Prenatal exposure to mixtures of persistent endocrine disrupting chemicals and early menarche in a population-based cohort of British girls

Kristin J Marks*, Penelope Howards, Melissa Smarr, W Dana Flanders, Kate Northstone, Johnni Daniel, Antonia M Calafat, Andreas Sjodin, Michele Marcus, Terryl J Hartman

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)
128 Downloads (Pure)


Exposure to endocrine disrupting chemicals (EDCs) is ubiquitous. EDC exposure, especially during critical periods of development like the prenatal window, may interfere with the body’s endocrine system, which can affect growth and developmental outcomes such as puberty. Most studies have examined one EDC at a time in relation to disease; however, humans are exposed to many EDCs. By studying mixtures, the human experience can be more closely replicated. We investigated the association of prenatal exposure to persistent EDCs (poly- and perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with early menarche among female offspring in a nested case-control study within the Avon Longitudinal Study of Parents and Children (ALSPAC) recruited in the United Kingdom in 1991–1992. Concentrations of 52 EDCs were quantified in maternal serum samples collected during pregnancy. Daughter’s age at menarche was ascertained through mailed questionnaires sent annually. We used repeated holdout weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to examine the association between prenatal exposure to multiple EDCs and early menarche (<11.5 (n = 218) vs. ≥11.5 years (n = 230)) for each chemical class separately (PFAS, PCBs, and OCPs) and for all three classes combined. Models adjusted for maternal age at menarche, maternal education, parity, pre-pregnancy body mass index, maternal age, prenatal smoking, and gestational week at sample collection. Mixture models showed null associations between prenatal exposure to EDC mixtures and early menarche. Using WQS regression, the odds ratio for early menarche for a one-decile increase in chemical concentrations for all three classes combined was 0.89 (95% CI: 0.76, 1.05); using BKMR, the odds ratio when all exposures were at the 60th percentile compared to the median was 0.98 (95% CI: 0.91, 1.05). Results suggest the overall effect of prenatal exposure to persistent EDC mixtures is not associated with early menarche.
Original languageEnglish
Article number116705
Number of pages11
JournalEnvironmental Pollution
Early online date9 Feb 2021
Publication statusPublished - 1 May 2021

Bibliographical note

Funding Information:
The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z ) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and they will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (grant-acknowledgements.pdf" title = " "> ). This work was specifically funded by the Centers for Disease Control and Prevention (AY5350).

Funding Information:
This research was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC.

Publisher Copyright:
© 2021 Elsevier Ltd

Structured keywords



  • Puberty
  • Menarche
  • Poly- and perfluoroalkyl substances
  • Polychlorinated biphenyls
  • Organochlorine pesticides


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