Display options
Cite
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.
Copy Download .nbib Format: NLM
Share it on

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. Environ Health Perspect. 2016 Jul 1;124(7):A118-22 - PubMed
  2. Hum Reprod. 2012 Apr;27(4):1191-201 - PubMed
  3. Transl Psychiatry. 2019 Jan 31;9(1):58 - PubMed
  4. Hum Reprod. 2013 Jul;28(7):1890-8 - PubMed
  5. Prog Mol Biol Transl Sci. 2020;173:183-208 - PubMed
  6. Paediatr Perinat Epidemiol. 2020 May;34(3):247-256 - PubMed
  7. BMC Pregnancy Childbirth. 2017 Dec 8;17(1):413 - PubMed
  8. Autism Res. 2019 Oct;12(10):1551-1561 - PubMed
  9. Sci Rep. 2016 Jan 27;6:19789 - PubMed
  10. Int J Epidemiol. 2016 Dec 1;45(6):1987-1996 - PubMed
  11. Paediatr Perinat Epidemiol. 2020 May;34(3):233-236 - PubMed
  12. F1000Res. 2019 Aug 7;8:1372 - PubMed
  13. Am J Pathol. 2015 Oct;185(10):2805-18 - PubMed
  14. Curr Pharm Des. 2019;25(5):469-482 - PubMed
  15. PLoS One. 2014 Sep 24;9(9):e108210 - PubMed
  16. Am J Epidemiol. 2019 Apr 1;188(4):768-775 - PubMed
  17. Andrology. 2017 Nov;5(6):1082-1088 - PubMed
  18. Neurotoxicol Teratol. 2020 Jan - Feb;77:106838 - PubMed
  19. Pharmacol Biochem Behav. 2018 May;168:25-32 - PubMed
  20. Curr Environ Health Rep. 2021 Mar;8(1):23-33 - PubMed
  21. Fundam Appl Toxicol. 1992 Feb;18(2):233-9 - PubMed
  22. Ann Epidemiol. 2017 Oct;27(10):645-653.e2 - PubMed
  23. Reproduction. 2014 Mar 04;147(4):R105-17 - PubMed
  24. Am J Obstet Gynecol. 2018 Sep;219(3):275.e1-275.e8 - PubMed
  25. Eur Psychiatry. 2018 Jun;51:98-103 - PubMed
  26. Pharmacoepidemiol Drug Saf. 2017 Jun;26(6):625-634 - PubMed
  27. Am Fam Physician. 2014 Oct 15;90(8):548-55 - PubMed
  28. JAMA Psychiatry. 2019 Aug 1;76(8):834-842 - PubMed
  29. Cell. 1997 Oct 17;91(2):197-208 - PubMed
  30. Mol Psychiatry. 2020 Nov;25(11):2970-2978 - PubMed
  31. EBioMedicine. 2018 Feb;28:316-323 - PubMed
  32. JAMA Pediatr. 2016 Oct 1;170(10):964-970 - PubMed
  33. Paediatr Perinat Epidemiol. 2020 May;34(3):287-298 - PubMed
  34. Am J Epidemiol. 2019 Jan 1;188(1):34-46 - PubMed
  35. Obstet Gynecol. 2021 Jul 1;138(1):e40-e54 - 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. Toxics. 2020 Aug 13;8(3): - PubMed
  42. Dev Med Child Neurol. 2015 Aug;57(8):718-24 - PubMed
  43. EBioMedicine. 2017 Dec;26:146-151 - PubMed
  44. Hepatology. 2005 Dec;42(6):1364-72 - PubMed
  45. BMJ Open. 2014 Feb 17;4(2):e004365 - PubMed
  46. Eur J Clin Pharmacol. 2010 Feb;66(2):207-14 - PubMed
  47. Environ Epigenet. 2019 Aug 06;5(2):dvz010 - PubMed
  48. Biol Psychiatry. 2021 Mar 1;89(5):451-462 - PubMed
  49. World J Hepatol. 2020 Apr 27;12(4):125-136 - PubMed
  50. Sci Transl Med. 2015 May 20;7(288):288ra80 - PubMed
  51. Toxicol Lett. 2018 Sep 15;294:95-104 - PubMed
  52. J Neurosci. 2016 Sep 28;36(39):10039-49 - PubMed
  53. Cochrane Database Syst Rev. 2016 Jun 07;(6):CD012230 - PubMed
  54. J Psychiatr Res. 2018 Jun;101:63-71 - PubMed
  55. Biochem Biophys Rep. 2018 Apr 10;14:43-53 - PubMed
  56. Obstet Gynecol. 2010 Jan;115(1):109-115 - PubMed
  57. Epidemiology. 2016 Nov;27(6):912-8 - PubMed
  58. Nat Rev Endocrinol. 2020 Jan;16(1):45-57 - PubMed
  59. Br J Community Nurs. 2014 Jul;19(7):335-9 - PubMed
  60. J Clin Psychiatry. 2019 Sep 10;80(5): - PubMed
  61. BJOG. 2019 Mar;126(4):e114-e124 - PubMed
  62. Autism Res. 2016 Sep;9(9):951-8 - PubMed
  63. Eur J Pain. 2019 Jul;23(6):1162-1170 - PubMed
  64. Autism Res. 2017 Nov;10(11):1878-1890 - PubMed
  65. Genes Brain Behav. 2019 Jan;18(1):e12506 - PubMed
  66. Pediatr Gastroenterol Hepatol Nutr. 2020 Nov;23(6):501-510 - PubMed
  67. Am J Epidemiol. 2018 Aug 1;187(8):1817-1827 - PubMed
  68. Drugs. 2016 Jun;76(9):915-24 - PubMed
  69. Placenta. 2021 Jan 15;104:146-160 - PubMed
  70. Environ Health Perspect. 2018 Mar 09;126(3):032001 - PubMed
  71. Hum Reprod. 2011 Jan;26(1):235-44 - PubMed
  72. Hum Reprod. 2016 Nov;31(11):2642-2650 - PubMed
  73. J Appl Toxicol. 2017 Oct;37(10):1174-1181 - PubMed
  74. JAMA Pediatr. 2020 Nov 1;174(11):1073-1081 - PubMed
  75. Br J Clin Pharmacol. 1980 Oct;10 Suppl 2:291S-298S - PubMed
  76. Toxicol Sci. 2015 Nov;148(1):288-98 - PubMed
  77. Pharmacoepidemiol Drug Saf. 2013 Jul;22(7):783-93 - PubMed
  78. FASEB J. 2008 Mar;22(3):659-61 - PubMed
  79. Hum Reprod. 2017 Jan;32(1):223-231 - PubMed
  80. Nat Rev Endocrinol. 2016 Jul;12(7):381-93 - PubMed
  81. Birth Defects Res A Clin Mol Teratol. 2007 Apr;79(4):295-300 - PubMed
  82. Reproduction. 2017 Aug;154(2):145-152 - PubMed
  83. Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):184-9 - PubMed
  84. Br J Clin Pharmacol. 2021 May;87(5):2392-2396 - PubMed
  85. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 1):771-7 - PubMed
  86. Paediatr Perinat Epidemiol. 2020 May;34(3):237-246 - PubMed
  87. J Hepatol. 2015 May;62(5):1085-91 - PubMed
  88. Int J Androl. 2011 Oct;34(5 Pt 2):e499-510 - PubMed
  89. FASEB J. 2018 Oct;32(10):5751-5759 - PubMed
  90. Arch Toxicol. 2019 Feb;93(2):253-272 - PubMed
  91. Hum Reprod Update. 2017 Nov 1;23(6):646-659 - PubMed
  92. Nat Commun. 2011 Nov 22;2:551 - PubMed
  93. Am J Obstet Gynecol. 2017 Mar;216(3):B14-B15 - PubMed
  94. Clin Epigenetics. 2017 Aug 2;9:77 - PubMed
  95. Development. 2002 Mar;129(5):1155-64 - PubMed
  96. Pediatrics. 2017 Nov;140(5): - PubMed
  97. Int J Epidemiol. 2013 Dec;42(6):1702-13 - PubMed
  98. Toxicol Sci. 2021 Jan 6;179(1):44-52 - PubMed
  99. Epidemiology. 2010 Nov;21(6):779-85 - PubMed
  100. BMC Psychiatry. 2018 Nov 20;18(1):368 - PubMed
  101. Respirology. 2016 Feb;21(2):370-7 - PubMed
  102. Arch Dis Child. 2015 Jan;100(1):81-9 - PubMed
  103. Behav Brain Res. 2017 Apr 14;323:162-171 - PubMed
  104. Int J Epidemiol. 2018 Feb 1;47(1):121-130 - PubMed
  105. Toxicol Sci. 2016 Mar;150(1):178-89 - PubMed
  106. Autism Res. 2021 Jul;14(7):1375-1389 - PubMed
  107. Br J Clin Pharmacol. 2019 Jan;85(1):245-251 - PubMed
  108. Clin Exp Allergy. 2015 Jan;45(1):108-13 - PubMed
  109. J Clin Invest. 2008 Apr;118(4):1479-90 - PubMed
  110. Childs Nerv Syst. 2014 Apr;30(4):665-71 - PubMed
  111. Environ Health Perspect. 2018 Apr 16;126(4):047006 - PubMed
  112. Behav Brain Res. 2021 Jun 25;408:113294 - PubMed
  113. Hum Reprod Update. 2021 Jan 4;27(1):67-95 - PubMed
  114. Clin Exp Pharmacol Physiol. 2020 Aug 7;: - PubMed
  115. Eur J Neurosci. 2012 Apr;35(8):1218-29 - PubMed
  116. Birth Defects Res. 2020 Jul 15;112(12):943-952 - PubMed
  117. Paediatr Perinat Epidemiol. 2020 May;34(3):278-286 - PubMed
  118. Physiol Rev. 2016 Jan;96(1):55-97 - PubMed
  119. Int J Epidemiol. 2016 Dec 1;45(6):2009-2017 - PubMed
  120. Expert Opin Drug Saf. 2017 Dec;16(12):1395-1398 - PubMed
  121. Environ Int. 2021 Apr;149:106388 - PubMed
  122. Front Pediatr. 2020 Mar 18;8:89 - PubMed
  123. Reprod Toxicol. 2016 Jun;61:186-94 - PubMed
  124. Environ Health Perspect. 2000 Jun;108 Suppl 3:511-33 - PubMed
  125. Toxicol Sci. 2019 Jan 1;167(1):138-144 - PubMed
  126. Toxicol Sci. 2014 Mar;138(1):139-47 - PubMed
  127. Clin Pharmacol Ther. 2008 Jul;84(1):47-51 - PubMed
  128. Paediatr Perinat Epidemiol. 2020 May;34(3):257-266 - PubMed
  129. J Biol Chem. 2005 Sep 9;280(36):31405-12 - PubMed
  130. Cochrane Database Syst Rev. 2019 Feb 25;2:CD013273 - PubMed
  131. Allergol Immunopathol (Madr). 2017 Nov - Dec;45(6):528-533 - PubMed
  132. Cephalalgia. 2014 Feb 20;34(9):645-655 - PubMed
  133. PLoS One. 2020 Dec 18;15(12):e0242773 - PubMed
  134. Pediatrics. 2019 Oct;144(4): - PubMed
  135. Andrology. 2019 Nov;7(6):762-768 - PubMed
  136. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Aug 7;38(2):260-9 - PubMed
  137. Endocrinology. 2020 Jun 1;161(6): - PubMed
  138. Int J Mol Sci. 2017 Jul 03;18(7): - PubMed
  139. Molecules. 2021 Mar 25;26(7): - PubMed
  140. Neuroscientist. 2021 Dec;27(6):650-667 - PubMed
  141. Commun Biol. 2019 Aug 13;2:310 - PubMed
  142. Am J Obstet Gynecol. 2008 Feb;198(2):178.e1-7 - PubMed
  143. Int J Epidemiol. 2016 Dec 1;45(6):1998-2008 - PubMed
  144. Sci Rep. 2019 Jul 2;9(1):9519 - PubMed
  145. Biol Psychiatry. 2017 Mar 1;81(5):402-410 - PubMed
  146. JAMA Psychiatry. 2020 Feb 1;77(2):180-189 - PubMed
  147. Pain Pract. 2019 Nov;19(8):875-899 - PubMed
  148. Clin Pharmacokinet. 2020 Jan;59(1):97-110 - PubMed
  149. Paediatr Perinat Epidemiol. 2020 May;34(3):267-277 - PubMed
  150. Pediatrics. 1975 Jun;55(6):895 - PubMed
  151. Cochrane Database Syst Rev. 2016 Jun 16;(6):CD011889 - PubMed
  152. JAMA Pediatr. 2014 Apr;168(4):313-20 - PubMed
  153. Endocr Connect. 2018 Jan;7(1):149-158 - PubMed
  154. Inflammopharmacology. 2013 Jun;21(3):201-32 - PubMed
  155. Occup Environ Med. 2007 Aug;64(8):562-8 - PubMed
  156. Horm Behav. 2018 May;101:125-147 - PubMed

Publication Types