Is paracetamol (acetaminophen) safe to use during pregnancy?

Paracetamol Use During Pregnancy

Primary Recommendation

Paracetamol should be used as the first-line medication for pain and fever during pregnancy, but only when medically necessary, at the lowest effective dose for the shortest possible duration. 1, 2

Evidence-Based Guidance

Safety Profile and Positioning

• Paracetamol remains the safest analgesic option during pregnancy compared to alternatives, with the Society for Maternal-Fetal Medicine (SMFM) and American College of Obstetricians and Gynecologists endorsing it as reasonable and appropriate for treating pain and fever throughout all trimesters. 1, 3

• Unlike NSAIDs, paracetamol does not cause premature closure of the fetal ductus arteriosus or oligohydramnios, making it particularly safer for third-trimester use. 1, 2 However, one case series reported prenatal ductus arteriosus closure with maternal paracetamol use after the sixth month, though this remains rare. 4

• NSAIDs must be avoided after 28 weeks gestation due to fetal risks, leaving paracetamol as the primary pharmacologic option for pain management in late pregnancy. 2

Dosing Parameters

• Maximum daily dose: 4 grams (4000 mg) to prevent liver toxicity. 3, 5

• Use the lowest effective dose for the shortest duration necessary. 1, 2

• For chronic administration, consider limiting to 3 grams or less per day. 2

• Avoid combination products containing paracetamol to prevent inadvertent overdosing. 3

Emerging Neurodevelopmental Concerns

The evidence regarding neurodevelopmental risks remains inconclusive but warrants cautious use:

• Multiple systematic reviews have identified associations between prenatal paracetamol exposure and increased risk of ADHD symptoms (12-25% increased risk) and autism spectrum disorder (12-13% increased risk). 6, 1

• Prolonged exposure (>28 days) and second-trimester use showed marginally higher associations with neurodevelopmental outcomes. 6

• However, the FDA and SMFM have concluded that "the weight of evidence is inconclusive regarding a possible causal relationship between acetaminophen use and neurobehavioral disorders in offspring." 1

• These studies have significant methodological limitations including inability to control for all confounders (maternal illness, fever, infection), recall bias, and lack of dose-response data. 6, 1

Clinical Decision Algorithm

When a pregnant patient presents with pain or fever:

1. First, attempt non-pharmacological approaches: rest, physical therapy, heat/cold therapy. 3, 2

2. If medication is medically necessary:

   • Use paracetamol as first-line agent 6, 1
   • Prescribe lowest effective dose 1, 2
   • Limit duration to shortest time needed 1, 2
   • Avoid prolonged daily use (>28 days) when possible 6

3. For second trimester only: NSAIDs may be considered as alternative if paracetamol insufficient. 6

4. For third trimester: Paracetamol remains the only safe NSAID-alternative; opioids only if absolutely necessary under close supervision. 2

5. Monitor closely across all trimesters if paracetamol use is ongoing. 6, 1

Critical Counseling Points

• Inform patients that paracetamol is considered the safest option available, but should only be used when medically indicated. 1, 7

• Discuss the balance between treating maternal pain/fever (which itself can harm the fetus) versus theoretical neurodevelopmental risks from medication. 1

• Emphasize that untreated fever and severe pain carry their own fetal risks. 8

• Advise patients to consult before long-term use and to avoid self-medication beyond short-term symptomatic relief. 7

Common Pitfalls to Avoid

• Do not withhold paracetamol when medically indicated due to fear of neurodevelopmental effects—the evidence remains inconclusive and untreated maternal conditions pose known risks. 8

• Do not use NSAIDs after 28 weeks gestation under any circumstances due to well-established fetal risks. 2

• Do not exceed 4 grams daily or use for prolonged periods without medical supervision. 3, 5

• Do not forget to account for paracetamol in combination products (cold medications, prescription combinations). 3

Special Populations

For migraine in pregnancy: Despite relatively poor efficacy, paracetamol should be used as first-line medication; NSAIDs only during second trimester; triptans only under strict specialist supervision. 6

For post-surgical pain: Paracetamol is essential for multimodal analgesia; adequate pain relief prevents reactive preterm contractions. 1