Is tramadol (ultram) safe to use during pregnancy?

Tramadol Safety in Pregnancy

Tramadol should be avoided during pregnancy, particularly in the first trimester, due to documented risks of congenital malformations, and should not be used prior to or during labor due to risks of neonatal withdrawal syndrome and respiratory depression.

Evidence of Teratogenic Risk

The FDA drug label explicitly states that "safe use in pregnancy has not been established" and classifies tramadol as Pregnancy Category C, indicating embryotoxic and fetotoxic effects in animal studies 1. More critically:

• A large Swedish registry study of 1,751 women exposed to tramadol in early pregnancy demonstrated a significantly increased risk of congenital malformations with an adjusted odds ratio of 1.33 (95% CI 1.05-1.70) for relatively severe malformations 2
• Specific malformations showed even higher risks: cardiovascular defects (OR 1.56,95% CI 1.04-2.29) and pes equinovarus/clubfoot (OR 3.63,95% CI 1.61-6.89) 2
• This represents the highest quality evidence directly addressing pregnancy outcomes, published in 2015 with nearly 1.8 million births analyzed 2

Neonatal Risks

Chronic use during pregnancy leads to serious neonatal complications:

• Neonatal withdrawal syndrome is well-documented, with the FDA label warning that "chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn" 1
• Case reports confirm neonatal abstinence syndrome occurring 36 hours after delivery, requiring phenobarbital treatment for up to 9 days 3
• The FDA label specifically reports "neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth" during post-marketing surveillance 1

Labor and Delivery Contraindication

The FDA explicitly contraindicates tramadol use prior to or during labor:

• "Tramadol hydrochloride should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks" 1
• Tramadol crosses the placenta with a mean umbilical vein to maternal vein ratio of 0.83, ensuring significant fetal exposure 1
• Neonatal respiratory depression is a documented risk 1

Clinical Pitfalls to Avoid

• Do not assume tramadol is safer than other opioids simply because it has mixed mechanism of action; the teratogenic data suggests otherwise 2
• If a patient has already used tramadol in early pregnancy, counsel about the moderate increased risk (33% relative increase) but recognize absolute risk remains relatively low 2
• For chronic pain management in pregnancy, consider acetaminophen as first-line, or consult maternal-fetal medicine for alternative strategies 2
• If delivery occurs after chronic tramadol use, ensure neonatal observation for at least 3 days for withdrawal symptoms, with phenobarbital available for treatment 3

Alternative Considerations

While the evidence provided focuses on breastfeeding rather than pregnancy, it's worth noting that even in lactation, tramadol carries FDA warnings about respiratory depression and death, further supporting its problematic safety profile in the perinatal period 4.