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Maternal smoking during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis

  • Chengjun Yu
  • Yi Wei
  • Xiangliang Tang
  • Bin Liu
  • Lianju Shen
  • Chunlan Long
  • Tao Lin
  • Dawei He
  • Shengde Wu
  • Guanghui Wei
Original Article

Abstract

The risk factors for undescended testes in male infants and the underlying pathogenesis still remain unclear. The aim of this study is to identify the relationship between maternal smoking during pregnancy and risk of cryptorchidism. A systematic review was conducted using appropriate search terms to identify articles pertaining to maternal smoking during pregnancy and risk of cryptorchidism. Entries up to December 23, 2017 were taken into consideration, without any language or regional restriction. The crude ORs and their 95% CIs were computed by using the fixed-effect model. Twenty studies involving 111,712 infants were included in our meta-analysis. The risk of having a male infant with cryptorchidism was significantly different between mothers who smoked during pregnancy and those who did not (pooled crude OR 1.18, 95% confidence interval [CI] 1.12–1.24, p < 0.00001).

Conclusion: Our findings suggest that smoking during pregnancy increased the risk of cryptorchidism by 1.18 times. Further investigations that are well-designed, multicentric studies measuring variables, such as the number of cigarettes smoked in a day and the stage of pregnancy during which the mothers smoked, are necessary to precisely determine the relationship between maternal smoking and risk of cryptorchidism.

What is Known:

Preterm and low birth weight have been definitively shown to be risk factors for cryptorchidism.

The relationship between with maternal smoking during pregnancy and risk of cryptorchidism remains controversial all the time.

What is New:

Mothers who smoked during pregnancy had a 1.18 times higher risk of having a child with cryptorchidism as compared to those who did not smoke.

Evidence has been found that maternal smoking during pregnancy is a definitive risk factor for cryptorchidism.

Keywords

Cryptorchidism Maternal smoking Meta-analysis 

Abbreviations

CI

Confidence interval

OR

Odds ratio

Notes

Acknowledgements

I would acknowledge the support of Dept. of Urology of Children’s Hospital of Chongqing Medical University, the financial support of National Natural Science Foundation of China, and I would especially express my thanks to Professor John Hutson for language editing.

Authors’ contributions

CJY and SDW conceived and designed the meta-analysis. CJY and YW independently searched the Pubmed, Cochrane Librery, Web of Science database, China National Knowledge Infrastructure (CNKI), WanFang Data, VIP database and China Biology Medical disc (CBM), and independently extracted the data. CJY led analysis and interpretation of data, drafted the manuscript and revised content based on feedback. YW acted as second reviewer. XLT and BL assisted with the retrieval of the database and acquisition of data. LJS and CLL assisted with the interpretation of data and provided critical revision of drafts. TL, DWH, and GHW assisted with the conception and design, interpretation of data, and critical revision of drafts. SDW acted as the corresponding author, provided funding support, assisted with interpretation of data, provided critical revision of drafts and acted as the third (mediating) reviewer.

Funding

This study is supported by the National Natural Science Foundation of China (No. 81571425), Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJ1600229), and Postgraduate scientific research innovation project of Chongqing Medical university (CYB16105).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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

References

  1. 1.
    Adams SV, Hastert TA, Huang Y, Starr JR (2011) No association between maternal pre-pregnancy obesity and risk of hypospadias or cryptorchidism in male newborns. Birth Defects Res A Clin Mol Teratol 91:241–248CrossRefGoogle Scholar
  2. 2.
    Akre O, Lipworth L, Cnattingius S, Sparen P, Ekbom A (1999) Risk factor patterns for cryptorchidism and hypospadias. Epidemiology (Cambridge, Mass) 10:364–369CrossRefGoogle Scholar
  3. 3.
    Barthold J, Robbins A, Wang Y, Pugarelli J, Mateson A, Anand-Ivell R, Ivell R, McCahan S, Akins R (2014) Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling. Biol Reprod 91:41CrossRefGoogle Scholar
  4. 4.
    Bay K, Anand-Ivell R (2014) Human testicular insulin-like factor 3 and endocrine disrupters. Vitam Horm 94:327–348CrossRefGoogle Scholar
  5. 5.
    Beard CM, Melton LJ 3rd, O'Fallon WM, Noller KL, Benson RC (1984) Cryptorchism and maternal estrogen exposure. Am J Epidemiol 120:707–716CrossRefGoogle Scholar
  6. 6.
    Berkowitz G, Lapinski R (1996) Risk factors for cryptorchidism: a nested case-control study. Paediatr Perinat Epidemiol 10:39–51CrossRefGoogle Scholar
  7. 7.
    Biggs ML, Baer A, Critchlow CW (2002) Maternal, delivery, and perinatal characteristics associated with cryptorchidism: a population-based case-control study among births in Washington State. Epidemiology (Cambridge, Mass) 13:197–204CrossRefGoogle Scholar
  8. 8.
    Braga L, Lorenzo A, Romao R (2017) Canadian Urological Association-Pediatric Urologists of Canada (CUA-PUC) guideline for the diagnosis, management, and followup of cryptorchidism. Can Urol Assoc J 11:E251–E260CrossRefGoogle Scholar
  9. 9.
    Brouwers M, de Bruijne L, de Gier R, Zielhuis G, Feitz W, Roeleveld N (2012) Risk factors for undescended testis. J Pediatr Urol 8:59–66CrossRefGoogle Scholar
  10. 10.
    Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, Figà-Talamanca I (2007) The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. Int J Androl 30:3–13CrossRefGoogle Scholar
  11. 11.
    Giordano F, Carbone P, Nori F, Mantovani A, Taruscio D, Figà-Talamanca I (2008) Maternal diet and the risk of hypospadias and cryptorchidism in the offspring. Paediatr Perinat Epidemiol 22:249–260Google Scholar
  12. 12.
    Davies T, Williams D, Whitaker R (1986) Risk factors for undescended testis. Int J Epidemiol 15:197–201CrossRefGoogle Scholar
  13. 13.
    Duarte A, Bessa J, Mrad F, Tibiriçá S, Camargo M, Vieira A, Araujo F, Figueiredo A, Bastos-Netto J (2017) Smoking and its association with cryptorchidism in Down syndrome. Rev Assoc Med Bras (1992) 63:693–696CrossRefGoogle Scholar
  14. 14.
    Fernandez M, Olmos B, Granada A, López-Espinosa M, Molina-Molina J, Fernandez J, Cruz M, Olea-Serrano F, Olea N (2007) Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study. Environ Health Perspect 115(Suppl 1):8–14CrossRefGoogle Scholar
  15. 15.
    Flück C, Meyer-Böni M, Pandey A, Kempná P, Miller W, Schoenle E, Biason-Lauber A (2011) Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation. Am J Hum Genet 89:201–218CrossRefGoogle Scholar
  16. 16.
    Fowler P, Cassie S, Rhind S, Brewer M, Collinson J, Lea R, Baker P, Bhattacharya S, O'Shaughnessy P (2008) Maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development. J Clin Endocrinol Metab 93:619–626CrossRefGoogle Scholar
  17. 17.
    Fowler P, Bhattacharya S, Gromoll J, Monteiro A, O’Shaughnessy P (2009) Maternal smoking and developmental changes in luteinizing hormone (LH) and the LH receptor in the fetal testis. J Clin Endocrinol Metab 94:4688–4695CrossRefGoogle Scholar
  18. 18.
    Fowler P, Filis P, Bhattacharya S, le Bizec B, Antignac J, Morvan M, Drake A, Soffientini U, O’Shaughnessy P (2016) Human anogenital distance: an update on fetal smoke-exposure and integration of the perinatal literature on sex differences. Hum Reprod 31:463–472CrossRefGoogle Scholar
  19. 19.
    Gurney J, Richiardi L, McGlynn K, Signal V, Sarfati D (2017) Analgesia use during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis. Hum Reprod 32:1118–1129CrossRefGoogle Scholar
  20. 20.
    Higgins J, Thompson S, Deeks J, Altman D (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefGoogle Scholar
  21. 21.
    Huff D, Fenig D, Canning D, Carr M, Zderic S, Snyder H (2001) Abnormal germ cell development in cryptorchidism. Horm Res 55:11–17PubMedGoogle Scholar
  22. 22.
    Hutson J, Thorup J (2015) Evaluation and management of the infant with cryptorchidism. Curr Opin Pediatr 27:520–524CrossRefGoogle Scholar
  23. 23.
    Hutson J, Southwell B, Li R, Lie G, Ismail K, Harisis G, Chen N (2013) The regulation of testicular descent and the effects of cryptorchidism. Endocr Rev 34:725–752CrossRefGoogle Scholar
  24. 24.
    Ion R, Wills A, Bernal A (2015) Environmental tobacco smoke exposure in pregnancy is associated with earlier delivery and reduced birth weight. Reprod Sci 22:1603–1611CrossRefGoogle Scholar
  25. 25.
    Jensen MS, Toft G, Thulstrup AM, Bonde JP, Olsen J (2007) Cryptorchidism according to maternal gestational smoking. Epidemiology (Cambridge, Mass) 18:220–225CrossRefGoogle Scholar
  26. 26.
    Jones M, Swerdlow A, Griffith M, Goldacre M (1998) Prenatal risk factors for cryptorchidism: a record linkage study. Paediatr Perinat Epidemiol 12:383–396CrossRefGoogle Scholar
  27. 27.
    Ko T, Tsai L, Chu L, Yeh S, Leung C, Chen C, Chou H, Tsao P, Chen P, Hsieh W (2014) Parental smoking during pregnancy and its association with low birth weight, small for gestational age, and preterm birth offspring: a birth cohort study. Pediatr Neonatol 55:20–27CrossRefGoogle Scholar
  28. 28.
    Kurahashi N, Kasai S, Shibata T, Kakizaki H, Nonomura K, Sata F, Kishi R (2005) Parental and neonatal risk factors for cryptorchidism. Med Sci Monit 11:Cr274–Cr283PubMedGoogle Scholar
  29. 29.
    Levine H, Keinan-Boker L, Leiba A, Derazne E, Rais A, Kark J (2017) Paternal age and risk of testicular germ cell tumors: a cohort study of 1,000,000 men. Andrology 5:1124–1130CrossRefGoogle Scholar
  30. 30.
    McBride ML, Van den Steen N, Lamb CW, Gallagher RP (1991) Maternal and gestational factors in cryptorchidism. Int J Epidemiol 20:964–970CrossRefGoogle Scholar
  31. 31.
    Moher D, Liberati A, Tetzlaff J, Altman D (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefGoogle Scholar
  32. 32.
    Moller H, Skakkebaek NE (1996) Risks of testicular cancer and cryptorchidism in relation to socio-economic status and related factors: case-control studies in Denmark. Int J Cancer 66:287–293CrossRefGoogle Scholar
  33. 33.
    Mongraw-Chaffin ML, Cohn BA, Cohen RD, Christianson RE (2008) Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son’s risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies cohort, 1959-1967. Am J Epidemiol 167:257–261CrossRefGoogle Scholar
  34. 34.
    Mori M, Davies T, Tsukamoto T, Kumamoto Y, Fukuda K (1992) Maternal and other factors of cryptorchidism—a case-control study in Japan. Kurume Med J 39:53–60CrossRefGoogle Scholar
  35. 35.
    Nef S, Parada L (1999) Cryptorchidism in mice mutant for Insl3. Nat Genet 22:295–299CrossRefGoogle Scholar
  36. 36.
    Preiksa R, Zilaitiene B, Matulevicius V, Skakkebaek N, Petersen J, Jørgensen N, Toppari J (2005) Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod 20:1928–1932CrossRefGoogle Scholar
  37. 37.
    Shiono P, Klebanoff M, Berendes H (1986) Congenital malformations and maternal smoking during pregnancy. Teratology 34:65–71CrossRefGoogle Scholar
  38. 38.
    Tanyel F (2004) Obliteration of processus vaginalis: aberrations in the regulatory mechanism result in an inguinal hernia, hydrocele or undescended testis. Turk J Pediatr 46(Suppl):18–27PubMedGoogle Scholar
  39. 39.
    Tanyel F, Ertunç M, Ekinci S, Yildirim M, Onur R (2005) Anti-androgen induced inhibition of testicular descent is associated with a decrease in sympathetic tonus. Eur J Pediatr Surg 15:273–278CrossRefGoogle Scholar
  40. 40.
    Varvarigou A, Liatsis S, Vassilakos P, Decavalas G, Beratis N (2009) Effect of maternal smoking on cord blood estriol, placental lactogen, chorionic gonadotropin, FSH, LH, and cortisol. J Perinat Med 37:364–369CrossRefGoogle Scholar
  41. 41.
    Virtanen HE, Tapanainen AE, Kaleva MM, Suomi AM, Main KM, Skakkebaek NE, Toppari J (2006) Mild gestational diabetes as a risk factor for congenital cryptorchidism. J Clin Endocrinol Metab 91:4862–4865CrossRefGoogle Scholar
  42. 42.
    Wagner-Mahler K, Kurzenne J, Delattre I, Bérard E, Mas J, Bornebush L, Tommasi C, Boda-Buccino M, Ducot B, Boullé C, Ferrari P, Azuar P, Bongain A, Fénichel P, Brucker-Davis F (2011) Prospective study on the prevalence and associated risk factors of cryptorchidism in 6246 newborn boys from Nice area, France. Int J Androl 34:e499–e510CrossRefGoogle Scholar
  43. 43.
    Zhang L, Wang XH, Zheng XM, Liu TZ, Zhang WB, Zheng H, Chen MF (2015) Maternal gestational smoking, diabetes, alcohol drinking, pre-pregnancy obesity and the risk of cryptorchidism: a systematic review and meta-analysis of observational studies. PLoS One 10:e0119006CrossRefGoogle Scholar
  44. 44.
    Zimmermann S, Steding G, Emmen J, Brinkmann A, Nayernia K, Holstein A, Engel W, Adham I (1999) Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol Endocrinol 13:681–691CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018
corrected publication 2019

Authors and Affiliations

  1. 1.Department of UrologyChildren’s Hospital of Chongqing Medical UniversityChongqing CityChina
  2. 2.Chongqing Key Laboratory of Children Urogenital Development and Tissue EngineeringChongqingChina
  3. 3.Ministry of Education Key Laboratory of Child Development and DisordersChongqingChina
  4. 4.China International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqingChina
  5. 5.Chongqing Key Laboratory of Pediatrics ChongqingChongqingChina

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