Is tramadol (opioid analgesic) safe to use during pregnancy?

Tramadol Safety in Pregnancy

Tramadol should be strongly avoided during pregnancy due to risks of birth defects, neonatal opioid withdrawal syndrome, and lack of established safety, with alternative analgesics prioritized instead. 1, 2

Primary Safety Concerns

Teratogenic Risk

• Tramadol use in early pregnancy is associated with increased risk of congenital malformations, with an adjusted odds ratio of 1.33 for relatively severe malformations 3
• Specific elevated risks include:
  • Cardiovascular defects (OR 1.56) 3
  • Pes equinovarus/clubfoot (OR 3.63) 3
• The FDA classifies tramadol as Pregnancy Category C, indicating animal studies showed embryotoxicity and fetotoxicity at maternally toxic doses, though not frank teratogenicity 2

Neonatal Withdrawal Syndrome

• Chronic tramadol use during pregnancy leads to physical dependence and post-partum withdrawal symptoms in newborns 2
• Tramadol crosses the placenta freely with a mean umbilical vein to maternal vein ratio of 0.83 2
• Neonatal abstinence syndrome typically develops 36 hours after delivery and requires treatment with phenobarbital 4
• Post-marketing surveillance has documented neonatal seizures, neonatal withdrawal syndrome, fetal death, and stillbirth 2

Clinical Management Algorithm

If Tramadol Has NOT Been Used Yet

• Use NSAIDs and acetaminophen as first-line analgesics (unless contraindicated) 5
• For labor pain specifically, neuraxial analgesia (epidural) should be encouraged 5
• Tramadol should not be used prior to or during labor unless potential benefits outweigh risks 2

If Tramadol Has Been Used Chronically

• Do NOT abruptly discontinue tramadol due to risk of maternal and fetal withdrawal 1
• Access appropriate expertise for supervised tapering 1
• Delivery must occur at a facility prepared to monitor, evaluate, and treat neonatal opioid withdrawal syndrome 1
• The newborn requires observation for at least 3 days post-delivery 4

Important Distinctions from Other Opioids

• Unlike methadone and buprenorphine, which are considered safe throughout all trimesters for opioid use disorder treatment, tramadol has no such safety profile 5
• Tramadol carries similar concerns to codeine, which is contraindicated in breastfeeding due to reports of neonatal toxicity and death 1, 5
• The safety profile of tramadol contrasts sharply with medications that have decades of established safe use in pregnancy 1

Breastfeeding Considerations

• Tramadol is not recommended for post-delivery analgesia in nursing mothers 2
• If used during breastfeeding, close infant monitoring is mandatory for drowsiness, respiratory depression, decreased alertness, difficulty breathing, and feeding problems 1
• Tramadol and its active metabolite O-desmethyltramadol are excreted in breast milk and detected in neonatal oral fluid at significant concentrations 6

Critical Pitfall to Avoid

The most dangerous error is abruptly discontinuing tramadol in a woman with chronic use during pregnancy, as this precipitates withdrawal that poses serious risks to both mother and fetus 1, 2. Any discontinuation requires expert-guided tapering with appropriate monitoring.