Placental cadmium, placental genetic variations, and birth size

Maternal cadmium (Cd) burden has been associated with offspring birth size measures, yet associations of placental Cd with birth size are less clear. Further, the role of genetics in these associations has not been examined. We investigated associations of placental Cd with birth size and placental genotypes. We also examined the potential role of placental genotypes as modifiers of placental Cd and birth size associations.

Participants were 490 mother-child pairs from the Omega and Placenta Microarray studies based in Seattle, WA. Placental Cd was measured using Agilent 7500 ICP-MS. The birth size was characterized using birth weight (BW), ponderal index (PI), and head circumference (HC). Eleven placental single nucleotide polymorphisms (SNPs) related to metal transport, growth regulation, endocrine response, and cell signaling were genotyped. Adjusted multivariable linear regression models were used to examine overall and sex-specific associations of placental Cd with birth size (BW, PI and HC), as well as associations of placental genotypes with placental Cd. Effect modification of placenta Cd and birth size associations by placental SNPs was examined using interaction terms and stratified analyses.

Mean maternal age was 33.6 years (SD = 4.4). Mean and median placental Cd levels were 4.0 ng/g tissue (SD = 2.7 ng/g tissue) and 3.6 ng/g (IQR 2.5 - 5.2 ng/g), respectively. Overall, compared with infants in the lowest quartile for placental Cd, infants in the second (ß = -102.8 g, 95% CI: -220.7, 15.1), third (ß = -83.2 g, 95% CI: -199.3, 32.9) and fourth (ß = -109.2 g, 95% CI: -225.4, 7.1) quartiles had lower BW, though associations were not statistically significant (all p-values > .05, trend p-value = .11). Among male infants, infants in the second (ß = -203.3 g, 95% CI: -379.7, -27.0) and fourth quartiles (ß = -198.3 g, 95% CI: -364.2, -32.5) had lower BW compared with those in the first quartiles (p-values < .05, trend p-value = .08). Similar relationships were not observed among female infants, though infant sex-placental Cd interaction terms were not significant. Similarly, male, but not female, infants had marginally significant positive associations between placental Cd and ponderal index (trend p-value = .06). The minor rs3811647 allele of the placental transferrin gene (NCBI Gene ID: 7018) was associated with an increase in Cd among all infants (p-value = .04). We did not find differences in associations of placental Cd with birth size markers among infants stratified by rs3811647 genotype.

Placental Cd was inversely associated with BW among male infants. The rs3811647 SNP of the transferrin gene was associated with placental Cd.