Does Gabapentin (Gabapentin) cause congenital malformations?

From the Guidelines

Gabapentin is classified as FDA Pregnancy Category C, indicating that animal studies have shown adverse effects on the fetus, but adequate human studies are lacking, and its use during pregnancy should be carefully considered due to potential risks to the fetus 1.

Key Considerations

• The medication has been associated with a possible small increased risk of certain birth defects, particularly oral clefts, compared to the general population, though most studies have not found a strong association.
• Animal studies have shown adverse effects on the fetus, but human studies are limited, leading to its classification as FDA Pregnancy Category C.
• If you're pregnant or planning pregnancy while taking gabapentin, it's crucial not to stop the medication suddenly, as this could trigger seizures or worsen the condition being treated.

Recommendations

• Consult your healthcare provider immediately to discuss the risks and benefits specific to your situation.
• Your doctor may consider alternative medications with better safety profiles during pregnancy or adjust your treatment plan based on your individual medical needs.
• The decision to continue or discontinue gabapentin during pregnancy requires careful consideration of both the potential risks to the developing baby and the risks of untreated maternal conditions, as noted in the study published in the European Respiratory Journal 1.

Important Factors

• The use of any drugs during pregnancy and lactation needs to balance the maternal risk of therapy versus no therapy and the fetal risk of uncontrolled maternal disease with the risk of therapy on the newborn.
• Clinicians should compare the benefits and risks of each medication, taking into account the specific circumstances of the patient, as emphasized in the study 1.

From the FDA Drug Label

Use in Specific Populations 8. 1 Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic when administered to pregnant animals at doses similar to or lower than those used clinically. Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus When pregnant mice received oral doses of gabapentin (500 mg, 1000 mg, or 3000 mg/kg/day) during the period of organogenesis, embryo-fetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses The no-effect dose for embryo-fetal developmental toxicity in mice was 500 mg/kg/day or approximately ½ of the maximum recommended human dose (MRHD) of 3600 mg/kg on a body surface area (mg/m2) basis In studies in which rats received oral doses of gabapentin (500 to 2000 mg/kg/day), during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. The lowest effect dose for developmental toxicity in rats is approximately equal to the MRHD on a mg/m2 basis When pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses tested (60 mg, 300 mg, or 1500 mg/kg). The lowest effect dose for embryo-fetal developmental toxicity in rabbits is less than the MRHD on a mg/m2 basis

Gabapentin may cause birth defects. The drug label indicates that gabapentin was developmentally toxic in nonclinical studies in mice, rats, and rabbits at doses similar to or lower than those used clinically.

• Embryo-fetal toxicity was observed in mice at high doses.
• Adverse effects on offspring development were seen in rats at all doses tested.
• Embryo-fetal mortality increased in rabbits at all doses tested. Given the potential risk to the fetus, gabapentin should be used during pregnancy only if the potential benefit justifies the risk 2.

From the Research

Gabapentin and Birth Defects

• The use of gabapentin during pregnancy has been associated with an increased risk of certain birth defects and adverse outcomes, according to several studies 3, 4, 5, 6, 7.
• A systematic review of gabapentinoid use during pregnancy found that prenatal exposure to pregabalin was associated with an increased risk of congenital anomalies and long-term neurodevelopmental outcomes, while gabapentin exposure was associated with an increased risk of preeclampsia, preterm birth, and small-for-gestational age 4.
• A population-based cohort study found that maternal use of gabapentin, particularly late in pregnancy, was associated with a higher risk of preterm birth, small-for-gestational age, and neonatal intensive care unit admission 5.
• Another study found that gabapentin exposure during early pregnancy was not associated with an increased risk of major malformations overall, although there was some evidence of a higher risk of cardiac malformations 5.
• A review of published pregnancy registries and cohorts found that gabapentin exposures were associated with a low rate of major congenital malformations, similar to the rate in the general population 6.

Adverse Outcomes

• Gabapentin use during pregnancy has been linked to an increased risk of adverse outcomes, including:
  • Preterm birth 4, 5
  • Small-for-gestational age 4, 5
  • Neonatal intensive care unit admission 5
  • Preeclampsia 4
  • Cardiac malformations 5
• However, other studies have found that gabapentin exposure during pregnancy did not lead to an increased risk for adverse maternal and fetal events 7.

Safety Considerations

• The safety of gabapentin use during pregnancy is still being studied, and more research is needed to fully understand its effects 3, 4, 5, 6, 7.
• The FDA has reported that gabapentin is potentially "developmentally toxic" and has an unknown risk of birth impacts 3.
• Healthcare providers should carefully evaluate the benefit-risk balance for both mother and fetus/infant when considering gabapentin use during pregnancy 4.