Risk estimation of fetal adverse effects after short-term second trimester exposure to non-steroidal anti-inflammatory drugs: a literature review

Eur J Clin Pharmacol. 2019 Oct;75(10):1347-1353. doi: 10.1007/s00228-019-02712-2. Epub 2019 Jul 4.


Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) are not recommended in the 3rd trimester of pregnancy due to known fetal adverse effects in an advanced gestational age. This investigation was performed to assess whether there is a significant risk of NSAIDs being used as an analgesic or antipyretic medication in the 2nd trimester.

Methods: A systematic search for publications reporting 2nd trimester NSAID exposure was performed in MEDLINE. The search focused on case descriptions reporting defined adverse effects including prenatal ductus arteriosus constriction, oligohydramnios, neonatal renal failure, and primary pulmonary hypertension. Original articles published until February 2018 were considered for evaluation.

Results: Out of 681 identified publications, 26 included relevant information on the defined adverse effects. Among these publications, premature labor was the major reason for 2nd trimester indomethacin treatment while other clinical indications and other NSAIDs were underrepresented. Narrowing or closure of the ductus arteriosus in the 2nd trimester was described in 33 fetuses. Only eight publications reported adverse effects after less than 7-day exposure during the 2nd trimester.

Conclusions: Based on these results, short-term use of NSAIDs as analgesics or antipyretics in the 2nd trimester does not appear to pose a substantial risk for fetal adverse effects. Long-term use in the late 2nd trimester, however, should always be monitored.

Keywords: Anti-inflammatory agents, non-steroidal [MeSH]; Ductus arteriosus [MeSH]; Oligohydramnios [MeSH]; Pregnancy trimester, second [MeSH]; Renal insufficiency [MeSH]; “Fetus” [MeSh].

Publication types

  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Female
  • Fetus / drug effects
  • Humans
  • Maternal-Fetal Exchange*
  • Pregnancy
  • Pregnancy Trimester, Second*
  • Risk Assessment


  • Anti-Inflammatory Agents, Non-Steroidal