Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants

Human Reproduction

Volumn 31, Issue 11, 2016, Pages 2642-2650

  Fisher, B G ^a   Thankamony, A ^a   Hughes, I A ^a   Ong, K K ^a,b   Dunger, D B ^a   Acerini, C L ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

anogenital distance; endocrine disruption; paracetamol; testicular descent; testicular dysgenesis syndrome; toxicology

Indexed keywords

PARACETAMOL; BIOLOGICAL MARKER;

ADVERSE OUTCOME; ANOGENITAL DISTANCE; ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; CRYPTORCHISM; FOLLOW UP; GESTATION PERIOD; GONAD DEVELOPMENT; HUMAN; HUMAN EXPERIMENT; INFANT; MALE; PENILE LENGTH; PENIS; PREGNANT WOMAN; PRENATAL DRUG EXPOSURE; PROSPECTIVE STUDY; TESTIS DESCENT; ANAL CANAL; ANATOMY AND HISTOLOGY; DRUG EFFECTS; FEMALE; MORPHOMETRY; NEWBORN; PREGNANCY; PRENATAL EXPOSURE; TESTIS;

ACETAMINOPHEN; ANAL CANAL; BIOMARKERS; BODY WEIGHTS AND MEASURES; FEMALE; HUMANS; INFANT, NEWBORN; MALE; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; TESTIS;

EID: 84996564681     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/dew196     Document Type: Article

References (40)

1. Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974;19:716-723.
2. Aselton P, Jick H, Milunsky A, Hunter JR, Stergachis A. First-trimester drug use and congenital disorders. Obstet Gynecol 1985;65:451-455.
3. Bay K, Asklund C, Skakkebaek NE, Andersson A-M. Testicular dysgenesis syndrome: possible role of endocrine disrupters. Best Pract Res Clin Endocrinol Metab 2006;20:77-90.
4. Christiansen S, Kortenkamp A, Axelstad M, Boberg J, Scholze M, Jacobsen PR, Faust M, Lichtensteiger W, Schlumpf M, Burdorf A et al. Mixtures of endocrine disrupting contaminants modelled on human high end exposures: an exploratory study in rats. Int J Androl 2012;35:303-316.
5. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet (London, England) 1994;343:619-629.
6. Correy JF, Newman NM, Collins JA, Burrows EA, Burrows RF, Curran JT. Use of prescription drugs in the first trimester and congenital malformations. Aust NZ J Obstet Gynaecol 1991;31:340-344.
7. Czeizel AE, Dudás I, Puhó E. Short-term paracetamol therapy during pregnancy and a lower rate of preterm birth. Paediatr Perinat Epidemiol 2005; 19:106-111.
8. Dean A, Sharpe RM. Anogenital distance or digit length ratio as measures of fetal androgen exposure: relationship to male reproductive development and its disorders. J Clin Endocrinol Metab 2013;98:2230-2238.
9. Van Den Driesche S, Macdonald J, Anderson RA, Johnston ZC, Chetty T, Smith LB, McKinnell C, Dean A, Homer NZ, Jorgensen A et al. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model. Sci Transl Med 2015; 7:288ra80.
10. Eisenberg ML, Hsieh MH, Walters RC, Krasnow R, Lipshultz LI. The relationship between anogenital distance, fatherhood, and fertility in adult men. PLoS One 2011;6:e18973.
11. Eisenberg ML, Jensen TK, Walters RC, Skakkebaek NE, Lipshultz LI. The relationship between anogenital distance and reproductive hormone levels in adult men. J Urol 2012;187:594-598.
12. Feldkamp ML, Meyer RE, Krikov S, Botto LD. Acetaminophen use in pregnancy and risk of birth defects: findings from the National Birth Defects Prevention Study. Obstet Gynecol 2010;115:109-115.
13. Feldman Y, Koren G, Mattice K, Shear H, Pellegrini E, MacLeod SM. Determinants of recall and recall bias in studying drug and chemical exposure in pregnancy. Teratology 1989;40:37-45.
14. Freeman JV, Cole TJ, Chinn S, Jones PR, White EM, Preece MA. Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995;73:17-24.
15. Gupta C, Goldman AS. The arachidonic acid cascade is involved in the masculinizing action of testosterone on embryonic external genitalia in mice. Proc Natl Acad Sci USA1986;83:4346-4349.
16. Holm JB, Chalmey C, Modick H, Jensen LS, Dierkes G, Weiss T, Jensen B, Nørregård MM, Borkowski K, Styrishave B et al. Aniline is rapidly converted into paracetamol impairing male reproductive development. Toxicol Sci 2015;148:288-298.
17. Hughes IA, Acerini CL. Factors controlling testis descent. Eur J Endocrinol 2008;159:S75-S82.
18. Jensen MS, Rebordosa C, Thulstrup AM, Toft G, Sørensen HT, Bonde JP, Henriksen TB, Olsen J. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology 2010;21:779-785.
19. Khan S, Somani B, Lam W, Donat R. Establishing a reference range for penile length in Caucasian British men: a prospective study of 609 men. BJU Int 2012;109:740-744.
20. Kristensen DM, Hass U, Lesn L, Lottrup G, Jacobsen PR, Desdoits-Lethimonier C, Boberg J, Petersen JH, Toppari J, Jensen TK et al. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum Reprod 2011;26:235-244.
21. Kristensen DM, Lesné L, Fol VL, Desdoits-Lethimonier C, Dejucq-Rainsford N, Leffers H, Jégou B. Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are anti-androgenic in the rat foetal testis. Int J Androl 2012;35:377-384.
22. Lind JN, Tinker SC, Broussard CS, Reefhuis J, Carmichael SL, Honein MA, Olney RS, Parker SE, Werler MM. Maternal medication and herbal use and risk for hypospadias: data from the National Birth Defects Prevention Study, 1997-2007. Pharmacoepidemiol Drug Saf 2013;22:783-793.
23. Lupattelli A, Spigset O, Twigg MJ, Zagorodnikova K, Mårdby AC, Moretti ME, Drozd M, Panchaud A, Hämeen-Anttila K, Rieutord A et al. Medication use in pregnancy: a cross-sectional, multinational web-based study. BMJ Open 2014;4:e004365.
24. Mazaud-Guittot S, Nicolas Nicolaz C, Desdoits-Lethimonier C, Coiffec I, Maamar MB, Balaguer P, Kristensen DM, Chevrier C, Lavoué V, Poulain P et al. Paracetamol, aspirin, and indomethacin induce endocrine disturbances in the human fetal testis capable of interfering with testicular descent. J Clin EndocrinolMetab 2013;98:E1757-E1767.
25. Pasterski V, Acerini CL, Dunger DB, Ong KK, Hughes IA, Thankamony A, Hines M. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys. Horm Behav 2015;69:98-105.
26. Elsevier B. V. Prentice P, Acerini CL, Eleftheriou A, Hughes IA, Ong KK, Dunger DB. Cohort Profile: the Cambridge Baby Growth Study (CBGS). Int J Epidemiol 2016;45:35.
27. Rayburn W, Shukla U, Stetson P, Piehl E. Acetaminophen pharmacokinetics: comparison between pregnant and nonpregnant women. Am J Obstet Gynecol 1986;155:1353-1356.
28. Rebordosa C, Kogevinas M, Bech BH, Sørensen HT, Olsen J. Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. Int J Epidemiol 2009;38:706-714.
29. Rebordosa C, Kogevinas M, Horváth-Puhó E, Nørgård B, Morales M, Czeizel AE, Vilstrup H, Sørensen HT, Olsen J. Acetaminophen use during pregnancy: effects on risk for congenital abnormalities. Am J Obstet Gynecol 2008;198:178. e1-e7.
30. Robinson JD, Judd HL, Young PE, Jones OW, Yen SS. Amniotic fluid androgens and estrogens in midgestation. J Clin Endocrinol Metab 1977; 45:755-761.
31. Shaheen SO, Newson RB, Sherriff A, Henderson AJ, Heron JE, Burney PGJ, Golding J, ALSPAC Study Team. Paracetamol use in pregnancy and wheezing in early childhood. Thorax 2002;57:958-963.
32. Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 2001;16:972-978.
33. Snijder CA, Kortenkamp A, Steegers EAP, Jaddoe VWV, Hofman A, Hass U, Burdorf A. Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study. Hum Reprod 2012;27:1191-1201.
34. Thankamony A, Lek N, Carroll D, Williams M, Dunger DB, Acerini CL, Ong KK, Hughes IA. Anogenital distance and penile length in infants with hypospadias or cryptorchidism: Comparison with normative data. Environ Health Perspect 2014;122:207-211.
35. Thankamony A, Ong KK, Dunger DB, Acerini CL, Hughes IA. Anogenital distance from birth to 2 years: a population study. Environ Health Perspect 2009;117:1786-1790.
36. Thulstrup AM, Sørensen HT, Nielsen GL, Andersen L, Barrett D, Vilstrup H, Olsen J. Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. EuroMap Study Group. Am J Perinatol 1999;16:321-326.
37. Vesterholm Lind D, Skakkebæk NE, Main KM, Kyhl HB, Jensen TK Use of mild analgesics in pregnancy and anogenital distance in boys and girls [Abstract]. COW 2015 8th Copenhagen Work Endocr Disrupters 2015.
38. Wagner-Mahler K, Kurzenne J-Y, Delattre I, Bérard E, Mas J-C, Bornebush L, Tommasi C, Boda-Buccino M, Ducot B, Boullé C et al. Prospective study on the prevalence and associated risk factors of cryptorchidism in 6246 newborn boys from Nice area, France. Int J Androl 2011;34:e499-e510.
39. Welsh M, Saunders PT, Fisken M, Scott HM, Hutchison GR, Smith LB, Sharpe RM. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J Clin Invest 2008;118:1479-1490.
40. Werler MM, Mitchell AA, Hernandez-Diaz S, Honein MA. Use of over-The-counter medications during pregnancy. Am J Obstet Gynecol 2005;193:771-777.