Is paracetamol (acetaminophen) safe to use during the third trimester of pregnancy?

Paracetamol Use in Third Trimester of Pregnancy

Paracetamol (acetaminophen) is considered safe and is the first-line medication for pain and fever management during the third trimester of pregnancy, but should be used at the lowest effective dose for the shortest possible duration. 1, 2

Safety Profile

• Paracetamol is the most widely used medication during pregnancy, with 40-65% of pregnant women using it at some point, primarily for headache and fever 2
• The Society for Maternal-Fetal Medicine (SMFM) advises that paracetamol is a reasonable and appropriate medication choice for treating pain and/or fever during pregnancy 2
• Unlike NSAIDs, paracetamol does not cause premature closure of the fetal ductus arteriosus or oligohydramnios, making it safer for third-trimester use 2
• NSAIDs should be discontinued after gestational week 28 (end of second trimester) due to increased risks for the fetus 3

Dosing Recommendations

• Paracetamol should be used at the lowest effective dose for the shortest possible duration 2
• For post-cesarean delivery pain management, a dose of 975 mg every 8 hours is recommended as a standing medication 1
• For post-vaginal delivery pain, 975 mg every 8 hours or 650 mg every 6 hours is recommended as part of a multimodal approach 1
• Daily intake should be limited to a maximum of 4g to reduce the risk of liver injury, with consideration for limiting chronic administration to 3g or less per day 1

Potential Concerns

• Recent observational studies have suggested associations between prenatal paracetamol exposure and neurodevelopmental outcomes in children, including:
  • Increased risk of ADHD symptoms (12.2-25%) 3, 2
  • Autism spectrum disorder (12.9% increased risk) 3, 2
• These associations appear stronger with prolonged use (≥28 days) rather than short-term use 3
• Rare cases of prenatal ductus arteriosus closure have been reported with paracetamol use in late pregnancy 4

Clinical Guidance

• Use paracetamol only when medically necessary in the third trimester 1, 2
• Consider non-pharmacological approaches first (rest, physical therapy, heat/cold therapy) 1
• Monitor pregnant women using paracetamol closely throughout the third trimester 2
• Be cautious with combination products containing paracetamol to prevent excess dosing 1

Comparison with Other Pain Medications

• NSAIDs should be avoided during the third trimester due to risks of premature closure of the fetal ductus arteriosus 3, 2
• Opioid medications carry significant risks during pregnancy and should be avoided when possible 1
• If paracetamol alone is inadequate for pain control, short-term narcotic use may be considered under close medical supervision 2

Important Considerations

• Severe pain during pregnancy that doesn't respond to paracetamol warrants immediate medical evaluation 1
• The FDA and SMFM have evaluated studies on neurodevelopmental effects and determined that "the weight of evidence is inconclusive regarding a possible causal relationship" 2
• A recent study found no increased risk of adverse perinatal outcomes such as preterm birth or small for gestational age with paracetamol use during pregnancy 5