Table 2.
Multiple metals linear regression analyses presenting interactions between mixture components with respective birth measurements in Project viva in sex-combined and sex-stratified analysis. Estimates (95% CI) were calculated as the marginal effect for an IQR increase in erythrocyte concentration of selected metal at 25th, 50th, and 75th percentiles of other metal(s).
| Outcome | Effect of | at quartiles of metal 1 |
at quartiles of metal 2 | Full cohort (n= 1391) |
Male (n= 718) |
Female (n= 673) |
|---|---|---|---|---|---|---|
| Birth weight (g) | As | Mn-Q1 (13.1 ng/g) | ---- | −20.9 (−61.2, 19.5) | −25.3 (−79.9, 29.3) | −18.9 (−79.3, 41.6) |
| As | Mn-Q2 (16.2 ng/g) | ---- | −28.7 (−64.5, 7.1) | −47.9 (−98.0, 2.1) | −9.1 (−60.8, 42.6) | |
| As | Mn-Q3 (20.3 ng/g) | ---- | −37.1 (−76.6, 2.3) | −72.2 (−129.8, −14.7)* | 1.4 (−53.2, 56.0) | |
| As*Mn interaction p-value | 0.369 | 0.067 | 0.437 | |||
|
| ||||||
| Birth length (cm) a | Mn | Hg-Q1 (1.6 ng/g) | ---- | 0.11 (−0.09, 0.31) | 0.17 (−0.17, 0.52) | 0.08 (−0.18, 0.33) |
| Mn | Hg-Q2 (3.3 ng/g) | ---- | 0.23 (0.05, 0.40)* | 0.26 (−0.02, 0.54) | 0.21 (−0.02, 0.44) | |
| Mn | Hg-Q3 (6.4 ng/g) | ---- | 0.36 (0.14, 0.59)* | 0.36 (0.00, 0.72)* | 0.36 (0.05, 0.67)* | |
| Mn*Hg interaction p-value | 0.045 | 0.378 | 0.078 | |||
| Zn | Hg-Q1 (1.6 ng/g) | ---- | 0.01 (−0.2, 0.23) | −0.19 (−0.52, 0.14) | 0.24 (−0.05, 0.53) | |
| Zn | Hg-Q2 (3.3 ng/g) | ---- | −0.02 (−0.19, 0.16) | −0.07 (−0.34, 0.19) | 0.06 (−0.19, 0.31) | |
| Zn | Hg-Q3 (6.4 ng/g) | ---- | −0.05 (−0.29, 0.18) | 0.07 (−0.28, 0.42) | −0.14 (−0.47, 0.19) | |
| Zn*Hg interaction p-value | 0.623 | 0.229 | 0.043 | |||
|
| ||||||
| Head Circumference (cm) a | Pb | Zn-Q1 (9273.3 ng/g) | ---- | −0.15 (−0.27, −0.03)* | −0.18 (−0.35, −0.02)* | −0.10 (−0.28, 0.08) |
| Pb | Zn-Q2 (10403.6 ng/g) | ---- | −0.08 (−0.18, 0.03) | −0.10 (−0.25, 0.04) | −0.06 (−0.21, 0.09) | |
| Pb | Zn-Q3 (11601.8 ng/g) | ---- | −0.01 (−0.13, 0.11) | −0.03 (−0.20, 0.15) | −0.03 (−0.21, 0.15) | |
| Mn*Hg interaction p-value | 0.024 | 0.066 | 0.463 | |||
|
| ||||||
| Gestational age (weeks) | As | Mn-Q1 (13.1 ng/g) | Pb-Q1 (13.5 ng/g) | 0.05 (−0.14, 0.25) | 0.03 (−0.24, 0.30) | 0.09 (−0.19, 0.37) |
| As | Mn-Q1 (13.1 ng/g) | Pb-Q2 (17.7 ng/g) | 0.01 (−0.16, 0.18) | −0.04 (−0.28, 0.19) | 0.05 (−0.20, 0.29) | |
| As | Mn-Q1 (13.1 ng/g) | Pb-Q3 (23.6 ng/g) | −0.03 (−0.23, 0.17) | −0.12 (−0.40, 0.16) | 0.01 (−0.27, 0.29) | |
| As | Mn-Q2 (16.2 ng/g) | Pb-Q1 (13.5 ng/g) | 0.01 (−0.16, 0.19 ) | 0.02 (−0.24, 0.28) | 0.03 (−0.22, 0.28) | |
| As | Mn-Q2 (16.2 ng/g) | Pb-Q2 (17.7 ng/g) | −0.03 (−0.18, 0.12) | −0.11 (−0.33, 0.11) | 0.03 (−0.18, 0.24) | |
| As | Mn-Q2 (16.2 ng/g) | Pb-Q3 (23.6 ng/g) | −0.09 (−0.25, 0.08) | −0.25 (−0.49, −0.01)* | 0.03 (−0.20, 0.25) | |
| As | Mn-Q3 (20.3 ng/g) | Pb-Q1 (13.5 ng/g) | −0.03 (−0.24, 0.19) | 0.01 (−0.31, 0.33) | 0.03 (−0.31, 0.26) | |
| As | Mn-Q3 (20.3 ng/g) | Pb-Q2 (17.7 ng/g) | −0.08 (−0.26, 0.09) | −0.18 (−0.44, 0.08) | 0.01 (−0.23, 0.24) | |
| As | Mn-Q3 (20.3 ng/g) | Pb-Q3 (23.6 ng/g) | −0.14 (−0.31, 0.02) | −0.39 (−0.65, −0.13)* | 0.04 (−0.18, 0.27) | |
| As*Mn*Pb interaction p-value | 0.786 | 0.08 | 0.237 | |||
| Pb | Zn-Q1 (9273.3 ng/g) | ---- | −0.04 (−0.19, 0.11) | −0.06 (−0.27, 0.16) | −0.03 (−0.25, 0.19) | |
| Pb | Zn-Q2 (10403.6 ng/g) | ---- | 0.01 (−0.13, 0.15) | 0.06 (−0.13, 0.25) | −0.06 (−0.25, 0.13) | |
| Pb | Zn-Q3 (11601.8 ng/g) | ---- | 0.06 (−0.10, 0.22) | 0.17 (−0.05, 0.40) | −0.08 (−0.30, 0.14) | |
| Pb*Zn interaction p-value | 0.202 | 0.032 | 0.611 | |||
Sample size for head circumference was 791 (male = 394, female = 397) and for birth length was 729 (male = 363, female = 366)
Models were adjusted for gestational age at delivery (except when gestational age was an outcome), maternal age, education, pre-pregnancy BMI, parity, smoking status, race/ethnicity, and household income. The sex-combined analysis was additionally adjusted for infant sex. Models included all six metals (As, Cd, Mn, Pb, Zn, Hg) and selected two-way or three-way interactions and quadratic terms, where indicated. Models with a three-way interaction also included all lower-level two-way interactions. Standard errors were estimated based on the delta method. P-for-interaction <0.10 was considered statistically significant.
p-value <0.05