Could maternal thyroid function during pregnancy affect daughters’ age at menarche through child growth? A mediation analysis

Abstract

Early menarche is associated with adverse health outcomes during adolescence as well as breast and other reproductive cancers later in adulthood. However, the causes of early menarche and the pathways through which they operate are not fully understood. Though maternal thyroid function during pregnancy affects child growth, and rapid childhood growth is associated with a decreased age at menarche, the relationship between prenatal maternal thyroid function and daughters’ age at menarche has not been examined. We conducted a mediation analysis in a historical cohort of 260 mother-child pairs to estimate the total and indirect effects of maternal prenatal thyroid function on daughters’ age at menarche. No association was observed between thyroid stimulating hormone (TSH) or anti-thyroid peroxidase antibodies (ATPO) and daughters’ age at menarche. Using a sample-specific, a-priori cutoff at the 10th percentile, low levels of maternal free thyroxine (FT4) were associated with earlier daughter age at menarche, with a hazard ratio (95 % CI) of 1.70 (1.02, 2.84) comparing the bottom 10th percentile with the top 90th percentile of exposure levels. Higher maternal FT4 was associated with rapid child weight gain from ages 5–9, and rapid child weight gain from ages 5–9 was associated with earlier age at menarche; the estimated indirect effect of this pathway was null. While maternal FT4 is associated with earlier age at menarche in daughters, this is not mediated by rapid weight gain in our study population, suggesting that maternal FT4 is operating through a different pathway.