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. Neuroscientist. 2020 Sep 11;:1073858420952046 - PubMed
  51. Sci Transl Med. 2015 May 20;7(288):288ra80 - PubMed
  52. Toxicol Lett. 2018 Sep 15;294:95-104 - PubMed
  53. J Neurosci. 2016 Sep 28;36(39):10039-49 - PubMed
  54. Cochrane Database Syst Rev. 2016 Jun 07;(6):CD012230 - PubMed
  55. J Psychiatr Res. 2018 Jun;101:63-71 - PubMed
  56. Biochem Biophys Rep. 2018 Apr 10;14:43-53 - PubMed
  57. Obstet Gynecol. 2010 Jan;115(1):109-115 - PubMed
  58. Epidemiology. 2016 Nov;27(6):912-8 - PubMed
  59. Nat Rev Endocrinol. 2020 Jan;16(1):45-57 - PubMed
  60. Br J Community Nurs. 2014 Jul;19(7):335-9 - PubMed
  61. J Clin Psychiatry. 2019 Sep 10;80(5): - PubMed
  62. BJOG. 2019 Mar;126(4):e114-e124 - PubMed
  63. Autism Res. 2016 Sep;9(9):951-8 - PubMed
  64. Eur J Pain. 2019 Jul;23(6):1162-1170 - PubMed
  65. Autism Res. 2017 Nov;10(11):1878-1890 - PubMed
  66. Genes Brain Behav. 2019 Jan;18(1):e12506 - PubMed
  67. Pediatr Gastroenterol Hepatol Nutr. 2020 Nov;23(6):501-510 - PubMed
  68. Am J Epidemiol. 2018 Aug 1;187(8):1817-1827 - PubMed
  69. Drugs. 2016 Jun;76(9):915-24 - PubMed
  70. Placenta. 2021 Jan 15;104:146-160 - PubMed
  71. Environ Health Perspect. 2018 Mar 09;126(3):032001 - PubMed
  72. Hum Reprod. 2011 Jan;26(1):235-44 - PubMed
  73. Hum Reprod. 2016 Nov;31(11):2642-2650 - PubMed
  74. J Appl Toxicol. 2017 Oct;37(10):1174-1181 - PubMed
  75. JAMA Pediatr. 2020 Nov 1;174(11):1073-1081 - PubMed
  76. Br J Clin Pharmacol. 1980 Oct;10 Suppl 2:291S-298S - PubMed
  77. Toxicol Sci. 2015 Nov;148(1):288-98 - PubMed
  78. Pharmacoepidemiol Drug Saf. 2013 Jul;22(7):783-93 - PubMed
  79. FASEB J. 2008 Mar;22(3):659-61 - PubMed
  80. Hum Reprod. 2017 Jan;32(1):223-231 - PubMed
  81. Nat Rev Endocrinol. 2016 Jul;12(7):381-93 - PubMed
  82. Birth Defects Res A Clin Mol Teratol. 2007 Apr;79(4):295-300 - PubMed
  83. Reproduction. 2017 Aug;154(2):145-152 - PubMed
  84. Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):184-9 - PubMed
  85. Br J Clin Pharmacol. 2021 May;87(5):2392-2396 - PubMed
  86. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 1):771-7 - PubMed
  87. Paediatr Perinat Epidemiol. 2020 May;34(3):237-246 - PubMed
  88. J Hepatol. 2015 May;62(5):1085-91 - PubMed
  89. Int J Androl. 2011 Oct;34(5 Pt 2):e499-510 - PubMed
  90. FASEB J. 2018 Oct;32(10):5751-5759 - PubMed
  91. Arch Toxicol. 2019 Feb;93(2):253-272 - PubMed
  92. Hum Reprod Update. 2017 Nov 1;23(6):646-659 - PubMed
  93. Nat Commun. 2011 Nov 22;2:551 - PubMed
  94. Am J Obstet Gynecol. 2017 Mar;216(3):B14-B15 - PubMed
  95. Clin Epigenetics. 2017 Aug 2;9:77 - PubMed
  96. Development. 2002 Mar;129(5):1155-64 - PubMed
  97. Pediatrics. 2017 Nov;140(5): - PubMed
  98. Int J Epidemiol. 2013 Dec;42(6):1702-13 - PubMed
  99. Toxicol Sci. 2021 Jan 6;179(1):44-52 - PubMed
  100. Epidemiology. 2010 Nov;21(6):779-85 - PubMed
  101. BMC Psychiatry. 2018 Nov 20;18(1):368 - PubMed
  102. Respirology. 2016 Feb;21(2):370-7 - PubMed
  103. Arch Dis Child. 2015 Jan;100(1):81-9 - PubMed
  104. Behav Brain Res. 2017 Apr 14;323:162-171 - PubMed
  105. Int J Epidemiol. 2018 Feb 1;47(1):121-130 - PubMed
  106. Toxicol Sci. 2016 Mar;150(1):178-89 - PubMed
  107. Autism Res. 2021 Jul;14(7):1375-1389 - PubMed
  108. Br J Clin Pharmacol. 2019 Jan;85(1):245-251 - PubMed
  109. Clin Exp Allergy. 2015 Jan;45(1):108-13 - PubMed
  110. J Clin Invest. 2008 Apr;118(4):1479-90 - PubMed
  111. Childs Nerv Syst. 2014 Apr;30(4):665-71 - PubMed
  112. Environ Health Perspect. 2018 Apr 16;126(4):047006 - PubMed
  113. Behav Brain Res. 2021 Jun 25;408:113294 - PubMed
  114. Hum Reprod Update. 2021 Jan 4;27(1):67-95 - PubMed
  115. Clin Exp Pharmacol Physiol. 2020 Aug 7;: - PubMed
  116. Eur J Neurosci. 2012 Apr;35(8):1218-29 - PubMed
  117. Birth Defects Res. 2020 Jul 15;112(12):943-952 - PubMed
  118. Paediatr Perinat Epidemiol. 2020 May;34(3):278-286 - PubMed
  119. Physiol Rev. 2016 Jan;96(1):55-97 - PubMed
  120. Int J Epidemiol. 2016 Dec 1;45(6):2009-2017 - PubMed
  121. Expert Opin Drug Saf. 2017 Dec;16(12):1395-1398 - PubMed
  122. Environ Int. 2021 Apr;149:106388 - PubMed
  123. Front Pediatr. 2020 Mar 18;8:89 - PubMed
  124. Reprod Toxicol. 2016 Jun;61:186-94 - PubMed
  125. Environ Health Perspect. 2000 Jun;108 Suppl 3:511-33 - PubMed
  126. Toxicol Sci. 2019 Jan 1;167(1):138-144 - PubMed
  127. Toxicol Sci. 2014 Mar;138(1):139-47 - PubMed
  128. Clin Pharmacol Ther. 2008 Jul;84(1):47-51 - PubMed
  129. Paediatr Perinat Epidemiol. 2020 May;34(3):257-266 - PubMed
  130. J Biol Chem. 2005 Sep 9;280(36):31405-12 - PubMed
  131. Cochrane Database Syst Rev. 2019 Feb 25;2:CD013273 - PubMed
  132. Allergol Immunopathol (Madr). 2017 Nov - Dec;45(6):528-533 - PubMed
  133. Cephalalgia. 2014 Feb 20;34(9):645-655 - PubMed
  134. PLoS One. 2020 Dec 18;15(12):e0242773 - PubMed
  135. Pediatrics. 2019 Oct;144(4): - PubMed
  136. Andrology. 2019 Nov;7(6):762-768 - PubMed
  137. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Aug 7;38(2):260-9 - PubMed
  138. Endocrinology. 2020 Jun 1;161(6): - PubMed
  139. Int J Mol Sci. 2017 Jul 03;18(7): - PubMed
  140. Molecules. 2021 Mar 25;26(7): - 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