Animal studies have shown administration of this drug during organogenesis to pregnant animals resulted in embryofetal death, fetal malformations, and decreased fetal growth in multiple animal species at clinically relevant doses. Meta-analyses data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal exposure to this drug compared to controls. An increased risk of heart defects, facial clefts, and digital hypoplasia has been reported. The fetal hydantoin syndrome, a pattern of congenital anomalies including craniofacial anomalies, nail and digital hypoplasia, prenatal-onset growth deficiency, and neurodevelopmental deficiencies, has been reported among children born to women who took this drug alone or in combination with other antiepileptic drugs during pregnancy. There are no controlled data in human pregnancy.

Clinical Considerations:
-Medical advice regarding the potential risks to a fetus caused by both seizures and antiepileptic treatment should be given to all women of childbearing potential taking antiepileptic treatment, and especially to women planning pregnancy and women who are pregnant.
-Antiepileptic treatment should be reviewed regularly and especially when a woman is planning to become pregnant. In pregnant women being treated for epilepsy, sudden discontinuation of antiepileptic drug therapy should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child. As a general principle, monotherapy is preferred for treating epilepsy in pregnancy whenever possible because therapy with multiple antiepileptics could be associated with a higher risk of congenital malformations than monotherapy, depending on the associated antiepileptics; women should consider taking folic acid supplementation 4 weeks prior to and for 12 weeks after conception .
-An increase in seizure frequency may occur during pregnancy because of altered pharmacokinetics. Periodic measurements of serum concentrations are recommended as a guide to appropriate adjustment of dose; due to potential changes in protein binding during pregnancy, the monitoring of serum levels should be based on the unbound fraction.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned

Risk Summary: Prenatal exposure to this drug may increase the risks for major congenital malformations and other adverse developmental outcomes; children exposed to this drug in utero, alone or in combination with other antiepileptic drugs, have experienced fetal hydantoin syndrome. There have been several cases of malignancies, including neuroblastoma, reported in children whose mothers received this drug during pregnancy. Animal studies have shown increased incidence of fetal malformations and other manifestations of developmental toxicity at clinically relevant doses.

Comments:
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential harm to the fetus.
-An increase in seizure frequency may occur during pregnancy because of altered pharmacokinetics; plasma concentrations should be monitored more frequently and doses adjusted as appropriate; postpartum restoration of the original dosage will probably be indicated.
-A potentially fatal bleeding disorder may occur in newborns exposed to this drug in utero; this can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth.
-Women of childbearing potential should use effective contraception and should be counseled on effective contraception as this drug may cause a failure of hormonal contraceptives.
-Patients who become pregnant during therapy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry: Phone: 1-888-233-2334; website: http://www.aedpregnancyregistry.org/

See references

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Breastfeeding during monotherapy does not appear to adversely affect infant growth or development; although rare idiosyncratic reactions are possible.
-Some authorities advise against breastfeeding while taking this drug.

It is estimated that a breastfed infant would receive between 0.5% and 8% of the maternal weight-adjusted dosage of this drug in breastmilk. In one study of breastfed children of women taking antiepileptic drugs, cognitive outcomes at 6 years showed higher IQs and enhanced verbal abilities compared to nonbreastfed infants. Combination therapy may result in more reactions in the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug and any potential adverse effects on the breastfed infant from this drug or from the underlying maternal condition.

See references