Insights: Opioid Use in Pregnancy and Preconception
Written by Evan Fu, PharmD Candidate 2025, and Regina Ginzburg, Pharm.D., CDCES, BC-ADM
Opioid use has increased dramatically over the last two decades, including among people of reproductive age. The number of pregnant people with opioid use disorder (OUD) presenting to the hospital at labor and delivery quadrupled between 1999 and 2014.1 A recent data analysis encompassing over 56 million American women*, showed increased pregnancy complications associated with maternal opioid use,2 such as maternal death, cardiac arrest, intrauterine growth restriction, placental abruption, preterm labor, oligohydramnios, the need for blood transfusions, stillbirth, premature rupture of membranes, and cesarean delivery.2
For the fetus, the risks of opioid exposure include Neonatal Abstinence Syndrome (NAS). Symptoms of NAS include irritability, poor feeding, tremors, vomiting, and seizures in severe cases.3 The management of NAS typically includes treatment with methadone or buprenorphine, along with supportive care and close monitoring. Infants exposed to opioids during pregnancy may also face a higher risk of birth defects, including congenital malformations, and are more likely to experience preterm birth and low birth weight.4
Opioid use has also been linked to reduced fertility, affecting menstrual cycles, ovulatory function, and sperm quality.5 One study found a dose-related association between opioid use, sperm DNA damage, and impaired semen parameters.6 In a retrospective study, opioid use prior to attempting pregnancy was linked to a 29% reduced likelihood of achieving pregnancy during a given menstrual cycle compared to those who did not use opioids.5 Among those who did become pregnant, those who used opioids around the time of implantation had a 1.5 times higher risk of miscarriage compared to those who did not use opioids. Additionally, people who used opioids during the first four weeks of pregnancy were more than twice as likely to experience a miscarriage.
The American College of Obstetricians and Gynecologists (ACOG) advises preconception counseling on opioid use during pregnancy. They emphasize that opioids should be used sparingly, only when necessary, and for the shortest duration possible.7 Buprenorphine or methadone are recommended for individuals with opioid use disorder, as they may be safer for the mother and fetus compared to other opiates. Clinicians should consider a range of pharmacological pain management options, depending on the type of pain (see table). Nonpharmacologic modalities, such as acupuncture, transcutaneous nerve stimulation, or biofeedback, are safe options as well.
| Medication | Typical Dosing | Type of Pain Treated | Pregnancy Safety |
|---|---|---|---|
| Acetaminophen | 325–1000 mg every 4–6 hrs (max 4g/day) | Mild to moderate pain, headache | Generally considered safe (Pregnancy Cat B) |
| NSAIDs (ibuprofen, naproxen, celecoxib) | Doses vary | Mild to moderate pain, inflammation | Increased risk of miscarriage close to conception. Numerous concerns in pregnancy. Avoid |
| Aspirin | 325 mg every 4-6 hours | Anti-inflammatory | Low dose (< 150 mg daily) may be used for preeclampsia prevention and not associated with negative fetal outcomes. High doses can cause intrauterine growth restrictions, bleeding abnormalities, neonatal acidosis. |
| Opioids (i.e. oxycodone, hydrocodone, hydromorphone, morphine, tramadol) | See individual medications | Moderate to severe pain | Not preferred in noncancer pain during pregnancy; may be associated with poor fetal growth, stillbirth, and preterm delivery. If truly needed, use the lowest effective dose for only the expected duration of pain. |
| Gabapentin | 300–1200 mg up to 3 times daily | Neuropathic pain | Crosses the placenta. Folic acid supplementation is recommended during pregnancy in those using gabapentin. Insufficient evidence to recommend using in pregnancy. |
| Pregabalin | 75–150 mg twice daily | Neuropathic, fibromyalgia | Crosses the placenta. May have decreased levels due to increased renal clearance in pregnancy. |
| Buprenorphine | Transdermal: 5-10 mcg/hour every 7 days | Moderate to severe pain, opioid dependence | Although crosses the placenta and can be detected in newborn, opioid agonist is preferred in pregnancy if an opiate is needed. Transmucosal form is a recommended treatment option. Pharmacokinetic properties of sublingual may be altered in pregnancy. |
| Methadone | 2.5–10 mg every 8–12 hrs (dosing individualized) | Chronic severe pain | Although crosses the placenta and can be detected in newborn, opioid agonist is preferred in pregnancy if an opiate is needed. Increased risk of major malformations or other adverse effects has not been observed. Some pharmacokinetic properties of the drug may be altered as pregnancy progresses, requiring dose adjustments. |
| Duloxetine | 30–60 mg once daily | Neuropathic pain Fibromyalgia |
An increased risk of preeclampsia and spontaneous abortion may be associated; however, the quality of evidence for these outcomes is low. May increase the risk of bleeding and postpartum hemorrhage (theoretical; clinical data is lacking). May see decreased duloxetine concentration in the third trimester. Persistent pulmonary hypertension is rare but can occur with third-trimester use. Observe newborn in the first few hours of life. |
| Topical diclofenac | 2–4 g applied to affected area 2–4x daily | Localized inflammatory pain | Reversible constriction of the ductus arteriosus in utero has been observed with topical diclofenac. Avoid using after 20 weeks of gestation. |
*The studies cited in this Insights use the term “women.” RHAP recognizes that this language is not inclusive of all people who seek care. A person’s biology does not determine their gender.
RHAP Resources:
Insights: Benzodiazepine Use in Pregnancy and Lactation
Download and print our resources for free from our website or visit our store to buy physical copies!
Partner Resources:
Reproductive Health Hotline (ReproHH)
A free, confidential phone service (1-844-737-7644) offering evidence-based clinical information for healthcare providers across the US who have questions related to sexual and reproductive health.
Sources:
9. UpToDate Lexidrug; UpToDate, Inc. Retrieved February 10, 2024, from https://online.lexi.com.
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