Valpros Pedia Use In Pregnancy & Lactation

Pregnancy: Pregnancy Category D. Valproate has a high teratogenic potential and can cause fetal harm when administered to pregnant women. Valproate polytherapy with other AEDs has been associated with increased frequency of congenital malformations than with AED monotherapy. Children exposed to valproate in utero are at high risk for congenital malformations and neurodevelopmental disorders, such as neural tube defects (e.g., spina bifida), craniofacial defects, cleft palate, cardiovascular malformations (e.g., atrial septal defect), hypospadias, etc. Although the risk is dose-dependent, a threshold dose below which no risks exist is not established. The risk of major structural malformation is highest during the first trimester, but other serious developmental effects can occur throughout pregnancy. The rate of congenital malformations in infants born to epileptic mothers who used valproate during pregnancy was four times higher compared to infants born to epileptic mothers administered with other AED monotherapies. Fatal outcomes have been reported.
Studies demonstrated that up to 30% to 40% of preschool children exposed to valproate in utero experience delay in their early neurodevelopmental skills such as talking and walking later, lower intellectual abilities, poor language skills (speaking and understanding), and memory problems. Valproate can also decrease the IQ scores of children exposed to the drug in utero. Public epidemiological studies indicated that children exposed to valproate in utero had lower cognitive test scores compared to children who had no in utero exposure to any AED or to those exposed in utero to other AEDs. Since the women in this study were exposed to AEDs throughout their pregnancy, the particular time period during pregnancy when the cognitive effects occur cannot be determined, and whether the risks for decreased IQ was related to a certain period of pregnancy could not be assessed. The risks of autism spectrum disorders and childhood autism also increased by 3-fold and 5-fold, respectively, in valproate-exposed children in utero.
Cases of hemorrhagic syndrome related to thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors were reported very rarely in neonates exposed to valproate in utero. Afibrinogenemia has also been reported and can be fatal. However, this syndrome must be distinguished from the decrease of vitamin K factors induced by other medications (e.g., phenobarbital). Platelet counts, plasma fibrinogen levels, coagulation tests and coagulation factors should be investigated in neonates.
Hypoglycemia has been reported in neonates whose mothers have taken valproate during pregnancy. Hypothyroidism occurred in neonates exposed to valproate in utero during the third trimester of pregnancy. Symptoms of withdrawal syndrome such as agitation, irritability, hyperexcitability, jitteriness, hyperkinesia, tonicity disorders, tremor, convulsions, and feeding disorders, have occurred at days following birth of neonates whose mothers have taken valproate during the last trimester of pregnancy.
If a woman becomes pregnant while on valproate therapy, she must be immediately referred to a specialist to re-evaluate treatment and consider alternative options. The pregnant patient and her partner should also be referred to an obstetrician for evaluation and adequate counseling. The physician should advise the patient or the parent/caregiver not to discontinue valproate treatment abruptly to avoid precipitation of status epilepticus and to immediately contact a specialist in case of planned or suspected pregnancy. Routine ultrasound and amniocenteses may also be encouraged in women planning to become pregnant. Prenatal diagnostic testing should be made available to detect neural tube and other defects.
Maternal tonic-clonic seizures and status epilepticus with hypoxia experienced during pregnancy due to abrupt discontinuation of treatment may threaten the life of the mother and the fetus. Even minor seizures may be dangerous for the developing embryo or fetus. The discontinuation of the drug may be considered before or during pregnancy in individual cases if the seizure disorder severity and frequency do not pose a serious risk to the patient. If, despite the risks in pregnancy and after careful considerations for alternative treatment, it was decided that a pregnant woman must be given valproate for epilepsy, the following should be recommended: Monotherapy should be used, if possible, at the lowest effective dose. The daily dose should be divided into several small doses to be taken throughout the day.
The use of prolonged-release formulation of valproate should be considered, which may be preferred over the immediate release to avoid high peak plasma concentrations.
Although available evidence does not demonstrate that folate can prevent birth defects and malformations due to valproate, folate supplementation (5 mg daily) is still recommended to be given before pregnancy to decrease the risk of neural tube defects which may occur in all pregnancies.
Fertility: Amenorrhea, polycystic ovaries, and increased testosterone levels have been reported in women on valproate therapy. In addition, valproate administration may also impair male infertility. Case reports demonstrated that fertility dysfunctions are reversible upon treatment discontinuation.
Lactation: Valproate is secreted in breast milk, with concentrations reported to be 1% to 10% of maternal serum concentration. Hematological disorders and hepatic failure have been reported in infants breastfed by women on valproate therapy.
A decision should be made whether to abstain from breastfeeding or to discontinue the valproate therapy, considering the developmental and health benefits of breastfeeding, together with the mother's clinical need for valproate therapy and the potential adverse effects of the drug or of the underlying maternal condition to the breastfed child. Women should not breastfeed while taking valproate and for one month after treatment discontinuation. The breastfed infant should be monitored for signs of liver damage (e.g., jaundice) and unusual bruising or bleeding.