Friday, October 14, 2011

Exercise Before and During Early Pregnancy Increases Two Beneficial Proteins for Mothers-to-Be

A role in preventing preeclampsia?

Bethesda, Md. –Although exercise is generally considered to be a good thing for people with high blood pressure, it has traditionally been considered too risky for women who are also pregnant. Some studies suggest that exercise has benefits such as decreasing the risk of women developing preeclampsia, a condition that raises blood pressure to dangerously high levels but how this might happen has remained unknown. New research using an animal model falls into the “pro-exercise” camp: It suggests that exercise before conception and in the early stages of pregnancy may protect a mother-to-be by stimulating the expression of two proteins thought to play a role in blood vessel health.

The study was led by Jeffrey Gilbert of the University of Oregon’s Department of Human Physiology, while he was with the University of Minnesota Medical School. Dr. Gilbert will present the research at the Physiology of Cardiovascular Disease: Gender Disparities conference, October 12–14 at the University of Mississippi in Jackson. The conference is sponsored by the American Physiological Society with additional support from the American Heart Association. His presentation is entitled, “Exercise Training Before and During Pregnancy Improves Endothelial Function and Stimulates Cytoprotective and Antioxidant Pathways in the Pregnant Rat.”


In the study, female rats were separated into two groups, the exercise group and the control group, and later impregnated. The exercise group ran voluntarily on an activity wheel for six weeks prior to and during pregnancy, with running times and distances monitored weekly. The control group did not exercise. The team analyzed tissue samples taken from both groups late in their pregnancies.

The researchers found that the rats in the exercise group had higher levels of a circulating protein called vascular endothelial growth factor (VEGF) than those in the control group. VEGF and a pregnancy specific version of the protein called placental growth factor (PlGF) are important because not only do they stimulate the development of new blood vessels, they also maintain normal vessel function which in turn promotes good cardiovascular health.

According to Dr. Gilbert, finding increased VEGF in the exercise group has important implications for understanding, and perhaps preventing, preeclampsia. He noted that clinical and experimental studies have found that high levels of a protein called sFlt-1 can bind up the mothers’ circulating levels of PlGF and VEGF and can lead to preeclampsia.

The researchers also saw that when VEGF increased, endothelial function increased. The endothelium is a thin layer of cells that line the inside of blood vessels. It reduces turbulence in blood flow, which allows blood to be pumped further with each heartbeat, thus taking stress off the heart.

Heat Shock Proteins

The team also found that the rats in the exercise group had increased amounts of heat shock proteins (HSPs) compared to those that did not exercise. One HSP in particular, HSP 90, is thought to play a vital role in maintaining the blood vessels of the heart. It works in sync with VEGF and nitric oxide to dilate blood vessels so that blood flows more freely, which lowers blood pressure. Increased expression of HSPs as a result of exercise could provide a preconditioning effect that may help protect against cellular damage in the placenta during pregnancies complicated by high blood pressure.

“There have been many studies about exercise and pregnancy, but not at the molecular level,” said Dr. Gilbert. “We hope to learn whether stimulating these proteins with exercise before pregnancy or early during pregnancy can lower a woman’s risk for preeclampsia.”

Wednesday, October 12, 2011

Folic Acid in Early Pregnancy Associated With Reduced Risk of Severe Language Delay in Children

Use of folic acid supplements by women in Norway in the period 4 weeks before to 8 weeks after conception was associated with a reduced risk of the child having severe language delay at age 3 years, according to a study in the October 12 issue of JAMA

"Randomized controlled trials and other studies have demonstrated that periconceptional [the period from before conception to early pregnancy] folic acid supplements reduce the risk of neural tube defects. To our knowledge, none of the trials have followed up their sample to investigate whether these supplements have effects on neurodevelopment that are only manifest after birth," the authors write.

Christine Roth, M.Sc., Clin.Psy.D., of the Norwegian Institute of Public Health, Oslo, and colleagues conducted a study to investigate whether maternal use of folic acid supplements was associated with a reduced risk of severe language delay among offspring at age 3 years. "Unlike the United States, Norway does not fortify foods with folic acid, increasing the contrast in relative folate status between women who do and do not take folic acid supplements," the researchers write. Pregnant women were recruited for the study beginning in 1999, and data were included on children born before 2008 whose mothers returned the 3-year follow-up questionnaire by June 16, 2010. Maternal use of folic acid supplements within the interval from 4 weeks before to 8 weeks after conception was the exposure. The primary outcome measured for the study was children's language competency at age 3 years as gauged by maternal report on a 6-point ordinal language grammar scale. Children with minimal expressive language (only 1-word or unintelligible utterances) were rated as having severe language delay.

The main analysis for the study included 38,954 children (19,956 boys and 18,998 girls). Of these children, 204 (0.5 percent) were rated as having severe language delay (159 [0.8 percent] boys and 45 [0.2 percent) girls). Children whose mothers took no dietary supplements in the specified exposure interval were the reference group (n = 9,052 [24.0 percent], with severe language delay in 81 children [0.9 percent]). Data for 3 patterns of exposure to maternal dietary supplements were: other supplements, but no folic acid (n = 2,480 [6.6 percent], with severe language delay in 22 children [0.9 percent]); folic acid only (n = 7,127 [18.9 percent], with severe language delay in 28 children [0.4 percent]); and folic acid in combination with other supplements (n = 19,005 [50.5 percent], with severe language delay in 73 children [0.4 percent]).

The researchers write that maternal use of supplements containing folic acid within the period from 4 weeks before to 8 weeks after conception was associated with a substantially reduced risk of severe language delay in children at age 3 years. "We found no association, however, between maternal use of folic acid supplements and significant delay in gross motor skills at age 3 years. The specificity provides some reassurance that there is not confounding by an unmeasured factor. Such a factor might be expected to relate to both language and motor delay."

The authors add that to their knowledge, no previous prospective observational study has examined the relation of prenatal folic acid supplements to severe language delay in children.

"If in future research this relationship were shown to be causal, it would have important implications for understanding the biological processes underlying disrupted neurodevelopment, for the prevention of neurodevelopmental disorders, and for policies of folic acid supplementation for women of reproductive age."

Thursday, October 6, 2011

Evidence Review: Extra Calcium During Pregnancy Has No Benefits

Except To Prevent Hypertension

Source: Health Behavior News Service

Most physicians instruct pregnant women to increase their calcium intake, but a new evidence review of potential benefits of calcium supplementation for mom and baby found none, except for the prevention of pregnancy-related hypertension.
Experts agree that during pregnancy, a mother’s diet and nutritional status contribute significantly to the health and well-being of her offspring. Yet, the effects of supplementation with calcium, or the amounts to supplement, have remained unclear.
A review led by researcher Pranom Buppasiri, MD, of the department of obstetrics and gynecology at Khon Kaen University in Thailand, shows that calcium supplementation has no effect on preventing preterm birth or low infant birth weight and no effect on bone density in pregnant women. Bupparsiri notes, however, that previous reviews have shown that calcium supplementation does help in the prevention of preeclampsia.
Preeclampsia is a dangerous condition marked by hypertension and protein in the urine that can develop into serious complications for the mother and baby. The definitive treatment for preeclampsia is delivery of the baby, often resulting in preterm and/or low birth weight babies.
More than 16,000 women participated in the 21 studies included in the review. The review did find a small difference in average infant birth weight, but the authors were unable to ascertain the clinical significance in the diverse population examined.
Buppasiri and colleagues’ review appears in the latest issue of The Cochrane Library, a publication of the Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Stephen Contag, MD, a perinatalogist at Sinai Hospital of Baltimore's Institute of Maternal Fetal Medicine called the review confusing and said, “There is an inherent confounding effect between the two interventions in that whenever maternal hypertensive disease is prevented, preterm labor is less likely to occur.” In other words, calcium supplementation might prevent preterm labor indirectly by preventing high blood pressure. He added that, “the definitive treatment for pregnancy related hypertensive disease is delivery, which often occurs preterm depending on the severity and timing of onset.”
Contag stated that according to current Institute of Medicine recommendations, “calcium supplementation is recommended in addition to dietary calcium intake, in order to achieve recommended daily allowance of 1,000 mg/day.”
However, John McDougall, MD, an internist, nutrition expert and medical director of the McDougall Program in Santa Rosa, California, cited a July 2010 study in the British Medical Journal to support the fact that he does not prescribe calcium supplements, because they increase the risk of heart attacks and strokes.
“Certainly, taking isolated concentrated minerals, such as calcium, creates physiological imbalances in the body,” McDougall said in a commentary regarding the July study. “Immediately after consuming calcium supplements, the calcium in the blood increases. Thereafter, the body must adjust to this large burden of minerals. One of the adverse effects appears to be artery damage.”
Buppasiri said there were still not enough studies to draw a meaningful conclusion about supplementation. “We need more high quality studies to address this review question, especially in low calcium intake populations,” he said.

Tuesday, October 4, 2011

Higher quality diet associated with reduced risk of some birth defects

Healthier dietary choices by pregnant women are associated with reduced risks of birth defects, including neural tube defects and orofacial clefts, according to a study published Online First by the Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

The authors state in background information that folic acid supplementation and food fortification has been effective in preventing neural tube defects, but folic acid does not prevent all birth defects. "Nutrition research on birth defects has tended to focus on one nutrient (or nutritional factor) at a time," the authors write. "However, the reality of nutrition is much more complex."

Suzan L. Carmichael, Ph.D., from Stanford University, Stanford, Calif., and colleagues used data from the National Birth Defects Prevention Study "to examine whether better maternal diet quality was associated with reduced risk for selected birth defects." The data were collected in 10 states from pregnant women with estimated due dates from October 1997 through December 2005. Information was collected via telephone interviews with 72 percent of case and 67 percent of control mothers. Included in the analysis were 936 cases with neural tube defects, 2,475 with orofacial clefts, and 6, 147 controls without birth defects. Mothers reported their food intake using a questionnaire. The researchers developed two diet quality indices that focused on overall diet quality based on the Mediterranean Diet (Mediterranean Diet Score or MDS) and the U.S. Department of Agriculture Food Guide Pyramid (Diet Quality Index or DQI).

"…Increasing diet quality based on either index was associated with reduced risks for the birth defects studied," the authors found. "Most mothers of controls [children without birth defects] were non-Hispanic white and had more than a high school education; 19 percent smoked, 38 percent drank alcohol, and 78 percent took folic-acid-containing supplements during early pregnancy; and 16 percent were obese," the authors report. "Women who were Hispanic had substantially higher values for the DQI and the MDS, whereas values were lower among women with less education and women who smoked, did not take supplements, or were obese…"

"Based on two diet quality indices, higher maternal diet quality in the year before pregnancy was associated with lower risk for neural tube defects and orofacial clefts. This finding persisted even after adjusting for multiple potential confounders such as maternal intake of vitamin/mineral supplements," the authors write. "These results suggest that dietary approaches could lead to further reduction in risks of major birth defects and complement existing efforts to fortify foods and encourage periconceptional multivitamin use," the authors conclude.

(Arch Pediatr Adolesc Med. Published online October 3, 2011. doi:10.1001/archpediatrics.2011.185. Available pre-embargo to the media at

Editor's Note: This project was partially supported by grants from the National Institutes of Health and the Centers for Disease Control and Prevention. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: The Importance of Food

In an accompanying editorial, David R. Jacobs, Jr., Ph.D., from the University of Minnesota, Minneapolis, and colleagues note that while maternal intake of folate is important for fetal development, recent studies suggest the supplemental folic acid may have adverse health effects on older adults.

"The importance of the findings of Carmichael et al lies in showing that women obtain benefit from the consumption of a high-quality diet, beyond the benefits derived through grain fortification. This raises the question of whether a high-quality diet alone may be sufficient to prevent NTDs (neural tube defects) – a strategy that would also remove the potential harm from fortification."

"The lesson from the article by Carmichael et al is an important one: people, including women of childbearing age, should eat good food."

"Reduction of NTDs may be achievable by diet alone, at the same time reducing potential risk for other chronic diseases in the rest of the population."