Tuesday, November 3, 2009

CDC Study Links 2 Antibiotics to Birth Defects

CDC Study Links 2 Antibiotics to Birth Defects
No added risk was found, however, for most commonly used infection-fighters
Posted November 2, 2009

By Jennifer Thomas
HealthDay Reporter

MONDAY, Nov. 2 (HealthDay News) -- Taking antibiotics during pregnancy does not raise the risk for most birth defects, though there are some exceptions, new research has found.

Penicillin, which is the most commonly used antibiotic during pregnancy, as well as erythromycin, cephalosporins and quinolones, other widely prescribed antibiotics, were not associated with increased risk for about 30 different birth defects.

However, the study found that two types of antibiotics were linked with a higher risk for several birth defects: nitrofurantoins and sulfonamides, sometimes called "sulfa drugs," which are prescribed for urinary tract and other infections.

Women whose children had anencephaly, a fatal malformation of the skull and brain, were three times more likely to have taken sulfonamides, the study found. Sulfonamides were also tied to an increased risk for such heart defects as hypoplastic left heart syndrome and coarctation of the aorta, choanal atresia (a blockage of the nasal passage), transverse limb deficiency and diaphragmatic hernia, an abnormal opening in the diaphragm that results in severe breathing difficulties.

Nitrofurantoins were also associated with multiple birth defects, including anophthalmia and microphthalmos (eye defects) and several congenital heart defects. Mothers whose children were born with a cleft lip or cleft palate were twice as likely to have taken nitrofurantoins, the study found.

But pregnant women should not be overly worried if they need an antibiotic to treat an infection during pregnancy, stressed the study's lead author, Krista Crider, a geneticist with the National Center on Birth Defects and Developmental Disabilities, part of the U.S. Centers for Disease Control and Prevention.

"The most important message is that most commonly used antibiotics do not seem to be associated with the birth defects we studied," Crider said.

The findings are published in the November issue of Archives of Pediatrics & Adolescent Medicine.

Crider and her colleagues analyzed data on more than 13,000 women whose babies had one of more than 30 birth defects, including cleft palate, heart or limb defects and anencephaly. They compared the women's rates of antibiotic usage, from the month leading up to pregnancy through the end of the first trimester, with that of almost 5,000 women whose children did not have a birth defect. The data was culled from the National Birth Defects Prevention Study, which began in 1997 and includes about 30,000 women from 10 states.

Information on the impact of many prescription drugs on developing fetuses is sorely lacking, Crider pointed out. Much of that stems from the fact that ethical considerations preclude conducting drugs trials in pregnant women, she said.

Though many antibiotics have been used safely for decades, resistant strains of bacteria are forcing doctors to use a wider array of antibiotics. For some, little data exist.

The researchers found that about 30 percent of women took an antibiotic between the three months prior to conception and the end of the pregnancy.

Even antibiotics that generally were safe were found to be associated with a few specific birth defects. Women whose babies were born with a certain type of limb malformation were three times more likely to have taken penicillin. Erythromycin, cephalosporins and quinolones were also associated with an increased risk for one or two specific birth defects.

However, the researchers said they did not know if the birth defects were caused by the antibiotics or the underlying infection.

One expert said women need to remember the good antibiotics can do mom and baby, as well. Though many pregnant women want to avoid taking any drugs during pregnancy, infections pose a risk to mother and baby and often need to be treated, said Dr. Jennifer Wu, an obstetrician-gynecologist at Lenox Hill Hospital in New York City.

"Untreated infections during pregnancy can lead to severe consequences, such as maternal sepsis [blood infection] and preterm labor," Wu said. "Yet many patients are afraid to take medications such as antibiotics during pregnancy."

The study "supports the evidence that antibiotics are safe for pregnant women," she said. "It is reassuring for doctors and patients to have more data on necessary drugs for pregnancy."

Crider also stressed that the chances of having a baby with a birth defect remain small, even if an antibiotic has been linked to an elevated risk. For example, the risk of having a child with hypoplastic left heart syndrome is about one in 4,200. Sulfonamides were associated with a three-fold increase, making the likelihood about one in 1,400, she said.

Brand names for nitrofurantoins include Furadantin, Macrobid and Macrodantin. Bactrim and Septra are among the brand names of sulfonamides.

Given the data, Crider said, women should be cautious about taking either of those types of drugs during pregnancy and should discuss other options with their physicians,.

According to the study, the overall risk for having a child with a birth defect is about three percent.

The study did not look at chromosomal defects, including Down syndrome.

Monday, September 14, 2009

VitaPath gets $6M to fight spina bifida

VitaPath gets $6M to fight spina bifida

VitaPath Genetics, developer of a diagnostic that could be used to lessen rates of the birth defect spina bifida, has raised $6 million in a first round of funding led by Mohr Davidow Ventures. The money should provide the Foster City, Calif. with runway through next year, covering testing for women with a high chance of having a baby with spina bifida.

The condition, which causes a underdeveloped spinal column often leading to nerve and brain damage, occurs in eight babies born every day. VitaPath’s mission is to identify women at high risk for the defect before they even conceive. Those who are can potentially fix the problem by taking high amounts of folic acid.

X/Seed Capital Management also participated in the financing. It previously provided see money which was rolled into the round.

Wednesday, August 19, 2009

Low Choline Level in Pregnancy Tied to Birth Defects

Low Choline Level in Pregnancy Tied to Birth Defects
Anencephaly, spina bifida linked to nutrient found in foods, study shows
Posted August 14, 2009

FRIDAY, Aug. 14 (HealthDay News) -- Low blood levels of the nutrient choline during pregnancy increases the risk of brain and spinal-cord defects in newborns, U.S. researchers report.

They focused on two types of neural tube birth defects -- anencephaly and spina bifida. Anencephaly is a lethal condition in which the brain and skull don't develop, and spina bifida is a spinal-cord malformation that causes paralysis and lifelong disability.

The Stanford University School of Medicine team compared pregnancy blood samples from 80 women who gave birth to children with anencephaly and spina bifida to pregnancy blood samples from 409 women whose infants had no birth defects.

The results showed that choline levels were linked to risk of neural tube defects. Choline is found in egg yolks, soy, wheat germ and meats.

Women with the lowest blood choline levels during pregnancy were 2.4 times more likely to have infants with neural tube defects than women with average blood choline levels. Women with the highest choline levels had the lowest risk.

The study appears in the Aug. 14 issue of Epidemiology.

Primary author Gary Shaw, a professor of neonatology, noted that prenatal vitamins contain little or no choline. For women planning to get pregnant, "the best source for choline is still eating a variety of foods," he said in a university news release.

More information

The U.S. National Institute of Child Health and Human Development has more about neural tube defects.

Monday, May 4, 2009

Medical Technology: 'SmartShunt' To Regulate Pressure In The Brain

Medical Technology: 'SmartShunt' To Regulate Pressure In The Brain

ScienceDaily (Apr. 19, 2009) — ETH Zurich researchers have simulated the motion of the cerebrospinal fluid in the human brain. They are using the results to develop a self-regulating system to treat hydrocephalus.

Cerebrospinal fluid is a colorless liquid surrounding the brain and the spinal cord and filling the cavities in the brain. It protects the brain from impact and vibrations, carries nutrients to it and harmful substances away from it, and acts as one of the brain’s communication routes. If too much of this fluid is produced or too little flows away, excessive pressure builds up in the head and hydrocephalus occurs.

The liquid flows into the abdomen

As a rule nowadays, hydrocephalus is treated by using a “shunt”: this involves implanting into the patient a thin tube that carries excess cerebrospinal fluid from the head into the abdomen via a pressure relief valve. However, this process often drains away too much or too little fluid. Most valves can no longer be adjusted after implantation. Although some valves have this option, the patient must visit the doctor for adjustments to be made.

ETH Zurich researchers led by Dimos Poulikakos, Professor of Thermodynamics, and Vartan Kurtcuoglu, Director of the Biofluidics group in the Laboratory for Thermodynamics in Emerging Technologies, want to go one step further. They are working on a “SmartShunt”, a self-regulating pressure relief device. To achieve their aim they must understand exactly how the cerebrospinal fluid flows within the skull. For this, they simulated the motion of the fluid in three dimensions on a computer. Initial results were published in the February issue of the Journal of Biomechanical Engineering. Its title page shows a graphic image of the results, the research group having already made the title page in the January issue with a publication on aortic aneurysms (see the Literature references).

A brain scan is the first step

The cerebrospinal fluid fills the space between the skull and the brain, called the sub-arachnoid space, in which it pulses in a cycle controlled indirectly by the heart. With each heartbeat, the heart pumps blood through the brain, causing the blood vessels to expand and the space available for the cerebrospinal fluid to decrease correspondingly. The blood flows away again before the next heartbeat, and the space for the cerebrospinal fluid increases.

The publication came into being in collaboration with Peter Bösiger, Professor at the Institute of Biomedical Technology of ETH Zurich. His group scanned the sub-arachnoid space of a healthy 25-year-old man by magnetic resonance imaging (MRI). They also used a special MRI technique to measure the velocity of the fluid in three planes to provide the boundary conditions for the calculations.

The scientists built a computer model based on the results of the measurements. They used a series of partial differential equations to describe the motion of the cerebrospinal fluid. At the same time, they had to take into account the fact that the sub-arachnoid space is criss-crossed by a sort of fine, networklike bar of tissues that retard the movement of the fluid. Instead of computing with the single bar, they represented the sub-arachnoid space in their model as a uniform porous medium similar to a sponge.

Valve for self-regulation

Based on the results, the researchers in the multi-disciplinary “SmartShunt” Project are now developing the basis for a shunt to control the outflow of cerebrospinal fluid automatically in accordance with the patient’s specific needs. The goal is a valve that controls the pressure in the patient’s head in real time, saving him or her regular visits to the doctor.

Dimos Poulikakos says, “We attach importance to the fact that definitereal medical problems are addressed in the continuation of basic research.” The researchers work in close collaboration with the medical staff of the University Hospital Zurich and with other ETH Zurich institutes. The Swiss National Science Foundation is funding the interdisciplinary project to the tune of approximately CHF 850,000. Poulikakos plans to start developing the actual product together with the industry in about three year’s time.

Knowledge of the cerebrospinal fluid motion will also be useful for other medical applications. The liquid plays a part in Alzheimer’s disease, in multiple sclerosis and in meningitis. In addition, drugs that cannot cross the blood-brain barrier can be injected into the cerebrospinal fluid, from where they reach the brain. In other cases, for example regarding painkillers, injection into the cerebrospinal fluid can allow the dose to be decreased to reduce side-effects.

Smurf Genes Help Cells Find the Path Ahead

Smurf Genes Help Cells Find the Path Ahead
April 16, 2009
Howard Hughes Medical Institute

Two critical genes that serve as beacons and give cells a much needed sense of direction in the chaotic days of early development have been identified by researchers at the University of Toronto.

The new findings, from the laboratory of Jeffrey L. Wrana, a Howard Hughes Medical Institute international research scholar, were published April 17, 2009, in the journal Cell, and help explain how a cell determines its sense of space. A better understanding of this phenomenon, called planar cell polarity, may also help scientists learn how improper cellular orientation can lead to spina bifida, polycystic kidney disease, and metastatic cancer. Each of these illnesses involves cells that don’t have a proper sense of direction, so they cannot tell which way they are going.

In a developing embryo, cells need to be in the right position at the right time. To get to their proper destination, cells must understand the difference between top and bottom, forward and backward. If this orientation is off just a little, development can be disrupted or derailed. In spina bifida, for example, cells can fail to recognize front from back, leading to improper formation of the spine.

In the past decade, Wrana has helped identify the importance of two Smurf genes (Smurf stands for Smad ubiquitination regulatory factor) in helping cells move and distinguish top from bottom. Cells rely on cues from their neighbors to sense this kind of orientation, and Wrana has been trying to understand how the Smurf genes facilitate the process. Until now, he didn’t know Smurf proteins had anything to with orienting cells in the backward/forward direction, as well.

“Our results were unexpected, but also exciting because they suggest the Smurf genes are coordinating different types of cell polarity,” says Wrana, who also works at Mount Sinai Hospital in Toronto.

As part of his study, Wrana and his team genetically engineered mouse embryos so they did not have functional copies of both Smurf genes, but the embryos failed to develop properly and died before birth. When Wrana examined the embryos, he observed that they had an atypical shape—they were short and wide instead of long and thin. In addition, he saw that the neural tube—the precursor to the spinal cord—had failed to close into its proper tubular shape. This type of developmental anomaly is similar to what happens in human babies who are born with spina bifida. The findings surprised Wrana because he did not expect that the changes in top/bottom polarity would be vital in this aspect of embryo development.

Instead, these characteristics suggested that the Smurf genes were related to an important network of genes called the Wnt signaling pathway. When this pathway goes awry in early development—which can happen for a variety of reasons—a number of defects can arise, including those Wrana saw in his Smurf-deficient mice. Researchers had known that Wnt signaling helps establish planar cell polarity, so Wrana investigated whether Smurfs were involved, too.

His first stop was the inner ear of the embryonic mouse. The inner ear contains hair cells, which vibrate in response to sound. To do their job, hair cells must line up neatly in a hexagonal pattern, like paving stones on a cobblestone street—a pattern made possible by planar cell polarity. But in the Smurf-deficient mice, the hair cells looked like they were laid by a drunken mason. “In the normal embryos, the hair cells were all pointing the same way in a beautiful array,” Wrana says. “But in the mutants they were disorganized and rotated and pointing the wrong way.”

This disruption suggested the Smurf genes were critical for planar cell polarity. To strengthen his case, Wrana used advanced proteomics techniques to map the interactions of proteins in a cell. Those analyses showed that the proteins made by the Smurf genes interacted with two proteins, called Prickle and Disheveled, that are also linked to planar cell polarity.

In healthy cells that know front from back, Prickle accumulates on one side of the cell, and Disheveled on the other side. This lopsidedness appears critical for planar cell polarity. Wrana found that the Smurf genes actually create this lopsidedness by destroying Prickle on one side of the cell. We believe that through this destruction of Prickle, cells establish an asymmetrical distribution of proteins, and that’s how the cells become polarized properly,” Wrana says.

Wrana is now investigating what role Smurf genes play in other tissues, such as the trachea and kidneys, where planar cell polarity is known to be important. He also wants to study their role in diseases. For example, “there are lots of hints that planar cell polarity is important in cancer,” he says. Other researchers have found that cancer cells often have an excess of the proteins made by the Smurf genes. “We think the elevated expression of Smurfs interferes with the polarity of the cells,” he says. “Within the tumor, the cells become disorganized and display aberrant behaviors, which may help them escape and metastasize.”

Do Pesticides Make Birth Defects Crop Up?

Do Pesticides Make Birth Defects Crop Up?
High Pesticide Levels in Spring and Summer May Be Linked to an Increase in Birth Defects, Study Says
By Salynn Boyles
WebMD Health News
Reviewed by Louise Chang, MD

March 27, 2009 -- New research shows that babies conceived in the spring and early summer have a higher risk for a wide range of birth defects, including Down syndrome, cleft palate, and spina bifida.

The reported increase in birth defects was modest, but it coincided with a similar spike in groundwater pesticide levels during the spring-early summer planting season.

These findings suggest that pesticide exposure may influence birth outcomes nationwide, researchers say.

“There appears to be a season of conception in which the risk of having a child with a birth defect is higher,” Indiana University School of Medicine neonatology professor Paul D. Winchester, MD, tells WebMD.

“This study does not prove that pesticides cause birth defects, but we set out to show that they did not and we were not reassured.”
Pesticide Levels Measured in Water

In earlier studies, researchers have reported increases in birth defects, pregnancy complications, and miscarriages in babies born to farm workers with high levels of exposure to agricultural pesticides.

But the study is one of the first to suggest that indirect exposure to agricultural chemical may influence birth outcomes.

Winchester and colleagues compared data on pesticide levels in surface water between 1996 and 2002 to data on birth defects at the national level during the same period.

The researchers used the U.S. Geological Survey’s National Water Quality Assessment (NAWQA), which includes samples from 186 streams across the United States, representing 50% of the drinking water consumed in the country.

Statistics on birth defects were reported to the CDC by individual states.

The NAWQA analysis confirmed that concentrations of widely used pesticides in ground water were highest in the months of April through July during the period examined.

During this same period, women who conceived in these months were about 3% more likely to deliver a baby with a birth defect than women who conceived in other months, Winchester says.

“That doesn’t sound like much, but at a population level it could mean thousands of additional birth defects,” he says.
Prospective Study Under Way

Winchester adds that inconsistent recording of birth defects from state to state during the time the data were collected probably resulted in an underestimation of birth defects.

During this time, 13 states and the District of Columbia had only passive birth defects surveillance programs.

March of Dimes medical Director Alan R. Fleischman, MD, tells WebMD that even with the limitations, the study raises important questions about the impact of environmental chemical exposures on birth outcomes.

“There is a limit to what you can imply from this type of study,” he says. “But it does focus attention on an important issue.”

Fleischman chairs the advisory committee for the National Children’s Study, the largest prospective study ever in the U.S. to examine the effect of environmental influences on children’s health.

Researchers are now recruiting women for the trial. The goal is to follow 100,000 children nationwide from conception to age 21.

“We will certainly be measuring exposure to environmental chemicals before conception and during pregnancy,” he says. “This is not easy to do, but it is important to better understand the relationship between chemical exposures and birth outcomes.”
pregnancy week-by-week newslet

Panel: Avoid Epilepsy Drug in Pregnancy

Panel: Avoid Epilepsy Drug in Pregnancy
New Guidelines Urge Pregnant Women to Avoid Taking Valproate Because of Risk of Birth Defects
By Charlene Laino
WebMD Health News
Reviewed by Louise Chang, MD

April 27, 2009 (Seattle) -- Women with epilepsy should avoid taking the drug valproate (Depakote) during pregnancy if possible, according to new guidelines developed by the American Academy of Neurology (AAN) and the American Epilepsy Society.

"There is good evidence that valproate, whether used by itself or in combination with other medications, increases the risk of major birth defects, including cleft palate and spinal bifida," says guideline co-author Gary S. Gronseth, MD, vice chairman of neurology at the University of Kansas Medical Center in Kansas City.

Additionally, taking valproate during pregnancy has been linked to lower IQs in children, he tells WebMD.

The guidelines come on the heels of a study showing that women with epilepsy who took valproate during pregnancy gave birth to children whose IQ at age 3 averaged up to 9 points lower than the scores of children exposed to other epilepsy drugs.

In response to the guidelines, a spokesperson for Abbott, which makes valproate, said the drug may be the only effective medication for some women, but doctors and patients should discuss risks and benefits of treatment.

Pregnant women may also want to avoid taking the seizure drugs phenytoin (Dilantin) and phenobarbital, as they too have been linked to lower IQs in children, Gronseth says.
Epilepsy and Pregnancy

Gronseth and other panel members stress that pregnancy is safe for most women with epilepsy.

"Overall, what we found was very reassuring to woman with epilepsy planning to become pregnant," says lead guideline author Cynthia Harden, MD, director of the epilepsy division at the University of Miami's Miller School of Medicine.

"Contrary to previous dogma, women with epilepsy are not at a substantially increased risk of having a cesarean section, late pregnancy bleeding, or premature contractions or premature labor and delivery," she says.

Also, if a woman is seizure-free for nine months to one year before she becomes pregnant, it's likely that she will not have any seizures during the pregnancy -- even if she switches medications, Harden tells WebMD.

About 500,000 women of childbearing age in the U.S. have some form of epilepsy, which is characterized by brief disturbances of electrical activity in the brain, according to Harden. Three to five out of every 1,000 births are to women with epilepsy.

The guidelines were prompted by a thorough review of more than 50 articles published over the last 10 years. They were presented here at the AAN's annual meeting and simultaneously published online in the journal Neurology.

Other recommendations include:

* If possible, women with epilepsy should avoid taking more than one epilepsy drug at a time during pregnancy, as doing so raises the risk of birth defects compared with taking only one medication.
* Pregnant women with epilepsy should have their blood tested regularly. "Pregnancy has been shown to lower the levels of anti-epileptic drugs in the blood, which may put women at risk of seizures. Checking these levels and adjusting the medication doses should help to keep the pregnant woman seizure-free," Harden says.
* Women planning to become pregnant should take at least 400 micrograms of folic acid a day, as supplementation has been shown to be "possibly effective" in preventing major birth defects. That's the same amount of folic acid already recommended by the CDC to prevent neural tube defects, especially spina bifida.
* Smoking during pregnancy may increase substantially the risk of premature contractions and premature labor and delivery during pregnancy.
Epilepsy Drugs and Breastfeeding

The epilepsy drugs primidone (Mysoline) and levetiracetam (Keppra) were detected in breast milk at various levels "that may be clinically important," while valproate, phenobarbital, phenytoin, and carbamazepine ( Tegretol) were not, the panel says.

"We didn't find much evidence one way or another that any of the drugs caused adverse effects in babies who were breastfed, but this information can help women and their doctors to make decisions about breastfeeding," Harden says.

Women should not stop taking any drug without consulting their physician, Harden stresses.

She suggests that women with epilepsy have a discussion with their doctor about seizure medications at least six months before becoming pregnant.

Valproate is an "excellent drug," and for some women, it may be the only medication that effectively controls their seizures, Gronseth says. "Women and their doctors have to weigh the potential risk of birth defects against the potential risk of uncontrolled seizures."
Valproate Also Used to Treat Migraines

"Luckily, it's not that hard to avoid valproate during pregnancy," as there are now more than a dozen seizure drugs available, says AAN spokesman Joseph Sirven, MD, professor of neurology at the Mayo Clinic in Phoenix.

Sirven points out that many more people, including pregnant women, take valproate to relieve migraine headaches.

"Lower doses are used than for epilepsy, so the drug may not pose the same problems [as when used to treat seizures]," he tells WebMD.

Nonetheless, women who have been prescribed valproate for any reason "should have a frank discussion with their doctors if they are planning to become pregnant," Sirven says.

Folic acid may raise cancer risk in offspring

Folic acid may raise cancer risk in offspring
From Monday's Globe and Mail
April 20, 2009 at 9:09 AM EDT

Canadian researchers have discovered that folic acid consumed during pregnancy can alter the gene function of offspring, potentially affecting their susceptibility to disease.

The finding is part of a growing - and controversial - body of research that raises serious questions about whether long-term consumption of folate and folic acid may increase the risk of developing certain cancers in some people.

The debate is far from benign. Food manufacturers are required to add folic acid to enriched flour and grain products under federal regulations that came into force in 1998. The premise behind fortification, which was also mandated in the United States, is to ensure that women receive adequate levels of folate in order to reduce the risk of birth defects in their offspring.

A decade later, however, new research and scientific studies have found evidence that increased consumption of folic acid may help trigger the onset of colon and other types of cancer.

Folic acid is the synthetic form of folate, which is a B vitamin that occurs naturally in leafy greens and other fruits and vegetables. It has been shown to significantly reduce the chance of neural tube defects, such as spina bifida, and helps produce and maintain healthy cells and is involved in numerous biological functions.

The new Canadian research, presented yesterday at the annual meeting of the American Association for Cancer Research in Denver, found that folic acid consumption by the mother has effects on her offspring.

The research is part of a burgeoning field of science known as epigenetics, which studies how gene activities are changed or influenced by diet, lifestyle and other environmental factors. Certain genes can become activated or rendered dormant depending on these factors.

In some cases, genes that protect the body against certain types of cancer can be shut off, while genes that promote tumour formation can be turned on. Changes to genes can also trigger mutations, which explains why epigenetics has been gaining so much attention in the scientific community for its potential ability to help explain the mystery of disease risk.

In the new study, led by Karen Sie, a research scientist in the University of Toronto's faculty of medicine, researchers gave two groups of laboratory rats folic acid supplementation. One group received the equivalent of the daily recommended intake for humans, 0.4 milligrams, and the other group received a higher dose, equal to 1 milligram in humans, which is the maximum recommended daily intake for women during pregnancy.

They found that offspring of rats that received the higher dose experienced a much higher degree of changes to genes in the colon and liver shortly after birth. But as the rats aged, there was a significant drop in the changes to genes.

The researchers don't yet know which specific gene functions were changed. It could be that the high degree of changes noted shortly after birth could silence genes designed to suppress tumours. But the changes could also activate genes that help protect against cancer.

Regardless, the discovery that folic acid can turn genes on or off could help in the quest to determine whether the supplement does contribute to increased risk of cancer in some people.

"The concern is with the high dose that people are getting nowadays," Ms. Sie said.

Despite the new findings, there are still strong defenders of folic acid fortification.

"We know ... folic acid is needed to prevent neural tube defects," said Gideon Koren, director of the Motherisk program at Toronto's Hospital for Sick Children. "As we talk now, 40 per cent of women in Canada do not have enough folic acid to protect the baby from spina bifida and other malformations."

Dr. Koren said Canada's fortification program is one of the key elements needed to reduce the incidence of neural tube defects, and that considering changes because of results from studies that primarily involve rats could be dangerous.

However, others say it's becoming harder to ignore the growing debate about folic acid. Despite its clear benefits when taken by pregnant women, the move to fortify food with folic acid means a major portion of the population is consuming a higher level of the supplement than they would otherwise.

Now, concern is growing that parts of the population that may be susceptible to colon cancer and other diseases could be put at greater risk due to their inadvertent exposure to folic acid.

"It's a real dilemma," said Joel Mason, associate professor of medicine and nutrition and director of the Vitamins and Carcinogenesis laboratory at Tufts University in Boston, who specializes in folic acid and folate.

And there are no simple solutions. Putting an end to fortification could put more women at risk of having babies with neural tube defects. But keeping folic acid supplements in the food supply could put certain people at a higher risk of disease.

A significant amount of research is currently being conducted to answer these questions, including studies looking at whether North American folic acid fortification led to changes in the population rates of certain types of cancer.

Dr. Mason said that despite any fears over safety, the research is too preliminary to warrant changes to fortification programs. But government regulators should be paying close attention as new research emerges, he said.

Canadian study finds immigrant women may be at greater risk of having a baby with a birth defect

Canadian study finds immigrant women may be at greater risk of having a baby with a birth defect

Published: Sunday, 19-Apr-2009

Immigrant women are less likely to use folic acid supplements before pregnancy to prevent spina bifida, particularly those who recently immigrated to the country, according to a new study led by a St. Michael's Hospital physician in collaboration with Statistics Canada, Health Canada and the University of Toronto.

The study is the first to provide national estimates of pre-pregnancy folic acid use in Canada.

"Our study's findings report that while about six in 10 Canadian-born mothers take folic-acid supplements in the three-month period before conception, mothers from non-western countries - China, Northern African, Middle Eastern, Caribbean, Latin American or South Pacific countries - are less likely to use the supplements," St. Michael's Hospital's Dr. Joel Ray said. "This information is important for policy makers and health practitioners as we aim to better educate new mothers and prevent neural tube defects in their babies."

Neural tube defects are birth defects of the spinal cord and brain, otherwise known as spina bifida and anencephaly. Research has shown the risk of neural tube defects can be reduced by nearly 50 per cent with folic acid supplements taken just before and soon after conception, or through consumption of food fortified with folic acid. However, an estimated six to 12 in every 10,000 fetuses in Canada still develop neural tube defects.

The study, an analysis of 6,349 new mothers aged 18 to 45 years, examined the relationship between folic acid supplement use in the three months before conception and the mother's maternal country of birth and years of residence in Canada.

Sixty one per cent of Canadian-born women in the study reported using folic acid supplements in the three month period before conception. However, these rates were much lower among women born in the Caribbean or Latin America (41%), Sub-Sahara Africa (44%), Northern Africa or the Middle East (31%), or South Asia (46%). What's more, only 39% of foreign-born women living in Canada less than four years reported using supplements compared to 64% of foreign-born women living in Canada at least 17 years.

"The disparity in pre-conceptual folic acid supplement use may be due to unplanned/unintended pregnancies or lack of awareness of the benefits of folic acid supplements," Ray said. "Immigrant women, especially those from non-Western countries, are least likely to have this information, which can otherwise be easily provided to these women through various communication mediums."

The study's authors suggest immigrant women be provided with a language-specific pamphlet on the benefits of folic acid, or even with free supplements.


Wednesday, March 18, 2009

Mediterranean diet may help prevent spina bifida

Mediterranean diet may help prevent spina bifida

Reuters Health
Thursday, February 12, 2009
By Anne Harding

NEW YORK (Reuters Health) - Moms-to-be can help prevent their babies from developing a serious spinal cord defect by eating a Mediterranean diet, Dutch researchers say.

Dr. Regine P. M. Steegers-Theunissen of Erasmus Medical Center in Rotterdam and colleagues found that women who ate more fruit, vegetables, healthy oils, fish and whole grains were less likely to give birth to a child with spina bifida.

Folic acid supplementation has been shown to help prevent this birth defect, in which the spinal cord fails to close completely. Some countries, including the United States, now fortify foods with folate to ensure pregnant women are getting enough of the nutrient. But folate isn't the whole story, Steegers-Theunissen told Reuters Health. "It's not only folate which is protective, but it's the whole diet. It's the balance of the diet in which folate is an important component."

In southern Europe, where the Mediterranean diet originated, rates of spina bifida are lower, and the defect is also less common in countries that fortify food with folate, the investigators note in their report.

To investigate whether diet might play a role in spina bifida risk, the researchers studied the diets of 50 women who had given birth to a child with spina bifida and 81 women whose children did not have the birth defect.

Women with the least Mediterranean-like diet were about three times more likely to have had a child with spina bifida, the researchers found. And the more closely a woman's diet adhered to the Mediterranean pattern, the higher her blood levels of folate and vitamin B12.

In the Netherlands, food is not fortified with folate, Steegers-Theunissen noted in an interview. Some of the women in the study, but not all, were taking folic acid supplements. But when the researchers controlled for the effects of the supplements, as well as body mass index (another known risk factor for having a baby with spina bifida), they found the Mediterranean diet independently reduced spina bifida risk.

SOURCE: BJOG, February 200

Low Levels of Vitamin B12 May Increase Risk for Neural Tube Defects

Low Levels of Vitamin B12 May Increase Risk for Neural Tube Defects
Monday, March 2, 2009

Children born to women who have low blood levels of vitamin B12 shortly before and after conception may have an increased risk of a neural tube defect, according to an analysis by researchers at the National Institutes of Health, Trinity College Dublin, and the Health Research Board of Ireland.

Women with the lowest B12 levels had 5 times the risk of having a child with a neural tube defect compared to women with the highest B12 levels.

Women who consume little or no meat or animal based foods are the most likely group of women to have low B12 levels, along with women who have intestinal disorders that prevent them from absorbing sufficient amounts of B12.

Neural tube defects are a class of birth defects affecting the brain and spinal cord. One type, spina bifida, can cause partial paralysis. Another type, anencephaly, is a fatal defect in which the brain and skull are severely underdeveloped.

Researchers have known that taking another nutrient, folic acid, during the weeks before and after conception can greatly reduce a woman’s chances of having a child with a neural tube defect. Folic acid is the synthetic form of the vitamin folate. In the United States, cereal grains are fortified with folic acid to reduce the occurrence of neural tube defects in the U.S. population.

The study appears in the March Pediatrics. The study’s first author was Anne M. Molloy, Ph.D., Trinity College Dublin. Scientists from the Health Research Board of Ireland and two NIH institutes, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Human Genome Research Institute, also took part in the study.

"Vitamin B12 is essential for the functioning of the nervous system and for the production of red blood cells,” said Duane Alexander, M.D., director of the NICHD. "The results of this study suggest that women with low levels of B12 not only may risk health problems of their own, but also may increase the chance that their children may be born with a serious birth defect."

Ireland has a high rate of neural tube defects, and NIH scientists have frequently collaborated with Irish researchers to gain insight into the causes of this group of disorders.

To conduct the study, the researchers analyzed stored blood samples originally collected during early pregnancy from three groups of Irish women between 1983 and 1990. During that time, pregnant women in Ireland rarely took vitamin supplements. The study authors reasoned that the lack of routine vitamin supplementation would allow them to identify a sufficient number of women with low Vitamin B12 to conduct their analysis.

For their analysis, the researchers classified the women into three groups. The first group consisted of 95 women who were pregnant with a child having a neural tube defect at the time the blood was taken. The second group was composed of 107 women who had previously given birth to a child with a neural tube defect but whose current pregnancy was not affected. Like the first group, women in the third group (a total of 76) were pregnant with a child having a neural tube defect at the time the blood sample was obtained, but were enrolled in a different study than the women in group 1. The researchers measured the Vitamin B12 and folate levels of the women’s blood samples, and compared them to those of control groups whose pregnancies were unaffected by a neural tube defect.

Because low folate levels are a known risk factor for neural tube defects, the researchers used statistical techniques to evaluate the role of Vitamin B12 independently of the role of folate. In all three groups, women with low B12 concentrations (estimated at less than 250 ng/L, before pregnancy) had 2.5-3 times the risk of having a child with a neural tube defect compared to those with higher levels. Women with levels in the deficient range (0-149 ng/L ) were at the highest risk: 5 times that of women with higher levels.

The study authors wrote that it is not known how B12 and folate might interact to influence the formation of the neural tube, the embryonic structure that gives rise to the spine and brain. They noted that the two vitamins are jointly involved with several key biochemical reactions, as well as with the synthesis of DNA. Lack of either Vitamin B12 or folate in any of these chemical processes theoretically could increase the risk of a neural tube defect.

The authors noted that their results needed to be confirmed by other studies among other populations of women. They suggested, however, that women should have Vitamin B12 levels above 300 ng/L before becoming pregnant. (Because B12 levels drop sharply during pregnancy, the researchers adjusted the levels measured during pregnancy to provide a target level for women to achieve before they become pregnant.)

Because Vitamin B12 comes from foods of animal origin, women who adhere to a strict vegan diet may be at risk for a B12 deficiency, said an NICHD author of the paper, James L. Mills, M.D., senior investigator in the Division of Epidemiology, Statistics, and Prevention Research. He added it is advisable for women with digestive disorders that interfere with the absorption of foods to consult a physician before getting pregnant, to make sure they are receiving adequate amounts of B12.

Dr. Mills explained that critical events in the formation of the brain and spinal column occur very early in pregnancy—in the first 28 days after conception—before many women even realize they are pregnant.

He added that the U.S. Public Health Service recommends that all women of childbearing age consume 400 micrograms of folic acid each day. This amount assures that a woman will have adequate stores of the vitamin, in the event of an unintended pregnancy.

"If women wait until they realize that they are pregnant before they start taking folic acid, it is usually too late," Dr. Mills said.

Similarly, he said, it would be wise for all women of childbearing age to consume the recommended amount of Vitamin B12, whether they are planning a pregnancy or not. "Half of the women who become pregnant each year in the U.S. were not planning to become pregnant."

"Our results offer evidence that women who have adequate B12 levels before they become pregnant may further reduce the occurrence of this class of birth defects," Dr. Mills said.

Vitamin B12 is available in milk, meats, poultry, eggs, as well as fortified cereals and some other fortified foods. Information on foods that contain Vitamin B12, as well as the Recommended Dietary Allowances for the vitamin, is available from the NIH Office of Dietary Supplements, http://dietary-supplements.info.nih.gov/factsheets/vitaminb12.asp.

Folate is found in leafy green vegetables, fruits, and dried beans and peas. Information on sources of folate also is available from the NIH Office of Dietary Supplements, http://ods.od.nih.gov/factsheets/folate.asp.

Dr. Mills explains the study findings in the accompanying online video at http://www.nichd.nih.gov/news/resources/links/videoNTDS-B12

A transcript of the video is available on the NICHD Web site at http://www.nichd.nih.gov/news/resources/links/transcriptNTDS-B12.cfm

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Filmmakers to tackle Canadian Agent Orange scandal

Filmmakers to tackle Agent Orange scandal
Published Monday March 9th, 2009

A group of New York moviemakers will settle into the Fredericton region for the next few weeks to film what it calls "Canada's dirty secret" to a worldwide audience.

Filmmakers Danny Feighery and Gregg de Domenico and two colleagues arrive in Fredericton today to work on their documentary about the lingering effects of the spraying of Agent Orange and other toxic chemicals at Canadian Forces Base Gagetown.

They will remain until the April 1 deadline for the federal government's $20,000 ex-gratia compensation payments passes.

"It's such a bizarre story," said Feighery. "There's all these different qualifiers and rules and absurdities to it."

"The whole story seems to be pretty absurd. There's never been anything so massive in western civilization for a government to poison their own people on this scale."

He's personally invested in the story.

His grandfather was a member of the provost corps at CFB Gagetown - the precursor to the military police - so his mother Sharon grew up on the base, ate blueberries that had grown on the base and played there.

When his sister Theresa was born, she had spina bifida. It's a congenital defect of the spine, in which part of the spinal cord and the meninges are exposed through a gap in the backbone. The condition has been linked to exposure to Agent Orange and a whole host of other toxic chemicals that were sprayed on the base.

It wasn't until a family reunion last year in Nova Scotia where relatives talked about Agent Orange that Feighery's family began drawing possible links to his sister's spina bifida and exposure to toxic defoliants.

"No democracy has ever let half a million people be contaminated by a toxin and then never tell them about it and cover it up," he said.

De Domenico said the story deserves a wider audience.

"I'm curious about the story and I'd like to see somebody see this through to get some answers," he said. "I know, personally, I feel like - especially coming out of the Bush administration in the United States - we're all looking for some degree of accountability from our governments.

"I know I personally feel like I want to see transparency and I want to see fairness. I want to know we're not being taken advantage of by corporate interests."

They plan to delve into the involvement of chemical companies, the military and the government.

"We want to go further, looking into the factfinder's mission, the results of the factfinder's mission, how that affected Veterans Affairs and the compensation packages. Then straight into the compensation packages ending April 1 and where does everyone go from there," de Domenico said.

Veterans Affairs Minister Greg Thompson has said the April 1 deadline isn't absolute and if a late application is received, it will be considered.

Payments are also considered for primary caregivers of qualifying individuals who died on or after Feb. 6, 2006, the date the federal Conservative government took office.

Thankfully, he said, many people in the region have taken up the challenge of doing the research.

He just hopes to do them justice on the big screen.

"We're very much doing our best to tell their story."

"There's only so many times you can sit with them and hold their hands while they're crying, saying they feel left in the cold. I want to feel like we can get the word out and maybe bring some more attention to this."

And for de Domenico and Feighery, who have long worked making commercials and feature films, it's a chance to put their craft to a higher use.

"We want to get back to a place where filmmaking is about helping society and making a difference."

"What we really need now is to talk to politicians who understand the story and are sympathetic.''

The film is tentatively titled Gagetown: Canada's Dirty Secret. They hope to have an 80- to 90-minute film ready by later this spring, the deadline for entering the Toronto Film Festival.

Feighery and de Domenico have been keeping in touch with people involved with the movie through their website: www.gagetownmovie.com.

Neuroscientists isolate gene essential to early brain development

Neuroscientists isolate gene essential to early brain development
November 27th, 2008

University of Queensland neuroscientists have discovered the crucial role a specific gene plays in forming the neural tube, the earliest identifiable structure in the developing brain and an essential precursor to the entire central nervous system.

While investigating neural tube closure in the clawed toad (Xenopus laevis) and in zebrafish, Associate Professor Helen Cooper at the Queensland Brain Institute (QBI) has, for the first time, described one of the processes that drive this crucial stage of brain development, which is common to all vertebrates.

“Globally, neural tube closure defects occur in about one-in-a-thousand human pregnancies, resulting in malformations of the central nervous system and conditions such as spina bifida or anencephaly,” Dr Cooper said.

In spina bifida, for example, incomplete closure of the embryonic neural tube leads to incorrect development of the spinal cord, often resulting in significant disability.

“Although it has been known for some time that regular intake of folic acid before conception greatly reduces the incidence of neural tube abnormalities, scientists are still trying to understand the complex interplay of genes during this crucial early stage of brain development.”

“Our laboratory has now established that a copy of one particular gene (Neogenin) is essential for proper formation of neural folds, the first stages in the development of neural tubes.

“If the neural folds do not develop then the neural tube cannot close, resulting in neural tube defects,” Dr Cooper said.

“And just as importantly, our lab has also discovered that Neogenin is vital for differentiation of neural stems cells throughout the development of the early central nervous system.”

Neuroscientists studying early brain development often investigate zebrafish because these small freshwater animals produce several hundred embryos, which develop rapidly and are almost totally transparent from fertilisation to hatching (about 48 hours), allowing scientists to view brain development as it happens.

Dr Cooper's research: “Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity” is published in this week's edition of the Journal of Neuroscience.

Babies & Robots: Infant power mobility on display

Babies & Robots: Infant power mobility on display
February 4th, 2009

Children with mobility issues, like cerebral palsy and spina bifida, can't explore the world like other babies, because they can't crawl or walk. Infant development emerges from the thousands of daily discoveries experienced by babies as they move and explore their worlds.

Mobility-deprived kids start exploring when they can operate a traditional power wheelchair, typically at age 3 or often older.

Research done by University of Delaware researchers is turning that on its head and could potentially change the way these children's brains develop.

Physical therapy professor Cole Galloway and mechanical engineering professor Sunil Agrawal have developed tiny power chairs babies as young as 6 months can operate using a joystick.

Now, they've paired with Permobil, a national producer of power chairs, and outfitted a chair for toddlers.

Galloway will be showcasing this research next week in Las Vegas at the American Physical Therapy Association's Combined Sections Meeting. (Tuesday, February 10, 10am-3pm)

A 17-month-old boy, Andrew, who's been driving the robots for more than a year, will be on hand to demonstrate the technology. On an average day, Andrew uses his chair to navigate his home and the outside world. He is ready to attend pre-K next year, impressive progress for a child with spina bifida.

Galloway believes providing mobility to children who wouldn't have it otherwise could impact their lives in countless ways, especially when you consider the rapid brain development during infancy.

"Babies literally build their own brains through their exploration and learning in the complex world," he says. "Their actions, feelings and thinking all shape their own brain's development.

"Mobility is linked to widespread advances in cognitive development and learning abilities in typically developing infants."

The University of Delaware has filed patents and is working to bring to market a robot-enhanced mini wheelchair for children aged 6 months-2 years.

For more information, check out:

http://www.udel.edu/PT/About Us/People/galloway.html

Source: University of Delaware

Obesity during pregnancy linked to increased risk of babies born with abnormalities

Obesity during pregnancy linked to increased risk of babies born with abnormalities
February 11th, 2009

(PhysOrg.com) -- A Newcastle University study has shown that obese women who become pregnant have an increased risk of their baby being born with certain abnormalities, including spina bifida.

They found that women who were obese were more than twice as likely to have a baby with spina bifida, a condition which affects a very small number of pregnancies but which may result in disability.

Dr Judith Rankin from the team who carried out the study says, “Women who are thinking about trying for a baby need to check their own weight first and then think about seeking help if they are overweight. While you are pregnant it’s not the time to start a weight loss diet but it is more important to eat sensibly and healthily.”

Recent studies suggest up to a fifth of pregnant mothers are classed as obese in the UK - a figure that has doubled in the last 10 years.*

In the United States, a third of women age 15 years and older were obese in 2004.

Obese is considered as a Body Mass Index (BMI) over 30, while overweight is classed as a BMI over 25, as categorized by the World Health Organisation.

The study, out today in the academic journal JAMA, analysed and combined data from 39 previous studies to look at the risks of abnormalities in the baby for mothers who were obese or overweight.

It showed that obese women were nearly twice as likely to have a baby with neural tube defects which are caused by the incomplete development of the brain, spinal cord and/or their protective coverings. For one of those conditions, spina bifida, the risk was more than doubled.

Researchers also detected an increased risk in heart defects (cardiovascular anomaly), cleft lip and palate, a malformation of the lower bowel (anorectal atresia), increased risk of water on the brain (hydrocephaly) and problems in the growth of arms and legs (limb reduction anomaly).

For the first time, researchers found a possible link between mothers who are overweight and babies with neural tube defects, although they say more research needs to be done in this area.

“This is the first time that so many studies have been combined to build a more accurate picture and it shows a link between a mother’s weight and many of these serious conditions in the newborn baby. Given that we are seeing an increase in the number of people who are overweight or obese, then we may see an increase in the number of babies born with abnormalities”, says Dr Rankin.

Despite their findings, the researchers were keen to stress that these abnormalities are uncommon. “Spina bifida only occurs in approximately one in every two thousand births, so the risk, even among obese women, remains very low.”

The Newcastle University team will now continue the work to examine why there is a link between a mother’s weight and abnormalities in the baby.

Academic paper: Maternal Overweight and Obesity and the Risk of Congenital Anomalies. A systematic review and Meta-analysis. Katherine J. Stothard, PhD, Peter W.G Tennant, MSc, Ruth Bell, MD, Judith Rankin, PhD.

More information: JAMA. 2009;3016:636-650.


*There are no national published figures relating to pregnancy so this figure is based on a study published in 2006 in BJOG which showed 16% of women are obese at booking in Middlesbrough.

Birth brain defect could be treated with vitamin supplement

Birth brain defect could be treated with vitamin supplement
March 17th, 2009

(PhysOrg.com) -- Pioneering research published today suggests that a vitamin supplement taken during pregnancy could prevent hydrocephalus - one of the common forms of birth brain defect.

Scientists at The University of Manchester and Lancaster University say laboratory tests have shown that administering a combination of vitamins (tetrahydrofolate and folinic acid), dramatically reduces the risk of hydrocephalus.

Dr Jaleel Miyan, who led the research in Manchester’s Faculty of Life Sciences, said: “Hydrocephalus is a condition arising from an abnormal build-up of fluid within the chambers of the brain.

“This fluid build-up - usually caused by a blockage in the fluid’s pathway due to trauma, infection or abnormal development - is associated with an increase in the pressure on the brain resulting in brain damage. When this happens, doctors can relieve this pressure only by performing surgery.

“Our studies have revealed that hydrocephalus is associated with a change in the composition of the cerebrospinal fluid and it is this chemical change that prevents normal growth of the brain cells resulting in arrested brain development. This occurs prior to any brain damage due to raised pressure.”

The findings of the study, funded by Association for Spina Bifida & Hydrocephalus (ASBAH) and published in the Journal of Neuropathology and Experimental Neurology, led the team to examine ways of stimulating cell division to encourage normal brain development.

Dr Miyan explained: “A combination of tetrahydrofolate and folinic acid - both naturally occurring substances - stimulated brain cell growth and had a significant positive effect on brain development in laboratory experiments on rats and reduced the incidence of hydrocephalus.

“In laboratory experiments, the combined folate supplement works at any stage during pregnancy which means that it may be effective even if it is commenced after the diagnosis of hydrocephalus is made at an 18 to 20 week pregnancy scan.