Fetal valproate syndrome

Información en español Title

Other Names:

Valproic acid embryopathy; Susceptibility to valproate embryopathy; FVS; Valproic acid embryopathy; Susceptibility to valproate embryopathy; FVS; Fetal valproic acid syndrome See More

Categories:

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases

Summary Summary

Fetal valproate syndrome (FVS) may occur if a developing baby is exposed to valproic acid during pregnancy. Valproic acid, also known as valproate, is a medication that is often used to treat epilepsy, bipolar disorder, and migraines. Many babies who are exposed to this medication during pregnancy are born healthy with normal growth and development. However, studies have found that women who take valproate during pregnancy have a greater chance of having a baby with a major birth defect or other health problem. Symptoms of FVS vary but may include characteristic facial features, spina bifida, congenital heart defects, cleft lip and/or cleft palate, genital abnormalities, skeletal abnormalities, and developmental delay. A child exposed to valproic acid may be at a higher risk for learning and behavioral problems. Although there is no cure for FVS, many of the possible signs and symptoms of FVS do have treatments or therapies available. Early intervention programs may also be helpful.^[1]^[2]^[3]

The U.S. Food and Drug Administration (FDA) advises that valproate and related products should not be taken by women for the prevention of migraine headaches during pregancy. With regard to valproate use in pregnant women with epilepsy or bipolar disorder, valproate products should only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable. However, it is important to note that women who are pregnant and taking a valproate medication should not stop their medication but should talk to their doctor or other trusted medical professional immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby. For example, the sudden discontinuation of valproate in pregnant women with seizures can result in persistent seizures, which can cause harm, including death, to the mother and/or the unborn baby.^[4]

The FDA suggests a pregnant woman taking valproate or other anti-seizure medication should talk to her doctor or other trusted medical professional about registering with the North American Antiepileptic Drug Pregnancy Registry. The purpose of this registry is to collect information about the safety of anti-seizure medications during pregnancy. A pregnant woman taking anti-seizure medication can enroll in this registry by calling 1-888-233-2334. You can read more about the registry on the North American AED (Antiepileptic Drug) Pregnancy Registry website.^[4]

It is suggested that physicians refer pregnant patients who are using valproate to register for an antiepileptic drug registration program called North American Antiepileptic Drug (NAAED) Pregnancy Registry: http://www.aedpregnancyregistry.org/

Last updated: 9/22/2017

Symptoms Symptoms

Many babies who are exposed to valproic acid during pregnancy are born healthy and do not have fetal valproate syndrome (FVS). However, studies have found that pregnant women who take valproic acid have a greater chance of having a baby with a major or minor birth defect. When present, the signs and symptoms of FVS can vary significantly from baby to baby. Symptoms may include:^[1]^[2]^[3]

Characteristic facial features - such as a high, broad forehead; skin of the upper eyelid covering the inner corner of the eye (epicanthal folds); thin, arched, wide-spaced eyebrows; a small, upturned nose with a wide bridge; a long, shallow midline groove between upper lip and nose (philtrum); and a thick lower lip. These features may become less noticeable over time.
Spina bifida or other birth defects of the brain, spine, or spinal cord (also called neural tube defects)
Congenital heart defects
Cleft lip and/or cleft palate
Genital abnormalities - most commonly undescended testicles and/or the opening of the urethra forms on the underside of the penis (hypospadias) rather than the tip
Skeletal abnormalities - most commonly overlapping, long fingers; abnormalities of the feet such as club foot; rib cage abnormalities; stiff or tight joints (joint contractures); and nail abnormalities
Developmental delay, attention deficit disorder, learning disabilities, behavior problems, autism spectrum disorder, and/or communication problems

Last updated: 9/22/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 8 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Depressed nasal ridge	Flat nose Recessed nasal ridge [ more ]	0000457
Downturned corners of mouth	Downturned corners of the mouth Downturned mouth [ more ]	0002714
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Long philtrum		0000343
Narrow mouth	Small mouth	0000160
Omphalocele		0001539
Short nose	Decreased length of nose Shortened nose [ more ]	0003196
Thin vermilion border	Decreased volume of lip Thin lips [ more ]	0000233

Showing of 8 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2019

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Fetal valproate syndrome (FVS) may be caused by exposure of a developing baby to valproic acid when a pregnant woman takes it during pregnancy. The risk for the baby to have one or more of the major birth defects associated with FVS is highest if exposure occurs during the first trimester, especially if the mother is taking doses greater than 800 mg/day. This is because the brain and spinal cord, heart, facial features, bones, muscles, and genitals all begin to develop in the first trimester.^[2]^[3]

Last updated: 9/22/2017

Diagnosis Diagnosis

Fetal valproate syndrome (FVS) is often suspected in an infant who has one or more of the signs and symptoms associated with FVS and whose mother reports having taken valproic acid during the pregnancy. There is no test that can confirm the diagnosis of FVS, instead other possible causes of the signs and symptoms seen in the baby must be ruled out.^[1]

Last updated: 9/22/2017

Treatment Treatment

The treatment of fetal valproate syndrome (FVS) is based on the signs and symptoms present in each baby or child. Management often involves a team of medical specialists and may include:^[1]^[2]

Birth defects such as spina bifida and other neural tube defects, congenital heart defects, and cleft lip and/or cleft palate may require surgery shortly after birth
Long-term follow-up to detect and treat early behavioral or developmental issues
Early speech therapy, occupational therapy, and/or physical therapy
Extra assistance at school

Last updated: 9/22/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other types of AED-related embryofetopathies (e.g. fetal hydantoin syndrome) and fetal alcohol syndrome (see these terms). Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Birth Defect Research for Children, Inc.
976 Lake Baldwin Lane, Suite 104
Orlando, FL 32814
Telephone: 407-895-0802
E-mail: staff@birthdefects.org
Website: http://www.birthdefects.org/
MotherToBaby
5034A Thoroughbred Lane
Brentwood, TN 37027
Toll-free: 866-626-6847
Website: http://mothertobaby.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

MotherToBaby is a service of the non-profit Organization of Teratology Information Specialists (OTIS), a leading authority on information regarding the safety of medications and other exposures during pregnancy and breastfeeding. They can be reached directly by calling 1-866-626-6847.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Fetal valproate syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

NIH Hosts Rare Disease Day Event, Twitter Chat
January 24, 2019

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My child may have fetal valproate syndrome. I'd like to learn more about this syndrome including how it is diagnosed, its symptoms, and treatment. See answer

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References References

Fetal valproate syndrome. Orphanet. November 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1906.
Mutlu-Albayrak H, Bulut C, Çaksen H. Fetal Valproate Syndrome. Pediatr Neonatol. June 2016; pii: S1875-9572(16):300072-9. http://www.pediatr-neonatol.com/article/S1875-9572(16)30072-9/fulltext.
Ornoy A.. Valproic acid in pregnancy: how much are we endangering the embryo and fetus. Reprod Toxicol. July 2009; 28(1):1-10. https://www.ncbi.nlm.nih.gov/pubmed/19490988.
FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children. US Food and Drug Administration (FDA). February, 2016; https://www.fda.gov/Drugs/DrugSafety/ucm350684.htm.