Tramadol use during pregnancy is associated with a higher rate of miscarriage. In a large comparative study using the EFEMERIS database, women who took tramadol had a miscarriage rate of 5.6%, compared to 2.9% among unexposed women and 2.4% among women taking codeine instead. After adjusting for factors like maternal age, other medications, and pre-existing health conditions, tramadol users were roughly 1.9 times more likely to experience a spontaneous pregnancy loss than women who took no opioid painkillers.
The FDA labels tramadol with a warning that it “may cause fetal harm,” though it also notes that the available human data are still insufficient to precisely quantify the risk for miscarriage and birth defects. What the existing evidence does show is enough to make tramadol a poor choice during pregnancy when alternatives exist.
What the Research Shows
The most detailed study on this question compared three groups of pregnant women: those dispensed tramadol, those dispensed codeine, and those with no opioid exposure. The tramadol group had a spontaneous pregnancy loss rate roughly double that of the other two groups. That elevated risk held up even after researchers controlled for maternal age, folic acid use, exposure to other potentially harmful drugs, NSAIDs, high blood pressure, diabetes, and chronic health conditions. In statistical terms, the adjusted hazard ratio was 1.86 compared to unexposed women, meaning the risk was 86% higher.
What makes this finding notable is that tramadol performed worse than codeine, another opioid. The adjusted hazard ratio comparing tramadol to codeine was 2.23, meaning tramadol users were more than twice as likely to miscarry. This suggests the risk is not simply a general opioid effect but something more specific to tramadol or its breakdown products in the body.
How Tramadol Reaches the Fetus
Like most opioids, tramadol crosses the placenta. Research on opioid drugs generally shows that both the parent drug and the active compounds it breaks down into pass readily from maternal blood into fetal tissue. The placenta has some ability to metabolize certain opioids, but it does not act as a reliable filter. The rate of transfer can also change depending on the stage of pregnancy, with preterm placentas handling some opioids differently than full-term placentas.
Tramadol is unusual among opioids because it works through two different pathways: it activates opioid receptors (like other painkillers in its class) and also affects serotonin and norepinephrine signaling in the nervous system. This dual action may help explain why its pregnancy risks don’t perfectly mirror those of other opioids like codeine. Animal studies have shown that tramadol reduces fetal weight and slows bone development in mice, rats, and rabbits at doses that are not far above the maximum recommended human dose.
Risks Beyond Miscarriage
If tramadol is used regularly later in pregnancy, the main concern shifts to neonatal opioid withdrawal syndrome, or NOWS. This happens when a baby who has been exposed to opioids in the womb suddenly loses that exposure after birth. Reports of NOWS linked to tramadol typically involve women taking 200 to 400 mg daily throughout pregnancy, though not every baby exposed at those doses develops symptoms.
Withdrawal symptoms usually appear within the first two days after birth and can last more than two weeks. They include irritability, excessive crying, tremors, vomiting, poor feeding, stiff muscles, fast heart rate, sneezing, sweating, and in severe cases, seizures. The likelihood and severity depend on several factors: how long the mother took the medication, the dose, whether other drugs were involved, whether the baby was born early, and the baby’s size at birth. The FDA warns that NOWS “may be life-threatening if not recognized and treated.”
Breastfeeding while taking tramadol is also not recommended. Tramadol and its active breakdown products pass into breast milk. In 2017, the FDA strengthened its warning on this point, and ACOG, the leading professional organization for obstetricians, advises prescribing a different opioid if one is needed during breastfeeding.
Safer Options for Pain During Pregnancy
For most types of pain during pregnancy, acetaminophen (Tylenol) is the standard first-line medication. It is generally well tolerated and does not carry the same risks as opioid painkillers. Ibuprofen is the most studied anti-inflammatory drug in pregnancy, though its use is typically limited to certain trimesters because of potential effects on fetal development later in pregnancy. Your provider can clarify when it’s appropriate.
Non-drug approaches can also make a meaningful difference, particularly for musculoskeletal pain. Options that have been used in obstetric settings include heat or ice application, abdominal binders, acupuncture or acupressure, mindful breathing, aromatherapy, and topical creams applied directly to the painful area. These strategies work best when combined with each other and with acetaminophen rather than used alone.
If your pain is severe enough that you feel you need something stronger than acetaminophen, that conversation with your provider is worth having sooner rather than later. The goal is finding effective pain control that doesn’t carry the pregnancy risks tramadol does, and there are usually options available before reaching for an opioid.