Is there an association between non-steroidal anti-inflammatory drugs (NSAIDs) and hypertension or preeclampsia during pregnancy?

Association Between NSAIDs and Hypertension or Preeclampsia During Pregnancy

NSAIDs are recognized as a potential cause of hypertension in the peripartum period and should be avoided in women with preeclampsia, especially in cases with acute kidney injury or other risk factors for renal dysfunction. 1

Mechanism of Association

NSAIDs can affect blood pressure and pregnancy outcomes through several mechanisms:

• Inhibition of prostaglandin synthesis, which can affect renal function and vascular tone
• Reduction of the natriuretic effect of diuretics in some patients 2
• Potential to cause fluid retention and edema

Evidence on NSAIDs and Hypertension During Pregnancy

During Pregnancy

• NSAIDs are listed as a potential iatrogenic cause of hypertension in pregnancy in the European Society of Cardiology (ESC) guidelines 1
• Drug labels for NSAIDs like ibuprofen warn that use at about 20 weeks gestation or later has been associated with:
  • Fetal renal dysfunction leading to oligohydramnios
  • Potential neonatal renal impairment 2
  • Premature closure of the fetal ductus arteriosus (especially after 30 weeks) 2

Postpartum Period

• The International Society for the Study of Hypertension in Pregnancy (ISSHP) specifically recommends avoiding NSAIDs for postpartum analgesia in women with preeclampsia unless other analgesics are not working 1
• This recommendation is especially important for women with:
  • Known renal disease
  • Preeclampsia associated with placental abruption
  • Acute kidney injury
  • Other risk factors for acute kidney injury (e.g., sepsis, postpartum hemorrhage) 1

Research on Postpartum NSAID Use

Some recent studies have challenged the traditional concern about NSAIDs worsening hypertension postpartum:

• A 2018 double-masked randomized controlled trial found that ibuprofen did not lengthen the duration of severe-range hypertension compared to acetaminophen in women with preeclampsia with severe features 3
• A 2017 retrospective cohort study showed NSAIDs were not associated with increased rates of persistent postpartum hypertension in women with preeclampsia and severe features 4
• A 2014 study found no association between NSAID exposure and increased postpartum mean arterial pressure or requirement for anti-hypertensive medications in women with severe hypertensive disorders of pregnancy 5

Clinical Recommendations

During Pregnancy

• Avoid NSAIDs during pregnancy, particularly after 20 weeks gestation due to risks of:
  • Renal injury
  • Oligohydramnios
  • Premature closure of the ductus arteriosus
  • Potential contribution to hypertensive disorders

Postpartum Period

• For women with preeclampsia, especially those with renal compromise:
  • Use alternative analgesics as first choice
  • Reserve NSAIDs for cases where other analgesics are ineffective
  • Monitor blood pressure and renal function if NSAIDs are used

Long-term Considerations

• Women with a history of preeclampsia should be aware of their increased lifetime risk of cardiovascular disease
• Regular blood pressure monitoring and cardiovascular risk assessment are recommended

Pitfalls and Caveats

• The evidence on NSAIDs and postpartum hypertension is mixed, with older guidelines recommending avoidance but newer studies suggesting limited impact
• Individual patient factors (renal function, severity of hypertension, other medications) may influence the risk of adverse effects from NSAIDs
• Self-medication with over-the-counter NSAIDs is common and patients should be specifically counseled about these medications
• The risk-benefit assessment may differ between pregnancy and the postpartum period

While recent research suggests NSAIDs may be safer in the postpartum period than previously thought, caution is still warranted during pregnancy, particularly after 20 weeks gestation, when NSAIDs have been associated with fetal renal dysfunction and other adverse outcomes.