What are the risks of using pregabalin (Lyrica) during pregnancy?

Pregabalin Should Be Avoided During Pregnancy Due to Significant Fetal Risks

Pregabalin (Lyrica) carries substantial risks during pregnancy and should be discontinued before conception whenever possible, or avoided entirely if the patient becomes pregnant, unless the maternal condition is life-threatening and no safer alternatives exist.

FDA Classification and Animal Data

The FDA classifies pregabalin as Pregnancy Category C, indicating proven fetal harm in animal studies 1. The official Lyrica label documents severe developmental toxicity:

• Structural abnormalities including skull malformations (premature fusion of jugal and nasal sutures) at exposures ≥17 times human exposure
• Skeletal malformations and visceral variations in rabbits at 16 times human exposure
• Growth retardation and decreased fetal body weight across multiple species
• Neurobehavioral abnormalities persisting into adulthood (learning/memory deficits, altered locomotor activity, decreased auditory startle response)
• Reproductive impairment in offspring (delayed sexual maturation, decreased fertility)
• Increased offspring mortality - 100% mortality at high doses during gestation/lactation
• Prolonged gestation and dystocia during labor

Critically, the FDA label states: "There are no adequate and well-controlled studies in pregnant women. Use LYRICA during pregnancy only if the potential benefit justifies the potential risk to the fetus" 1.

Human Evidence: Concerning Signals Despite Limited Data

Major Congenital Malformations

The human data reveals conflicting but concerning findings:

• A 2026 European case-malformed control study (170,126 registrants with major congenital anomalies) found a 2.5-fold increased risk of ventricular septal defects (adjusted OR 2.5,95% CI 1.1-5.3) with first-trimester pregabalin exposure 2. This is the most common cardiac anomaly and represents a clinically significant finding.

• A 2025 meta-analysis of 7 studies (701 pregabalin-exposed pregnancies) found no significant association with major congenital malformations overall (pooled OR 1.79,95% CI 0.80-3.99), but the authors emphasized this should be "interpreted with caution given the small number of studies and their critical risk of bias" 3.

• A 2024 systematic review identified 5 studies reporting significantly increased risks of overall congenital anomalies, specific anomalies (nervous system, eyes, oro-facial clefts, urinary and genital system), miscarriage, and stillbirth after pregabalin exposure 4.

Other Adverse Birth Outcomes

Multiple studies document concerning patterns:

• Preterm delivery: 18.5% vs. 5.7% in controls (OR 0.26,95% CI 0.07-1.01, p=0.04) 5
• Low birth weight: 22.2% vs. 6.6% in controls (OR 4.34,95% CI 1.20-15.65, p=0.016) 5
• Increased risks of small-for-gestational-age, preeclampsia, and NICU admission 4

Neurodevelopmental Concerns

The 2024 systematic review reported increased risks of ADHD, autism spectrum disorder, and intellectual disability with pregabalin exposure, though confounding by maternal illness cannot be excluded 4. This aligns with the persistent neurobehavioral abnormalities documented in animal offspring 1.

Critical Limitations and Clinical Reality

All human studies suffer from extremely small sample sizes - the largest meta-analysis included only 701 exposed pregnancies 3. The 2026 comprehensive review by Andrade acknowledged that "pregabalin-exposed pregnancy sample sizes were small in all studies" and noted "negligible adjustment for genetic, illness behavior, and environmental confounds" 6.

However, the convergence of animal toxicity data, FDA warnings, and emerging human signals creates a concerning safety profile that cannot be dismissed due to limited human data alone.

Labor, Delivery, and Breastfeeding

• Labor/Delivery: Effects unknown in humans; animal data shows prolonged gestation and dystocia at 50× human exposure 1
• Breastfeeding: Unknown if excreted in human milk (present in rat milk). The FDA recommends discontinuing either nursing or the drug due to tumorigenicity concerns in animal studies 1

Clinical Algorithm for Management

Preconception Planning

1. Attempt discontinuation at least 6 weeks before conception if clinically feasible
2. Switch to safer alternatives for the underlying condition (neuropathic pain, anxiety, seizures)
3. Document informed consent if continuation is absolutely necessary

If Pregnancy Discovered While on Pregabalin

1. Immediately assess maternal indication severity

   • Life-threatening condition with no alternatives → Continue with lowest effective dose
   • Non-life-threatening condition → Discontinue immediately
   • Moderate severity → Attempt switch to safer alternative (e.g., certain SSRIs for anxiety, other anticonvulsants for seizures with better safety profiles)

2. Enhanced fetal monitoring

   • Detailed anatomic ultrasound at 18-22 weeks focusing on cardiac structures (especially ventricular septum)
   • Fetal echocardiography if available
   • Serial growth assessments for IUGR

3. Enroll in pregnancy registry: North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334) 1

Common Pitfalls to Avoid

• Do not continue pregabalin "just because the patient is already pregnant" - the risk-benefit calculation changes dramatically with pregnancy
• Do not assume the risk is negligible because some meta-analyses show non-significant results - small sample sizes limit statistical power, not actual risk
• Do not ignore the animal data - the FDA Category C designation exists precisely because animal toxicity at clinically relevant exposures predicts human risk
• Do not forget that untreated maternal conditions also carry fetal risks - this is a genuine risk-benefit decision, not a blanket contraindication, but the threshold for continuing pregabalin should be very high

Bottom Line

The combination of definitive animal teratogenicity, FDA Category C classification, emerging human signals for cardiac malformations and adverse birth outcomes, and neurodevelopmental concerns makes pregabalin a poor choice during pregnancy. While the absolute risk magnitude remains uncertain due to limited human data, the precautionary principle strongly favors discontinuation or avoidance unless maternal benefit clearly outweighs fetal risk in life-threatening situations where no safer alternatives exist 1, 2, 3, 4, 5.