Table 8.
Association of maternal PFAAs exposure and maternal T4 and T3 by trimester (adjusted results)
| Reference | Author Country Year |
Effect estimate | TH | PFHxS | PFOS | PFOA | PFNA | PFDA | PFUnA | PFDoA |
|---|---|---|---|---|---|---|---|---|---|---|
| TH measured during 1st Trimester | ||||||||||
| [38] |
Kato Japan 2016 |
Linear regression: Adjusted β (p value) |
FT4 | – | ↑: 0.061 (0.236) | ↑: 0.004 (0.946) | – | – | – | – |
| [39] |
Preston USA 2018 |
Difference in maternal TH levels per quartile (Q2–4 vs. Q1) of PFAA concentrations (95% CI) | FT4Ic | ↓ Q2: −0.25 (− 3.55, 3.16) |
↓ Q2: − 0.56 (− 3.93, 2.93) |
↓ Q2: −4.68 (− 7.93,− 1.32)* |
↓ Q2: − 1.94 (−5.48, 1.72) |
– | – | – |
|
↓ Q3: − 0.35 (− 3.77, 3.18) |
↓ Q3: − 1.41 (− 4.80, 2.09) |
↓ Q3: −2.89 (− 6.23, 0.58) |
↓ Q3: − 0.53 (− 3.79, 2.85) |
– | – | – | ||||
|
↓ Q4: − 4.19 (− 7.43, − 0.85)* |
↓ Q4: − 1.51 (− 4.92, 2.02) |
↓ Q4: − 6.52 (−9.86, − 3.06)* |
↓ Q4: − 1.06 (− 4.27, 2.25) |
– | – | – | ||||
| TT4 |
↓ Q2: − 0.23 (− 0.61, 0.14) |
↑ Q2: 0.28 (− 0.10, 0.66) |
↓ Q2: − 0.12 (− 0.51, 0.27) |
↑ Q2: 0.02 (− 0.39, 0.43) |
– | – | – | |||
|
↑ Q3: 0.10 (− 0.28, 0.49) |
↑ Q3: 0.14 (− 0.25, 0.52) |
↑ Q3: 0.01 (− 0.38, 0.40) |
↑ Q3: 0.08 (− 0.29, 0.45) |
– | – | – | ||||
|
↓ Q4: − 0.34 (− 0.73, 0.04) |
↑ Q4: 0.31 (− 0.08, 0.70) |
↑ Q4: 0.02 (− 0.39, 0.43) |
↓ Q4: −0.09 (− 0.45, 0.28) |
– | – | – | ||||
| [40] |
Inoue Denmark 2019 |
Relative percentage difference per IQR increase | FT4 | ↑ 1.00 (0.98, 1.01) | ↑ 1.00 (0.99, 1.02) | ↑ 1.01 (0.99, 1.02) | ↑ 1.00 (0.99; 1.01) | ↑ 1.01 (1.00; 1.02) | ||
| TH measured during 2nd Trimester | ||||||||||
| [42] |
Webster Canada 2014 |
IQR increase in maternal PFAA concentrations: Adjusted β (95% CI) | FT4 |
↓:-0.02 (− 0.1, 0.07) |
↑: 0.03 (− 0.2, 0.2) |
↓: − 0.06 (− 0.3, 0.2) |
↓: − 0.03 (− 0.2, 0.2) |
– | – | – |
| TH measured during 3rd Trimester | ||||||||||
| [44] |
Wang Taiwan 2014 |
Linear regression: Adjusted β (95% CI) | FT4 |
↓: − 0.010 (− 0.023, 0.003) |
↑: 0.001 (− 0.002, 0.003) |
↓: − 0.003 (− 0.012, 0.005) |
↓: − 0.019 (− 0.028, − 0.009)* |
↓: − 0.001 (− 0.006, 0.005) |
↓: − 0.004 (− 0.007, − 0.002)* |
↓: − 0.132 (− 0.204, − 0.059)* |
| TT4 |
↓:-0.130 (− 0.316, 0.057) |
↑: 0.019 (− 0.016, 0.053) |
↑: 0.011 (− 0.108, 0.130) |
↓: − 0.189 (− 0.333, − 0.046)* |
↑: 0.047 (− 0.028, 0.123) |
↓: − 0.062 (− 0.097, − 0.026)* |
↓: − 1.742 (− 2.785, − 0.700)* |
|||
| TT3 |
↓:-0.002 (− 0.005, 0.001) |
↑: 0.000 (− 0.002, 0.001) |
↓:-0.000 (− 0.002, 0.009) |
↓: − 0.001 (− 0.003, 0.002) |
↑: 0.002 (0.000, 0.003)* |
↓: − 0.000 (− 0.001, 0.000) |
↓: − 0.005 (− 0.022, 0.011) |
|||
| [46] |
Yang China 2016 |
Spearmans partial correlation analysis Maternal exposure used. |
FT3 | ↑: 0.124 | ↑: 0.025 | ↑: 0.024 | ↓: − 0.063 | ↓: − 0.087 | ↓: − 0.121 | ↓: − 0.268* |
| FT4 | ↑: 0.038 | ↓: − 0.057 | ↑: 0.000 | ↓: −0.072 | ↓: − 0.086 | ↓: − 0.062 | ↓: − 0.160* | |||
| TT3 | ↑: 0.084 | ↑: 0.008 | ↑: 0.102 | ↓: −0.018 | ↓: −0.079 | ↓: − 0.097 | ↓: − 0.301* | |||
| TT4 | ↑: 0.084 | ↑: 0.021 | ↑: 0.062 | ↓: −0.006 | ↓: −0.010 | ↑: 0.030 | ↓: − 0.160* | |||
| [47] |
Xiao Faroe Island 2019 |
Percent change in thyroid hormone levels per doubling of PFAA concentrations (95% CI) | FT4I | ↑: 4.4 (− 2.3, 11.6) | ↓: −0.8 (− 8.2, 7.4) | ↓: − 0.6 (− 6.1, 5.1) | ↓: − 1.2 (− 8.9, 7.3) | ↑: 0.2 (− 7.2, 8.1) | ↑: 2.3 (− 3.1, 8.1) | ↑: 0.2 (− 2.2, 2.6) |
| FT3 | ↓: − 0.7 (−5.6, 4.5) | ↑: 2.2 (− 3.6, 8.5) | ↑: 3.1 (− 1.2, 7.6) | ↓: − 2.7 (− 8.5, 3.6) | ↓: − 1.4 (− 6.9, 4.5) | ↓: − 1.8 (− 5.8, 2.4) | ↑: 0.6 (− 1.3, 2.4) | |||
| FT4 | ↑: 5.9 (− 0.2, 12.4) | ↓: − 2.9 (− 9.4, 4.3) | ↓: − 0.4 (− 5.4, 4.8) | ↓: − 5.7 (− 12.4, 1.4) | ↓: − 1.5 (− 8.1, 5.5) | ↓: − 0.1 (− 5.0, 5.0) | ↑: 0.2 (− 2.0, 2.4) | |||
| TT4 | ↑: 0.4 (− 6.9, 8.2) | ↑: 0.1 (−8.3, 9.3) | ↑: 0.7 (− 5.5, 7.3) | ↓: − 1.2 (− 9.9, 8.2) | ↓: − 2.1 (− 10.1, 6.7) | ↑: 0.4 (− 5.6, 6.9) | ↑: 0.1 (− 2.6, 2.9) | |||
| T3RU | ↑: 4.0 (− 0.4, 8.5) | ↓: − 0.9 (− 5.8, 4.3) | ↓: − 1.3 (− 4.9, 2.3) | ↑: 0.1 (− 5.1, 5.5) | ↑: 2.2 (− 2.7, 7.5) | ↑: 1.9 (− 1.7, 5.7) | ↑: 0.1 (− 1.5, 1.7) | |||
| TH measured during multiple timepoints | ||||||||||
| [43] |
Berg Norway 2015 |
Mixed effects model estimated mean differences in thyroid hormone concentrations over time (2nd trimester, at birth and 6 weeks postpartum). Change across exposure quartiles (Q1 reference). NS: results not stated. | TT3 | NS | NS | NS | NS |
↓: Q2: − 0.04 (− 0.08. 0.04) |
NS | |
|
↓: Q3: −0.05 (− 0.08, 0.00) |
– | |||||||||
|
↓:Q4: −0.1 (− 0.14, − 0.06)* |
||||||||||
| FT3 | NS | NS | NS | NS | NS |
↓ Q2: −0.08 (−0.15, − 0.00)* |
||||
|
↓: Q3: − 0.09 (−0.16, − 0.01)* |
– | |||||||||
|
↓ Q4: −0.18 (− 0.25, − 0.12)* |
||||||||||
| TT4 | NS | NS | NS | NS | NS | NS | – | |||
| FT4 | NS | NS | NS | NS | NS | NS | – | |||
| [45] |
Reardon Canada 2019 |
Overall main effect of PFAAs on TH (all timepoints) from mixed effects models: Adjusted β (p-value) | FT4 | ↓:-0.006 (0.034)* | ↓:-0.000 (0.999) | ↓:-0.002 (0.138) | ↓:-0.004 (0.379) | ↓:-0.010 (0.314) | ↓:-0.037 (0.321) | – |
| FT3 | ↑:0.000 (0.955) | ↑:-0.003 (0.242) | ↑:0.001 (0.535) | ↑:0.004 (0.330) | ↑:0.003 (0.736) | ↑:0.014 (0.698) | – | |||
TT3 (total triiodothyronine), FT3 (total triiodothyronine), TT4 (total thyroxine), FT4 (free thyroxine), FT4I (free thyroxine index), ↓ decreasing, ↑ increasing, bold format and star* indicate significant results P < 0.05, NS: results not stated, −: PFAAs not examined, Q1 (1st quartile), Q2 (2nd quartile), Q3 (3rd quartile), Q4 (4th quartile), IQR (interquartile range)
PFAAs include: PFOS Perfluorooctane sulfonate, PFOA Perfluorooctanoate, PFHxS Perfluorohexane sulfonate, PFNA Perfluorononanoic acid, PFDA Perfluorodecanoic acid, PFUnA Perfluoroundecanoic acid, PFDoA Perfluorododecanoic acid