Pregnant women taking epilepsy drugs more likely to deliver babies with birth defects

Drugs prescribed to control epilepsy in pregnant women with migraine, pain and bipolar disorder are likely to deliver babies with birth defects, according to a new study.

The study lays focus on the drugs-- valproic acid and topiramate. The birth defects include spina bifida and cleft lip.
 

For the study, researchers used data to identify pregnancies that resulted in live births between January 2011 and March 2015.

From the 1,886,825 pregnancies reported during those years, the researchers looked for the mothers' use of 10 anti-epileptic-seizure drugs before and after conception.

Researchers further looked for 23 birth defects in the children delivered by these women. The findings indicated that 8,794 women were prescribed a single anti-epileptic drug.

Women who were prescribed with valproic acid (10.4 pc of the group of pregnant women prescribed anti-epileptic medication) had 19 times greater risk of having a baby with spina bifida as compared with women who did not take an epilepsy drug.

Among the 913 women prescribed valproic acid, six babies (0.66 pc) had spina bifida, as compared with 616 babies (0.03 pc) born to women not taking an epilepsy drug.

The drug also increased the risk of seven other birth defects, including cleft palate and four types of heart defects.

On the other hand, women prescribed topiramate (5.9 pc) had a seven times greater risk of having a baby with cleft lip (with or without cleft palate), the study has indicated.

Among the 517 women prescribed topiramate, three babies (0.60 pc) had cleft lip, compared with 1,637 babies (0.09 pc) born to women not taking an epilepsy drug.

"The new study confirms other large-scale studies where similar findings were found. It reinforces the risks associated with these particular two medications,"said a Dr.

"I also know that there are some women with difficult-to-control-epilepsy that valproic acid may be the only medication that might be effective for them. All these different medicines have different ways of working in the brain, and they're not necessarily completely interchangeable," said the Dr.

"Most notable, valproic acid use during pregnancy has been associated with a higher risk for lower IQ, autism and autism spectrum disorder, and the need for special education in the children who were exposed during pregnancy. Topiramate has also been associated with increased risk for low birth weight," said the Dr.

"A planned pregnancy allows the health care provider and the woman to decide on the best plan for her individually ... to lower fetal risk while keeping her seizures under optimal control," concluded the Dr.

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The Epilepsy-Autism Link

Until recently, there was only limited clinical research about the connection between autism spectrum disorder (ASD) and epilepsy. But according to the doctors, it is estimated that about 20 to 30 percent of children with ASD will develop epilepsy once they reach adulthood.

Additionally, research finds that adults with epilepsy are more likely to show signs of autism and Asperger's syndrome. In fact, a 2016 study suggests that the two conditions may even have a co-dependent, "bidirectional relationship." Other recent studies even detail how epileptic seizures short-circuit the neurological function in the brain that affects socialization and involves the same traits seen in autism— impairment of normal social interaction (eye contact, conversation, enjoying the act of sharing with someone else) and tightly regimented or repetitive cycles of behavior. This means that in many cases, epileptic adults may not have been properly diagnosed or treated for autism symptoms.

Shedding Light on Socialization Challenges for Epileptics

Epilepsy is a brain disorder marked by recurring seizures or convulsions. Autism is a neuro-behavioral disease that includes impairment in social interaction and language development which often includes rigid, systematic repetitive behaviors. Both conditions can affect patients with varying degrees of severity.

Up to now, the social and behavioral challengers for some people with epilepsy have been under-diagnosed, and research has not uncovered any underlying theory to explain them. Without diagnosis, there is no treatment plan. And not surprisingly, the more frequent the epileptic seizures, the more severely impacted the patient’s socialization may be.

But the research evidence suggesting that the misfiring of the brain during a seizure may explain the socialization issues, brings a vast set of opportunities for adults with both conditions. It could mean that adults with epilepsy can now benefit from the wide range of autism treatment services available to address the socialization issues many epileptic patients have experienced throughout their lives. This offers the possibility of significantly improving epileptics' overall quality of life. Up to this point, there have been few services to address these needs.

Recognizing Symptoms of Epilepsy in Infants

The highest incidence of epilepsy occurs during the first year of life, when many new parents can overlook or misinterpret physical symptoms. Each year, 150,000 people in the United States will have a newly occurring single seizure, that's 48 for every 100,000 people according to the doctors. During early childhood development, infants often exhibit a variety of erratic physical movements and mannerisms which may not cause immediate concern. But babies or children presenting any of these symptoms should be seen by a doctor immediately:

• A prolonged staring spell
• Uncontrollable jerking movements of the arms and legs
• Lack of response or awareness to verbal stimulation
• Shaking, loss of balance or smacking of the lips

Specialty Care for Children With Epilepsy

If you suspect your child may have experienced a seizure, contact your pediatrician immediately for an evaluation. While seizures are frightening for parents and caregivers, it is important to observe and record the duration of the episode as well as the symptoms the child exhibited before and after the episode. Be sure to share this valuable information with your doctor. Keep in mind, some hospitals offer specialized epilepsy treatment programs exclusively for pediatric patients.

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Researchers uncover molecular mechanisms linked to autism and schizophrenia

Since the completion of the groundbreaking Human Genome Project in 2003, researchers have discovered changes to hundreds of places in the DNA, called genetic variants, associated with psychiatric diseases such as autism spectrum disorder and schizophrenia. Now, new findings from a major study has linked many of these changes in DNA to their molecular effect in the brain, revealing new mechanisms of diseases. 

In the new papers, researchers and collaborators from more than a dozen institutions from around the world provide the largest-ever datasets on the molecular workings of the brain. The findings provide a roadmap for development of a new generation of therapies for psychiatric conditions.

"This work provides several missing links necessary for understanding the mechanisms of psychiatric diseases," said  a senior author.

During the last decade, scientists have conducted genetic studies of people with psychiatric diseases, comparing the results to healthy individuals to find genes that have different sequences in those with disease. Often, however, their findings led to more questions than answers. Scientists not only discovered genes linked to the diseases, they also uncovered hundreds of areas of DNA found in between genes, called regulatory DNA, that also seemed to have an association.

Scientists know these sections of DNA can control when, where and how genes are turned on and off in many ways. However, figuring out which "regulatory regions" affect which genes— and therefore the RNA and proteins encoded by the genes— is not straightforward.

In 2015, researchers at 15 institutions around the country, came together in the Consortium to study in more detail the brain's regulatory DNA. An earlier project, known as ENCODE, already had uncovered the roles sections of regulatory DNA, but it was clear that these might be different in the brain than other organs. The PsychENCODE has analyzed not just genetic variants linked to psychiatric diseases, but also patterns of RNA and proteins in 2,188 brain bank samples from both healthy individuals and those with a psychiatric disorder.

In one new paper, the researchers describe this new data, which helps explain the roles of tens of thousands of sections of regulatory DNA in affecting RNA and proteins in the brain. The data also reveals which genes are most often expressed at the same time as each other, suggesting new biological processes and pathways. The dataset—essentially a detailed model of the inner molecular workings of the human brain— is now publicly available as a starting point for other researchers to mine mechanisms of disease and potential drug targets.

"This resource is so vast that you can start by choosing one interesting disease associated genetic variant and begin digging into that and discovering how it impacts molecular networks in the brain," he said. "Having robust data of this scope provides a foundation for countless new studies."

In a second paper, assistant professor of psychiatry and biobehavioral Sciences  and other collaborators, used that new data to look specifically at how RNA molecules are dysregulated—either present at higher levels, lower levels, or in altered conformations— in autism spectrum disorder, schizophrenia and bipolar disorder.

Using nearly 1,700 brain bank samples, the researchers revealed thousands of RNA molecules that are either spliced differently— with different sections of genetic material—or present at higher or lower levels in the brains of people with one of the psychiatric diseases.

"You can't look at the brain under a microscope and see substantial differences in these  disorders" the Prof. said. "But we've now shown that if you look finely at patterns of how genes are expressed, you see pathways that are clearly dysregulated."

Among the surprises in the data— altered levels of RNA linked to neuroinflammation and the brain's immune cells showed very different trajectories in people with schizophrenia, autism spectrum disorder and bipolar disorder.

Additionally, the study showed the importance of looking at individual cell types within the brain when parsing the new RNA data— in some cases, alternately spliced RNA was linked to disease but only when the RNA was found in certain cell types and not others.

Finally, new genes were implicated in the diseases based on the RNA results; five were linked to autism spectrum disorder, 11 to bipolar disorder, and 56 to schizophrenia.

Once again, the data is mostly important as a jumping off point for future studies, the researchers said.

"This is the tip of the iceberg," a Prof. said. "The ability to compile together 2,000 brains has been revolutionary in terms of revealing new genetic mechanisms, but it also points to how much we don't know." 

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Blood, urine tests can detect autism in kids

Scientists have developed new blood and urine tests that can diagnose autism in children, allowing patients to get appropriate treatment much earlier in their lives. Autism spectrum disorders (ASD) are defined as developmental disorders mainly affecting social interaction and they can include a wide spectrum of behavioural problems. These include speech disturbances, repetitive and/or compulsive behaviour, hyperactivity, anxiety, and difficulty to adapt to new environments, some with or without cognitive impairment. Since there is a wide range of ASD symptoms diagnosis can be difficult and uncertain, particularly at the early stages of development. "Our discovery could lead to earlier diagnosis and intervention," said a researcher. "We hope the tests will also reveal new causative factors. With further testing we may reveal specific plasma and urinary profiles or "fingerprints" of compounds with damaging modifications," said the researcher. "This may help us improve the diagnosis of ASD and point the way to new causes of ASD," she said. The study found a link between ASD and damage to proteins in blood plasma by oxidation and glycation - processes where reactive oxygen species (ROS) and sugar molecules spontaneously modify proteins. They found the most reliable of the tests they developed was examining protein in blood plasma where, when tested, children with ASD were found to have higher levels of the oxidation marker dityrosine (DT) and certain sugar-modified compounds called "advanced glycation endproducts" (AGEs). Genetic causes have been found in 30-35 per cent of cases of ASD and the remaining 65-70 per cent of cases are thought to be caused by a combination of environmental factors, multiple mutations, and rare genetic variants. However the research team also believe that the new tests could reveal yet to be identified causes of ASD. The research also confirmed the previously held belief that mutations of amino acid transporters are a genetic variant associated with ASD. Researchers, recruited 38 children who were diagnosed with ASD (29 boys and nine girls) and a control group of 31 healthy children (23 boys and eight girls) between the ages of five and 12. Blood and urine samples were taken from the children for analysis. The team discovered that there were chemical differences between the two groups. The changes in multiple compounds were combined together using artificial intelligence algorithms techniques to develop a mathematical equation or "algorithm" to distinguish between ASD and healthy controls. The outcome was a diagnostic test better than any method currently available.

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Video games may improve posture in autistic kids

Children who suffer from autism often have difficulty in maintaining a normal posture and position. But video games might help these children and enable them to improve their balance.

Autism is a lifelong neuro-developmental disorder characterized by impaired social interaction, impaired verbal and non-verbal communication and restricted and repetitive behaviour.

The study, stated that video games, which are devised with action-based games involving quick movements and graphics with ninja poses help autistic kids to improve their postural stability and impaired daily activities.

“We think this video game-based training could be a unique way to help individuals with autism who have challenges with their balance address these issues,” said an Assistant Professor.

The researchers reviewed participants affected with autism spectrum disorder, aged between 7 and 17 years to study the effects of balance training.

The researchers used a gaming system with a  camera and a  balance board connected to software.

The results showed that the study participants made significant improvements in not only their in-game poses but also their balance and posture outside of the game environment.

The participants could see themselves on the screen doing different ninja poses and postures while playing the video games.

Previous studies have shown that playing video games also helped in rehabilitating stroke patients.

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Having brain scans for breakthrough in early detection of autism

With a shift in diagnostic criteria raising the number of children placed on the autism spectrum—and with families and professionals adjusting their approach to conceptualizing the disorder—researchers believe there may be promise in conducting brain scans to enable earlier detection of the condition. 

The multi-site Infant Brain Imaging Study, seeks to determine the predictive ability of functional connectivity magnetic resonance imaging (fcMRI) as a means of identifying brain activity patterns in six-month-old children who may be at risk to develop autism by two years of age. 
 
“2017 has been a breakthrough year for decades of research aimed at detecting the earliest changes in the brain that are associated with autism,” said a researcher who leads the site at the  Autism Research. “This current study reveals the foundational patterns of brain function at age 6 months, which set in motion developmental processes that yield behavioral symptoms of autism by age 24 months. This is an astounding observation that could fundamentally change clinical practice.”

Current estimates say autism affects roughly 1 out 68 children in a country, a rate that has climbed partly because fewer children are diagnosed with an intellectual disability. The neurodevelopmental disorder is about five times more likely to affect boys than girls, while younger siblings of those with autism have an approximately 7 percent higher chance of a diagnosis, according to an influential 2013 study. 

“Previous findings suggest that brain-related changes occur in autism before behavioral symptoms emerge,” said the director of the study. “If future studies confirm these results, detecting brain differences may enable physicians to diagnose and treat autism earlier than they do today.”

Researchers focused on the brain's functional connectivity, examining how different regions work together during activity and rest. 

With fcMRI, the research team scanned the brains of 59 high-risk six-month-olds—younger siblings of kids with autism—while they slept under natural conditions. Machine learning technology designed to parse through neuroimaging results was then used to make predictions about the children who would or would not develop autism. 


By the age of two, 11 out of the 59 children in the study had been diagnosed with autism. The research team successfully predicted that nine of those children would develop autism and correctly identified all of the infants who would not. A second, computer-based analysis to test these results against other cases predicted diagnoses for groups of 10 infants at an accuracy rate of 93 percent.

In total, researchers found 974 functional connections in the brains of 6-month-olds that were associated with autism-related behaviors, suggesting brain scans could be an accurate way to predict autism in high-risk infants. 

The full study, published in a medical journal.

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Autism and Heavy Metals Linked through Baby Teeth

Exposure to heavy metals, such as lead, mercury, and zinc, and the development of autism spectral disorder (ASD) has been a contentious relationship, to say the least. While the general scientific consensus is that the development of ASD is largely under the influence genetic mechanisms, there is substantial evidence to support that environmental exposure to various compounds has some association with the developmental disorder. Now, an international group of investigators led by scientists at an Institute has found that baby teeth from children with autism contain more toxic lead and less of the essential nutrients zinc and manganese, compared to teeth from children without autism.     

Findings from the new study—published recently  -suggest that differences in early-life exposure to metals, or more importantly how a child's body processes them, may affect the risk of autism.

"We think autism begins very early, most likely in the womb, and research suggests that our environment can increase a child's risk,” explained the scientist. “But by the time children are diagnosed at age 3 or 4, it's hard to go back and know what the moms were exposed to. With baby teeth, we can actually do that."

The research team observed higher levels of lead in children with autism throughout development, with the greatest disparity observed during the period following birth. Moreover, the team noticed lower uptake of manganese in children with autism, both before and after birth. Interestingly, the pattern was more complex for zinc, as children with autism had lower zinc levels earlier in the womb, but these levels then increased after birth, compared to children without autism. The researchers noted that replication in larger studies is needed to confirm the connection between metal uptake and autism.

Patterns of metal uptake were compared using teeth from 32 pairs of twins and 12 individual twins. The researchers compared patterns in twins where only one had autism, as well as in twins where both or neither had autism. Smaller differences in the patterns of metal uptake occurred when both twins had autism. Larger differences occurred in twins where only one sibling had autism.

We studied "monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk," the authors wrote. “Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits.”

The researchers employed a method they developed previously that used naturally shed baby teeth to measure children's exposure to lead and other metals while in the womb and during early childhood. The scientists used lasers to extract precise layers of dentine, the hard substance beneath tooth enamel, for metal analysis. The team previously showed that the amount of lead in different layers of dentine corresponds to lead exposure during different developmental periods.

"What is needed is a window into our fetal life," noted lead study investigator , who is also an environmental scientist and dentist. "Unlike genes, our environment is constantly changing, and our body's response to environmental stressors not only depends on just how much we were exposed to but at what age we experienced that exposure."

Prior studies relating toxic metals and essential nutrients to autism have faced key limitations, such as estimating exposure based on blood levels after autism diagnosis rather than before, or not being able to control for differences that could be due to genetic factors. This new method of using baby teeth to measure past exposure to metals also holds promise for other disorders, such as attention-deficit hyperactivity disorder.

"There is growing excitement about the potential of baby teeth as a rich record of a child's early life exposure to both helpful and harmful factors in the environment," concluded a researcher.

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