Overview

We take medication to treat specific conditions, ultimately promoting our wellbeing. But what if the same medicines that help us,  pose a risk to our unborn baby? This is the case with fetal valproate syndrome (FVS), which occurs when someone pregnant takes valproic acid, or sodium valproate, which is used to treat seizures, epilepsy, or migraine, exposing their unborn baby.

FVS is a rare condition, that causes a child to be born with facial abnormalities, neuronal defects, and organ malfunctions, specifically due to an exposure to valproic acid during the first three months of pregnancy.¹ Most of the babies exposed to valproate will be healthy; however, around 1-2% of the exposed fetus might develop FVS.² It is important to address the cause, exposure, risks, symptoms, and diagnostic tools that can be used to prevent and manage the condition; it is also important to explore various treatment options available for fetal valproate syndrome in a newborn.

Causes and Risk Factors of Fetal Valproate Syndrome

The primary cause of FVS is the use of the drug valproate during the first three months of pregnancy. Pregnant women usually take this medication to manage conditions such as seizures, convulsions, bipolar disorder, and migraines. It is usually advised for pregnant women to discontinue this medication or switch to a safer alternative. However, in some cases, the use of this drug is necessary for the mother. In such cases, the drug treatment continues throughout the first three months of pregnancy, posing a risk to the baby.

The risk factors behind the development of fetal valproate syndrome are:

• Genetic susceptibility - certain individuals will have a unique and complex genetic makeup which results in higher risk for FVS.
• Dosage and duration of exposure - the woman taking valproate in a dose of more than 1000 mg/day is at a higher risk, especially the one who takes a higher blood concentration of the drug during the first 3 months of pregnancy.³

Clinical Features of Fetal Valproate Syndrome

The symptoms of fetal valproate syndrome are manifested as physical abnormalities, neurodevelopmental disorders, and other associated conditions.³

Physical abnormalities

• Characteristic facial features include a fold under the skin of the nose which is small and upturned, groove under eyes, thin upper lips, and minor ear changes.
• Skeletal defects – including incomplete closure of spinal bone, spinal content leakage from the canal.

Neurodevelopmental disorders

• Autism spectrum disorder
• Poor cognitive function
• Attention deficit disorder

Other conditions

•  Toes and fingers with incomplete nail growth
•  Hip dislocation
•  Overlapping of fingers and toes
•  Heart abnormalities
•  Underdeveloped ribs

Diagnosis of Fetal Valproate Syndrome

Prenatal diagnosis refers to the process of diagnosing the condition when the baby is inside the womb is the main diagnostic test carried out for FVS, which consists of:

•   Ultrasound – used to identify organ abnormalities and other defects
•   Genetic testing – used to check genetic susceptibility for FVS

Post-natal diagnosis includes:

•  Evaluation of clinical signs and symptoms, and physical examination of the baby.
•  Imaging studies to diagnose neural tube defects and organ abnormalities.
•  Neurodevelopmental assessments to assess cognitive functions, and other neural defects after a few years of birth.³

Management and Treatment Strategies

The management and treatment of FVS can be administered at different phases, based on the time diagnosis and complexity of the syndrome

•     Prenatal Management
•     Postnatal Management

Prenatal Management

This management strategy involves preventing the syndrome by providing care and counseling to the woman carrying the child and is under valproate therapy. 

• Education and counseling regarding valproate information like its probable negative effects on babies, toxic dose, risk factors, diagnostic requirements, should be provided to the pregnant woman in her preconception stage. Do not stop taking valproate on your own before consulting with the doctor.
• Finding an alternative medication to valproate that may be safer for the fetus, is a good management strategy for  FVS; especially if there is a history of neural tube defect, or neurodevelopmental abnormalities in the family.

Postnatal management

Considering that FVS involves many complex body systems, a multidisciplinary approach is necessary to manage this syndrome.⁴ This includes approaches like:

• Pediatric care. It is recommended that infants exposed to valproate in the womb undergo a thorough checkup for anomalies like abnormal facial features, as well as hearing and visual defects. If any issues are found, the baby should be further evaluated by a specialist.
• Neurology. Neurological consultation is essential to assess any neural tube defects, proper spinal development, and to provide proper measures and surgical intervention if necessary.
• Developmental pediatrics. The baby should be taken to routine health checkups to monitor proper growth, skeletal abnormalities, and neurodevelopmental abnormalities, appropriate counseling is provided for managing the condition.
• Psychiatry. As the baby grows up an adequate psychiatric assessment for cognitive deficit, language deficit, attention disorder, autism spectrum disorder, should be carried out. Appropriate counseling should also be provided to both parents and the child on the disease as well as lifestyle changes.
• Genetic counseling. The possible genetic cause of the disorder should be identified in genetically susceptible individuals; appropriate counseling regarding predictive genetic involvement and contribution to developing fetal valproate syndrome should be discussed.⁵

Medical interventions

Currently, there is no intensive drug treatment available for FVS. However, the most recommended medical treatment for fetal valproate syndrome is a high dose of folic acid (4mg) taken during 6 weeks of preconception, which should be continued until the first trimester of pregnancy.¹

Avoidance or substitution of valproate is strongly recommended. However, consult the healthcare professional before medical intervention.

If no alternative medication is considered suitable, the dose of valproate could be lowered and the medication could be administered as a slow-release drug in divided doses along with a high dose of folic acid.²

Treatment for physical abnormalities commonly involves surgical intervention to correct the defect.

Educational support

Educational support is an important management strategy for children with FVS, as children affected with FAS usually have a decreased cognitive and understanding ability, alongside a lower IQ compared to the normal population.

Special education services, care, and training should be provided for children with FVS by tailored academics. This can be paired with social skills training, behavioral therapy, developmental therapies. Regular assessment of their improvement, and one-to-one sessions are also essential.⁶

Parents also play an important role in their child's education. They collaborate with special trainers, provide a proper environment for the child's growth, and help their child with academics.

Family support

Good parenting and family support is very much essential for children with neurodevelopmental disorders secondary to FVS. This can be a challenging journey, as it impacts both parents and the child's life. The family should provide the right environment for the child's development. They should also coordinate closely with the doctors or trainers to improve the quality of life of the child.

It can become extremely difficult for families with a low socioeconomic status to provide proper medical assistance and educational support for their children. Seeking support from non-governmental organizations, government programs, and fundraising events can significantly alleviate the financial burden for these families.

Preventive Measures

• Valproate use – consulting the doctor and receiving a proper guideline regarding the use of valproate, or an alternative option is an important preventive strategy for fetal valproate syndrome.
• Preconception counseling – a session before conception to understand the effects of valproate use on the baby, genetic impact, etc., and completely understanding the disease can help prevent the syndrome.
• Public health initiatives - public awareness regarding the syndrome, providing financial aid for families can help in preventing and managing the syndrome.

Summary

Fetal Valproate Syndrome (FVS) is a rare condition caused by the use of valproic acid during pregnancy. It can lead to facial abnormalities, neurodevelopmental disorders, and organ malfunctions in the newborn. The syndrome primarily results from valproate exposure in the first trimester, with risk factors including genetic susceptibility and high dosage. Diagnosis is achieved through prenatal ultrasound, genetic testing, and postnatal clinical evaluations. Management strategies include prenatal counseling, alternative medications, and multidisciplinary postnatal care involving pediatricians, neurologists, and psychiatrists. Educational interventions, including special education services and behavioral therapy, are crucial to support children with FVS. Family involvement and financial support are also vital. Preventive measures involve careful management of valproate use, preconception counseling, and public health initiatives to raise awareness and support affected families.