Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense Child Cohort

Frederik Damsgaard Højsager; Annika Sigvaldsen; Marianne Skovsager Andersen; Anders Juul; Flemming Nielsen; Sören Möller; Henrik Boye Thybo Christesen; Anders Grøntved; Philippe Grandjean; Tina Kold Jensen

doi:10.1016/j.envint.2023.108264

Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense Child Cohort

Environ Int. 2023 Nov:181:108264. doi: 10.1016/j.envint.2023.108264. Epub 2023 Oct 13.

Affiliations

¹ Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløwsvej 17A, 5000 Odense, Denmark.
² Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløwsvej 17A, 5000 Odense, Denmark. Electronic address: asigvaldsen@health.sdu.dk.
³ Department of Endocrinology and Metabolism, Odense University, Denmark; Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark.
⁴ Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Denmark.
⁵ Odense Patient Data Explorative Network (OPEN), Odense, Denmark.
⁶ Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
⁷ Exercise Epidemiology, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark; Centre of Research in Childhood Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
⁸ Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløwsvej 17A, 5000 Odense, Denmark; Depertment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA.
⁹ Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløwsvej 17A, 5000 Odense, Denmark; Odense Patient Data Explorative Network (OPEN), Odense, Denmark; Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

PMID: 37864903
DOI: 10.1016/j.envint.2023.108264

Abstract

Introduction: Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited.

Objectives: To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years.

Methods: In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010-2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid(PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 881) and/or at age 18 months (n = 668) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures.

Results: Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of 18-month exposure to PFNA or PFOS, BMD Z-scores were lowered by -0.10 (95 % CI -0.19;-0.00) and -0.08 (-0.17;-0.00), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure.

Discussion: Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Keywords: Bone mineral density; Children; Endocrine disruptors; Environmental epidemiology; Perfluoroalkyl substances.

MeSH terms

Alkanesulfonic Acids* / toxicity
Bone Density
Child
Child, Preschool
Chromatography, Liquid
Environmental Pollutants* / adverse effects
Female
Fluorocarbons* / toxicity
Humans
Infant
Pregnancy
Prospective Studies
Tandem Mass Spectrometry

Substances

Environmental Pollutants
perfluoro-n-nonanoic acid
Alkanesulfonic Acids
Fluorocarbons