Is tramadol (ultram) safe to use during pregnancy?

Tramadol Use During Pregnancy

Tramadol should be avoided during pregnancy, particularly in the first trimester and prior to delivery, due to documented risks of congenital malformations, neonatal withdrawal syndrome, and lack of established safety data.

FDA Drug Label Guidance

The FDA label explicitly states that tramadol should not be used in pregnant women prior to or during labor unless potential benefits outweigh risks, and that safe use in pregnancy has not been established 1. The label warns that:

• Chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn 1
• Tramadol crosses the placenta with a mean umbilical vein to maternal vein ratio of 0.83 1
• Post-marketing surveillance has documented neonatal seizures, neonatal withdrawal syndrome, fetal death, and stillbirth 1

Teratogenic Risk Evidence

The most recent high-quality evidence from 2022 provides reassurance regarding major malformations, but earlier data suggests caution:

• A 2022 Danish nationwide cohort study (n=36,467 pregnancies) found no increased risk of spontaneous abortion (HR 1.06,95% CI 0.99-1.14) or major congenital malformations (RR 1.04,95% CI 0.87-1.24) with tramadol exposure in early pregnancy 2

However, an earlier 2015 Swedish study (n=1,682,846 women) found concerning signals:

• Adjusted odds ratio for relatively severe malformations was 1.33 (95% CI 1.05-1.70) 3
• Significantly increased risk for cardiovascular defects (OR 1.56,95% CI 1.04-2.29) 3
• Significantly increased risk for pes equinovarus/clubfoot (OR 3.63,95% CI 1.61-6.89) 3

Neonatal Withdrawal Syndrome

The risk of neonatal abstinence syndrome is well-documented and clinically significant:

• Case reports demonstrate neonatal withdrawal symptoms developing 36 hours after delivery in infants exposed to chronic maternal tramadol use 4
• Symptoms require treatment with phenobarbital and prolonged hospitalization (9+ days) 4
• The FDA label specifically warns about this risk with chronic use 1

Clinical Recommendations

If tramadol use is being considered during pregnancy:

• First trimester exposure should be avoided when the risk of congenital malformations is greatest, consistent with general principles for medications with limited safety data 5
• Chronic use throughout pregnancy must be avoided due to the high risk of neonatal withdrawal syndrome requiring pharmacologic treatment 1, 4
• Use immediately prior to or during labor is contraindicated due to placental transfer and neonatal effects 1

Alternative pain management strategies should be prioritized:

• Consider non-opioid analgesics with better-established pregnancy safety profiles
• Use the lowest effective dose for the shortest duration if any medication is absolutely necessary 6
• Consultation with maternal-fetal medicine specialists is warranted for severe pain requiring opioid management 5

Critical Pitfalls to Avoid

• Do not assume tramadol is safer than other opioids simply because it has weak opioid activity—it still causes neonatal withdrawal 4
• Do not prescribe for chronic use without counseling about neonatal abstinence syndrome risk and planning for neonatal monitoring 1
• If a patient presents already taking tramadol chronically in pregnancy, coordinate delivery in a facility equipped to monitor and treat neonatal withdrawal for at least 3 days 4