Skip to main content
SpringerLink
Log in

Effects of Environmental Chemical Exposure on Birth Defects (Except Cryptorchidism and Hypospadias)

  • Chapter
  • First Online:
Health Impacts of Developmental Exposure to Environmental Chemicals

  • 659 Accesses

Abstract

Currently, the causes of birth defects remain unknown in approximately 80% of the cases. Here, the etiologies are likely multifactorial and may involve the genetic background, exposure to drugs, environmental chemical exposure, infections, maternal factors, and intrauterine mechanical factors. In this review, we discuss the effects of environmental chemical exposure on the incidence of birth defects by summarizing the previous epidemiological studies. Notably, chemical exposure was most frequently associated with elevated risks of central nervous system and congenital heart defects and oral clefts than with other types of birth defects. Although exposure to air pollutants, persistent organic pollutants, polycyclic aromatic hydrocarbons, and perfluorinated compounds were associated with increased risks, no substance-specific birth defects were identified. Many case–control studies had the limitation due to poor exposure assessment. In terms of the risk assessment, it is difficult that epidemiological study indicates the hazard identification including the dose-response relationship. We conclude that descriptions of the disease prevalence and individual chemical exposure levels are important roles of reproductive epidemiological study.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. ICBDSR. Annual report 2007. The Centre of the International Clearinghouse for Birth Defects Surveillance and Research, Roma, Italy; 2007.

    Google Scholar 

  2. ICBDSR. Annual report 2014. The Centre of the International Clearinghouse for Birth Defects Surveillance and Research, Roma, Italy; 2014.

    Google Scholar 

  3. St Louis AM, Kim K, Browne ML, Liu G, Liberman RF, Nembhard WN, Canfield MA, Copeland G, Fornoff J, Kirby RS, National Birth Defects Prevention N. Prevalence trends of selected major birth defects: a multi-state population-based retrospective study, United States, 1999 to 2007. Birth Defects Res. 2017;109(18):1442–50. https://doi.org/10.1002/bdr2.1113.

    Article  CAS  PubMed  Google Scholar 

  4. Feldkamp ML, Carey JC, Byrne JLB, Krikov S, Botto LD. Etiology and clinical presentation of birth defects: population based study. BMJ. 2017;357:j2249. https://doi.org/10.1136/bmj.j2249.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Levi P. Principles and mechanisms of teratogenesis. In: Kob V, editor. Teratogens: chemicals which cause birth defects. Amsterdam: Elsevier Science; 1993. p. 1–19.

    Google Scholar 

  6. Moore K, Persaud T, Torchia M. Essentials of embryology and birth defects. Philadelphia: Elsevier Health Sciences; 2016.

    Google Scholar 

  7. Smithells D. Does thalidomide cause second generation birth defects? Drug Saf. 1998;19(5):339–41. https://doi.org/10.2165/00002018-199819050-00001.

    Article  CAS  PubMed  Google Scholar 

  8. Jamilian A, Sarkarat F, Jafari M, Neshandar M, Amini E, Khosravi S, Ghassemi A. Family history and risk factors for cleft lip and palate patients and their associated anomalies. Stomatologija. 2017;19(3):78–83.

    PubMed  Google Scholar 

  9. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13(2):97–109. https://doi.org/10.1038/nrg3142.

    Article  CAS  PubMed  Google Scholar 

  10. Gomez-Duran A, Carvajal-Gonzalez JM, Mulero-Navarro S, Santiago-Josefat B, Puga A, Fernandez-Salguero PM. Fitting a xenobiotic receptor into cell homeostasis: how the dioxin receptor interacts with TGFbeta signaling. Biochem Pharmacol. 2009;77(4):700–12. https://doi.org/10.1016/j.bcp.2008.08.032.

    Article  CAS  PubMed  Google Scholar 

  11. Haarmann-Stemmann T, Bothe H, Abel J. Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways. Biochem Pharmacol. 2009;77(4):508–20. https://doi.org/10.1016/j.bcp.2008.09.013.

    Article  CAS  PubMed  Google Scholar 

  12. Kung T, Murphy KA, White LA. The aryl hydrocarbon receptor (AhR) pathway as a regulatory pathway for cell adhesion and matrix metabolism. Biochem Pharmacol. 2009;77(4):536–46. https://doi.org/10.1016/j.bcp.2008.09.031.

    Article  CAS  PubMed  Google Scholar 

  13. Puga A, Ma C, Marlowe JL. The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Biochem Pharmacol. 2009;77(4):713–22. https://doi.org/10.1016/j.bcp.2008.08.031.

    Article  CAS  PubMed  Google Scholar 

  14. Ma C, Marlowe JL, Puga A. The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways. EXS. 2009;99:231–57.

    CAS  PubMed  Google Scholar 

  15. Birnbaum LS, Weber H, Harris MW, Lamb JC, McKinney JD. Toxic interaction of specific polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin: increased incidence of cleft palate in mice. Toxicol Appl Pharmacol. 1985;77(2):292–302.

    Article  CAS  PubMed  Google Scholar 

  16. Courtney KD, Moore JA. Teratology studies with 2,4,5-trichlorophenoxyacetic acid and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 1971;20(3):396–403.

    Article  CAS  PubMed  Google Scholar 

  17. Neubert D, Zens P, Rothenwallner A, Merker HJ. A survey of the embryotoxic effects of TCDD in mammalian species. Environ Health Perspect. 1973;5:67–79. https://doi.org/10.1289/ehp.730567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Harada M. Congenital minamata disease: intrauterine methylmercury poisoning. Teratology. 1978;18(2):285–8. https://doi.org/10.1002/tera.1420180216.

    Article  CAS  PubMed  Google Scholar 

  19. CtRtHEiVVoEt H. Veterans and agent orange: update 1996. Washington, DC: The National Academy Press; 1996.

    Google Scholar 

  20. Kuehl KS, Loffredo CA. Population-based study of l-transposition of the great arteries: possible associations with environmental factors. Birth Defects Res A Clin Mol Teratol. 2003;67(3):162–7. https://doi.org/10.1002/bdra.10015.

    Article  CAS  PubMed  Google Scholar 

  21. Vinceti M, Malagoli C, Werler MM, Filippini T, De Girolamo G, Ghermandi G, Fabbi S, Astolfi G, Teggi S. Adverse pregnancy outcomes in women with changing patterns of exposure to the emissions of a municipal waste incinerator. Environ Res. 2018;164:444–51. https://doi.org/10.1016/j.envres.2018.03.024.

    Article  CAS  PubMed  Google Scholar 

  22. Tango T, Fujita T, Tanihata T, Minowa M, Doi Y, Kato N, Kunikane S, Uchiyama I, Tanaka M, Uehata T. Risk of adverse reproductive outcomes associated with proximity to municipal solid waste incinerators with high dioxin emission levels in Japan. J Epidemiol. 2004;14(3):83–93.

    Article  PubMed  Google Scholar 

  23. Cordier S, Lehebel A, Amar E, Anzivino-Viricel L, Hours M, Monfort C, Chevrier C, Chiron M, Robert-Gnansia E. Maternal residence near municipal waste incinerators and the risk of urinary tract birth defects. Occup Environ Med. 2010;67(7):493–9. https://doi.org/10.1136/oem.2009.052456.

    Article  CAS  PubMed  Google Scholar 

  24. Pettigrew SM, Bell EM, Van Zutphen AR, Rocheleau CM, Shaw GM, Romitti PA, Olshan A, Lupo PJ, Soim A, Makelarski JA, Michalski AM, Sanderson W, The National Birth Defects Prevention Study. Paternal and joint parental occupational pesticide exposure and spina bifida in the National Birth Defects Prevention Study, 1997 to 2002. Birth Defects Res A Clin Mol Teratol. 2016;106(11):963–71. https://doi.org/10.1002/bdra.23551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Barbee BD, Richards JH, Butenhoff JL, Stevenson LA, Lau C. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse I: maternal and prenatal evaluations. Toxicol Sci. 2003;74(2):369–81. https://doi.org/10.1093/toxsci/kfg121.

    Article  CAS  PubMed  Google Scholar 

  26. Stein CR, Savitz DA, Elston B, Thorpe PG, Gilboa SM. Perfluorooctanoate exposure and major birth defects. Reprod Toxicol. 2014;47:15–20. https://doi.org/10.1016/j.reprotox.2014.04.006.

    Article  CAS  PubMed  Google Scholar 

  27. Nolan LA, Nolan JM, Shofer FS, Rodway NV, Emmett EA. Congenital anomalies, labor/delivery complications, maternal risk factors and their relationship with perfluorooctanoic acid (PFOA)-contaminated public drinking water. Reprod Toxicol. 2010;29(2):147–55. https://doi.org/10.1016/j.reprotox.2009.10.012.

    Article  CAS  PubMed  Google Scholar 

  28. Vesterholm Jensen D, Christensen J, Virtanen HE, Skakkebaek NE, Main KM, Toppari J, Veje CW, Andersson AM, Nielsen F, Grandjean P, Jensen TK. No association between exposure to perfluorinated compounds and congenital cryptorchidism: a nested case-control study among 215 boys from Denmark and Finland. Reproduction. 2014;147(4):411–7. https://doi.org/10.1530/REP-13-0444.

    Article  CAS  PubMed  Google Scholar 

  29. Khattak S, Moghtader G, McMartin K, Barrera M, Kennedy D, Koren G. Pregnancy outcome following gestational exposure to organic solvents: a prospective controlled study. JAMA. 1999;281(12):1106–9.

    Article  CAS  PubMed  Google Scholar 

  30. Vaktskjold A, Talykova LV, Nieboer E. Congenital anomalies in newborns to women employed in jobs with frequent exposure to organic solvents--a register-based prospective study. BMC Pregnancy Childbirth. 2011;11:83. https://doi.org/10.1186/1471-2393-11-83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vrijheid M, Martinez D, Manzanares S, Dadvand P, Schembari A, Rankin J, Nieuwenhuijsen M. Ambient air pollution and risk of congenital anomalies: a systematic review and meta-analysis. Environ Health Perspect. 2011;119(5):598–606. https://doi.org/10.1289/ehp.1002946.

    Article  CAS  PubMed  Google Scholar 

  32. Gianicolo EA, Mangia C, Cervino M, Bruni A, Andreassi MG, Latini G. Congenital anomalies among live births in a high environmental risk area--a case-control study in Brindisi (southern Italy). Environ Res. 2014;128:9–14. https://doi.org/10.1016/j.envres.2013.11.002.

    Article  CAS  PubMed  Google Scholar 

  33. Vinceti M, Malagoli C, Malavolti M, Cherubini A, Maffeis G, Rodolfi R, Heck JE, Astolfi G, Calzolari E, Nicolini F. Does maternal exposure to benzene and PM10 during pregnancy increase the risk of congenital anomalies? A population-based case-control study. Sci Total Environ. 2016;541:444–50. https://doi.org/10.1016/j.scitotenv.2015.09.051.

    Article  CAS  PubMed  Google Scholar 

  34. Brender JD, Olive JM, Felkner M, Suarez L, Marckwardt W, Hendricks KA. Dietary nitrites and nitrates, nitrosatable drugs, and neural tube defects. Epidemiology. 2004;15(3):330–6.

    Article  PubMed  Google Scholar 

  35. Croen LA, Todoroff K, Shaw GM. Maternal exposure to nitrate from drinking water and diet and risk for neural tube defects. Am J Epidemiol. 2001;153(4):325–31.

    Article  CAS  PubMed  Google Scholar 

  36. Dorsch MM, Scragg RK, McMichael AJ, Baghurst PA, Dyer KF. Congenital malformations and maternal drinking water supply in rural South Australia: a case-control study. Am J Epidemiol. 1984;119(4):473–86.

    Article  CAS  PubMed  Google Scholar 

  37. Arbuckle TE, Sherman GJ, Corey PN, Walters D, Lo B. Water nitrates and CNS birth defects: a population-based case-control study. Arch Environ Health. 1988;43(2):162–7. https://doi.org/10.1080/00039896.1988.9935846.

    Article  CAS  PubMed  Google Scholar 

  38. Cedergren MI, Selbing AJ, Lofman O, Kallen BA. Chlorination byproducts and nitrate in drinking water and risk for congenital cardiac defects. Environ Res. 2002;89(2):124–30.

    Article  CAS  PubMed  Google Scholar 

  39. Hanaoka T, Tamura N, Ito K, Sasaki S, Araki A, Ikeno T, Miyashita C, Ito S, Minakami H, Cho K, Endo T, Baba T, Miyamoto T, Sengoku K, Kishi R, Hokkaido Study on Environment and Children’s Health. Prevalence and risk of birth defects observed in a prospective cohort study: The Hokkaido Study on Environment and Children’s Health. J Epidemiol. 2018;28(3):125–32. https://doi.org/10.2188/jea.JE20160108.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Padula AM, Tager IB, Carmichael SL, Hammond SK, Lurmann F, Shaw GM. The association of ambient air pollution and traffic exposures with selected congenital anomalies in the San Joaquin Valley of California. Am J Epidemiol. 2013;177(10):1074–85. https://doi.org/10.1093/aje/kws367.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rull RP, Ritz B, Shaw GM. Neural tube defects and maternal residential proximity to agricultural pesticide applications. Am J Epidemiol. 2006;163(8):743–53. https://doi.org/10.1093/aje/kwj101.

    Article  PubMed  Google Scholar 

  42. Yang W, Carmichael SL, Roberts EM, Kegley SE, Padula AM, English PB, Shaw GM. Residential agricultural pesticide exposures and risk of neural tube defects and orofacial clefts among offspring in the San Joaquin Valley of California. Am J Epidemiol. 2014;179(6):740–8. https://doi.org/10.1093/aje/kwt324.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ma J, Qiu X, Ren A, Jin L, Zhu T. Using placenta to evaluate the polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) exposure of fetus in a region with high prevalence of neural tube defects. Ecotoxicol Environ Saf. 2012;86:141–6. https://doi.org/10.1016/j.ecoenv.2012.09.005.

    Article  CAS  PubMed  Google Scholar 

  44. Ren A, Qiu X, Jin L, Ma J, Li Z, Zhang L, Zhu H, Finnell RH, Zhu T. Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects. Proc Natl Acad Sci U S A. 2011;108(31):12770–5. https://doi.org/10.1073/pnas.1105209108.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Li Z, Zhang L, Ye R, Pei L, Liu J, Zheng X, Ren A. Indoor air pollution from coal combustion and the risk of neural tube defects in a rural population in Shanxi Province, China. Am J Epidemiol. 2011;174(4):451–8. https://doi.org/10.1093/aje/kwr108.

    Article  PubMed  Google Scholar 

  46. Naufal Z, Zhiwen L, Zhu L, Zhou GD, McDonald T, He LY, Mitchell L, Ren A, Zhu H, Finnell R, Donnelly KC. Biomarkers of exposure to combustion by-products in a human population in Shanxi, China. J Expo Sci Environ Epidemiol. 2010;20(4):310–9. https://doi.org/10.1038/jes.2009.19.

    Article  CAS  PubMed  Google Scholar 

  47. Ritz B, Yu F, Fruin S, Chapa G, Shaw GM, Harris JA. Ambient air pollution and risk of birth defects in Southern California. Am J Epidemiol. 2002;155(1):17–25.

    Article  PubMed  Google Scholar 

  48. Gilboa SM, Mendola P, Olshan AF, Langlois PH, Savitz DA, Loomis D, Herring AH, Fixler DE. Relation between ambient air quality and selected birth defects, seven county study, Texas, 1997-2000. Am J Epidemiol. 2005;162(3):238–52. https://doi.org/10.1093/aje/kwi189.

    Article  CAS  PubMed  Google Scholar 

  49. Stingone JA, Luben TJ, Daniels JL, Fuentes M, Richardson DB, Aylsworth AS, Herring AH, Anderka M, Botto L, Correa A, Gilboa SM, Langlois PH, Mosley B, Shaw GM, Siffel C, Olshan AF, National Birth Defects Prevention Study. Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the national birth defects prevention study. Environ Health Perspect. 2014;122(8):863–72. https://doi.org/10.1289/ehp.1307289.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Hansen CA, Barnett AG, Jalaludin BB, Morgan GG. Ambient air pollution and birth defects in Brisbane, Australia. PLoS One. 2009;4(4):e5408. https://doi.org/10.1371/journal.pone.0005408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann F, Shaw GM. Ambient air pollution and traffic exposures and congenital heart defects in the San Joaquin Valley of California. Paediatr Perinat Epidemiol. 2013;27(4):329–39. https://doi.org/10.1111/ppe.12055.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Agay-Shay K, Friger M, Linn S, Peled A, Amitai Y, Peretz C. Air pollution and congenital heart defects. Environ Res. 2013;124:28–34. https://doi.org/10.1016/j.envres.2013.03.005.

    Article  CAS  PubMed  Google Scholar 

  53. Schreinemachers DM. Birth malformations and other adverse perinatal outcomes in four U.S. Wheat-producing states. Environ Health Perspect. 2003;111(9):1259–64. https://doi.org/10.1289/ehp.5830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hwang BF, Jaakkola JJ. Ozone and other air pollutants and the risk of oral clefts. Environ Health Perspect. 2008;116(10):1411–5. https://doi.org/10.1289/ehp.11311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Marshall EG, Harris G, Wartenberg D. Oral cleft defects and maternal exposure to ambient air pollutants in New Jersey. Birth Defects Res A Clin Mol Teratol. 2010;88(4):205–15. https://doi.org/10.1002/bdra.20650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Winchester PD, Huskins J, Ying J. Agrichemicals in surface water and birth defects in the United States. Acta Paediatr. 2009;98(4):664–9. https://doi.org/10.1111/j.1651-2227.2008.01207.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Loffredo CA, Silbergeld EK, Ferencz C, Zhang J. Association of transposition of the great arteries in infants with maternal exposures to herbicides and rodenticides. Am J Epidemiol. 2001;153(6):529–36.

    Article  CAS  PubMed  Google Scholar 

  58. Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann FW, Shaw GM. Traffic-related air pollution and selected birth defects in the San Joaquin Valley of California. Birth Defects Res A Clin Mol Teratol. 2013;97(11):730–5. https://doi.org/10.1002/bdra.23175.

    Article  CAS  PubMed  Google Scholar 

  59. Waller SA, Paul K, Peterson SE, Hitti JE. Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State. Am J Obstet Gynecol. 2010;202(3):241–6. https://doi.org/10.1016/j.ajog.2010.01.023.

    Article  CAS  PubMed  Google Scholar 

  60. Felix JF, van Dooren MF, Klaassens M, Hop WC, Torfs CP, Tibboel D. Environmental factors in the etiology of esophageal atresia and congenital diaphragmatic hernia: results of a case-control study. Birth Defects Res A Clin Mol Teratol. 2008;82(2):98–105. https://doi.org/10.1002/bdra.20423.

    Article  CAS  PubMed  Google Scholar 

  61. Mattix KD, Winchester PD, Scherer LR. Incidence of abdominal wall defects is related to surface water atrazine and nitrate levels. J Pediatr Surg. 2007;42(6):947–9. https://doi.org/10.1016/j.jpedsurg.2007.01.027.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported in part by Grants-in-Aid for Scientific Research from the Japan Ministry of Health, Labour, and Welfare; and the Japan Agency for Medical Research and Development (AMED) under Grant Number JP18gk0110032.

Author information

Authors and Affiliations

  1. Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan

    Tomoyuki Hanaoka, Chihiro Miyashita & Reiko Kishi

  2. Department of Nursing, Faculty of Health Science, Hokkaido University of Science, Sapporo, Hokkaido, Japan

    Kumiko Itoh

Authors
  1. Tomoyuki Hanaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chihiro Miyashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kumiko Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reiko Kishi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reiko Kishi .

Editor information

Editors and Affiliations

  1. Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan

    Reiko Kishi

  2. Department of Environmental Health Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Philippe Grandjean

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hanaoka, T., Miyashita, C., Itoh, K., Kishi, R. (2020). Effects of Environmental Chemical Exposure on Birth Defects (Except Cryptorchidism and Hypospadias). In: Kishi, R., Grandjean, P. (eds) Health Impacts of Developmental Exposure to Environmental Chemicals. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-15-0520-1_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-0520-1_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-0519-5

  • Online ISBN: 978-981-15-0520-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation