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Impact of Periconceptional Exposure to Phthalates on Pregnancy, Birth, and Neonatal Outcomes

  • Environmental Epidemiology (J Braun, Section Editor)
  • Published:
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Abstract

Purpose of Review

The purpose of this review was to evaluate recent available evidence on exposure to phthalates during pregnancy and the immediate periconceptional period and the health effects in the mother and offspring during the peripartum period. Articles were included if they included biospecimen-based exposure assessment and consideration of quantifiable health effects in either the mother or the offspring.

Recent Findings

Outcome assessment variables were indicators of fetal growth and indicators of hormonal effects—including genital endpoints and pregnancy duration. The studies reviewed provided inconsistent and weak evidence of relationships between phthalate exposure during pregnancy and these outcomes. Some trends emerged involving high molecular weight phthalate metabolites and genital endpoints, including anogenital distance and male genital anomalies, particularly with the metabolites of di(2-ethylhexyl) phthalate (DEHP). Some evidence implicated high molecular weight phthalate metabolites and biomarkers of thyroid and immune function. Results surrounding fetal growth were mixed and varied by metabolite, infant gender, time of exposure ascertainment, and parent exposed.

Summary

Difficulties with exposure assessment likely limit the findings. All reviewed studies relied on between one and three exposure measurements, constraining reliability of results and knowledge regarding gestational windows of development. Additionally, the difficulty of applying standardized methodology in the measurement of anogenital distance restricts the weight that can be placed on findings across studies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, et al. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010-2012). Environ Health Perspect. 2016;124(7):1107–13. doi:10.1289/ehp.1509870.

    PubMed  Google Scholar 

  2. Barrett ES, Parlett LE, Sathyanarayana S, Redmon JB, Nguyen RH, Swan SH. Prenatal stress as a modifier of associations between phthalate exposure and reproductive development: results from a multicentre pregnancy cohort study. Paediatr Perinat Epidemiol. 2016;30(2):105–14. doi:10.1111/ppe.12264.

    Article  PubMed  Google Scholar 

  3. WHO | State of the science of endocrine disrupting chemicals—2012. WHO. 2016. doi:/entity/ceh/publications/endocrine/en/index.html.

  4. Arbuckle TE, Fisher M, MacPherson S, Lang C, Provencher G, LeBlanc A, et al. Maternal and early life exposure to phthalates: the Plastics and Personal-care Products use in Pregnancy (P4) study. Sci Total Environ. 2016;551-552:344–56. doi:10.1016/j.scitotenv.2016.02.022.

    Article  CAS  PubMed  Google Scholar 

  5. Li LX, Chen L, Meng XZ, Chen BH, Chen SQ, Zhao Y et al. Exposure levels of environmental endocrine disruptors in mother-newborn pairs in China and their placental transfer characteristics. PLoS One. vol 52013.

  6. • Botton J, Philippat C, Calafat AM, Carles S, Charles MA, Slama R, et al. Phthalate pregnancy exposure and male offspring growth from the intra-uterine period to five years of age. Environ Res. 2016;151:601–9. doi:10.1016/j.envres.2016.08.033. Extended follow-up time sets this paper apart, allowing observance of a positive association between MEP and weight growth velocity between two and five years old, in addition to findings related to in utero growth and birth size. While this sheds light on prenatal phthalates’ varied impacts over time, reliance on one exposure measurement is problematic.

    Article  CAS  PubMed  Google Scholar 

  7. Casas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernandez MF, Garcia-Esteban R, et al. Exposure to bisphenol A and phthalates during pregnancy and ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health Perspect. 2016;124(4):521–8. doi:10.1289/ehp.1409190.

    PubMed  Google Scholar 

  8. Tanaka T. Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice. Food Chem Toxicol. 2005;43(4):581–9. doi:10.1016/j.fct.2005.01.001.

    Article  CAS  PubMed  Google Scholar 

  9. Marsman D. NTP technical report on the toxicity studies of dibutyl phthalate (CAS no. 84-74-2) administered in feed to F344/N rats and B6C3F1 mice. Toxicity report series. 1995;30:1–g5.

    PubMed  Google Scholar 

  10. Sathyanarayana S, Barrett E, Nguyen R, Redmon B, Haaland W, Swan SH. First trimester phthalate exposure and infant birth weight in the infant development and environment study. Int J Environ Res Public Health. 2016;13(10). doi:10.3390/ijerph13100945.

  11. Hauser R, Calafat AM. Phthalates and human health. Occup Environ Med. 2005;62:806–818. doi:10.1136/oem.2004.017590.

  12. •• Smarr MM, Grantz KL, Sundaram R, Maisog JM, Kannan K, Louis GM. Parental urinary biomarkers of preconception exposure to bisphenol A and phthalates in relation to birth outcomes. Environ Health. 2015;14:73. doi:10.1186/s12940-015-0060-5. Separate analyses of paternal and maternal phthalate exposure around time of conception make this paper a valuable early contributor to understanding the different ways each parent’s exposure may impact the neonate. Findings of different impacts by infant sex are interesting. The single exposure measurement and parental self-reporting of birth anthropometry limit the data’s reliability

    Article  PubMed  PubMed Central  Google Scholar 

  13. Calafat HMK, Antonia M. Human body burdens of chemicals used in plastic manufacture. 2009. doi:10.1098/rstb.2008.0208.

  14. • Lenters V, Portengen L, Rignell-Hydbom A, Jonsson BA, Lindh CH, Piersma AH, et al. Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts: multi-pollutant models based on elastic net regression. Environ Health Perspect. 2016;124(3):365–72. doi:10.1289/ehp.1408933. Multiple international study sites and large sample size lend weight to the findings of this report. Additionally, the researchers’ use of a multi-pollutant model adds robustness to findings of an association between MEHHP and birthweight

    PubMed  Google Scholar 

  15. • Zhao Y, Shi HJ, Xie CM, Chen J, Laue H, Zhang YH. Prenatal phthalate exposure, infant growth, and global DNA methylation of human placenta. Environ Mol Mutagen. 2015;56(3):286–92. doi:10.1002/em.21916. Case-control model makes findings here of an association between DEHP metabolites and restricted fetal growth stronger. Additionally, findings of differences in associations in term and preterm infants are intriguing and may direct future study

    Article  CAS  PubMed  Google Scholar 

  16. • Shoaff JR, Romano ME, Yolton K, Lanphear BP, Calafat AM, Braun JM. Prenatal phthalate exposure and infant size at birth and gestational duration. Environ Res. 2016;150:52–8. doi:10.1016/j.envres.2016.05.033. While most of the findings in this report were nonsignificant when adjusted for covariates, a few noteworthy associations were identified. Findings regarding likelihood of preterm birth being negatively associated with MCPP concentrations were interesting, and possibly consistent with observations made by Zhao. Findings of gender mediation in the impact of MBzP exposure on gestational age were also intriguing. Use of multiple exposure measurements adds strength to findings that might have achieved significance with a larger sample size.

    Article  CAS  PubMed  Google Scholar 

  17. Polanska K, Ligocka D, Sobala W, Hanke W. Effect of environmental phthalate exposure on pregnancy duration and birth outcomes. Int J Occup Med Environ Health. 2016;29(4):683–97. doi:10.13075/ijomeh.1896.00691.

    Article  PubMed  Google Scholar 

  18. Kuo FC, Su SW, Wu CF, Huang MC, Shiea J, Chen BH, et al. Relationship of urinary phthalate metabolites with serum thyroid hormones in pregnant women and their newborns: a prospective birth cohort in Taiwan. PLoS One. 2015;10(6):e0123884. doi:10.1371/journal.pone.0123884.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yao HY, Han Y, Gao H, Huang K, Ge X, Xu YY, et al. Maternal phthalate exposure during the first trimester and serum thyroid hormones in pregnant women and their newborns. Chemosphere. 2016;157:42–8. doi:10.1016/j.chemosphere.2016.05.02310.1016/j.chemosphere.2016.05.023.

    Article  CAS  PubMed  Google Scholar 

  20. Johns LE, Ferguson KK, Soldin OP, Cantonwine DE, Rivera-Gonzalez LO, Del Toro LV, et al. Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis. Reprod Biol Endocrinol. 2015;13:4. doi:10.1186/1477-7827-13-4.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Huang P-C, Tsai C-H, Liang W-Y, Li S-S, Huang H-B, Kuo P-L. Early phthalates exposure in pregnant women is associated with alteration of thyroid hormones. 2016. doi:10.1371/journal.pone.0159398

  22. Ashley-Martin J, Dodds L, Levy AR, Platt RW, Marshall JS, Arbuckle TE. Prenatal exposure to phthalates, bisphenol A and perfluoroalkyl substances and cord blood levels of IgE, TSLP and IL-33. Environ Res. 2015;140:360–8. doi:10.1016/j.envres.2015.04.010.

    Article  CAS  PubMed  Google Scholar 

  23. Robledo CA, Peck JD, Stoner J, Calafat AM, Carabin H, Cowan L, et al. Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy. Int J Hyg Environ Health. 2015;218(3):324–30. doi:10.1016/j.ijheh.2015.01.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gray LE, Barlow NJ, Howdeshell KL, Ostby JS, Furr JR, Gray CL. Transgenerational effects of di (2-ethylhexyl) phthalate in the male CRL:CD(SD) rat: added value of assessing multiple offspring per litter. Toxicol Sci. 2009;110(2):411–25. doi:10.1093/toxsci/kfp10910.1093/toxsci/kfp109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. • Martino-Andrade AJ, Liu F, Sathyanarayana S, Barrett ES, Redmon JB, Nguyen RH, et al. Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns. Andrology. 2016;4(4):585–93. doi:10.1111/andr.12180. Exposure measurement in each trimester allowed analysis of the impacts timing of phthalate exposure had on male genital development. Interesting findings on relationships between timing of DEHP metabolites and this development, with penile width inversely associated with second trimester exposure and analgenital distance inversely associated with exposure in the first trimester

    Article  CAS  PubMed  Google Scholar 

  26. Swan SH, Sathyanarayana S, Barrett ES, Janssen S, Liu F, Nguyen RH, et al. First trimester phthalate exposure and anogenital distance in newborns. Hum Reprod. 2015;30(4):963–72. doi:10.1093/humrep/deu36310.1093/humrep/deu363. Epub 2015 Feb 18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bustamante-Montes LP, Hernández-Valero MA, Flores-Pimentel D, García-Fábila M, Amaya-Chávez A, Barr DB, et al. Prenatal exposure to phthalates is associated with decreased anogenital distance and penile size in male newborns. J Dev Orig Health Dis. 2013;4(4) doi:10.1017/s204017441300017210.1017/S2040174413000172.

  28. Sathyanarayana S, Grady R, Barrett ES, Redmon B, Nguyen RH, Barthold JS, et al. First trimester phthalate exposure and male newborn genital anomalies. Environ Res. 2016;151:777–82. doi:10.1016/j.envres.2016.07.043.

    Article  CAS  PubMed  Google Scholar 

  29. Foster PMD, Mylchreest E, Endocrine R, Developmental Toxicology Program CCfHRRTPNCUSA et al. Effects of phthalate esters on the developing reproductive tract of male rats. APMIS. 2017;109(S103). doi:10.1111/j.1600-0463.2001.tb05776.x.

  30. Alur S, Wang H, Hoeger K, Swan SH, Sathyanarayana S, Redmon BJ, et al. Urinary phthalate metabolite concentrations in relation to history of infertility and use of assisted reproductive technology. Fertil Steril. 2015;104(5):1227–35. doi:10.1016/j.fertnstert.2015.07.1150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dodge LE, Williams PL, Williams MA, Missmer SA, Souter I, Calafat AM, et al. Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment. Reprod Toxicol. 2015;58:184–93. doi:10.1016/j.reprotox.2015.09.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Messerlian C, Wylie BJ, Mínguez-Alarcón L, Williams PL, Ford JB, Souter IC, et al. Urinary concentrations of phthalate metabolites and pregnancy loss among women conceiving with medically assisted reproduction. Epidemiology. 2016;27(6):879–88. doi:10.1097/ede.0000000000000525.

    Article  PubMed  Google Scholar 

  33. Velez MP, Arbuckle TE, Fraser WD. Female exposure to phenols and phthalates and time to pregnancy: the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. Fertil Steril. 2015;103(4):1011–20.e2. doi:10.1016/j.fertnstert.2015.01.005.

    Article  CAS  PubMed  Google Scholar 

  34. • Ferguson KK, McElrath TF, Meeker JD. Environmental phthalate exposure and preterm birth. JAMA Pediatr. 2013;168(1):61–7. doi:10.1001/jamapediatrics.2013.369910.1001/jamapediatrics.2013.3699. Multiple exposure ascertainments strengthened findings of DEHP’s association with preterm birth

    Article  Google Scholar 

  35. Sathyanarayana S, Beard L, Zhou C, Grady R. Measurement and correlates of ano-genital distance in healthy, newborn infants. Int J Androl. 2010;33(2):317–23. doi:10.1111/j.1365-2605.2009.01044.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sly PD, Carpenter DO, Van den Berg M, Stein RT, Landrigan PJ, Brune-Drisse M-N, et al. Health consequences of environmental exposures: causal thinking in global environmental epidemiology. Annals of Global Health. 2016;82(1):3–9. doi:10.1016/j.aogh.2016.01.004.

    Article  PubMed  Google Scholar 

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Correspondence to Christina A. Porucznik.

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Sarah H. Pollard and Christina A. Porucznik each declare no potential conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Environmental Epidemiology

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Pollard, S.H., Porucznik, C.A. Impact of Periconceptional Exposure to Phthalates on Pregnancy, Birth, and Neonatal Outcomes. Curr Epidemiol Rep 4, 199–210 (2017). https://doi.org/10.1007/s40471-017-0110-3

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  • DOI: https://doi.org/10.1007/s40471-017-0110-3

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