Associations between Prenatal Exposure to Phthalates and Features of the Metabolic Syndrome in Males from Childhood into Adulthood

Ye'elah E Berman; Dorota A Doherty; Trevor A Mori; Lawrence J Beilin; Oyekoya T Ayonrinde; Leon A Adams; Rae-Chi Huang; John K Olynyk; Jeffrey A Keelan; John P Newnham; Roger J Hart

doi:10.3390/ijerph192215244

Associations between Prenatal Exposure to Phthalates and Features of the Metabolic Syndrome in Males from Childhood into Adulthood

Int J Environ Res Public Health. 2022 Nov 18;19(22):15244. doi: 10.3390/ijerph192215244.

Authors

Ye'elah E Berman¹, Dorota A Doherty¹, Trevor A Mori², Lawrence J Beilin², Oyekoya T Ayonrinde^{2

3}, Leon A Adams^{2

4}, Rae-Chi Huang^{5

6}, John K Olynyk^{3

5}, Jeffrey A Keelan¹, John P Newnham¹, Roger J Hart¹

Affiliations

¹ Division of Obstetrics and Gynaecology, University of Western Australia, Perth, WA 6008, Australia.
² Medical School, University of Western Australia, Crawley, WA 6009, Australia.
³ Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA 6150, Australia.
⁴ Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
⁵ School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
⁶ Telethon Kids Institute, University of Western Australia, Nedlands, WA 6009, Australia.

Abstract

Phthalate metabolites are detectable within the majority of the population. Evidence suggests that a prenatal exposure to phthalates may be associated with the subsequent risks of obesity and elevated blood pressure. We hypothesised that a prenatal exposure to phthalates would lead to an increase in adverse cardiometabolic parameters through childhood and adulthood. The maternal serum phthalate measurements from the stored samples taken from Gen1 mothers at 18 and 34 weeks gestation were examined in relation to the cardiometabolic measures in 387 male offspring from the Raine Study. Data from the Gen2 follow-ups between 3 and 27 years were used. The primary outcomes were analysed longitudinally using linear mixed models for the repeated measures. Non-alcoholic fatty liver disease (NAFLD) was assessed at 17 years using logistic regression. A consistent positive relationship was observed between a prenatal exposure to mono-carboxy-iso-octyl phthalate (MCiOP) through adolescence into adulthood with systolic blood pressure. There were no other consistent cardiovascular associations. Mid-levels of prenatal exposures to Mono-n-butyl phthalate (MnBP) were associated with a greater incidence of NAFLD. Detectable Mono-3-carboxypropyl phthalate (MCPP) was associated with a lower serum HDL-C through late childhood into adulthood, while a higher prenatal exposure to mono-iso-butyl phthalate (MiBP), was associated with a higher LDL-C at 22 years of age. A mid-level prenatal exposure to mono-2-ethylhexyl phthalate (MEHP) metabolites was associated with higher insulin in adulthood, while a higher prenatal exposure to the sum of the Di-(2-ethyl-hexyl) phthalate (DEHP) and Di-iso-nonyl phthalate (DiNP) metabolites was associated with higher fasting serum glucose in adulthood. In conclusion, our study demonstrated that higher prenatal phthalate exposures to some phthalate metabolites was associated with some adverse metabolic profiles through adolescence into adulthood, although the consistent themes were limited to a few metabolites and the outcomes of systolic blood pressure, fasting insulin and glucose.

Keywords: adiposity; antenatal exposure; boys; cardiometabolic; metabolic disorder; phthalate metabolites.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Female
Humans
Hypertension*
Insulin
Male
Metabolic Syndrome* / epidemiology
Non-alcoholic Fatty Liver Disease*
Pregnancy
Prenatal Exposure Delayed Effects* / epidemiology

Substances

phthalic acid
Insulin

Grants and funding

The collection of maternal data and samples was funded by NH&MRC, the Raine Medical Research Foundation and the Women and Infants Research Foundation (WIRF) while the collection of adolescent data and samples was funded by NHMRC project grant number 634457 and by a UWA Ada Bartholomew grant. The Australian group was supported by a NHMRC project grant (no 403968) and received support from the Raine Medical Research Foundation, the Telethon Kids Institute, the University of Western Australia, Women and Infant Research Foundation, Curtin University and Edith Cowan University and EDMaRC (www.edmarc.net). The APC was funded by Roger Hart.