Exposure to high pollution levels during pregnancy may increase risk of having child with autism

AutismWomen in the U.S. exposed to high levels of air pollution while pregnant were up to twice as likely to have a child with autism as women who lived in areas with low pollution, according to a new study from Harvard School of Public Health (HSPH). It is the first large national study to examine links between autism and air pollution across the U.S.

“Our findings raise concerns since, depending on the pollutant, 20% to 60% of the women in our study lived in areas where risk of autism was elevated,” said lead author Andrea Roberts, research associate in the HSPH Department of Social and Behavioral Sciences.

The study appeared online June 18, 2013 in Environmental Health Perspectives.

Exposure to diesel particulates, lead, manganese, mercury, methylene chloride and other pollutants are known to affect brain function and to affect the developing baby. Two previous studies found associations between exposure to air pollution during pregnancy and autism in children, but those studies looked at data in just three locations in the U.S.

The researchers examined data from Nurses’ Health Study II, a long-term study based at Brigham and Women’s Hospital involving 116,430 nurses that began in 1989. Among that group, the authors studied 325 women who had a child with autism and 22,000 women who had a child without the disorder. They looked at associations between autism and levels of pollutants at the time and place of birth. They used air pollution data from the U.S. Environmental Protection Agency to estimate women’s exposure to pollutants while pregnant. They also adjusted for the influence of factors such as income, education, and smoking during pregnancy.

The results showed that women who lived in the 20% of locations with the highest levels of diesel particulates or mercury in the air were twice as likely to have a child with autism as those who lived in the 20% of areas with the lowest levels.

Other types of air pollution—lead, manganese, methylene chloride, and combined metal exposure—were associated with higher autism risk as well. Women who lived in the 20% of locations with the highest levels of these pollutants were about 50% more likely to have a child with autism than those who lived in the 20% of areas with the lowest concentrations.

Most pollutants were associated with autism more strongly in boys than girls. However, since there were few girls with autism in the study, the authors said this finding should be examined further.

Senior author Marc Weisskopf, associate professor of environmental and occupational epidemiology at HSPH, said, “Our results suggest that new studies should begin the process of measuring metals and other pollutants in the blood of pregnant women or newborn children to provide stronger evidence that specific pollutants increase risk of autism. A better understanding of this can help to develop interventions to reduce pregnant women’s exposure to these pollutants.”

 

Reference

Roberts AL, Lyall K, Hart JE, Laden F, Just AC, Bobb JF, Koenen KC, Ascherio A, Weisskopf MG. Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environmental Health Perspectives, online June 18, 2013.

 

Folic acid supplements early in pregnancy may reduce child’s risk of autism by 40 percent

Large study in Norway finds early timing of supplements is critical:

JAMAPrenatal folic acid supplements appear to reduce the risk for autistic spectrum disorders, according to a study published today (February 13) in the Journal of the American Medical Association (JAMA).

The Centers for Disease Control and Prevention estimate that about 1 in 88 children in the U.S. have been identified with an Autism Spectrum Disorder (ASD). ASDs are amongst the most heritable of mental disorders, but little is known about how the disorder develops. Consequently, methods for diagnosis, prevention, and treatment are limited.

Folic acid (Vitamin B9) is required for DNA synthesis and repair in the human body, and its naturally occurring form—folate—is found in leafy vegetables, peas, lentils, beans, eggs, yeast, and liver. Taking folic acid supplements during early pregnancy is known to protect against spina bifida and other neural tube defects in children. In the United States, Canada, and Chile, folic acid is added to flour, so as to automatically provide these supplements to consumers. Norway does not enrich its flour, and since 1998, the Norwegian Directorate of Health has recommended that all women planning to become pregnant take a daily supplement of folic acid from one month before the start of pregnancy through the first trimester.

Despite this policy, studies from North America and Europe have shown that many pregnant women have a lower dietary intake of folate than what is necessary to prevent neural tube defects.

The report in JAMA emerged from the Norwegian Mother and Child Cohort Study (MoBa) and its sub-study of autism, the Autism Birth Cohort (ABC) Study. This international collaboration (see list of members below) comprises the largest prospective birth cohort devoted to the investigation of gene-environment interactions and biomarker discovery for neuropsychiatric disorders.

A total of 85,176 MoBa babies—born from 2002-2008—and their parents participated in the study. Prenatal dietary habits were recorded, and families were regularly surveyed for 3-10 years to measure the development of autism spectrum disorders. A total of 270 cases of autism spectrum disorders were identified in the study population (114 autistic disorder; 56 Asperger syndrome; 100 atypical or unspecified autism; i.e., pervasive developmental disorder not otherwise specified, PDD-NOS).

Mothers who took folic acid supplements in early pregnancy had a 40% reduced risk of having children with autistic disorder compared with mothers who did not take folic acid. The reduction in risk was observed in those who took folic acid during the time interval from 4 weeks before to 8 weeks after the start of pregnancy. Autistic disorder is the most severe form of autism spectrum disorders in children. No reduction in risk was observed for PDD-NOS. For Asperger syndrome, the number of children was too low to obtain sufficient statistical power in the analyses.

The use of folic acid in early pregnancy increased substantially from 2002 to 2008 among women who participated in MoBa. In 2002, 43% of mothers took folic acid supplements; by 2008, 85% of mothers did. However, many women began taking folic acid later than recommended, and only half started before the beginning of pregnancy.

The timing of a mother’s intake of folate appears to be a critical factor. Her child’s risk of autism was reduced only when the supplements were taken between 4 weeks before to 8 weeks after the start of pregnancy.

“We examined the rate of autism spectrum disorders in children born to mothers who did or did not take folic acid during pregnancy. There was a dramatic reduction in the risk of autistic disorder in children born to mothers who took folic acid supplements,” says Pål Surén, first author and epidemiologist at the Norwegian Institute of Public Health (NIPH).

The researchers also analyzed whether the risk of autistic disorder was influenced by the use of other dietary supplements. They did not find any association between the mother’s use of fish oil supplements (cod liver oil and omega-3 fatty acids) in early pregnancy and the risk of autistic disorder, and no association for the mother’s use of other vitamins and minerals.

In recent years, researchers have started to investigate whether folic acid has other beneficial effects on the development of the fetus’ brain and spinal cord. A study of language development from MoBa, published in 2011, showed that children whose mothers took folic acid supplements in early pregnancy had only half the risk of severe language delay at age three years compared with other children. A separate 2011 study from the University of California, Davis, demonstrated a lower risk of autism spectrum disorders in children of mothers who had used prenatal vitamin supplements during pregnancy. Prenatal vitamin supplements contain folic acid in combination with other vitamins and minerals.

Joint senior author Ezra Susser, professor of Epidemiology at Columbia University’s Mailman School of Public Health and professor of Psychiatry at the College of Physicians and Surgeons, stated, “Our findings extend earlier work on the significance of folate in brain development and raise the possibility of an important and inexpensive public health intervention for reducing the burden of autism spectrum disorders.”

“This elegant work illustrates the power of the ABC cohort for not only chipping away at the riddle of what causes autism, but for developing new methods for early recognition, prevention and treatment,” says W. Ian Lipkin, John Snow Professor of Epidemiology at the Mailman School of Public Health and principal investigator of the ABC cohort.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Prenatal folic acid supplementation associated with lower risk of autism

JAMAIn a study that included approximately 85,000 Norwegian children, maternal use of supplemental folic acid from 4 weeks before to 8 weeks after the start of pregnancy was associated with a lower risk of autistic disorder in children, according to a study appearing in the February 13 issue of JAMA.

“Supplementation with folic acid around the time of conception reduces the risk of neural tube defects in children. This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement of folic acid starting 1 month before conception,” according to background information in the article. It has not been determined whether prenatal folic acid supplements protect against other neurodevelopmental disorders.

Pal Surén, M.D., M.P.H., of the Norwegian Institute of Public Health, Oslo, and colleagues investigated the association between the use of maternal folic acid supplements before and in early pregnancy and the subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (average age, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Analyses were adjusted for maternal education level, year of birth, and parity (the number of live-born children a woman has delivered).

A total of 270 children (0.32 percent) in the study sample have been diagnosed with ASDs: 114 (0.13 percent) with autistic disorder, 56 (0.07 percent) with Asperger syndrome, and 100 (0.12 percent) with PDD-NOS. The researchers found that there was an inverse association between folic acid use and subsequent risk of autistic disorder. Autistic disorder was present in 0.10 percent (64/61,042) of children whose mothers took folic acid, compared with 0.21 percent (50/24,134) in children whose mothers did not take folic acid, representing a 39 percent lower odds of autistic disorder in children of folic acid users.

Characteristics of women who used folic acid within the exposure interval included being more likely to have college- or university-level education, to have planned the pregnancy, to be nonsmokers, to have a pre-pregnancy body mass index below 25, and to be first-time mothers.

“No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use,” the authors write.

The researchers note that the inverse association found for folic acid use in early pregnancy was absent for folic acid use in mid pregnancy.

“Our main finding was that maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder. This finding does not establish a causal relation between folic acid use and autistic disorder but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association,” the authors conclude.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Antibiotics During Pregnancy Increases Risk of Epilepsy in Children

foodconsumer.org – Prenatal antibiotics linked to high risk of epilepsyMonday Oct 22, 2012 (foodconsumer.org) — A new study in Pediatric and Perinatal Epidemiology suggests that taking cystitis antibiotics during pregnancy increases risk of epilepsy in children. J. E. Miller of School of Public Health, University of California, Los Angeles, CA and colleagues conducted the study and found taking cystitis antibiotics during pregnancy was associated with 10 to 20 percent increased risk of epilepsy in children.

Embedly Powered

Reference
Miller JE, Pedersen LH, Sun Y, Olsen J. Maternal Use of Cystitis Medication and Childhood Epilepsy in a Danish Population-based Cohort. Paediatr Perinat Epidemiol 2012; 26 (6): 589-95.

 

A Diet High in Choline During Pregnancy May Mean Less Stress for Baby

New research from Cornell University indicates that pregnant women who increase choline intake in the third trimester of pregnancy may reduce the risk of the baby developing metabolic and chronic stress-related diseases like high blood pressure and diabetes later in life (1). The results, published in the latest edition of the Journal of the Federation of American Societies for Experimental Biology (The FASEB Journal), suggest that choline, a nutrient found in high quantities in eggs, may help protect against the effects of a mother’s stress during pregnancy (1).

Previous research indicates high exposure to the stress hormone cortisol during pregnancy, often due to maternal anxiety or depression, may make offspring vulnerable to stress-induced illness and chronic conditions (2, 3). This finding adds to the growing body of evidence demonstrating the importance of choline in fetal development.

A Closer Look at the Study

Twenty-four women in the third trimester of pregnancy were randomly assigned to consume either 480 milligrams (mg) choline per day or 930 mg per day for 12 weeks prior to delivery. Researchers collected maternal and placental blood samples as well as samples of placental tissue. They then compared cortisol levels and genetic differences among all the samples. The researchers observed lower levels of cortisol in the placental cord and changes in cortisol-regulating genes in both the placental and fetal tissue among women in the higher choline intake group. “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,” says Marie Caudill, PhD, Cornell University, who is an author of the study and a leading choline researcher.

Choline: A Vital Nutrient

Choline is especially important for pregnant women – it has been shown to play an important role in fetal and infant brain development, affecting the areas of the brain responsible for memory and life-long learning ability. In addition, research shows women with diets low in choline have four times greater risk of having babies with neural tube defects, such as spina bifida (4).

Emerging research also shows choline may have additional benefits in other areas, including:

  • Breast cancer prevention: A study funded by the National Institutes of Health concluded that dietary choline is associated with a 24 percent reduced risk of breast cancer (5).
  • Anti-inflammatory: Foods rich in choline may help reduce the risk of inflammation associated with chronic diseases such as cardiovascular disease, bone loss, dementia and Alzheimer’s disease (6).
  • Brain function: Choline also promotes adult brain function by preserving the structure of brain cell membranes and is an essential component of acetylcholine, the neurotransmitter involved in memory function and muscle control (7).

The Incredible Excellent Source of Choline

Despite its important role in the body, only one in 10 Americans is meeting the Adequate Intake (AI) guidelines for choline (8). Eggs are an excellent source of choline, containing 125 mg per egg. Neva Cochran, registered dietitian and nutrition communications consultant, explains that the nutritional benefits of eggs are not merely limited to choline. “Not only are eggs an excellent source of choline, they contain many other nutrients pregnant women need most, such as high-quality protein, iron and folate—all for just about 15 cents apiece,” says Cochran.

In order to get adequate amounts of choline, Cochran suggests the following tips:

  • Find it in Food: A great way to get your daily dose of choline is to include choline-rich foods in the diet, such as eggs, lean beef, cauliflower and peanuts. Also keep in mind most multivitamins, even prenatal vitamins, provide far less than the Adequate Intake for choline.
  • Don’t Skip the Yolk: Choline is found exclusively in the egg yolk, not the white. Nearly half of the protein and most of the vitamins and minerals are also contained in the yolk.

 

References

1. Jiang, X., J. Yan, A. A. West, C. A. Perry, O. V. Malysheva, S. Devapatla, E. Pressman, F. Vermeylen, and M. A. Caudill. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J 2012; 26: 3563-3574.

2. Levitt, N. S., Lindsay, R. S., Holmes, M. C., and Seckl, J. R. Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology 1996; 64: 412.

3. Levitt, N. S., Lambert, E. V., Woods, D., Hales, C. N., Andrew, R., and Seckl, J. R. Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young South African adults: early programming of cortisol axis. J Clin Endocrinol Metab 2000; 85: 4611.

4. Shaw GM, et al. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol 2004; 160: 102-9.

5. Xu X, et al. Choline metabolism and risk of breast cancer in population-based study. FASEB J 2008; 22: 1-8.

6. Cho E, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. AJCN 2006; 83: 905-11.

6. Cho E, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. AJCN 2006; 83: 905-11.

7. Moeller SM, et al. The Potential Role of Dietary Xanthophylls in Cataract and Age-Related Macular Degeneration. J Am Coll Nutr 2000; 19 (5): 522S-527S.

8. Jensen HH, et al. Choline in the diets of the US population: NHANES, 2003-2004. Abstract presented at Experimental Biology 2007.

 

Prenatal Choline May Program Healthier Babies

Increased maternal intake of the nutrient choline could reduce their kid’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 per cent 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 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 mother 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 said.

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 added.

The study has been published online in The Journal of the Federation of American Societies for Experimental Biology.

 

Reference

Jiang X, Yan J, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Caudill MA. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 2012 May 1. [Epub ahead of print]

 

Mother’s Diet Influences Baby’s Allergies — New Research

A possible link between what a mother eats during pregnancy and the risk of her child developing allergies has been identified in new research published in this month’s The Journal of Physiology.

The research found that if a mother’s diet contains a certain group of polyunsaturated fatty acids (PUFAs) – such as those found in fish, walnut oil or flaxseed – the baby’s gut develops differently. The PUFAs are thought to improve how gut immune cells respond to bacteria and foreign substances, making the baby less likely to suffer from allergies.

Until now, several clinical trials have shown that fish and walnut oil supplementation in pregnant women reduces the risk of allergy in their children, but the mechanism was unknown.

“There is intense research interest in maternal diet during pregnancy. In the western diet, the group of polyunsaturated fatty acids that we have shown to help gut function are actually disappearing – our dietary intake of fish and nut oils is being replaced by corn oils which contain a different kind of fatty acid”. Said Dr Gaëlle Boudry, of the INRA research institute in Rennes, France.

“Our study identifies that a certain group of polyunsaturated fatty acids – known as n-3PUFAs – causes a change in how a baby’s gut develops, which in turn might change how the gut immune system develops. These changes are likely to reduce the risk of developing allergies in later life.”

The team found that supplementing a mother’s diet with n-3PUFA caused the new-born’s gut to become more permeable. A more permeable gut enables bacteria and new substances to pass through the lining of the gut into the bloodstream more easily. These new substances then trigger the baby’s immune response and the production of antibodies.

“The end result is that the baby’s immune system may develop and mature faster – leading to better immune function and less likelihood of suffering allergies,” added Dr Boudry.

This research adds to previous studies which have shown that an intake of n-3 PUFAs during pregnancy increases gestational length and maturation of the central nervous system of a baby and that their performance on mental tasks also seemed to be improved in childhood.

“Other studies have found that a diet containing fish or walnut oil during pregnancy may make your baby smarter – our research adds to this, suggesting such supplements also accelerate the development of a healthy immune system to ward off food allergies.”

In terms of next steps, the team’s findings were based on piglets so research will continue to see if they translate to humans. The porcine intestine is an excellent model of the human gut however, so they are hopeful that the findings can be extrapolated. The team also plans to investigate whether the apparent gut function-boosting effects of n-3PUFA that they have identified in new-borns extends into later life.

 

Reference

De Quelen F, Chevalier J, Rolli-Derkinderen M, Mourot J, Neunlist M, Boudry G. n–3 polyunsaturated fatty acids in the maternal diet modify the postnatal development of nervous regulation of intestinal permeability in piglets J Physiol 2011; 589 (17): 4341-4352.

 

Vitamin D Supplements Found To Be Safe For Healthy Pregnant Women

Use of vitamin D supplements during pregnancy has long been a matter of concern but now researchers writing in theJournal of Bone and Mineral Research report that even a high supplementation amount in healthy pregnant women was safe and effective in raising circulating vitamin D to a level thought by some to be optimal. The study also found no adverse effects of vitamin D supplementation, even at the highest amount, in women or their newborns.

The research team, led by Dr. Bruce Hollis from the Medical University of South Carolina in Charleston, used a randomized controlled trial with healthy expectant mothers to discover how varying dosages of daily supplements could safely sustain a circulating vitamin D level of at least 32 nanograms per milliliter.

“Vitamin D supplementation during pregnancy remains controversial largely due to severe misconceptions about the potential harm it may cause to the fetus,” said Dr Hollis. “Surprisingly the scientific debate has made little progress since Dr. Gilbert Forbes made a recommendation of 200 IU (international units) per day in 1963, which was based on a hunch.”

While the threat of vitamin D during pregnancy has remained little known, it has been established that the vitamin plays a role in homeostasis, the body’s internal regulation, during pregnancy and that a deficiency can effect immune, pancreatic and cardiovascular systems.

Dr Hollis’ team monitored the pregnancies of 350 women, from a variety of ethnic and socio-economic backgrounds, who were all between 12 and 16 weeks into gestation. The women were randomly assigned to one of three groups. One group received 400 IU of vitamin D per day, the second group received 2,000 IU per day and the third received 4,000 IU daily.

The team found that women who received the highest level of supplementation (4,000 IU per day) were more likely to achieve and sustain the desired level of circulating levels of vitamin D throughout their pregnancy. Moreover, the researchers found that pregnant women who received lower levels of vitamin D supplementation did not attain the threshold circulating level of the vitamin.

“In our study subjects, a daily dosage of up to 4,000 IU of vitamin D was required to sustain normal metabolism in pregnant women,” concluded Dr Hollis. “Furthermore, following decades of speculation into its safety our research has demonstrated vitamin D supplementation to be both safe and effective.”

 

Full citation:
Hollis. B, Johnson. D, Hulsey. T, Ebeling. M, Wagner. L, “Vitamin D Supplementation during Pregnancy: Double Blind, Randomized Clinical Trial of Safety and Effectiveness”, Journal of Bone and Mineral Research, Wiley-Blackwell, June 2011: DOI