Acetaminophen in late pregnancy and potential for in utero closure of the ductus arteriosus-a pharmacokinetic evaluation and critical review of the literature

Am J Obstet Gynecol MFM. 2021 Jan;3(1):100288. doi: 10.1016/j.ajogmf.2020.100288. Epub 2020 Dec 5.


Acetaminophen has become a novel treatment option for patent ductus arteriosus closure in premature infants. This raises concerns about whether acetaminophen should be avoided in late pregnancy, similar to nonsteroidal anti-inflammatory drugs, because of the risk of in utero ductus arteriosus closure. This article critically evaluated the literature reporting an association between acetaminophen use and in utero ductus arteriosus closure and provided a comparative pharmacokinetic analysis of fetal acetaminophen exposure in pregnancy vs drug levels in neonates, with the goal of making an expert recommendation regarding its safety. Here, 1 prospective cohort study and 12 case reports and series evaluating the risk of premature ductus arteriosus closure with prenatal acetaminophen use were reported and overall do not suggest causation. Pharmacokinetic studies showed that acetaminophen fetal transplacental exposures are well below the levels shown to close the ductus arteriosus in neonates. Short-term use of acetaminophen in the third trimester of pregnancy poses a negligible risk of premature ductus arteriosus closure and can still be considered safe in the third trimester of pregnancy at recommended doses.

Keywords: acetaminophen; analgesia; ductus arteriosus; paracetamol; pregnancy.

Publication types

  • Review

MeSH terms

  • Acetaminophen / adverse effects
  • Ductus Arteriosus*
  • Ductus Arteriosus, Patent* / drug therapy
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Pregnancy
  • Prospective Studies


  • Acetaminophen