Environmental Research xxx (xxxx) xxx Please cite this article as: Ye’elah E. Berman, Environmental Research, https://doi.org/10.1016/j.envres.2020.110313 Available online 16 October 2020 0013-9351/© 2020 Elsevier Inc. All rights reserved. The infuence of prenatal exposure to phthalates on subsequent male growth and body composition in adolescence Ye’elah E. Berman a , Dorota A. Doherty a, b , Katharina M. Main c , Hanne Frederiksen c , Jeffrey A. Keelan a, b , John P. Newnham a, b , Roger J. Hart a, * a Women and Infants Research Foundation, Carson House, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, Perth, Australia b Division of Obstetrics and Gynaecology, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, Perth, WA, Australia, 6008 c Department of Growth and Reproduction and International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark A R T I C L E INFO Keywords: Growth Boys Body composition Adiposity Phthalate metabolites Antenatal exposure ABSTRACT Phthalates are ubiquitous environmental chemicals with predominantly anti-androgenic, and potentially obe- sogenic effects. We hypothesised that antenatal phthalate exposure may infuence subsequent boy’s growth and body composition through childhood and adolescence. Among 1399 singleton males from the Raine Study, 410 had maternal serum and at least one height, BMI or DEXA outcome available after birth and up to 20 years of age. Maternal serum collected at 18 and 34 weeks’ gestation was pooled, and analyzed for concentrations of 32 metabolites of 15 phthalate diesters. Their serum concentrations were categorized into undetectable/detectable levels or tertiles. Linear mixed models were used to determine associations between maternal serum phthalate levels and longitudinal height and body mass index (BMI) z-scores in boys from birth to 20 years of age (n = 250 and n = 295 respectively). Linear regression was used to determine associations between maternal phthalate levels and deviation from mid-parental height (n = 177) and DEXA scan outcomes (n = 191) at the 20 year follow-up. Weak positive associations of participants height z-score increase were detected with exposure to some phthalate metabolites in particular to the lower molecular weight phthalate metabolites. Less consistent fndings, by mixed model analyses, were detected for BMI and body composition, by dual energy X-ray ab- sorptiometry (DEXA), with some positive associations of phthalate metabolites with BMI and some negative associations with DEXA fat tissue measures, although no consistent fndings were evident. In conclusion, we derived some associations of childhood growth with prenatal phthalate exposure, particu- larly with respect to the lower molecular weight phthalate metabolites. 1. Introduction There is an increasing awareness amongst the scientifc community that environmental factors may adversely affect human health. It is well established that children have been getting taller over the last century, even in countries recognised to have tall individuals (Holmgren et al., 2019), and increasingly more overweight (Finucane et al., 2011). Indeed the World Health Organisation (WHO) state that since 1975 there has been a trebling in the prevalence of obesity worldwide (https://www. who.int/news-room/fact-sheets/detail/obesity-and-overweight), although there are signs that child obesity may have plateaued in developed countries subsequent to 2000 (Wabitsch et al., 2014). Adverse early childhood growth patterns are a strong predictor of adverse health outcomes later in life such as metabolic syndrome (Faienza et al., 2016). Furthermore, the timing of the growth spurt can predict changes in pubertal timing (Sloboda et al., 2007) and the sub- sequent development of metabolic syndrome (Bornhorst et al., 2016). Strong evidence exists from animal models that exposure to endo- crine disrupting chemicals can exert diverse adverse effects in the off- spring, ranging from infuences on behaviour, through to metabolic risk, growth and reproduction (Gore et al., 2015; Katsikantami et al., 2016). Diesters of phthalic acid (phthalates) are ubiquitous within our environment, and are widely used in industrial and consumer products such as various plastics and personal care products. Exposure occurs through ingestion, dermal absorption (Janjua et al., 2008) and inhala- tion (Hsu et al., 2012) (www.atsdr.cdc.gov). Phthalates cross the * Corresponding author. E-mail address: roger.hart@uwa.edu.au (R.J. Hart). Contents lists available at ScienceDirect Environmental Research journal homepage: www.elsevier.com/locate/envres https://doi.org/10.1016/j.envres.2020.110313 Received 12 August 2020; Received in revised form 29 September 2020; Accepted 2 October 2020