Maternal paraben exposure during early pregnancy is associated with altered cord blood DNA methylation: The PREDO cohort.

BACKGROUND

Prenatal exposure to parabens, which are environmental endocrine disrupting chemicals and widely used preservatives in cosmetics, may alter DNA methylation (DNAm) in cord blood. Study design In 328 mother-child dyads of the Finnish PREDO Study cohort, we studied with robust linear regression if paraben levels in early pregnancy associated with DNAm levels in cord blood. We measured genome-wide DNAm using Illumina Infinium Human Methylation 450 k or EPIC v1 arrays and concentrations of metabolites of six parabens, namely methyl-, ethyl-, propyl-, isopropyl-, butyl, and isobutylparaben, in early pregnancy urine samples with liquid chromatography - mass spectrometry. All parabens were analyzed as continuous and binary variables (high levels > 66th percentile). As isopropylparaben was present in only 8 % of samples it was analyzed separately as a dichotomic (detected/undetected) variable. Furthermore, we explored the putative functions of associated DNAm markers.

RESULTS

Every mother in the cohort had been exposed to parabens during early pregnancy. After correction for multiple testing there were significant associations (p-value ≤ 2.4 × 10 -7) between parabens and hypomethylation of four GpG sites: butylparaben associated with cg19246197 near USP2 (B = -0.009; p = 2.10 × 10-7), high level of isobutylparaben associated with cg27194164 near GLTD25D1 (B = -0.004; p = 1.89 × 10-7), detected isopropylparaben associated with cg00973732 in FAM38A (B = 0.007; p = 1.26 × 10-7), and high levels in the sum of the five most common parabens associated with cg21701043 in chromosome 11 (B = -0.016; p = 1.01 × 10-7). In total, 52 CpG sites associated with at least one of the parabens at a suggestive level (p-value < 1 × 10-5). Moreover, butyl- and isobutylparaben showed associations with differentially methylated regions located within PF4 and ABAT.

CONCLUSIONS

Paraben exposure during early pregnancy associates with altered DNAm in cord blood.