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Bauer AZ, Swan SH, Kriebel D, et al. Paracetamol use during pregnancy - a call for precautionary action. Nat Rev Endocrinol. 2021;17(12):757-766doi: 10.1038/s41574-021-00553-7.
Bauer, A. Z., Swan, S. H., Kriebel, D., Liew, Z., Taylor, H. S., Bornehag, C. G., Andrade, A. M., Olsen, J., Jensen, R. H., Mitchell, R. T., Skakkebaek, N. E., Jégou, B., & Kristensen, D. M. (2021). Paracetamol use during pregnancy - a call for precautionary action. Nature reviews. Endocrinology, 17(12), 757-766. https://doi.org/10.1038/s41574-021-00553-7
Bauer, Ann Z, et al. "Paracetamol use during pregnancy - a call for precautionary action." Nature reviews. Endocrinology vol. 17,12 (2021): 757-766. doi: https://doi.org/10.1038/s41574-021-00553-7
Bauer AZ, Swan SH, Kriebel D, Liew Z, Taylor HS, Bornehag CG, Andrade AM, Olsen J, Jensen RH, Mitchell RT, Skakkebaek NE, Jégou B, Kristensen DM. Paracetamol use during pregnancy - a call for precautionary action. Nat Rev Endocrinol. 2021 Dec;17(12):757-766. doi: 10.1038/s41574-021-00553-7. Epub 2021 Sep 23. PMID: 34556849; PMCID: PMC8580820.
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Nat Rev Endocrinol. 2021 Dec;17(12):757-766. doi: 10.1038/s41574-021-00553-7. Epub 2021 Sep 23.

Paracetamol use during pregnancy - a call for precautionary action.

Nature reviews. Endocrinology

Ann Z Bauer, Shanna H Swan, David Kriebel, Zeyan Liew, Hugh S Taylor, Carl-Gustaf Bornehag, Anderson M Andrade, Jørn Olsen, Rigmor H Jensen, Rod T Mitchell, Niels E Skakkebaek, Bernard Jégou, David M Kristensen

Affiliations

  1. Department of Public Health, University of Massachusetts School of Health Sciences, Lowell, MA, USA.
  2. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
  3. Yale Center for Perinatal, Paediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
  4. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, Yale-New Haven Hospital, New Haven, CT, USA.
  5. Department of Health Sciences, Karlstad University, Karlstad, Sweden.
  6. Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
  7. Department of Public Health, Aarhus University, Aarhus, Denmark.
  8. Department of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark.
  9. MRC Centre for Reproductive Health, Queens Medical Research Institute, Edinburgh, Scotland.
  10. Department of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  11. Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) UMR_S, 1085, Rennes, France.
  12. Department of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark. [email protected].
  13. Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) UMR_S, 1085, Rennes, France. [email protected].
  14. Department of Biology, University of Copenhagen, Copenhagen, Denmark. [email protected].

PMID: 34556849 PMCID: PMC8580820 DOI: 10.1038/s41574-021-00553-7

Abstract

Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.

© 2021. The Author(s).

References

  1. Eur J Clin Pharmacol. 2010 Feb;66(2):207-14 - PubMed
  2. Environ Health Perspect. 2016 Jul 1;124(7):A118-22 - PubMed
  3. Hum Reprod. 2012 Apr;27(4):1191-201 - PubMed
  4. Transl Psychiatry. 2019 Jan 31;9(1):58 - PubMed
  5. Hum Reprod. 2013 Jul;28(7):1890-8 - PubMed
  6. Prog Mol Biol Transl Sci. 2020;173:183-208 - PubMed
  7. Paediatr Perinat Epidemiol. 2020 May;34(3):247-256 - PubMed
  8. BMC Pregnancy Childbirth. 2017 Dec 8;17(1):413 - PubMed
  9. Autism Res. 2019 Oct;12(10):1551-1561 - PubMed
  10. Sci Rep. 2016 Jan 27;6:19789 - PubMed
  11. Int J Epidemiol. 2016 Dec 1;45(6):1987-1996 - PubMed
  12. Paediatr Perinat Epidemiol. 2020 May;34(3):233-236 - PubMed
  13. F1000Res. 2019 Aug 7;8:1372 - PubMed
  14. Am J Pathol. 2015 Oct;185(10):2805-18 - PubMed
  15. Curr Pharm Des. 2019;25(5):469-482 - PubMed
  16. PLoS One. 2014 Sep 24;9(9):e108210 - PubMed
  17. Am J Epidemiol. 2019 Apr 1;188(4):768-775 - PubMed
  18. Andrology. 2017 Nov;5(6):1082-1088 - PubMed
  19. Neurotoxicol Teratol. 2020 Jan - Feb;77:106838 - PubMed
  20. Pharmacol Biochem Behav. 2018 May;168:25-32 - PubMed
  21. Curr Environ Health Rep. 2021 Mar;8(1):23-33 - PubMed
  22. Fundam Appl Toxicol. 1992 Feb;18(2):233-9 - PubMed
  23. Ann Epidemiol. 2017 Oct;27(10):645-653.e2 - PubMed
  24. Reproduction. 2014 Mar 04;147(4):R105-17 - PubMed
  25. Am J Obstet Gynecol. 2018 Sep;219(3):275.e1-275.e8 - PubMed
  26. Eur Psychiatry. 2018 Jun;51:98-103 - PubMed
  27. Pharmacoepidemiol Drug Saf. 2017 Jun;26(6):625-634 - PubMed
  28. Am Fam Physician. 2014 Oct 15;90(8):548-55 - PubMed
  29. JAMA Psychiatry. 2019 Aug 1;76(8):834-842 - PubMed
  30. Cell. 1997 Oct 17;91(2):197-208 - PubMed
  31. Mol Psychiatry. 2020 Nov;25(11):2970-2978 - PubMed
  32. EBioMedicine. 2018 Feb;28:316-323 - PubMed
  33. JAMA Pediatr. 2016 Oct 1;170(10):964-970 - PubMed
  34. Paediatr Perinat Epidemiol. 2020 May;34(3):287-298 - PubMed
  35. Am J Epidemiol. 2019 Jan 1;188(1):34-46 - PubMed
  36. Pediatrics. 2014 Mar;133(3):e674-88 - PubMed
  37. Lancet Neurol. 2014 Mar;13(3):330-8 - PubMed
  38. Mol Psychiatry. 2021 Jan;26(1):66-69 - PubMed
  39. Nat Neurosci. 2004 Jun;7(6):643-50 - PubMed
  40. Hum Reprod. 2016 Sep;31(9):2119-27 - PubMed
  41. Dev Med Child Neurol. 2015 Aug;57(8):718-24 - PubMed
  42. EBioMedicine. 2017 Dec;26:146-151 - PubMed
  43. Hepatology. 2005 Dec;42(6):1364-72 - PubMed
  44. BMJ Open. 2014 Feb 17;4(2):e004365 - PubMed
  45. Biol Psychiatry. 2021 Mar 1;89(5):451-462 - PubMed
  46. World J Hepatol. 2020 Apr 27;12(4):125-136 - PubMed
  47. Sci Transl Med. 2015 May 20;7(288):288ra80 - PubMed
  48. Toxicol Lett. 2018 Sep 15;294:95-104 - PubMed
  49. J Neurosci. 2016 Sep 28;36(39):10039-49 - PubMed
  50. J Psychiatr Res. 2018 Jun;101:63-71 - PubMed
  51. Biochem Biophys Rep. 2018 Apr 10;14:43-53 - PubMed
  52. Obstet Gynecol. 2010 Jan;115(1):109-115 - PubMed
  53. Epidemiology. 2016 Nov;27(6):912-8 - PubMed
  54. Nat Rev Endocrinol. 2020 Jan;16(1):45-57 - PubMed
  55. Br J Community Nurs. 2014 Jul;19(7):335-9 - PubMed
  56. BJOG. 2019 Mar;126(4):e114-e124 - PubMed
  57. Autism Res. 2016 Sep;9(9):951-8 - PubMed
  58. Eur J Pain. 2019 Jul;23(6):1162-1170 - PubMed
  59. Autism Res. 2017 Nov;10(11):1878-1890 - PubMed
  60. Genes Brain Behav. 2019 Jan;18(1):e12506 - PubMed
  61. Pediatr Gastroenterol Hepatol Nutr. 2020 Nov;23(6):501-510 - PubMed
  62. Am J Epidemiol. 2018 Aug 1;187(8):1817-1827 - PubMed
  63. Drugs. 2016 Jun;76(9):915-24 - PubMed
  64. Placenta. 2021 Jan 15;104:146-160 - PubMed
  65. Environ Health Perspect. 2018 Mar 09;126(3):032001 - PubMed
  66. Hum Reprod. 2011 Jan;26(1):235-44 - PubMed
  67. Hum Reprod. 2016 Nov;31(11):2642-2650 - PubMed
  68. J Appl Toxicol. 2017 Oct;37(10):1174-1181 - PubMed
  69. JAMA Pediatr. 2020 Nov 1;174(11):1073-1081 - PubMed
  70. Br J Clin Pharmacol. 1980 Oct;10 Suppl 2:291S-298S - PubMed
  71. Toxicol Sci. 2015 Nov;148(1):288-98 - PubMed
  72. Pharmacoepidemiol Drug Saf. 2013 Jul;22(7):783-93 - PubMed
  73. FASEB J. 2008 Mar;22(3):659-61 - PubMed
  74. Hum Reprod. 2017 Jan;32(1):223-231 - PubMed
  75. Nat Rev Endocrinol. 2016 Jul;12(7):381-93 - PubMed
  76. Birth Defects Res A Clin Mol Teratol. 2007 Apr;79(4):295-300 - PubMed
  77. Reproduction. 2017 Aug;154(2):145-152 - PubMed
  78. Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):184-9 - PubMed
  79. Br J Clin Pharmacol. 2021 May;87(5):2392-2396 - PubMed
  80. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 1):771-7 - PubMed
  81. Paediatr Perinat Epidemiol. 2020 May;34(3):237-246 - PubMed
  82. J Hepatol. 2015 May;62(5):1085-91 - PubMed
  83. Int J Androl. 2011 Oct;34(5 Pt 2):e499-510 - PubMed
  84. FASEB J. 2018 Oct;32(10):5751-5759 - PubMed
  85. Arch Toxicol. 2019 Feb;93(2):253-272 - PubMed
  86. Hum Reprod Update. 2017 Nov 1;23(6):646-659 - PubMed
  87. Nat Commun. 2011 Nov 22;2:551 - PubMed
  88. Am J Obstet Gynecol. 2017 Mar;216(3):B14-B15 - PubMed
  89. Clin Epigenetics. 2017 Aug 2;9:77 - PubMed
  90. Development. 2002 Mar;129(5):1155-64 - PubMed
  91. Pediatrics. 2017 Nov;140(5): - PubMed
  92. Int J Epidemiol. 2013 Dec;42(6):1702-13 - PubMed
  93. Toxicol Sci. 2021 Jan 6;179(1):44-52 - PubMed
  94. Epidemiology. 2010 Nov;21(6):779-85 - PubMed
  95. BMC Psychiatry. 2018 Nov 20;18(1):368 - PubMed
  96. Respirology. 2016 Feb;21(2):370-7 - PubMed
  97. Arch Dis Child. 2015 Jan;100(1):81-9 - PubMed
  98. Behav Brain Res. 2017 Apr 14;323:162-171 - PubMed
  99. Int J Epidemiol. 2018 Feb 1;47(1):121-130 - PubMed
  100. Toxicol Sci. 2016 Mar;150(1):178-89 - PubMed
  101. Autism Res. 2021 Jul;14(7):1375-1389 - PubMed
  102. Br J Clin Pharmacol. 2019 Jan;85(1):245-251 - PubMed
  103. Clin Exp Allergy. 2015 Jan;45(1):108-13 - PubMed
  104. J Clin Invest. 2008 Apr;118(4):1479-90 - PubMed
  105. Childs Nerv Syst. 2014 Apr;30(4):665-71 - PubMed
  106. Environ Health Perspect. 2018 Apr 16;126(4):047006 - PubMed
  107. Behav Brain Res. 2021 Jun 25;408:113294 - PubMed
  108. Hum Reprod Update. 2021 Jan 4;27(1):67-95 - PubMed
  109. Clin Exp Pharmacol Physiol. 2020 Aug 7;: - PubMed
  110. Eur J Neurosci. 2012 Apr;35(8):1218-29 - PubMed
  111. Birth Defects Res. 2020 Jul 15;112(12):943-952 - PubMed
  112. Paediatr Perinat Epidemiol. 2020 May;34(3):278-286 - PubMed
  113. Physiol Rev. 2016 Jan;96(1):55-97 - PubMed
  114. Int J Epidemiol. 2016 Dec 1;45(6):2009-2017 - PubMed
  115. Expert Opin Drug Saf. 2017 Dec;16(12):1395-1398 - PubMed
  116. Environ Int. 2021 Apr;149:106388 - PubMed
  117. Front Pediatr. 2020 Mar 18;8:89 - PubMed
  118. Reprod Toxicol. 2016 Jun;61:186-94 - PubMed
  119. Environ Health Perspect. 2000 Jun;108 Suppl 3:511-33 - PubMed
  120. Toxicol Sci. 2019 Jan 1;167(1):138-144 - PubMed
  121. Toxicol Sci. 2014 Mar;138(1):139-47 - PubMed
  122. Clin Pharmacol Ther. 2008 Jul;84(1):47-51 - PubMed
  123. Paediatr Perinat Epidemiol. 2020 May;34(3):257-266 - PubMed
  124. J Biol Chem. 2005 Sep 9;280(36):31405-12 - PubMed
  125. Cochrane Database Syst Rev. 2019 Feb 25;2:CD013273 - PubMed
  126. PLoS One. 2020 Dec 18;15(12):e0242773 - PubMed
  127. Pediatrics. 2019 Oct;144(4): - PubMed
  128. Andrology. 2019 Nov;7(6):762-768 - PubMed
  129. Endocrinology. 2020 Jun 1;161(6): - PubMed
  130. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Aug 7;38(2):260-9 - PubMed
  131. Molecules. 2021 Mar 25;26(7): - PubMed
  132. Neuroscientist. 2021 Dec;27(6):650-667 - PubMed
  133. Commun Biol. 2019 Aug 13;2:310 - PubMed
  134. Am J Obstet Gynecol. 2008 Feb;198(2):178.e1-7 - PubMed
  135. Int J Epidemiol. 2016 Dec 1;45(6):1998-2008 - PubMed
  136. Folia Psychiatr Neurol Jpn. 1970;24(1):49-58 - PubMed
  137. Sci Rep. 2019 Jul 2;9(1):9519 - PubMed
  138. Biol Psychiatry. 2017 Mar 1;81(5):402-410 - PubMed
  139. JAMA Psychiatry. 2020 Feb 1;77(2):180-189 - PubMed
  140. Pain Pract. 2019 Nov;19(8):875-899 - PubMed
  141. Clin Pharmacokinet. 2020 Jan;59(1):97-110 - PubMed
  142. Paediatr Perinat Epidemiol. 2020 May;34(3):267-277 - PubMed
  143. Pediatrics. 1975 Jun;55(6):895 - PubMed
  144. JAMA Pediatr. 2014 Apr;168(4):313-20 - PubMed
  145. Endocr Connect. 2018 Jan;7(1):149-158 - PubMed
  146. Inflammopharmacology. 2013 Jun;21(3):201-32 - PubMed
  147. Occup Environ Med. 2007 Aug;64(8):562-8 - PubMed
  148. Horm Behav. 2018 May;101:125-147 - PubMed

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