Maternal paracetamol intake and fetal ductus arteriosus constriction or closure: a case series analysis

Br J Clin Pharmacol. 2019 Jan;85(1):245-251. doi: 10.1111/bcp.13778. Epub 2018 Oct 25.

Abstract

Recent case reports describe an association between maternal paracetamol intake and fetal ductus arteriosus constriction or closure. To put these cases into perspective and explore causality, a structured literature search was conducted. The World Health Organization Uppsala Monitoring Centre (WHO-UMC) causality tool was applied to the cases retrieved. The search resulted in 12 papers with 25 case descriptions, of which one case was classified as unlikely, nine as possible, 11 as probable and four as certain. Consequently, we concluded that a causal relationship between maternal paracetamol intake and fetal ductus arteriosus constriction or closure is likely. These findings suggest that pharmacovigilance studies on paracetamol safety during pregnancy are warranted to quantify the event and put the current findings into clinical perspective. Although analgesia during pregnancy and during the peripartum period is of obvious relevance, alternative analgesics such as opioids or other nonsteroidal anti-inflammatory drugs also have side effects.

Keywords: acetaminophen; causality; fetal ductus constriction/closure; paracetamol; pregnancy.

MeSH terms

  • Acetaminophen / adverse effects*
  • Analgesics, Non-Narcotic / adverse effects*
  • Constriction, Pathologic / chemically induced
  • Constriction, Pathologic / epidemiology
  • Ductus Arteriosus / drug effects
  • Ductus Arteriosus / pathology*
  • Female
  • Humans
  • Incidence
  • Infant, Newborn
  • Infant, Newborn, Diseases / chemically induced
  • Infant, Newborn, Diseases / epidemiology*
  • Maternal Exposure / adverse effects*
  • Maternal Exposure / statistics & numerical data
  • Pregnancy

Substances

  • Analgesics, Non-Narcotic
  • Acetaminophen