Is intravenous (IV) paracetamol (acetaminophen) safe for use in pregnant women?

Safety of IV Paracetamol During Pregnancy

IV paracetamol (acetaminophen) is safe for use during pregnancy when medically necessary, and should be administered at the lowest effective dose for the shortest possible duration. 1, 2

Safety Profile and Recommendations

• Paracetamol is considered the analgesic of choice for the treatment of mild to moderate pain during any stage of pregnancy 3
• It is the most widely used medication during pregnancy, with 40-65% of pregnant women using it at some point, primarily for headache and fever 1
• The Society for Maternal-Fetal Medicine (SMFM) advises that paracetamol is a reasonable and appropriate medication choice for pain and/or fever during pregnancy 1
• Paracetamol crosses the placenta relatively easily and has been detected in umbilical cord blood after maternal administration 1

Administration Guidelines

• IV paracetamol should be used at the lowest effective dose for the shortest possible duration to minimize potential risks 1, 2
• For adults, the optimum unit dose is 1g with a maximum daily dosage of 4g 4
• The analgesic effect typically lasts for about 6 hours 4
• When administering IV paracetamol during pregnancy, healthcare providers should:
  • Use only when medically indicated 2
  • Consult with a physician before long-term use 2
  • Monitor pregnant women who use paracetamol across all trimesters 2

Advantages of IV Administration

• IV paracetamol provides more rapid onset of action compared to oral formulations 4
• It can be particularly useful in perioperative settings or when oral administration is not possible 4
• Unlike NSAIDs, paracetamol does not cause premature closure of the fetal ductus arteriosus or oligohydramnios 3

Potential Concerns

• Recent observational studies have suggested associations between prenatal paracetamol exposure and neurodevelopmental outcomes in children 1, 2
• These include potential increased risks of ADHD symptoms (12.2-25%) and autism spectrum disorder (12.9%) 2
• However, the FDA and SMFM have evaluated these studies and determined that "the weight of evidence is inconclusive regarding a possible causal relationship" 1
• Most studies have significant methodological limitations, including recall bias and inability to control for all confounding factors 1, 2

Special Considerations for Surgery During Pregnancy

• Paracetamol is an essential component of multimodal analgesia for pregnant women undergoing surgery 3
• Adequate pain relief with paracetamol is essential postoperatively to prevent reactive preterm contractions 3
• If paracetamol alone is inadequate for pain control, short-term narcotic use is also considered safe during pregnancy 3
• NSAIDs should be avoided, particularly after 28 weeks of gestation, due to risks of premature closure of the fetal ductus arteriosus 3

Clinical Recommendations

• IV paracetamol remains the first-line treatment for pain and fever in pregnancy when indicated 5
• The pharmacokinetics of paracetamol at therapeutic concentrations are linear and constant with repeated administration 4
• Paracetamol has a very low level of binding to plasma proteins and undergoes hepatic metabolism mainly through glucuronide or sulphate conjugation, resulting in a low risk of drug interactions 4
• Despite recent concerns, current evidence supports that short-term use of paracetamol during pregnancy is safe, while long-term use should be approached with caution 6, 5