Pregabalin Safety in First Trimester
Pregabalin should be avoided during the first trimester of pregnancy and used only when the benefit clearly outweighs the risk, as emerging evidence suggests potential associations with increased congenital malformations and adverse pregnancy outcomes. 1, 2
FDA Classification and Official Warnings
The FDA label for pregabalin explicitly warns that pregabalin may harm the unborn baby and recommends shared decision-making between patients and healthcare providers regarding use during pregnancy. 1 The label advises pregnant women to register with the North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334) to help collect safety data. 1
Evidence on Congenital Malformations
The data on pregabalin and birth defects show concerning signals, though studies remain limited in size:
A 2024 systematic review identified five 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 first-trimester pregabalin exposure. 2
Individual study findings include major malformation rates ranging from 3.3% to 7.7%, with one adequately powered study (n=116) identifying a significantly increased rate of 6.0% major malformations. 3
The largest and best-controlled study (n=477 and n=174 in two datasets) found no increased malformation risk, but even this analysis was underpowered to detect moderate risk increases. 3
Additional Pregnancy Risks
Beyond structural malformations, pregabalin exposure carries other pregnancy-related concerns:
Increased rates of spontaneous abortion (23.3% in one small study, though not reaching statistical significance due to sample size). 3
Preterm birth risk of 25.0% reported in exposed pregnancies. 3
Long-term neurodevelopmental outcomes show concerning signals requiring further investigation. 2
Animal Data and Male-Mediated Risks
The FDA label warns that animal studies demonstrated male fertility problems and birth defects in offspring of male animals treated with pregabalin. 1 Men planning to father a child should be informed of potential male-mediated teratogenicity, though clinical significance remains uncertain. 1
Clinical Decision-Making Algorithm
When a woman of childbearing age requires treatment for epilepsy, neuropathic pain, or anxiety:
First trimester exposure should be avoided whenever possible - consider alternative medications with better safety profiles. 1, 2
If pregabalin cannot be discontinued, use the lowest effective dose and ensure the patient understands the potential risks through shared decision-making. 1
Enroll in pregnancy registry immediately upon pregnancy recognition to contribute to safety surveillance. 1
For epilepsy: Consider alternative antiepileptic drugs with more established safety profiles, though recognize that uncontrolled seizures also pose fetal risks. 1
For neuropathic pain: Evaluate non-pharmacologic options or medications with better pregnancy data. 1
For anxiety: Consider SSRIs or other anxiolytics with more robust pregnancy safety data. 1
Critical Caveats
All available studies are underpowered, making it impossible to definitively rule out moderate increases in malformation risk. 3
The combined evidence from systematic reviews and animal studies raises substantial concerns about gabapentinoid safety during pregnancy. 2
Confounding by indication cannot be ruled out in observational studies, as underlying maternal conditions may independently affect pregnancy outcomes. 3, 4
Abrupt discontinuation carries risks including increased seizure frequency in epilepsy patients, requiring careful tapering if medication changes are made. 1
Breastfeeding Considerations
Pregabalin passes into breast milk, and breastfeeding is not recommended during treatment. 1 Women should discuss alternative feeding methods with their healthcare provider. 1