Placental cadmium, placental genetic variations, and birth size

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Keywords:

• Placenta
• cadmium
• prenatal
• fetal growth
• infant-sex

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data that support the findings of this study are available from the corresponding author, MRH, upon reasonable request.

Additional information

Funding

This work was supported by grants from the National Heart, Lung, and Blood Institute, Bethesda, MD [T32HL007902 and K01HL103174], grants from the National Institute of Child Health and Human Development, National Institutes of Health [R01HD032562 and R01HD055566], and grants from the National Institute of Environmental Health Sciences [T32ES015459, P30ES007033]. The funding sources had no involvement in the conduct of the research and/or the preparation of this manuscript.