Tramadol Use During Pregnancy
Tramadol should generally be avoided during pregnancy, particularly in the first trimester and near delivery, due to documented risks of congenital malformations, neonatal withdrawal syndrome, and lack of established safety. 1
FDA Classification and Official Guidance
Tramadol is classified as Pregnancy Category C by the FDA, meaning animal studies have shown adverse effects and there are no adequate well-controlled studies in pregnant women. 1 The FDA drug label explicitly states that tramadol "should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus" and warns that "safe use in pregnancy has not been established." 1
Key Risks to Consider
Congenital Malformations
- A moderate increase in congenital malformations has been documented, with an adjusted odds ratio of 1.33 (95% CI 1.05-1.70) for relatively severe malformations when tramadol is used in early pregnancy. 2
- Specific malformations show elevated risk: cardiovascular defects (OR 1.56,95% CI 1.04-2.29) and clubfoot/pes equinovarus (OR 3.63,95% CI 1.61-6.89). 2
- However, a more recent 2022 Danish nationwide cohort study found no significant association with major congenital malformations (RR 1.04,95% CI 0.87-1.24), suggesting the evidence remains somewhat conflicting. 3
Neonatal Withdrawal Syndrome
- Chronic tramadol use during pregnancy leads to physical dependence and post-partum withdrawal symptoms in newborns. 1
- Neonatal abstinence syndrome typically develops 24-48 hours after delivery and requires hospitalization for observation (minimum 3 days) and potential treatment with phenobarbital. 4
- The FDA label specifically warns of "neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth" reported during post-marketing surveillance. 1
Placental Transfer
- Tramadol freely crosses the placenta due to its lipophilic characteristics, with a mean umbilical vein to maternal vein ratio of 0.83. 1, 4
Clinical Decision Algorithm
If tramadol use is being considered:
First Trimester (Weeks 1-13): Avoid entirely if possible due to risk of congenital malformations, particularly cardiovascular defects and clubfoot. 2 This is the period of organogenesis when teratogenic risk is highest.
Second/Third Trimester (Weeks 14-40): Use only if safer alternatives have failed and maternal benefit clearly outweighs fetal risk. 1
Near Term/Labor: Do not use tramadol prior to or during labor. 1 The risk of neonatal withdrawal syndrome is substantial and requires neonatal intensive monitoring.
If chronic use has occurred: Plan delivery in a hospital setting with neonatal observation for at least 72 hours post-delivery to monitor for withdrawal symptoms. 4
Safer Alternatives
While the provided evidence does not specifically address pain management alternatives during pregnancy, the FDA guidance emphasizes that tramadol should only be used when potential benefits justify risks, implying that other analgesic options should be exhausted first. 1
Lactation Considerations
- Tramadol is excreted in breast milk, with cumulative excretion of 100 μg tramadol (0.1% of maternal dose) within 16 hours post-dose. 1
- The manufacturer does not recommend tramadol for post-delivery analgesia in nursing mothers due to lack of safety data in infants and newborns. 1
- Neonatal oral fluid concentrations can reach significant levels (>1000 ng/mL for tramadol and its active metabolite O-desmethyltramadol), indicating substantial infant exposure through breast milk. 5
Common Pitfalls to Avoid
- Do not assume tramadol is safe because it is a "weak" opioid—it carries documented teratogenic and neonatal risks. 2, 4
- Do not continue tramadol through delivery without planning for neonatal withdrawal management. 4
- Do not rely solely on older safety data—recent large cohort studies provide conflicting evidence, with some showing increased malformation risk and others not, necessitating a cautious approach. 2, 3