n-PFOA, total PFOA, n-PFOS, Sm-PFOS, total PFOS, PFDA, PFHxS, MeFOSAA, PFNA | 6–10 years |
Median (IQR) PFOA: 4.5 (3.0) PFOS: 6.4 (5.9) PFDA: 0.3 (0.3) PFHxS: 1.9 (2.4) MeFOSAA: 0.3 (0.5) PFNA: 1.5 (1.2) |
BMI FM |
6–10 years and 11–16 years |
↑ PFOS—↓ BMI increase from mid-childhood to early adolescents m ↑ PFOS—↓ FM increase from mid-childhood to early adolescents ↑ PFHxS—↓ BMI increase from mid-childhood to early adolescents m ↑ PFHxS—↓ FM increase from mid-childhood to early adolescents ↑ PFDA—↑ FM increase from mid-childhood to early adolescents m ↑ PFNA—↑ FM increase from mid-childhood to early adolescents m ↑ PFDA—↑ FM increase from mid-childhood to early adolescents in boys ↑ PFAS mixture—↓ lean mass increase from mid-childhood to early adolescents |
Not suitable data (data expressed as BMI change) |
|
Fassler et al., 2019 [100] |
BCERP |
Cincinnati (U.S) |
2004–2006 | 353 (only girls) | N-MeFOSAA, PFDA, PFNA, PFOA, PFOS, PFHxS | 6–8 years |
Median Me-PFOSA-AcOH: 0.8 PFDeA: 0.30 PFHxS: 5.20 PFNA: 1.40 PFOA: 7.30 PFOS: 13.60 |
BMI WtHe WtHi FM |
6–8 years |
↑ PFOA—↓ BMI ↑ N-MeFOSAA—↓ BMI ↑ PFDeA—↓ BMI ↑ PFOS—↓ BMI ↑ PFOA—↓ WtHe ↑ N-MeFOSAA—↓ WtHe ↑ PFDeA—↓ WtHe ↑ PFOS—↓ WtHe ↑ PFOA—↓ FM |
Not suitable data (no confidence intervals) |
|
Li, Liu, et al. 2021 [72] |
HOME Study | Cincinnati, Ohio (U.S) | 2003–2006 | 221 | PFOA, PFOS, PFNA, PFHxS | 3, 8, and 12 years |
Median PFOA: from 1.3 to 5.4 PFOS: from 2.4 to 6.2 PFNA: from 0.3 to 1.3 PFHxS: from 0.7 to 1.9 |
WC FM |
12 years | No significant associations for the considered outcomes | Data not used as, for the HOME study, data from Liu et al., 2020 were chosen for completeness |
|
Thomsen et al., 2021 [101] |
Copenhagen Mother–Child Cohort | Copenaghen, Denmark | 2009 | 109 | PFOA, PFOS, PFHxS, PFNA, and PFDA |
Median (25th-75th percentiles) 12.6 years (11.5–13.2) |
Median (25th-75th percentiles) PFOA: 2.79 (2.18–3.58) PFOS: 6.81 (5.85–9.47) PFHxS: 0.50 (0.40–0.65) PFNA: 0.92 (0.73–1.17) PFDA: 0.31 (0.25–0.37) |
BFP |
Median (25th-75th percentiles) 12.6 years (11.5–13.2) |
↑ PFOS—↓ BFP m ↑ PFDA—↓ BFP m ↑ PFNA—↓ BFP m ↑ PFOA—↑ BFP m ↑ PFHxS—↓ BFPm |
Not suitable data (associations with DXA body fat, not enough from other studies to perform a meta-analysis) |
|
Koponen et al., 2018 [102] |
birth cohort study LUKAS2 | Eastern Finland | 2005–2015 | 54 | PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFHxS, PFHpS, PFDS; N-MeFOSAA, N-EtFOSAA, 6:2 diPAP, 8:2 diPAP | 1, 6 and 10.5 years |
Median PFOS: 1.5—6.3 PFOA: 1.4—7.1 PFNA: 0.35—0.84 PFHxS: 0.20—0.49 |
BMI | 1, 6, and 10.5 years | No significant associations for the considered outcomes | Not suitable data (no suitable estimates reported) |
|
Harris et al., 2017 [103] |
Project Viva |
Boston—urban and suburban Eastern Massachusetts (U.S) |
2007–2010 | 653 |
PFOS, PFOA, PFHxS PFNA, N-EtFOSAA N-MeFOSAA, PFDA, PFOSA |
7.7 years (median; range: 6.6 − 10.6) |
Median PFOS: 6.2 PFOA: 4.4 PFHxS: 1.9 PFNA: 1.5 Et-PFOSA-AcOH:LOD Me-PFOSA-AcOH: 0.3 PFDeA: 0.3 FOSA: < LOD |
BMI | 7.7 years (median; range: 6.6 − 10.6) |
↑ PFOA—↓ BMI ↑ PFDeA—↓BMI |
Not suitable data (estimates as PFASs concentration change depending on the outcome, instead of the contrary) |
|
Scinicariello et al., 2020 [104] |
NHANES | U.S | 2013–2014 | 600 | PFOA, PFNA, PFHxS, PFOS | 3–11 years |
Geometric mean PFOA: 1.92 PFNA: 0.80 PFHxS: 0.85 PFOS: 3.90 |
BMI | 3–11 years |
↑ PFOA—↓ BMI m ↑ PFHxS—↓ BMI m ↑ PFOS—↓ BMI m ↑ PFOA—↓ BMI (boys) ↑ PFHxS—↓ BMI (boys) |
BMI: PFOS, PFOA, PFHxS, PFNA (both sexes combined) |
| Sevelsted et al., 2022 [79] | COPSAC2010 birth cohort | Zealand, Denmark | 2009–2011 | 533 | PFOS and PFOA | 6 and 18 months |
Median [IQR]: PFOS: 5.29 [4.05–6.94] PFOA 2.33 [1.40–3.56] |
BMI BFP |
6, 8, and 10 years | No significant associations for the considered outcomes | BMI: PFOS, PFOA (both sexes combined) |
|
Liu et al., 2020 [81] |
HOME Study | Cincinnati, Ohio (U.S) | 2003–2006 | 212 | PFOA, PFOS, PFNA, PFHxS | at birth and ages 3, 8 and 12 years |
Median PFOA: 5.4 (3 y), 2.5 (8 y), 1.3 (12 y) PFOS: 6.2 (3 y), 3.6 (8 y), 2.4 (12 y) PFNA: 1.3 (3 y), 0.7 (8 y), 0.3 (12 y) PFHxS: 1.9 (3 y), 1.2 (8 y), 0.7 (12 y) |
BMI WC FM/BFP |
12 years | No significant associations for the considered outcomes | BMI: PFOS, PFOA, PFHxS (both sexes combined, only boys, and only girls) PFNA (both sexes combined) |
|
Timmermann et al., 2014 [105] |
EYHS | Odense, Denmark | 1997 | 499 | PFOA, PFOS | 8–10-year-old children (third-grade students) |
Median PFOS: 41.5 PFOA: 9.3 |
BMI WC FM/BFP |
8–10-year-old children (third-grade students) |
↑ PFOS—↓ FM/BFP in girlsm ↑ PFOS—↓ FM/BFP in boysm |
BMI: PFOS, PFOA (both sexes combined) |
|
Li, Li et al., 2021 [106] |
- | Shanghai, China | 2019 | 189 | PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFBS, PFHxS, PFOS, PFDS | 8–12 years |
Mean PFHxA: 21.06 PFHpA: 129.57 PFOA: 117.34 PFNA: 28.78 PFDA: < LOD PFUnA: < LOD PFBS: 21.57 PFHxS: 27.66 PFOS: 38.54 PFDS: < LOD ΣPFAAs: 394.83 |
BMI | 8–12 years |
↑ PFHpA—↓ children with overweight/obesity ↑ PFBS—↓ children with overweight/obesity ↑ PFOS—↓ children with overweight/obesity |
Not suitable data (no estimates with BMI) |
|
Ye et al.; 2018 [107] |
NHANES | U.S | 2013–2014 | 639 | PFOSA, N-MeFOSAA, N-EtFOSAA, PFBS, PFHxS, PFHpA, PFNA, PFDA, PFUnDA, PFDoDA, n-PFOA, Sb-PFOA, n-PFOS, Sm-PFOS | 3–11 years |
Median ΣPFOS: 3.75 ΣPFOA: 1.94 PFHxS: 0.810 PFNA: 0.700 n-PFOS: 2.47 Sm-PFOS: 1.28 n-PFOA: 1.82 Sb-PFOA: < LOD PFBS: < LOD PFOSA: < LOD N-MeFOSAA: 0.110 N-EtFOSAA: < LOD PFHpA: < LOD PFDA: < LOD PFUnDA: < LOD PFDoDA: < LOD |
BMI | 3–11 years |
↑ ΣPFOA—↓ BMIm ↑ n-PFOA—↓ BMIm |
Not suitable data (no beta estimates, only geometric mean) |
|
Domazet et al., 2016 [108] |
EYHS | Odense, Denmark | 1997 and 2003 | 501 | PFOA, PFOS |
9 yeas 15 years |
Medians PFOS: from 20.8 to 44.5 PFOA: from 3.4 to 9.7 |
BMI WC FM/BFP |
9 yeas 15 years |
↑ PFOS (at 9 y)—↑ BMI (at 15y) ↑ PFOS (at 9 y)—↑ WC (at 15 y) ↑ PFOS (at 9 y)—↑ FM/BFP (at 15 y) |
Overweight risk: PFOS, PFOA (both sexes combined) |
|
Karlsen et al., 2017 [90] |
Not specified | Faroe Islands, Denmark | 2007–2009 | 444 | PFOS, PFOA, PFHxS, PFNA, PFDA | 5 years |
Median PFOS: 4.70 PFOA: 2.20 PFHxS: 0.33 PFNA: 1.13 PFDA: 0.34 |
BMI | 5 years |
↑ PFNA—↓ BMI ↑ PFDA—↓ BMI ↑ PFOA—↓ BMI ↑ PFOS—↓ BMI |
BMI: PFOS, PFOA, PFHxS, PFNA (both sexes combined) Overweight risk: PFOS, PFOA (both sexes combined) |
|
Kim et al., 2014 [109] |
Not specified | Dae-gu City, South Korea | 2012 | 120 | PFBA, PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS, PFDS | 5—13 years |
Mean PFBA: 0.346 PFPeA: 0.497 PFHxA: 0.353 PFHpA: 0.312 PFOA: 5.15 PFNA: 1.72 PFDA: 0.604 PFUnDA: 0.748 PFDoDA: - PFTrDA: 0.306 PFTeDA: - PFBS: 0.105 PFHxS: 1.13 PFHpS: 0.203 PFOS: 6.58 PFDS: - |
BMI | 5—13 years |
↑ PFOA—↓ BMI ↑ PFHxS—↓ BMI ↑ total PFASs—↓ BMI |
Not suitable data (no beta estimates, only Pearson's correlation) |
|
Domazet et al., 2020 [110] |
Danish sub-study of the EYHS | Odense, Denmark | 1997 | 242 | PFOS, PFOA, PFNA, PFDA, PFHxS | 9 years |
Median PFOS: 42.0—42.9 PFOA: 9.5 PFNA: 0.41—0.44 PFDA: 0.11 PFHxS 0.89—0.95 |
BMI FM/BFP |
9 years |
↑ PFNA—↓ BMI ↑ PFDA—↓ BMI ↑ PFNA—↓ FM ↑ PFDA—↓ FM ↑ PFHxS—↓ FM |
Not suitable data (no beta estimates with BMI) |
|
Schillemans et al., 2023 [111] |
HBM4EU | Europe | 2014–2021 | 1957 | PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFBS, PFHxS, PFHpS, PFOS | 12–18 years old |
Median PFPeA: 0.10 PFHxA: 0.09 PFHpA: 0.05 PFOA: 0.99 PFNA: 0.32 PFDA: 0.14 PFUnDA: 0.08 PFHxS: 0.04 PFHpS: 0.03 PFOS: 2.1 |
BMI | 12–18 years old |
↑ PFPeA—↓ BMI ↑ PFHpA—↓ BMI ↑ PFOA—↓ BMI ↑ PFNA—↓ BMI ↑ PFOS—↓ BMI ↑ PFHxS—↑ BMIm ↑ PFHpS—↑ BMIm |
BMI: PFOS, PFOA, PFHxS (both sexes combined, only boys, and only girls), PFNA (both sexes combined) |
|
Pinney et al., 2019 [112] |
the female puberty cohort of the BCERP | San Francisco Bay Area and Cincinnati (U.S.) | 2004–2007 | 704 (only girls) | PFOA | 6–8 years at first enrolments |
Median: 6.4 |
BMI WtHe WtHi |
6–8 years at first enrolments Repeated measures up to 18 years |
↑ PFOA—↓ BMI ↑ PFOA—↓ WtHe |
BMI: PFOA (only girls) |
|
Vrijheid et al., 2020 [64] |
HELIX | Europe | 2013 – 2016 | 1301 | PFOA, PFNA, PFUnDA, PFHxS, PFOS | 6–11 years |
Inter Quartile Ranges PFOA: 0.78 PFNA: 0.43 PFUnDA: 0.08 PFHxS: 0.42 PFOS: 2.0 |
BMI WC FM/BFP |
6–11 years |
↑ PFNA—↓ BMI ↑ PFOA—↓ BMI ↑ PFUNDA—↓ BMI ↑ PFOA—↓ WC ↑ PFNA—↓ WC ↑ PFOS—↓ WC ↑ PFUNDA—↓ WC ↑ PFNA—↓ skinfold z-score/BFP ↑ PFOS—↓ skinfold z-score/BFP ↑ PFOA—↓ skinfold z-score/BFP |
BMI: PFOS, PFOA, PFHxS, PFNA (both sexes combined) Overweight risk: PFOA (both sexes combined) (mean concentrations of PFASs asked to the authors) |