Study: A mother's presence soothes infants' brains

A study shows that a mother's presence and care can make an infant's pain go away and changes the infant's brain activity.

A mother's "TLC" not only can help soothe pain in infants, but it may also impact early brain development by altering gene activity in a part of the brain involved in emotions, according to new study from NYU Langone Medical Center.

By carefully analyzing what genes were active in infant rat brains when the mother was present or not present, the NYU researchers found that several hundred genes were more, or less, active in rat infants experiencing pain than in those that were not. With their mothers present, however, fewer than 100 genes were similarly expressed.

According to senior study investigator and neurobiologist Regina Sullivan, PhD, who is scheduled to present her team's findings at the Society for Neuroscience annual meeting in Washington, D.C., on Nov. 18, the research is believed to be the first to show the short-term effects of maternal caregiving in a distressed infant pup's brain. The study was also designed to support her research into the long-term consequences of differences in how mammals, including humans, are nurtured from birth.

"Our study shows that a mother comforting her infant in pain does not just elicit a behavioral response, but also the comforting itself modifies -- for better or worse -- critical neural circuitry during early brain development," says Sullivan, a professor at the NYU School of Medicine and its affiliated Nathan S. Kline Institute for Psychiatric Research.

For the study, researchers performed genetic analyses on tissue from the almond-sized amygdala region of the infant rat pups' brains that is responsible for processing emotions, such as fear and pleasure.

Sullivan, whose earlier research showed how the mother's presence controlled electrical signaling in the infant pup's brain, says her latest findings shed insight on the complexity of treating pain in newborns.

"Nobody wants to see an infant suffer, in rats or any other species," says Sullivan. "But if opiate drugs are too dangerous to use in human infants because of their addictive properties, then the challenge remains for researchers to find alternative environmental stimuli, including maternal presence, coddling, or other cues, such as a mother's scent, that could relieve the pain."

Sullivan cautions, however, that the long-term consequences of these genetic modifications must also be compared to the short-term benefits for tying pain stimuli during infancy to such a powerful symbol of safety and security as the infant's mother.

"The more we learn about nurturing the infant brain during infancy, the better prepared we are to deal long-term with treating problems that arise from pain, and physical and mental abuse experienced during infancy," says Sullivan.

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New mothers sleepy for many months

A study from Australia shows that new mothers are still very sleepy four months after giving birth and should be cautious about returning to work too quickly.

New mothers are being urged to be cautious about returning to work too quickly, after a study found one in two were still excessively sleepy four months after giving birth.

Dr Ashleigh Filtness, from QUT's Centre for Accident Research & Road Safety -- Queensland (CARRS-Q), studied the sleep patterns and tiredness of postpartum mums and found despite new mums recording stable night sleep times at 18 weeks, they continued to report being excessively tired.

The CARRS-Q study, published in PLoS One, followed 33 healthy new mums who recorded their postpartum sleep patterns in 15 minute increments during weeks 6, 12 and 18.

"Sleep disruption strongly influences daytime function, with sleepiness recognized as a risk-factor for people performing critical and dangerous tasks," she said.

Dr Filtness said the study had significant implications for decisions-makers about when women should return to work, with current government paid parental leave entitlements ceasing at 18 weeks.

"This brings into question whether four months parental leave is sufficient to ensure daytime sleepiness has diminished to a manageable level before returning to work," she said.

"It is important when developing regulations for parental leave entitlements that policy makers take into account the high prevalence of excessive daytime sleepiness experienced by new mothers.

"With the birth of every baby the new mother must adjust to the demands of parenting and one aspect of that is to remain functional while experiencing potentially severe sleep disruption.

"To put this into context, the assessment tool used to determine new mums' sleepiness is also used by GPs to determine clinically relevant levels of sleepiness.

"If any other otherwise healthy person presented to a doctor with this degree of sleepiness they would likely have been offered advice regarding implications for daytime impairment including the impact on sustaining attention and decision making."

Dr Filtness said the study also found while new mums were still waking on average twice a night to attend to their babies at 6, 12 and 18 weeks -- their total sleep time was about 7 hours and 20 minutes.

She said Australian new mothers actually slept more than the average American worker (6h 53mins).

"So while postpartum women experienced disturbed sleep, they didn't necessarily experience total reduced sleep time," she said.

"What we found was that inevitably, new mothers will wake in the night to attend to their infant and the number of times they wake remains consistent during the first 18 postpartum weeks.

"Sleep disruption reduced over time and it appears this was driven by a reduction in the time it took for new mums to return to sleep, suggesting improved efficiency by mothers at settling their infant or the development of the infant's circadian rhythm.

"These findings highlight the importance of sleep quality as opposed to sleep quantity, especially during the first 12 weeks."

"Soon-to-be mums should be aware of the importance of their own sleep and consider how they are going to preserve their own sleep during the first few months of caring for a baby," she said.

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Study: Association between autism risk and a mother's birth place

A study claims that there is an association between a child's autism risk and where his or her mother was born.

A mother's birthplace may affect her children's risk of developing an autism spectrum disorder, according to new research.

Children of foreign-born black, Central and South American, Filipino and Vietnamese mothers were more likely to have an autism spectrum disorder (ASD) compared to children born to white mothers who were born in the United States, the study found.

"The rates [of ASDs] in the African immigrants was the highest," said lead researcher Dr. Beate Ritz, chair of epidemiology at the Fielding School of Public Health at the University of California, Los Angeles.

The study also found that U.S.-born African American and Hispanic mothers, as well as foreign-born black and Central/South American mothers, were more likely to have children with a type of autism that included severe emotional outbursts and expressive language impairment, compared to U.S.-born white mothers.

The study is published in the July print issue of Pediatrics.

Although this study found an association between a mother's birthplace or race and the development of an autism spectrum disorder, the study doesn't show that these factors cause autism.

Autism spectrum disorders describe a range of developmental disabilities that can cause social, communication and behavioral difficulties. About 1 in 68 U.S. children have an autism spectrum disorder, the U.S. Centers for Disease Control and Prevention (CDC) estimates.

The exact cause of autism is unknown, but a number of risk factors have been found, including genetic risk factors, being born to older parents and having a sibling with the disorder, according to the CDC.

Previous studies have found autism spectrum disorders are most common among white children, Ritz noted.

In her study, Ritz wanted to look at the influence of the mother's race, ethnicity and birthplace. She and her colleagues reviewed the records of 7,540 children with autism who were born in Los Angeles County during the years 1998 to 2009 and given an autism diagnosis at ages 3 to 5 years. The researchers adjusted for other factors such as maternal age and education.

Compared to white children of U.S.-born mothers, the risk of autism was 76 percent higher for children of foreign-born black mothers, she said.

Mothers born in Vietnam, the Philippines, Central and South America also were at higher risk of having a baby with autism.

The researchers also found a small subgroup of 806 children who had both an autism spectrum disorder and mental retardation. For this group, having a foreign-born mother further increased the risk of the disorder. In fact, the risk was doubled for children born to foreign-born black mothers or those from the Philippines or Vietnam compared to U.S.-born white mothers, the study reported.

Additionally, for a specific type of the disorder that included severe emotional outbursts and impaired expressive language, U.S.-born Hispanic and black mothers, and foreign-born black and Central/South American mothers were more likely to have a child with this type of autism than U.S.-born white mothers.

The study wasn't designed to tease out the reasons behind this association, but Ritz has some theories. She believes that it's possible that "a child is more likely to develop an ASD if the mother emigrated from a country which had political unrest or wars in the recent past."

Even if those events were 20 or 30 years ago, it could still have an effect, she said. The mother giving birth may have witnessed atrocities of war or other trauma as a child, perhaps programming her to react to stress in a certain way. These mothers may react to stress in a certain way when pregnant, and that could affect the baby's ''brain wiring," she speculated.

As for whether these mothers can obtain ideal care and a prompt diagnosis for an autism spectrum disorder, Ritz cannot say, as it was outside the scope of the study. However, the average age at diagnosis for all the youngsters in this study was in the child's third year, according to the study.

"It's an interesting study to have done. It's a first step to begin to try in a more detailed fashion to identify other causes of autism," said Dr. Trevor Resnick, chief of neurology at Miami Children's Hospital. Resnick was not involved in the research, but reviewed the study's findings.

Pinning down the cause of autism spectrum disorders is complex, he said. Experts know genetic, metabolic and structural factors affect risk. "We know there is not one cause, there are multiple causes," he said.

There may even be multiple causes within one child, Resnick noted.

What the new study seems to identify is the risk of autism in different ethnic groups, he said. But the common factor is the immigrant status, not the ethnicity itself, he noted.

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Breastfeeding while taking epilepsy medication does not harm infant

Brain development of breastfed infants is not harmed by the mother taking epilepsy medications.

Taking epilepsy drugs while breast-feeding does not appear to harm the developing brains of young children, a new study finds.

There have been concerns that using epilepsy drugs while breast-feeding could pose a threat to youngsters because it's been shown that some epilepsy drugs can cause cell death in young animals' brains.

And in spite of the fact that epilepsy experts recommend breast-feeding, "it is still a sensitive topic among women with epilepsy," noted one expert, Dr. Patricia Dugan, assistant professor of neurology at the Comprehensive Epilepsy Center at NYU Langone Medical Center, New York City.

"Despite reassuring published data, such as this article, patients frequently tell us that they receive contradictory advice from their obstetricians and pediatricians, resulting in a significant amount of distress for the mother," said Dugan, who was not connected to the new research. "Hopefully, papers such as these will encourage everyone involved in the care of women with epilepsy to promote breast-feeding," she said.

The new study included 181 children of mothers who had epilepsy and took drugs to control the condition. Nearly 43 percent of the children were breast-fed for an average of seven months.

IQ tests conducted on the children when they were 6 years old found no differences between those who were breast-fed and those who were not, according to the study published online June 16 in JAMA Pediatrics.

"Our study does not provide a final answer, but we recommend breast-feeding to mothers with epilepsy, informing them of the strength of evidence for risks and benefits," wrote a team led by Dr. Kimford Meador, of Stanford University in California

Another expert said the study offers valuable information.

"The authors controlled for many of the factors that might influence the intellectual outcome of this large number of children," noted Dr. Ian Holzman, chief of the division of newborn medicine at the Kravis Children's Hospital at Mount Sinai in New York City.

"By following these children through age 6, they were able to present information relevant to the important issue of school performance," he said. "This study allows us to counsel mothers who are planning to breast-feed that there doesn't seem to be any harm [in taking epilepsy medications]."

Dugan said the study also hinted at other benefits for breast-fed children.

"It also showed that testing of breast-fed children at 6 years old -- an age when more meticulous testing can be performed -- reflected beneficial effects of breast-feeding, with higher IQ and better verbal abilities than nonbreast-fed children," she said.

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Study claims no link between autism and induced labor

A study revealed that there is no link between autism and induced labor.

There is no connection between inducing labor in childbirth and autism, according to a new statement released Monday by the American College of Obstetricians and Gynecologists.

Existing guidelines on when and how labor should be induced or accelerated should not be changed, because limiting labor inductions could have negative effects on the health of women and their babies, ACOG's committee on obstetric practice recommended in a "committee opinion."

Although some studies have suggested there may be a link between autism and the use of oxytocin to induce or speed up labor, this research has significant limitations, according to an ACOG news release. The studies were small, inconsistent and retrospective, the opinion said, and limited comparison groups meant certain factors might not have been accounted for.

The committee concluded there is no evidence to prove that labor induction causes autism.

The group also cautioned that any reduction in labor induction would "almost certainly" have a negative effect on patient care, and likely result in more cesarean deliveries.

"In obstetric practice, labor induction and augmentation play an essential role in protecting the health of some mothers and in promoting safe delivery of many babies," Dr. Jeffrey Ecker, committee chair, said in the news release.

"When compared with these benefits, the research we reviewed in assembling this committee opinion, relative to the utilization of oxytocin, had clear limitations," Ecker said. "Because of this, these studies should not impact how obstetricians already safely and effectively use labor induction and augmentation when caring for their patients."

The committee's opinion was endorsed by the Society for Maternal-Fetal Medicine. The findings were published in the May issue of Obstetrics & Gynecology.

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Autism risk increases for children born to older mothers

A study looked into maternal age and autism and found that children born to older mothers have a higher risk for autism development.

Why autism strikes certain kids -- and not others -- has puzzled scientists for half a century. But one trend is clear: having older parents seems to increase the risk. Now, a study from Drexel University adds two more wrinkles to the story.

Brian Lee, a professor of epidemiology at Drexel University's School of Public Health, analyzed a Swedish database of more than 400,000 births to see how the ages of both parents related to a child's chances of autism.

"The mothers' risk seems to be, quantitatively speaking, more important than the father's," he said. "Having a mother who is 40 is going to have a bigger effect on the child's autism risk than having a father who is 40 years old."

The oldest mothers studied, ages 40 to 45, were 75 percent more likely than younger women to have kids with an autism spectrum disorder. Fathers of similar age had just a 14 percent added risk. How risk increased with age differed between parents, accelerating for moms but climbing in step for dads.

Lee also examined the interaction of both parents' age, finding older fathers increased risk only with younger mothers.

"The effect of the father seems to essentially be washed out when you have older mothers," he said.

Lee said the results aren't meant to discourage older couples from having children. Less than 1.9 percent of the oldest women in the study gave birth to children who would go on to develop autism.

"The reason we're interested in parental age in the first place is because it's a marker for some underlying mechanism that really we're interested in," he said.

According to Lee, knowing age seems to affect moms and dads differently opens up new avenues of investigation.

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Autism not related to mother's antidepressant use

A large study has shown that a mother's antidepressant use while pregnant is not linked to her child having autism.

Despite some concerns to the contrary, children whose moms used antidepressants during pregnancy do not appear to be at increased risk of autism, a large new Danish study suggests.

The results, published Dec. 19 in the New England Journal of Medicine, offer some reassurance, experts said.

There have been some hints that antidepressants called selective serotonin reuptake inhibitors (SSRIs) could be linked to autism. SSRIs are the "first-line" drug against depression, and include medications such as fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa) and paroxetine (Paxil).

In one recent U.S. study, mothers' SSRI use during pregnancy was tied to a twofold increase in the odds that her child would have autism. A Swedish study saw a similar pattern, though the risk linked to the drugs was smaller.

But both studies included only small numbers of children who had autism and were exposed to antidepressants in the womb.

The new study is "the largest to date" to look at the issue, using records for more than 600,000 children born in Denmark, said lead researcher Anders Hviid, of the Statens Serum Institute in Copenhagen.

And overall, his team found, there was no clear link between SSRI use during pregnancy and children's autism risk.

Hviid cautioned that the finding is still based on a small number of children who had autism and prenatal exposure to an SSRI -- 52, to be exact. The researchers noted that it's not possible to rule out a small increase in autism risk.

But, Hviid said, "at this point, I do not think this potential association should feature prominently when evaluating the risks and benefits of SSRI use in pregnancy."

Commenting on the findings, Christina Chambers, director of the Center for the Promotion of Maternal Health and Infant Development at the University of California, San Diego, stated, "I think this study is reassuring."

One "important" point, Chambers added, is that the researchers factored in mothers' mental health diagnoses -- which ranged from depression to eating disorders to schizophrenia.

"How much of the risk is related to the medication, and how much is related to the underlying condition?" Chambers said. "It's hard to tease out."

In theory, she noted, depression or other mental health disorders could contribute to autism risk because those moms may be more likely to make unhealthy lifestyle choices, such as smoking or drinking.

In this study, Hviid's team did initially see a slightly increased risk of autism among children whose mothers used SSRIs during pregnancy. But once the researchers factored in the psychiatric disorders themselves, that statistical link fell away.

On top of that, there was a slight increase in autism risk among children whose mothers had used an SSRI in the two years before pregnancy, but not during pregnancy.

Hviid said that all suggests it's the underlying conditions, rather than the drugs, that are associated with a small autism risk -- though the reasons, he added, are unknown.

The study, which was funded by the Danish government, is based on records from Denmark's national system of health databases. Of nearly 627,000 children born between 1996 and 2005, just under 3,900 were later diagnosed with autism.

Among those children, 52 were born to mothers who filled an SSRI prescription during pregnancy. There were just over 6,000 other children whose mothers used the antidepressants during pregnancy but did not develop autism.

Both Hviid and Chambers said the findings do not prove that SSRIs carry no autism risk. And a connection is biologically plausible, Hviid said.

No one knows what causes autism, which affects an estimated one in 88 children. But it involves a disruption in fetal brain development. It's thought that serotonin -- the chemical that SSRIs target -- contributes to early brain development, and in animals, altered serotonin levels can affect brain function and behavior.

"It's still worthwhile to continue to study this," Chambers said.

But, she added, based on the human studies so far, "if there is any increased risk of autism, it appears small."

And for any one woman, Chambers said, that possible risk would have to be balanced against the risks of leaving major depression untreated.

"For some women, the optimal situation may be to take an SSRI, even if there is an association [with autism]," Chambers said.

Hviid agreed, saying that's a decision that has to be left up to women and their health care provider.

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Children are more likely to develop PTSD if mother has PTSD

An Israeli study finds that a child is more likely to develop PTSD if his or her mother has PTSD.

A Ben-Gurion University of the Negev (BGU) study indicates that children are more likely to develop Post Traumatic Stress Disorder (PTSD) if their mother is already afflicted.

In the study published in the Journal of Depression & Anxiety, while fewer than 10 percent (8.4 percent) of the mothers were suffering from PTSD, more than a fifth (21 percent) of their children presented PTSD symptoms. Children who developed PTSD symptoms also had more psychosomatic complaints such as constipation, diarrhea and headaches.

"This study reinforces the existing body of knowledge regarding the importance of evaluating and treating parental responses in time of stress," the researchers explain.

"Parents are often the key to understanding children's responses generally and specifically in times of stress. The study also highlights the close interrelations between 'body and soul' among children and adults."

In the study, some 160 mothers of preschool children were interviewed about symptoms exhibited by their children and their own responses during Operation Cast Lead. More than 750 rockets were fired into Southern Israel from Gaza from December 2008 to January 2009.

Working with the Preschool Psychiatric Unit at Soroka University Medical Center, the BGU researchers examined the relationship between PTSD symptoms and socio-demographic, family attributes and psychosomatic symptoms among children exposed to Grad missile attacks in Beer-Sheva, Israel.

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Mothers with lupus more likely to have child with autism

A study claims that children of mothers who have lupus are more likely to have autism spectrum disorders.

According to research presented this week at the American College of Rheumatology Annual Meeting in San Diego, children born to mothers with lupus may be at twice the risk of autism spectrum disorders than those born to mothers without the disease.

Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties -- prime child-bearing age.

Recent experimental studies suggest exposure to a mother's antibodies and cytokines while in the womb are important risk factors for autism spectrum disorders (commonly called ASD). Interestingly, women with lupus display autoantibodies and cytokines, which -- when studied in animals -- have been shown to alter fetal brain development and induce behavioural irregularities in offspring.

Despite these studies, no studies have specifically assessed the risk of ASD in children of women with lupus, and researchers recently aimed to determine if children born to these mothers might have an increased risk of ASD when compared to children born to mothers without lupus.

"A handful of small studies suggest an increased risk of learning disabilities in children born to women with lupus. However, no study has specifically assessed the risk of ASD in offspring of mothers with lupus, explains Evelyne Vinet, MD, FRCPC; assistant professor, Department of Rheumatology; McGill University Health Centre, Montreal; and lead investigator in the study. "We undertook this study because women with lupus often ask: 'Will my disease affect the future health of my children?' By providing evidence to answer this relevant question, our study will help clinicians to appropriately counsel women with lupus who are planning a pregnancy."

The Offspring of Systemic Lupus Erythematosus mothers Registry ( OSLER) is a large, Canadian, population-based cohort which includes all women who have had one or more hospitalizations for childbirth after lupus diagnosis as identified through health care databases between the years of 1989 and 2009. Using OSLER, Dr. Vinet's team compared 719 children born to 509 mothers with lupus to 8,493 children born to 5,824 randomly-selected women without the disease.

The average age of mothers in the study was just over 30 years, and the average time of follow up for the children in the study was just over nine years. Dr. Vinet's team matched each mother with lupus to at least four women without the disease, based on their age and the year they delivered their children. The researchers also took into consideration each mother's demographics, sex and birth order of the children delivered, and obstetrical complications.

Dr. Vinet's team discovered that children born to mothers with lupus had more ASD diagnoses compared to the children born to mothers without the disease (1.4 percent vs. 0.6 percent, respectively). Additionally, the researchers found that children born to mothers with lupus might be diagnosed with ASD earlier in life -- with an average of 3.8 years at the time of diagnosis (compared to 5.7 years in children born to mothers without lupus).

Finally, Dr. Vinet's team looked at whether medications taken during pregnancy potentially played a role in ASD diagnosis in this study. They looked at a smaller group of 1,925 children, whose mothers had public drug coverage, and found exposures to medications during pregnancy were rare. In fact, in the 18 ASD cases observed in offspring of lupus mothers with public drug coverage, none of the children were exposed to antimalarials, antidepressants, or immunosuppressants during pregnancy. And, only one child born to a mother with lupus and another born to a mother without the disease were exposed to corticosteroids and anticonvulsants, respectively.

"The findings from this study suggest that, although the absolute risk is relatively small, when compared to children from the general population, children born to women with lupus have a two-fold increased risk of autism spectrum disorders," says Dr. Vinet. "Hopefully, this study will prompt further research on the potential role of lupus-related autoantibodies, such as N-methyl-D-aspartate receptor antibodies, in ASD. In the meantime, women with lupus who are contemplating a pregnancy should discuss with their physician to ideally plan the pregnancy at a time of low disease activity and review the safety of their medications."

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Smoking during pregnancy may result in bipolar disorder in child

This study claims that a mother who smokes while pregnant has two times the risk of her child developing bipolar disorder compared to a mother who does not smoke while pregnant.

A study published today in theAmerican Journal of Psychiatry suggests an association between smoking during pregnancy and increased risk for developing bipolar disorder (BD) in adult children. Researchers at the New York State Psychiatric Institute and the Department of Epidemiology at the Mailman School of Public Health at Columbia University, in collaboration with scientists at the Kaiser Permanente Division of Research in Oakland, California, evaluated offspring from a large cohort of pregnant women who participated in the Child Health and Development Study (CHDS) from 1959-1966. The study was based on 79 cases and 654 comparison subjects. Maternal smoking during pregnancy was associated with a twofold increased risk of BD in their offspring.

Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and attentional difficulties. This is the first study to suggest an association between prenatal tobacco exposure and BD, a serious psychiatric illness marked by significant shifts in mood that alternate between periods of depression and mania. Symptoms typically become noticeable in the late teens or early adulthood.

"These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time," said Alan Brown, MD, MPH, senior author and Professor of Clinical Psychiatry and Epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health.

The authors wrote: "Much of the psychopathology associated with prenatal tobacco exposure clusters around the 'externalizing' spectrum, which includes attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and substance abuse disorders. Although not diagnostically classified along the externalizing spectrum, BD shares a number of clinical characteristics with these disorders, including inattention, irritability, loss of self-control, and proclivity to drug/alcohol use." In effect, children who were exposed to tobacco smoke in utero may exhibit some symptoms and behaviors that are found in BD.

A previous study by Dr. Brown and colleagues found that flu virus in pregnant mothers was associated with a fourfold increased risk that their child would develop BD.

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Epilepsy drugs used during pregnancy may be linked adverse outcomes!

This study looked at women who used certain epilepsy medications while pregnant and if there was an association with the drug and adverse outcomes.

Talk to your neurologist if you are planning pregnancy and have epilepsy. Certain medications may have less adverse effects than others. JR

Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure to antiepileptic drugs during pregnancy has an effect on early child development. Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers.

 Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains.

Methods

• From mid-1999 through December 2008, children of mothers recruited at 13–17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study.
• Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age.
• The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios (ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight.

Results

• A total of 333 children were exposed to antiepileptic drugs in utero.
• At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval [CI] 1.1–3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1–6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1–4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2–3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6–7.0).
• The drug-exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4–3.4), but exclusion of congenital malformations did not affect the risk of adverse development.
• Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks.
• Children of fathers with epilepsy generally scored within the normal range.

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Combination of brain-attacking antibodies signals autism

Researchers at the University of California Davis found that mothers who have a certain combination of brain-attacking antibodies have a 99% chance of giving birth to a child with autism.

A significant portion of autism cases can be identified with nearly perfect accuracy before symptoms appear, possibly even before conception, according to research published Tuesday.

It found that 23 percent of children with autism spectrum disordershave mothers with a certain combination of antibodies in their blood. Mothers who have this combination are 99 percent likely to have autistic children, according to researchers at the University of California Davis.

A study led by Judy Van de Water of UC Davis finds that 23 percent of those with autism spectrum disorders have mothers with a specific combination of autoantibodies that attack seven proteins involved in fetal brain development.

Experts not involved with the work said it could represent a major advance if validated. The studies don’t deal with the great majority of other cases of the disorder; in which a variety of factors appear to be involved.Two studies based on the research were published in the open access journal Translational Psychiatry. One study, led by UC Davis researcher Judy Van de Water, is here. The second, led by her UC Davis colleague Melissa Bauman, is here. Open access means the complete studies are free to readers.

San Diego-based Pediatric Bioscience is developing a test for the autism-linked antibodies, said Jan D’Alvise, chief executive of the privately held company. The test is expected to be commercially available in late 2014.

The studies found that seven proteins active in fetal brains were targeted by the maternal antibodies, said Van de Water, an immunologist at UC Davis School of Medicine, who took part in both studies. Van de Water is also the chief scientific adviser to Pediatric Bioscience. Some maternal antibodies normally cross over through the placenta, guarding the developing baby against infection.

The main study, led by Van de Water, examined the maternal antibodies’ effects on the seven fetal brain proteins and correlated them with an autism or autism spectrum diagnosis in 246 children. Maternal antibodies were also examined in a control group of 149 normally developing children.

The study found certain combinations of antibodies that were found in 23 percent of mothers of autism spectrum disorder children, but in less than 1 percent of a control group of mothers who did not have ASD children.

The second study, led by colleague Melissa Bauman, examined the autism-linked antibodies’ effects in young rhesus monkeys. It found significant disruptions in the social behavior of these monkeys; monkeys not exposed to the antibodies did not experience the disruptions.

Pediatric Bioscience is developing the antibody test for two uses, D’Alvise said.

“One is a simple blood test that will tell women their risk of having an autistic child before they conceive,” D’Alvise said.

Prospective mothers who test positive could avoid the risk by using a surrogate mother who tests negative to carry the baby, she said.

Secondly, the test can also be taken by new mothers to assess autism risk in their infants, so those at risk can be treated promptly.

“It’s very hard to diagnose these kids early, and they benefit from interventional therapy, if you catch them early,” D’Alvise said.

About 1 in 88 children are diagnosed with autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention. At the mild end, those with Asperger’s syndrome experience significant difficulties in social interaction. At the severe end, classic autism includes delay in language development, repetitive behavior and intense fascination with certain objects or patterns.

While more work is needed before a test can be approved, Van de Water said the study results were solid, and she is confident in their accuracy. Further down the road, a preventive therapy might be possible, she said. Such a therapy would block the antibodies in the pregnant mothers, allowing normal development of the baby.

Maternal immune response dysfunction

The study represents “a great advance forward to explaining a substantial sub-set of cases of ASD,” said Cheryl Dissanayake, director of the Olga Tennison Autism Research Centre at La Trobe University, near Melbourne, Australia.

Dissanayake said by email that she had been aware of the research, and considers the rhesus monkey study to give more validity to Van de Water’s work.

“My own interest in dysregulated growth (both physical and brain growth) in a subset of cases is also modeled in the rhesus monkeys,” Dissanayake said. “These really are significant findings, although as always, more research is needed. I couldn’t recommend this work strongly enough.”

Eric Courchesne, a UCSD researcher studying the neurobiology of autism, was cautious in evaluating the results. He said the study covers an important area of research, identifying molecular markers in those with autism.

"The study suggests an important future study: Do mothers who already have an ASD child and these markers, have an increased risk of having another child with ASD?" Courchesne asked.

Elizabeth A. Thomas, a neuroscientist at The Scripps Research Institute, said the study results could be useful in assessing autism risk.

“These findings could have enormous potential to serve as a biomarker for disease risk in children, however, whether such a diagnostic test would have predictive value in assessing a woman’s risk of having a child with autism prior to conception, is less clear,” Thomas said. “This is because the samples were obtained from mothers of children at the time of the child’s diagnosis, not before pregnancy.”

The results make sense in light of what is already known about autism, Thomas said.

“Although autism spectrum disorders are highly heterogeneous, there is substantial evidence for maternal immune dysregulation during pregnancy and increased risk for autism, as well as other neuropsychiatric disorders, in offspring,” Thomas said. “However, exactly how maternal immune dysregulation is related to altered brain development and subsequent behavioral abnormalities is not clear.”

Identifying the seven target proteins represents “a critical advancement in the field,” Thomas said. “Because autism is known to have a strong genetic contribution, it would be important to see if any of these target proteins converge with the autism-associated genetic data that has been published in recent years.”

“Because several of the target proteins identified in this study are known to play important roles in neurodevelopment, it would be of interest to see if any of these maternal autoantibodies are associated with increased risk for other neuropsychiatric or neurodevelopmental disorders."

Monkey parallel

The studies builds on previous research by Van De Water and colleagues that found women with certain antibodies were at greater risk of having a child with autism than woman without the antibodies.

The study led by UC Davis researcher Bauman found a parallel in rhesus monkeys exposed to the autism-linked antibodies. These well-studied monkeys have their own complex social system, and the researchers looked for signs of disruption.

That study included three groups, one exposed to the maternal autism-linked antibodies, a second exposed to antibodies from human mothers whose children did not have autism, and a third group that did not receive any antibodies. Thus, the study had three groups, one test and two control.

Monkey offspring exposed to the autism-linked antibodies showed abnormal social behavior not displayed by the control offspring, the study said. This behavior included approaching unfamiliar monkeys, unusual for young rhesus monkeys.

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Epilepsy Drug Sodium Valproate Linked to Increased Chance of Autism and ADHD during Pregnancy

Children to mothers who took epilepsy drug sodium valoprate while pregnant have an increased risk of developing autism. These children should be watched closely.

Children born to mothers who took the antiepileptic drug sodium valproate during pregnancy are at significantly increased risk of autism and other neruodevelopmental disorders.

The finding came from new research published in the Journal of Neurology, Neurosurgery and Psychiatry

The research involved kids born to 528 pregnant women in England between 2000 and 2004. Fifty percent (243) of the moms had epilepsy, only 34 of those women did not take antiepileptic drugs while pregnant.

Carbamazepine was taken by 59 of the women, valproate was taken by another 59 women, lamotrigine was taken by 36, forty-one of the females took a combination, and 15 took other medications.

The researchers evaluated the physical and intellectual development of the kids at 12 months, three years, and 6 years of age.

The mothers also provided the scientists with information on whether they ever had to seek professional advice concerning their child's development, behavior, health, or educational progress.

There were 415 kids who had complete data on all 3 evaluations. A neurodevelopmental disorder was diagnosed in 19 kids by the time they were 6 years old, three of those children were affected by a physical abnormality.

Twelve of these kids had a form of autism, one child also had ADHD (attention deficit hyperactivity disorder). Three had ADHD alone and another four had dyspraxia - a condition that causes poor physical coordination and uncontrolled clumsiness.

The experts discovered that neurodevelopmental issues were notably more prevalent among those kids whose mothers had epilepsy - 7.46% vs. 1.87% of those whose mothers did not struggle with the condition.

The children whose moms took valproate by itself or with another drug during pregnancy had a considerably higher chance of being diagnosed with a neurodevelopmental condition, compared to those whose mothers took other medications for their disorder.

After examining all of the figures and adjusting for factors likely to impact the results, the investigators found that kids exposed to valproate in the womb were 6 times more likely to have a neurodevelopmental disorder.

Kids who were exposed to valporate and other drugs were 10 times more likely to have a neurodevelopment disorder than those whose moms did not have epilepsy.

Six out of 50 children (12%) whose mothers had taken valproate alone while pregnant had a neurodevelopmental problem, as did 3 out of 20 (15%) of those whose mothers had taken valproate with other treatments.

The women who had epilepsy and did not take drugs to treat the condition during pregnancy did not have any children diagnosed with a neurodevelopment disorder. However, the experts noted, there was only a small number of females in this group.

Boys had a 3 times higher chance of being diagnosed with a nuerodevelopmental disorder. However, no notable links were identified for the mother's age or IQ, epileptic seizure type, or length of pregnancy.

Although further studies are necessary before conclusions can be drawn, the findings of this research support prior reports that have demonstrated that there are potentially negative effects of valproate on the developing fetus.

For example, one study indicated that kids born to moms who took valproate while pregnant tended to score notably lower in IQ tests by an average of 6 to 9 points at age 3, than kids born to moms who took other anti-epilepsy drugs.

The experts concluded:

"If sodium valproate is the treatment of choice, women should be provided with as much information as possible to enable them to make an informed decision.

But on no account should pregnant women just stop taking the drug for fear of harming their developing child," the scientists concluded."

The researchers added that kids born to mothers who took the medication while pregnant need to be observed closely.


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Study Shows Abnormal Brain Development in Fetuses of Obese Women

A new study shows that there is abnormal gene expression showing abnormal brain development in fetuses whose mothers were obese.

In a study to be presented on February 15 between 8 a.m. and 10 a.m. PST, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting ™, in San Francisco, California, researchers from Tufts Medical Center will present findings showing the effects of maternal obesity on a fetus, specifically in the development of the brain.

The study, conducted at the Mother Infant Research Institute (MIRI) at Tufts Medical Center in Boston, Mass., looked at the fetal development of 16 pregnant women, eight obese and eight lean, to see what effects maternal obesity had on fetal gene expression. Researchers have found that fetuses of obese women had differences in gene expression as early as the second trimester, compared to fetuses of women who were a healthy weight. Of particular note were patterns of gene expression suggestive of abnormal brain development in fetuses of obese women.

During gestation, fetuses go through apoptosis, a developmental process of programmed cell death. However, fetuses of the obese women were observed to have decreased apoptosis, which is an important part of normal fetal neurodevelopment. Dr. Diana Bianchi, senior author of the study and executive director of MIRI, describes apoptosis as a pruning process, clearing out space for new growth.

"Women won't be surprised to hear being obese while pregnant can lead to obesity in the child," said Dr. Andrea Edlow, lead author of the study and fellow in Maternal-Fetal Medicine at Tufts Medical Center. "But what might surprise them is the potential effect it has on the brain development of their unborn child."

It is too early to know the implications of their findings, but maternal obesity is a rapidly growing problem in the U.S., with one in three women being obese at conception. The conclusion of the study points to the role of gene expression studies such as this one in helping elucidate possible mechanisms for recently-described postnatal neurodevelopmental abnormalities in children of obese women, including increased rates of autism and altered hypothalamic appetite regulation.

The research team hopes their findings and any future data will push women looking to become pregnant to be healthier, minimizing risk to their child.

Drs. Bianchi and Edlow, say the next step in their research will be to use a mouse model to examine the genes that are differentially expressed in fetuses of obese women, genes that may be involved in abnormal fetal neurodevelopment.

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Risk of ADHD higher in children whose parents are depressed or violent

A study shows that young children whose parents are depressed or are involved in partner violence are more likely to develop ADHD by age 6.

Preschoolers whose parents reportdepression and intimate partner violence may be more likely to develop attention-deficit/hyperactivity disorder (ADHD) by the age of 6, new research suggests.

And young children with depressed moms may be more likely to receive prescription drugs to treat behavioral and mental health issues down the road.

"Our study indicates that preschoolers who are diagnosed with ADHD are more likely to have been exposed to both intimate partner violence and parental depression within the first three years of life than their peers not exposed to either risk factor," said study author Dr. Nerissa Bauer, an assistant professor of pediatrics at Indiana University School of Medicine, in Indianapolis.

"There has been increasing awareness that certain psychosocial risk factors can impact the behavioral presentation of children at very young ages," she said. Still, not all children who are exposed to maternal depression and intimate partner violence will develop ADHD, she noted.

"There are other factors that can be associated with a child's higher likelihood of being diagnosed with ADHD, including a family history of ADHD," Bauer explained.

ADHD symptoms can include impulsiveness, hyperactivity and difficulty focusing.Kids with ADHD may have difficulty in school, holding down jobs and sustaining relationships. They are also at greater risk for alcohol or substance abuse, depression and anxiety disorders. Treatment typically involves medication and behavioral modifications.

"Pediatricians and family practitioners know to routinely screen for the presence of these psychosocial risk factors because of the potential negative effects on the child," Bauer said. "Families who experience intimate partner violence will need help, not only to make sure the victims stay safe from physical harm, but there [are] also psychological effects."

The study, which appeared online Feb. 4 in the journal JAMA Pediatrics, included more than 2,400 children who were 3 years old. Parents who brought them to four different pediatric community clinics filled out questionnaires regarding their personal history of depression and domestic violence while in the pediatricians' waiting room.

Fifty-eight caregivers reported a history of intimate partner violence and depression before their child turned 3. In addition, 69 reported a history of intimate partner violence and 704 had symptoms of depression during this time frame. Close to 66 percent of the parents reported neither depression nor intimate partner violence. Children who were exposed to intimate partner violence and/or parental depression were four times more likely to be diagnosed with ADHD by the age of 6.

What's more, 2.9 percent of kids whose parents reported depression received prescription drugs to treat behavioral and mental health issues, compared with 1.6 percent of children whose parents did not report a history of depression. Medications included those that treat anxiety, depression and sleep problems.

While the study showed an association, it did not prove a cause-and-effect link between intimate partner violence and/or maternal depression and likelihood of anADHD diagnosis.

Experts said the findings make sense, but more study is needed.

"This study adds to the already robust literature revealing that early life experiences can have profound effects on brain development," said Dr. Michael Duchowny, a pediatric neurologist at Miami Children's Hospital. "While heredity is known to play a strong role in the expression of ADHD symptoms, the study further suggests that additional environmental factors operating during the formative years of brain maturation are also significant."

New York City-based child psychoanalyst Dr. Leon Hoffman said the new findings make sense. "Unquestionably, intimate partner violence and maternal depression have a profound effect on children," he said.

Exactly how to deal with this is another story, said Hoffman, who is the co-director of the New York Psychoanalytic Society's Pacella Parent Child Center. "This is a public health problem that needs a lot of funds if reasonably effective programs are to be developed," he noted.

Dr. Rachel Klein, professor of child and adolescent psychiatry at NYU Langone Medical Center in New York City, said the study shows an association based on how parents answered certain questions, but it can't say how, or even if, maternal depression and intimate partner violence predict a child's risk of ADHD.

"If parents are worried, ask the pediatrician to evaluate your child for possible ADHD or refer the child to a mental health professional," she added.

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