Pregnant Women Consuming Choline - Nutrient in Eggs and Meat A Key To Healthy Children

Just as women are advised to get plenty of folic acid around the time of conception and throughout early pregnancy, new research suggests another very similar nutrient may one day deserve a spot on the obstetrician’s list of recommendations.

Consuming greater amounts of choline – a nutrient found in eggs and meat – during pregnancy may lower an infant’s vulnerability to stress-related illnesses, such as mental health disturbances, and chronic conditions, like hypertension, later in life.

In an early study in The FASEB Journal, nutrition scientists and obstetricians at Cornell University and the University of Rochester Medical Center found that higher-than-normal amounts of choline in the diet during pregnancy changed epigenetic markers – modifications on our DNA that tell our genes to switch on or off, to go gangbusters or keep a low profile – in the fetus. While epigenetic markers don’t change our genes, they make a permanent imprint by dictating their fate: If a gene is not expressed – turned on – it’s as if it didn’t exist.


The finding became particularly exciting when researchers discovered that the affected markers were those that regulated the hypothalamic-pituitary-adrenal or HPA axis, which controls virtually all hormone activity in the body, including the production of the hormone cortisol that reflects our response to stress and regulates our metabolism, among other things.

More choline in the mother’s diet led to a more stable HPA axis and consequently less cortisol in the fetus. As with many aspects of our health, stability is a very good thing: Past research has shown that early exposure to high levels of cortisol, often a result of a mother’s anxiety or depression, can increase a baby’s lifelong risk of stress-related and metabolic disorders.


Eva K. Pressman, M.D.
“The study is important because it shows that a relatively simple nutrient can have significant effects in prenatal life, and that these effects likely continue to have a long-lasting influence on adult life,” said Eva K. Pressman, M.D., study author and director of the high-risk pregnancy program at the University of Rochester Medical Center. “While our results won’t change practice at this point, the idea that maternal choline intake could essentially change fetal genetic expression into adulthood is quite novel.”

Pressman, who advises pregnant women every day, says choline isn’t something people think a lot about because it is already present in many things we eat and there is usually no concern of choline deficiency. Though much more research has focused on folate – functionally very similar to choline and used to decrease the risk of neural tube defects like spina bifida – a few very compelling studies sparked her interest, including animal studies on the role of choline in mitigating fetal alcohol syndrome and changing outcomes in Down syndrome.

A long-time collaborator with researchers at Cornell, Pressman joined a team led by Marie Caudill, Ph.D., R.D., professor in the Division of Nutritional Sciences at Cornell, in studying 26 pregnant women in their third trimester who were assigned to take 480 mg of choline per day, an amount slightly above the standard recommendation of 450 mg per day, or about double that amount, 930 mg per day. The choline was derived from the diet and from supplements and was consumed up until delivery.

The team found that higher maternal choline intake led to a greater amount of DNA methylation, a process in which methyl groups – one carbon atom linked to three hydrogen atoms – are added to our DNA. Choline is one of a handful of nutrients that provides methyl groups for this process. The addition of a single methyl group is all it takes to change an individual’s epigenome.

Measurements of cord blood and samples from the placenta showed that increased choline, via the addition of methyl groups, altered epigenetic markers that govern cortisol-regulating genes. Higher choline lessened the expression of these genes, leading to 33 percent lower cortisol in the blood of babies whose mom’s consumed 930 mg per day.

Study authors say the findings raise the exciting possibility that choline may be used therapeutically in cases where excess maternal stress from anxiety, depression or other prenatal conditions might make the fetal HPA axis more reactive and more likely to release greater-than-expected amounts of cortisol.

While more research is needed, Caudill says that her message to pregnant women would be to consume a diet that includes choline rich foods such as eggs, lean meat, beans and cruciferous vegetables like broccoli. For women who limit their consumption of animal products, which are richer sources of choline than plant foods, she adds that supplemental choline may be warranted as choline is generally absent in prenatal vitamin supplements.

“One day we might prescribe choline in the same way we prescribe folate to all pregnant women,” notes Pressman, the James R. Woods Professor in the Department of Obstetrics and Gynecology. “It is cheap and has virtually no side effects at the doses provided in this study. In the future, we could use choline to do even more good than we are doing right now.”

Choline During Pregnancy May Prevent Stress-Related Problems In Offspring

New research in the FASEB Journal suggests that choline supplementation in pregnant women lowers cortisol in the baby by changing epigenetic expression of genes involved in cortisol production

If you're sick from stress, a new research report appearing in the August 2012 issue of The FASEB Journal suggests that what your mother ate - or didn't eat - may be part of the cause. The report shows that choline intake that is higher than what is generally recommended during pregnancy may improve how a child responds to stress. These improvements are the result of epigenetic changes that ultimately lead to lower cortisol levels. Epigenetic changes affect how a gene functions, even if the gene itself is not changed. Lowering cortisol is important as high levels of cortisol are linked to a wide range of problems ranging from mental health to metabolic and cardiovascular disorders.

"We hope that our data will inform the development of choline intake recommendations for pregnant women that ensure optimal fetal development and reduce the risk of stress-related diseases throughout the life of the child," said Marie A. Caudill, Ph.D., a researcher involved in the work from the Division of Nutritional Sciences and Genomics at Cornell University in Ithaca, New York.

To make this discovery, Caudill and colleagues conducted a 12-week study involving pregnant women in their third trimester who consumed either the control diet providing 480 mg choline per day, a level that approximates current dietary recommendations, or the treatment diet which provided 930 mg choline per day. Maternal blood, cord blood and placenta tissue were collected to measure the blood levels of cortisol, the expression levels of genes that regulate cortisol, and the number of methyl groups attached to the DNA of the cortisol regulating genes (the epigenetic changes). Those from mothers who consumed the higher levels of choline showed reduced levels of cortisol.

"Depending on the relationship, one's mother can either produce stress or relieve it," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This report shows that her effect on stress begins even before birth. The importance of choline cannot be overstated as we continue to unravel the role it plays in human health and development."

FOLIC ACID INTAKE DURING EARLY PREGNANCY ASSOCIATED WITH REDUCED RISK OF AUTISM IN OFFSPRING

A new study by researchers at the UC Davis MIND Institute suggests that women who consume the recommended daily dosage of folic acid, the synthetic form of folate or vitamin B-9, during the first month of pregnancy may have a reduced risk of having a child with autism.

The study furthers the researchers' earlier investigations, which found that women who take prenatal vitamins around the time of conception have a reduced risk of having a child with autism. The current study sought to determine whether the folic acid consumed in those supplements was the source of the protective effect. The finding suggests that, in addition to women who already have conceived, those who are attempting to become pregnant should consider consuming folic acid supplements, the authors said.

_Rebecca J. Schmidt

The study found that women who each day consumed the recommended amount of folic acid (600 micrograms, or .6 milligrams) during the first month of pregnancy experienced a reduced risk of having a child with autism spectrum disorder, specifically when the mother and/or her child had a specific genetic variant (MTHFR 677 C>T) associated with less efficient folate metabolism. The study will be published in the July issue of the American Journal of Clinical Nutrition.

"This research is congruent with the findings of earlier studies that suggest that improved neurodevelopmental outcomes are associated with folic acid intake in early pregnancy," said lead study author Rebecca J. Schmidt, assistant professor of public health sciences in the UC Davis School of Medicine and a researcher with the UC Davis MIND Institute. "It further supports recommendations that women with any chance of becoming pregnant should consider consuming folic acid at levels of 600 micrograms or greater per day."_ _Autism is a neurodevelopmental disorder characterized by impairments in social interaction, communication deficits and repetitive behaviors and often is accompanied by intellectual disability. An estimated 1 in 88 children born today will be diagnosed with autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention.

"What's reassuring here is knowing that, by taking specific action in terms of their intake of folic acid from food or supplements, women can reduce the risk of autism spectrum disorder in their future children," said study senior author Irva Hertz-Picciotto, chief of the division of environmental and occupational health in the Department of Public Health Sciences and a MIND Institute researcher.

The study authors said that folic acid might offer protection against problems in embryonic brain development by facilitating DNA methylation reactions that can lead to changes in the way that the genetic code is read. An ample supply of methyl donors such as folic acid could be especially important in the period around conception, when the DNA methylation road map is set forth.

For the study, the researchers collected data from approximately 835 Northern California mothers of 2- to 5-year-old children who had autism, developmental delay or typical development and who were participants in the Childhood Autism Risk from Genetics and the Environment (CHARGE) study between 2003 and 2009.

_The study found that women who each day consumed the recommended amount of folic acid (600 micrograms, or .6 milligrams) during the first month of pregnancy experienced a reduced risk of having a child with autism spectrum disorder.

Each mother's average daily folic acid intake was assessed on the basis of the amount and the frequency of consumption of folic acid-containing dietary supplements such as prenatal vitamins and multivitamins, as well as the consumption of food supplemented with folic acid such as fortified breakfast cereals or energy bars. Information was collected for the period when the women were pregnant and for the three months before they became pregnant.

The study found that mothers of typically developing children reported greater-than-average intake of folic acid, and were more likely to meet intake recommendations during the first month of pregnancy than were mothers of children with autism spectrum disorder. Among study participants, as the amount of folic acid consumed increased, the associated risk for autism spectrum disorder decreased. Mothers of children with developmental delay tended to have lower estimated folic acid intake when compared with mothers of typically developing children during the three months before pregnancy.

The mothers of infants who were developing normally said they consumed an estimated average of 779 micrograms of folic acid daily and 69 percent of them at least met the daily guidelines. The mothers of children with autism consumed an estimated average of 655 micrograms of folic acid. Fifty-four percent of them consumed the recommended 600 micrograms or more per day.

Consuming supplemental folic acid before and during early pregnancy has been recommended for decades, after studies demonstrated its potential to prevent up to 70 percent of neural tube defects, or improper formation of the embryonic brain and spinal cord. Folic acid's protective effect on neural tube defects also was stronger when mothers and/or children carried the MTHFR 677 C>T gene variant. Early maternal folic acid supplementation has more recently been shown to improve other social, attention and behavioral outcomes in the developing child.

Vitamin C improves pulmonary function in newborns of pregnant smoking women

Vitamin C supplementation in pregnant women who are unable to quit smoking significantly improves pulmonary function in their newborns, according to a new study.

"Smoking during pregnancy is known to adversely affect the lung development of the developing baby," said Cindy McEvoy, MD, associate professor of pediatrics at Oregon Health & Science University Doernbecher Children's Hospital. "We found that daily use of vitamin C (500 mg/day) by smoking pregnant woman significantly improved pulmonary function tests administered to their offspring at about 48 hours postpartum."

The results will be presented at the ATS 2012 International Conference in San Francisco.

The study enrolled the newborns of 159 smoking women and randomized them to daily vitamin C (500 mg) or placebo before 22 weeks gestation and treatment was continued through delivery.76 non smoking pregnant women were also studied. The primary outcome of the study was the measurement of the newborn's lung function with a pulmonary function test at about 48 hours of life. This assessment included measurement of peak tidal expiratory flow to expiratory time (TPTEF:TE) and respiratory compliance (Crs).

Smokers treated with placebo had significantly lower levels of ascorbic acid than non-smokers, but levels returned to those of non-smokers in smokers randomized to vitamin C. Newborns of smoking women randomized to placebo had decreased TPTEF:TE and Crs compared to non-smokers. Both TPTEF:TE and Crs were significantly increased by vitamin C supplementation, returning them nearly to the levels seen in non-smokers.

"In our pilot study, we were able to show that babies born to smoking pregnant women who were randomized to daily supplemental vitamin C had significantly improved pulmonary/lung function tests compared to babies born to smoking women who were randomized to placebo," said Dr. McEvoy.

"Moreover, although our study numbers were small, we found that one particular genetic variant that has been shown to increase the risk of smokers developing cancer and is associated with both a reduced ability to quit smoking and a high likelihood of relapse, also seemed to intensify the harmful effects of maternal smoking on babies' lungs. Although the lung function of all babies born to smokers in our study was improved by supplemental vitamin C, our preliminary data suggest, importantly, that vitamin C may help those babies at the greatest risk of harm during their development from their mother's smoking in pregnancy."

"Getting women to quit smoking during pregnancy has to be priority one, but this study provides a way to potentially help the infants born to at least 12% of pregnant women who cannot quit smoking when pregnant." said Dr. McEvoy. "Vitamin C supplementation may block some of the in-utero effects of smoking on fetal lung development."

"Our findings are important because improved lung function tests at birth are associated with less wheezing and asthma in childhood," concluded Dr. McEvoy. "Vitamin C is a simple, safe, and inexpensive treatment that may decrease the impact of smoking during pregnancy on the respiratory health of children."

Flu shot during pregnancy shows unexpected benefits in large study

Getting a flu shot during pregnancy provides unanticipated benefits to the baby, according to the authors of a large population-based study examining the issue. Specifically, the study showed that H1N1 vaccination during the pandemic was associated with a significantly reduced risk of stillbirth, preterm birth and extremely small babies at birth.

Researchers at the Ottawa Hospital Research Institute (OHRI), the CHEO Research Institute and the University of Ottawa (uOttawa) used data from Ontario's birth record database, BORN, to examine 55,570 single-child births that took place in Ontario during the H1N1 pandemic. The resulting paper, "H1N1 Influenza Vaccination during Pregnancy and Fetal and Neonatal Outcomes," was recently published by the American Journal of Public Health.

The study shows that, compared to pregnant women who were not immunized against H1N1, mothers who received the H1N1 vaccination were:
•
34% less likely to have a stillbirth, •
•
28% less likely to deliver before 32 weeks, and •
•
19% less likely to give birth to a child with a birth weight for gestational age in the bottom third percentile. •

"These are all significant results, but especially interesting is the finding that the vaccinated mothers were one-third less likely to have a stillborn child," says lead author Deshayne Fell, an epidemiologist for BORN Ontario. "This is one of the only studies large enough to evaluate the association between maternal flu vaccination and stillbirth—a very rare event."

"What surprised me and the research team was the strength of the protective benefits we found," says co-author Dr. Ann Sprague, the Scientific Manager of BORN Ontario at the Children's Hospital of Eastern Ontario (CHEO) Research Institute.

The study also found no increase in adverse outcomes for H1N1-vaccinated mothers and their babies during the weeks before and just after birth, also referred to as the perinatal period.

"The findings of this study are very helpful," says co-author Dr. Mark Walker, a Senior Scientist at OHRI, a High-Risk Obstetrician at The Ottawa Hospital, and a Professor and Tier One Research Chair in Perinatal Research at the University of Ottawa.

"Pregnant women are generally very, very careful about what they put into their bodies. For health-care providers like me, such a large-scale study that shows no adverse perinatal outcomes resulting from the H1N1 flu vaccine will be extremely helpful when discussing maternal vaccination."

Of all the single-child births recorded from November 2009 to April 2010, 42% of the women received the H1N1 vaccination, which makes the findings robust. BORN—the Better Outcomes Registry & Network—collects data from all births in Ontario. In order to conduct the research for this study, questions about H1N1 vaccination were added to the database in advance of the H1N1 vaccine becoming available. BORN includes demographic data that allowed the research team to correct for smoking, education and income; however, as with any population-based study, it may not be possible to account for all influencing factors.

LINK BETWEEN PREPREGNANCY OBESITY AND LOWER CHILD TEST SCORES

Women who are obese before they become pregnant are at higher risk of having children with lower cognitive function - as measured by math and reading tests taken between ages 5 to 7 years - than are mothers with a healthy prepregnancy weight, new research suggests.

In this large observational study, prepregnancy obesity was associated, on average, with a three-point drop in reading scores and a two-point reduction in math scores on a commonly used test of children’s cognitive function.

Previous research has suggested that a woman’s prepregnancy obesity can have a negative effect on fetal organs, such as the heart, liver and pancreas. Because fetal development is rapid and sensitive to a mother’s physiological characteristics, Ohio State University researchers sought to find out whether a mother’s obesity also could affect the fetal brain.

“One way you measure the effects on the brain is by measuring cognition,” said Rika Tanda, lead author of the study and a doctoral candidate in nursing at Ohio State.

The research also supported findings in previous studies suggesting that several other conditions affect childhood cognition, including how stimulating the home environment is, family income and a mother’s education and cognitive skills.

“The new piece here is we have a measure associated with the fetus’s environment to add to that set of potential risk factors,” said Pamela Salsberry, senior author of the study and a professor of nursing at Ohio State. “If we have a good way to understand the risks each child is born with, we could tailor the post-birth environment in such a way that they could reach their maximum capabilities.”

The research appears online and is scheduled for future print publication in the Maternal and Child Health Journal.

The researchers used data from the National Longitudinal Survey of Youth (NLSY) 1979 Mother and Child Survey, a nationally representative sample of men and women who were 14-21 years old in December 1978. From that dataset, Tanda collected information on 3,412 children born to NLSY mothers who had been full-term births, were between 5 and almost 7 years old at the time of their interview and who had no diagnosed physical or cognition problems.

In addition to documenting a number of characteristics about the mothers and the family environment, the researchers gauged the children’s cognitive function based on their performance on Peabody Individual Achievement Test reading recognition and math assessments.

The researchers calculated the mothers’ body mass index (BMI) based on their reported heights and weights. More than half of mothers had normal BMIs before pregnancy, and 9.6 percent were obese, meaning they had a BMI of 30 or higher.

Controlling for all other variables, the analysis showed that maternal prepregnancy obesity was negatively associated with math and reading test scores. Children of obese women scored, on average, three points lower on reading and two points lower on math than did children of healthy-weight women. The mean reading score among all the children was 106.1 points and the mean math score was 99.9.

Though the score differences seem small, Tanda noted that these effects of prepregnancy obesity were equivalent to a seven-year decrease in the mothers’ education and significantly lower family income, two other known risk factors that negatively affect childhood cognitive function.

Tanda said clinicians could use these findings to help encourage women patients of childbearing age to maintain a healthy weight, especially if they plan to get pregnant.

“This is a large population study, so at the individual level we can’t say that one person’s decision to change her weight will change her child’s outcome,” she said. “But these findings suggest that children born to women who are obese before pregnancy might need extra support.”

Added Salsberry, “It’s not only for their child’s sake. It’s also important for the health of the mother. But it is important to understand that maternal obesity during pregnancy could have implications for their children as well.”

“If we have a good way to understand the risks each child is born with, we could tailor the post-birth environment in such a way that they could reach their maximum capabilities.”

Without actual measures of women’s and fetuses’ insulin levels, inflammation and blood sugar readings, scientists can’t say for sure how prepregnancy obesity might affect the fetal brain. But previous studies have suggested that a mother’s impaired metabolic processes affect the fetal brain cell growth and formation of synapses.

The researchers also noted that obesity doesn’t automatically equate to unhealthy.

“There may be two obese moms that in fact have very different metabolic profiles. For the purposes of this study, her weight is a stand-in for biological data that we would like to have but don’t,” Salsberry said.

Socioeconomic data from the study supported previous findings that several post-birth conditions can have a positive association with higher children’s test scores. These include a stimulating home environment with plenty of books, a safe play environment and frequent family meals; higher family income; and higher maternal education levels and cognitive function. Girls and first-born children also performed better on the math and reading tests than did boys and younger siblings.

With all these data combined, Tanda said, the study also reveals how health disparities can have long-lasting effects.

“Young females who grow up poor, who have less access to healthy foods resulting in diets that are of poorer quality, are at higher risk of having children with disadvantages and repeating this cycle,” she said.

The researchers are continuing to examine additional influences on childhood cognition, including race, sex and age differences among mothers.

Prenatal choline may 'program' healthier babies

Pregnant women may have added incentive to bulk up on broccoli and eggs now that a Cornell University study has found increased maternal intake of the nutrient choline could decrease their children's chances of developing hypertension and diabetes later in life.

In a study led by Marie Caudill, associate professor of nutritional sciences, and graduate student Xinyin Jiang, a group of third-trimester pregnant women consumed 930 milligrams of choline, more than double the recommended 450 milligram daily intake. The result for their babies was 33 percent lower concentrations of cortisol – a hormone produced in response to stress that also increases blood sugar – compared to those from a control group of women who consumed about 480 milligrams of choline.

Caudill believes this happened because the choline changed the expression patterns of genes involved in cortisol production. The work, published online this week in The Journal of the Federation of American Societies for Experimental Biology, is the first human study to suggest a role for choline in the "programming" of key biological processes in the baby.

"The study findings raise the exciting possibility that a higher maternal choline intake may counter some of the adverse effects of prenatal stress on behavioral, neuroendocrine and metabolic development in the offspring," Caudill said.

This could be especially useful for women experiencing anxiety and depression during their pregnancy, as well as conditions such as pre-eclampsia.

"A dampening of the baby's response to stress as a result of mom consuming extra choline during pregnancy would be expected to reduce the risk of stress-related diseases such as hypertension and type 2 diabetes throughout the life of the child," she added.

She said additional studies are needed to confirm the study findings and further explore long-term effects. Dietary sources of choline include egg yolks, beef, pork, chicken, milk, legumes and some vegetables. Most prenatal vitamin supplements do not include choline.

"We hope that our data will inform the development of choline intake recommendations for pregnant women that ensure optimal fetal development and reduce the risk of stress-related diseases," Caudill said.