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MotherToBaby | Fact Sheets [Internet]. Brentwood (TN): Organization of Teratology Information Specialists (OTIS); 1994-.
MotherToBaby | Fact Sheets [Internet].
Show detailsThis sheet is about using valproic acid in pregnancy and while breastfeeding. This information is based on available published literature. It should not take the place of medical care and advice from your healthcare provider.
What is valproic acid?
Valproic acid is a medication that has been used to control seizures in the treatment of epilepsy, and to treat bipolar disorder and migraines. Valproic acid is sometimes also called sodium valproate or valproate sodium. Some brand names for valproic acid are Depakene®, Stavzor®, and Depacon®. A similar medication, divalproex (Depakote®), breaks down into valproic acid in the body.
The Food and Drug Administration recommends that women who are pregnant do not take valproate sodium and related products, valproic acid and divalproex sodium to prevent migraine headaches. For epilepsy or bipolar disorder, valproate products should only be prescribed during pregnancy if other medications are not effective in treating the condition or cannot be used for another reason.
Sometimes when women find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take your medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
I am taking valproic acid, but I would like to stop taking it before getting pregnant. How long does the drug stay in my body?
People eliminate medications at different rates. In healthy non-pregnant adults, it takes 2-4 days, on average, for most of the valproic acid to be gone from the body.
What might happen if I stopped taking my valproic acid and then had a seizure during my pregnancy?
Having a seizure while pregnant might be harmful to the fetus. Complications depend on many things, such as the type of seizure, how long the seizure lasts, and the number of seizures that happen. Epileptic seizures might cause periods of time when the fetus is not getting enough oxygen, which could lead to problems with development. These seizures could also be life-threatening for both the woman who is pregnant and the fetus. A seizure could cause a woman who is pregnant to fall or have an accident that could injure themselves or the fetus.
What might happen if I stopped taking my valproic acid and then had a relapse of bipolar disorder during my pregnancy?
Women who are pregnant and have bipolar disorder who stop taking their medication during pregnancy might have a higher chance for symptoms of depression or mania that could be harmful to both the woman who is pregnant and the fetus. Episodes of depression or mania are very stressful for a woman who is pregnant. During manic or depressive episodes, the woman who is pregnant might have more trouble taking care of themselves and keeping themselves safe.
I take valproic acid. Can it make it harder for me to get pregnant?
Some studies suggest that women on valproic acid might have a higher chance of developing polycystic ovary syndrome (PCOS), a condition associated with trouble getting pregnant. Studies have found that women with seizure disorders and women with bipolar disorder might have problems with their periods and trouble getting pregnant. This possible increase might be due to the conditions that the women have, rather than the use of medication.
Does taking valproic acid increase the chance of miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. It is not known if valproic acid increases the chance of miscarriage.
Does taking valproic acid increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Studies have found that taking valproic acid in pregnancy is associated with a chance of having a baby with fetal valproate spectrum disorder which includes minor and major birth defects. Birth defects are typically classified as major if they need surgery to be repaired. Some of the birth defects that are more likely to happen include heart defects, cleft lip (when the lip does not form correctly and needs surgery to repair after birth), or neural tube defects (an opening in the baby’s spine or skull). Some babies exposed to valproic acid might also have more minor birth defects like facial differences, such as a thin upper lip. The chance of a birth defect seems to be greater with higher doses of valproic acid or with taking it with another seizure medication.
The most common neural tube defect linked to valproic acid use is spina bifida (opening in the spine). The chance of a neural tube defect when taking valproic acid is approximately 1 in 50 to 1 in 100 (1-2%). Taking extra folic acid before trying to get pregnant and in early pregnancy might help lower the chance of some birth defects in pregnancies exposed to valproic acid. Talk to your healthcare provider about how much folic acid you should take. For more information on folic acid, please see the MotherToBaby fact sheet at: https://mothertobaby.org/fact-sheets/folic-acid/.
Does taking valproic in pregnancy increase the chance of other pregnancy-related problems?
Valproic acid might increase the chance of low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth). There have been reports of temporary low blood sugar levels (hypoglycemia) in newborns.
Does taking valproic in pregnancy affect future behavior or learning for the child?
Prenatal exposure to valproic acid can increase the chance of problems with learning and development. Different studies have shown an increased chance of intellectual disability, developmental delay, autism spectrum disorder, other developmental disorders, attention deficit/hyperactivity disorder, attachment disorder, decreased language and memory skills, and decreased social and adaptive behavior skills. Not all studies have shown the same results. Some of the long-term problems in the exposed children might be due to how severe the seizure disorder is in the woman who is pregnant.
What screenings or tests are available to see if my pregnancy has birth defects or other issues?
There are ways to screen for neural tube defects in pregnancy. A blood test can be done to measure the amount of a protein called alpha fetoprotein (AFP) in the blood of the woman who is pregnant. Babies with spina bifida have higher levels of AFP. If the AFP is higher than usual in the blood test, more testing or screenings might be offered to you to get more information.
An ultrasound that looks at the fetal spine can be used to screen for spina bifida. Ultrasounds can also screen for some other birth defects, such as a heart defect or cleft lip. Talk with your healthcare provider about any prenatal screenings or testing that are available to you. There are no tests available during pregnancy that can tell how much effect there could be on future behavior or learning.
Breastfeeding while taking valproic acid:
The amount of valproic acid that passes into breast milk is low and blood levels from exposed infants are low to undetectable. There is a theoretical (not proven) concern that infants exposed to valproic acid through breastmilk could develop liver toxicity, so infants should be monitored for any changes or problems. If you suspect the baby has symptoms such as jaundice (yellowing of the skin or eyes), rash, or fever, contact the child’s healthcare provider. Be sure to talk to your healthcare provider about all your breastfeeding questions.
If a man takes valproic acid, could it affect fertility or increase the chance of birth defects?
It is not known if valproic acid could affect a man’s fertility (ability to get a woman pregnant) or increase the chance of birth defects above the background risk. In general, exposures that sperm donors or fathers have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.
Selected References:
- Abe K, et al. 2014. Impact of planning of pregnancy in women with epilepsy on seizure control during pregnancy and on maternal and neonatal outcomes. Seizure 23(2):112-6. [PubMed: 24183922]
- Aydin B, et al. 2015. Olanzapine and quetiapine use during breastfeeding: excretion into breast milk and safe breastfeeding strategy. J Clin Psychopharmacol 35(2):206-8. [PubMed: 25679127]
- Barton S, et al. 2018. Memory dysfunction in school-aged children exposed prenatally to antiepileptic drugs. Neuropsychology 32:784-796. doi:10.1037/neu0000465. [PubMed: 29975072] [CrossRef]
- Blotière PO et al. Risk of early neurodevelopmental outcomes associated with prenatal exposure to the antiepileptic drugs most commonly used during pregnancy: a French nationwide population-based cohort study. BMJ Open. 2020 Jun 7;10(6):e034829. doi: 10.1136/bmjopen-2019-034829. PMID: ; PMCID: . [PMC free article: PMC7282331] [PubMed: 32513880] [CrossRef]
- Christensen J, et al. 2013. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 24;309(16). [PMC free article: PMC4511955] [PubMed: 23613074]
- Coban D, et al. 2010. Neonatal episodic hypoglycemia: a finding of valproic acid withdrawal. J Clin Res Pediatr Endocrinol 2(2):92-4. [PMC free article: PMC3005670] [PubMed: 21274347]
- Daugaard CA et al.Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Intellectual Disability and Delayed Childhood Milestones. JAMA Netw Open. 2020 Nov 2;3(11):e2025570. doi: 10.1001/jamanetworkopen.2020.25570. PMID: ; PMCID: . [PMC free article: PMC7656282] [PubMed: 33170264] [CrossRef]
- Coste J et al.Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France. Sci Rep. 2020 Oct 22;10(1):17362. doi: 10.1038/s41598-020-74409-x. PMID: ; PMCID: . [PMC free article: PMC7581762] [PubMed: 33093466] [CrossRef]
- Deshmukh U, et al. 2016. Behavioral outcomes in children exposed prenatally to lamotrigine, valproate, or carbamazepine. Neurotoxicol Teratol 54:5-14. [PMC free article: PMC5340722] [PubMed: 26791321]
- Di Y et al. Maternal folic acid supplementation prevents autistic behaviors in a rat model induced by prenatal exposure to valproic acid. Food Funct. 2021 May 21;12(10):4544-4555. doi: 10.1039/d0fo02926b. Epub 2021 Apr 27. PMID: . [PubMed: 33903876] [CrossRef]
- Diav-Citrin O, et al. 2009. Pregnancy outcome after in utero exposure to valproate: evidence of dose relationship in teratogenic effect. CNS Drugs 22(4):325-34. [PubMed: 18336060]
- Dreier JW, Bjork MH, et al. 2023. Prenatal exposure to antiseizure medication and incidence of childhood- and adolescence-onset psychiatric disorders. JAMA neurology; 80(6):568-577. [PMC free article: PMC10111234] [PubMed: 37067807]
- Einarson A et al. 2009. Use and safety of antipsychotic drugs during pregnancy. J Psychiatr Pract 15: 183-92. [PubMed: 19461391]
- Harden CL, et al. 2009. Management issues for women with epilepsy - Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 50: 1237-46. [PubMed: 19507301]
- Huber-Mollema Y et al.Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure. J Neurol. 2020 Jun;267(6):1724-1736. doi: 10.1007/s00415-020-09764-w. Epub 2020 Feb 28. PMID: ; PMCID: . [PMC free article: PMC7293688] [PubMed: 32112258] [CrossRef]
- Jentink J, et al. 2010. Valproic Acid Monotherapy in Pregnancy and Major Congenital Malformations. N Engl J Med 362:2185-93. [PubMed: 20558369]
- Joffe H et al. 2006 Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report. Biol Psychiatry. Dec 15;60(12):1378-81. [PubMed: 16950230]
- Kacirova I, Grundmann M, Brozmanova H. Valproic acid concentrations in nursing mothers, mature milk, and breastfed infants in monotherapy and combination therapy. Epilepsy Behav. 2019 Jun;95:112-116. doi: 10.1016/j.yebeh.2019.04.002. Epub 2019 Apr 28. PMID: . [PubMed: 31035102] [CrossRef]
- Keni et al. Anti-epileptic drug and folic acid usage during pregnancy, seizure and malformation outcomes: Changes over two decades in the Kerala Registry of Epilepsy and Pregnancy. Epilepsy Res. 2020 Jan;159:106250. doi: 10.1016/j.eplepsyres.2019.106250. Epub 2019 Dec 9. PMID: . [PubMed: 31855827] [CrossRef]
- Markoula S, et al. 2020. Reproductive health in patients with epilepsy. Epilepsy & Behavior, 113, 107563. [PubMed: 33242778]
- Mawhinney E, et al. 2012. Valproate and the risk for congenital malformations: Is formulation and dosage regime important? Seizure 21(3):215-218. [PubMed: 22364656]
- Meador KJ, et al. 2012. Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology 78(16):1207-14. [PMC free article: PMC3324322] [PubMed: 22491865]
- Meador KJ, et al. 2014. Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years. JAMA Pediatr. 168:729-36. [PMC free article: PMC4122685] [PubMed: 24934501]
- Ornoy A. 2009. Valproic acid in pregnancy: how much are we endangering the embryo and fetus? ReprodToxicol 28: 1-10. [PubMed: 19490988]
- Shallcross R, et al. 2014. In utero exposure to levetiracetam vs valproate: development and language at 3 years of age. Neurology 82(3):213-21. [PubMed: 24401687]
- Smith, J et al. 2009. Sodium valproate and the fetus: a case study and review of the literature. Neonatal Netw 28: 363-7. [PubMed: 19892633]
- Sveberg L, et al. 2015. The impact of seizures on pregnancy and delivery. Seizure. 28:35-8. [PubMed: 25746572]
- Tomson T, et al. 2015. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia 56(7):1006-19. [PubMed: 25851171]
- United States Food and Drug Administration. 2013. FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children. Accessed on 3/204 from https://www
.fda.gov/drugs /drug-safety-and-availability /fda-drug-safety-communication-valproate-anti-seizure-products-contraindicated-migraine-prevention. - Vajda FJ, et al. 2013. Dose dependence of fetal malformations associated with valproate. Neurology; 81(11):999-1003. [PubMed: 23911758]
- Vajda FJE, et al. 2019. Valproate-associated foetal malformations-Rates of occurrence, risks in attempted avoidance. Acta Neurol Scand 139(1):42-48. [PubMed: 30109700]
- Vajda FJE et al. Folic acid dose, valproate, and fetal malformations. Epilepsy Behav. 2021 Jan;114(Pt A):107569. doi: 10.1016/j.yebeh.2020.107569. Epub 2020 Dec 1. PMID: . [PubMed: 33272896] [CrossRef]
- Veiby G, et al. 2014. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol 261: 579-588. [PubMed: 24449062]
- Veroniki AA, et al. 2017. Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC medicine 15(1):95. [PMC free article: PMC5418725] [PubMed: 28472982]
- Weston J, et al. 2016. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev 11:Cd010224. [PMC free article: PMC6465055] [PubMed: 27819746]
- Wiggs KK et al.Antiseizure medication use during pregnancy and risk of ASD and ADHD in children. Neurology. 2020 Dec 15;95(24):e3232-e3240. doi: 10.1212/WNL.0000000000010993. Epub 2020 Oct 28. PMID: ; PMCID: . [PMC free article: PMC7836668] [PubMed: 33115775] [CrossRef]
- Yerby MS, McCoy GB. 1999. Male infertility: possible association with valproate exposure. Epilepsia 40:520-1. [PubMed: 10219283]
- Yonkers KA et al. 2004. Management of bipolar disorders during pregnancy and the postpartum period. Am J Psych 161:608-20. [PubMed: 15056503]
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