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Smoking Before, After Pregnancy Harms Daughters’ Fertility

December 6th, 2007

Researchers have identified the chemical pathway by which a mother’s smoking before and after pregnancy might reduce her daughter’s fertility by as much as two-thirds.

Cigarette smoking during pregnancy has been shown in retrospective studies to affect the fertility of a woman’s offspring, but this is the first study to offer an explanation of the biology behind the effect, the Canadian scientists claim.

A team at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto investigated the impact of polycyclic aromatic hydrocarbons (PAH), a byproduct of smoking, on mouse fertility.

Researchers injected three groups of female mice with a low-dose mixture of PAH: One group received PAH before conception and again when they were providing milk for their pups; one group received PAH only before conception; and the third group received PAH only during lactation. A fourth control group did not receive PAH but were mated at the same time as the others. The total amount of PAH given to each mouse over the three-week injection cycle was equivalent to 25 packs of cigarettes, according to the researchers. The exposed mice did not have fewer pups in their own litters, but when researchers investigated the number of eggs in their female offspring, they found about 70 percent fewer follicles available to produce eggs.

“Mothers, mice in this case, exposed to PAHs — environmental pollutants found in cigarette smoke, car exhaust, smoke produced by fossil fuel combustion, as well as in smoked food –before pregnancy and/or during breast-feeding, but not during pregnancy, can cause a reduction in the number of eggs in the ovaries of their female offspring by two-thirds. This limits the window in which the daughter will be able to reproduce,” explained lead researcher Dr. Andrea Jurisicova.

Further analysis indicated that the effects of PAHs on the number of follicles in female offspring were mediated through a receptor that affects the expression of a gene that makes a protein that causes cells to die. The researchers then demonstrated similar effects in human ovarian tissue transplanted into immunocompromised mice.

Jurisicova described the process: “Toxic compounds were injected under the skin of mice and were picked up by the bloodstream and carried throughout the body until they reached the ovaries. Once at the ovaries, they passed through the cell membrane and bound to the receptor. When this happens, it activates the receptor, which then enters the cell nucleus. The receptor then finds a specific DNA sequence that turns on the gene, which accumulates and eventually kills the eggs.”

“This study now is providing a chemical pathway, which is very nice,” said Dr. Norman Edelman, consultant for scientific affairs with the American Lung Association. The new data provides biological support for epidemiological results, such as the previously observed reduction in fertility among daughters of smoking women, he added.

Whether the news will have an impact on a woman’s decision to smoke is another question, said Edelman.

“If we do our job right and these results get good press, this data could remind women of what they are doing to their unborn fetuses,” Edelman said.

Another expert noted this latest finding adds to a growing body of evidence that shows a strong connection between smoking and fertility.

“I think it is an interesting study, but it doesn’t add much new. Other studies have shown similar outcomes. The theory is that smoking could affect the follicles or the fallopian tubes,” said Dr. Amos Grunebaum, director of obstetrics at New York Weill Cornell Medical Center, in New York City. “We have known for many years that smoking affects fertility on many levels.”

“The key is women should quit smoking before they are thinking of getting pregnant,” Grunebaum said.

The Canadian researchers did offer some good news in their report, published in the Dec. 3 edition of the Journal of Clinical Investigation. Injecting resveratrol in the mice who were exposed to PAH prevented the reduction in egg follicles in their offspring. Resveratrol is a naturally occurring antioxidant found in wine and grape skins. However, that reversal of damage does not mean that women who smoke can counter the effects with a nutritional supplement or a glass of red wine, the researchers stressed.

“We have found that oral consumption of resveratrol as a food supplement, at least in mice, is not effective, as levels of resveratrol do not reach sufficient amount in the bloodstream to provide protection,” Jurisicova said.

Although the findings do not define the length of time between quitting smoking and healthier fertility in offspring, Jurisicova noted that previous studies have shown that women who smoke have better results with in vitro fertilization one year after they quit smoking. The mice in the current study conceived up to two weeks after their final PAH injection, which is approximately equivalent to three menstrual cycles in women.

The effect of a mother’s cigarette smoking is not limited to her female children. A study published in the Jan. 1 issue of the American Journal of Epidemiology suggested that the male offspring of mothers who smoke have lower sperm counts.

There is still more research to be done, Jurisicova noted.

“We hope to continue studying the female offspring to see if they enter the mouse version of menopause earlier than mice whose mothers were not exposed to PAHs,” Jurisicova said. “We also hope to study if their reduced fertility passes on to subsequent generations, and if the granddaughters are predisposed to similar problems.”

More information

Need to quit smoking? Visit the U.S. Surgeon General or the National Institutes of Health.

SOURCES: Norman H. Edelman, M.D., consultant, scientific affairs, American Lung Association; Andrea Jurisicova, M.D., assistant professor, University of Toronto, and Canada Research Chair, Molecular and Reproductive Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto; Amos Grunebaum, M.D., director, obstetrics, New York Weill Cornell Medical Center, New York City; Dec. 3, 2007, Journal of Clinical Investigation

Breast milk helps lungs but not if mom has asthma

November 21st, 2007

From News – Revolution Health

Breast-feeding seems to protect children from asthma later in life, but only when the mother does not have the respiratory disorder herself, U.S. researchers said on Thursday.

They found that breast-feeding for more than four months helped improve lung function in children whose mothers did not have asthma.

But breast-fed children whose mothers had asthma did not benefit and actually showed a significant drop in lung function later in life.

That does not mean women with asthma should stop breast-feeding.

The researchers cautioned that the study, published in the American Journal of Respiratory and Critical Care Medicine, was preliminary and the findings needed more study.

Breast milk is almost always considered best for infants. It can be digested easily and supplies antibodies that can protect babies from bacterial and viral infections, including many of the respiratory tract.

Dr. Theresa Guilbert of the University of Wisconsin-Madison wanted to see if longer breast-feeding — lasting four months or more — improved lung function in children.

She and colleagues at the Arizona Respiratory Center analyzed data from the Children’s Respiratory Study in Tucson, which followed 1,246 healthy infants through adolescence.

Of those, 697 had lung function tests from the ages of 11 to 16 that evaluated air flow and lung volume.

For the most part, breast-fed children with non-asthmatic mothers had better lung volume and no decrease in air flow.

But children of mothers with asthma who were breast-fed four months or more did not show any improvement. In fact, these children had a significant reduction in airflow.

The reason, Guilbert suggested, may be altered lung growth.

Guilbert believes breast milk may contain certain factors that promote lung development, factors that may be impaired in mothers with asthma.

“These findings suggest that growth factors in milk have the potential to modify lung development, which might account for some of the protective effect of breast-feeding,” she wrote.

Researchers found a similar effect in mice born to non-asthmatic mothers who were breast-fed by mothers with asthma. These mice developed airway inflammation.

“It is important to emphasize that the clinical significance of these findings is unknown,” Guilbert wrote.

“Further study is needed to confirm our findings and to determine a biological basis for the relationships observed.”

The gene that turns breast-milk into brain food

November 15th, 2007

From Nature News

Does breast-feeding a child boost its brain development and raise its intelligence? Only if the child carries a version of a gene that can harness the goodness of breast-milk, say researchers.

The results add to the nature versus nurture debate over intelligence, by showing how the two effects can interact.

The question of whether people are born intelligent or made intelligent by their environment has been debated for decades. Research with identical twins separated at birth has shown that both genetics and rearing conditions are important in determining intelligence.

One of the important environmental effects seems to be breast-feeding. Children who are breast-fed generally perform better in IQ tests than do those fed on other types of milk. Researchers think that this might be because specific fatty acids found in human milk, but not in cows milk or infant formulas, improve brain development.

Avshalom Caspi and Terrie Moffitt, psychologists at Kings College, London, and their colleagues looked at the relationship between breast-feeding and intelligence to explore the possibility that in this case nature and nurture might be intimately linked.

The group first looked for genes that metabolize fatty acids, which in turn are important for the growth of neurons. Differences in such genes, they hypothesized, might moderate the intellectual advantage associated with breast-feeding. They searched the literature and gene databases and found a good candidate: a gene called FADS2 .

Class test

The team then looked at more than 1,000 children in New Zealand who were born in 1972 and IQ tested at ages 7, 9, 11, and 13; a record was kept of which children had been breast-fed. The study was repeated with about 2,200 children in Britain who were born in 199495 and IQ tested at age 5. DNA tests were used to look at a specific spot in their FADS2 genes, to see which version or allele of the gene they carried.

In children who carried at least one copy of a C allele for FASD2 , those who were breast-fed generally had a higher IQ than those who were not: by an average of 6.4 IQ points in the New Zealand study, and by 7.0 IQ points in the British one. By contrast, children carrying two G alleles had roughly the same IQ irrespective of their diet. About 10% of the population is thought to be GG.

We had a very strong hypothesis, but it could easily have turned out wrong, so we were pleased when the data fit the hypothesis in New Zealand, and then really delighted when it was confirmed in Britain, says Moffitt. The team reports their findings in the Proceedings of the National Academy of Sciences 1.

Why and how this genetic difference came into being is unclear. It is almost as though the G allele evolved as a protective genotype for children who might not get enough breast-milk, says developmental psychologist Linda Gottfredson at the University of Delaware in Newark.

Mother care

The result will help to settle the debate over whether breast-feeding is linked to intelligence because of the nutritional quality of the milk, or because mothers who breast-feed are the sorts of mothers who encourage child learning. I think this research will settle that debate, or at the very least bring it near a close, says epidemiologist Jean Golding at the University of Bristol, UK.

Avshalom CaspiIt might also serve as a guide for researchers aiming to find the genetic factors that affect other complex developmental factors, such as height. Such studies are usually approached by scanning thousands of people in search for different alleles associated with the trait of interest. This research is suggesting that simply looking at huge samples may be missing the point, says psychologist and geneticist Matt McGue of the University of Minnesota in Twin Cities. He notes that using specific context clues, as was done in this study, is a more efficient way to look for a gene.

And the finding contributes to the growing feeling that scientists shouldnt think of nature or nurture acting in isolation from each other. Our team has reported geneenvironment interactions involved in depression, violence and psychosis … with these new data, many of us are starting to think that nature via nurture might be a better catch phrase, says Caspi.

FDA Warns Nursing Mothers of Possible Codeine Risk

August 23rd, 2007

From Washingtonpost.com

The Food and Drug Administration yesterday warned nursing mothers who are taking the painkiller codeine to be vigilant for unusual drowsiness or other signs of overdose in their babies, because a significant fraction of women carry a gene that leads to high concentrations of narcotic substances in their breast milk.

The warning is not meant to discourage women who are prescribed codeine from breast-feeding. But it should spur them to contact their doctors if they or their babies seem overly sleepy while taking usual doses of the painkiller, an agency official said.

“If you as a mom are experiencing side effects, you should absolutely be watching your baby for the same kind of things,” said Sandra Kweder, a physician and a deputy director in the FDA’s Center for Drug Evaluation and Research.

Codeine is frequently prescribed for the pain of an episiotomy or a Caesarean section because it is safe, can be taken in pill form and acts for only a short period.

In the body, codeine is transformed into morphine. People who are “ultra-rapid metabolizers” of the drug do this very quickly and more completely than others. The morphine is excreted into breast milk in amounts that can cause limpness, excessive sleepiness, feeding difficulties and breathing problems in newborns. If a nursing mother taking the drug notices those symptoms, she should contact a physician immediately or go to an emergency room, Kweder said.

Last year, a 13-day-old baby in Toronto died of a morphine overdose that was traceable directly to the mother’s ultra-rapid metabolism of codeine. That is the only known death from the condition.

Ultra-rapid metabolism occurs when a person has a particular variant of the gene for a liver enzyme called CYP2D6.

As much as 10 percent of whites, 3 percent of blacks and 1 percent of Hispanics and Asians carry the ultra-metabolizing variant. Between 16 and 28 percent of North Africans, Ethiopians and Saudis carry it, FDA officials said. A test for the gene is widely available.

“Anyone can be an ultra-rapid metabolizer without knowing it,” Kweder said.

The agency did not recommend that all breast-feeding women be tested before taking codeine because there is currently no evidence that such a strategy would measurably reduce complications. Women who have experienced unusually pronounced effects from codeine, however, may want to be tested.

Other opioid drugs also pass into breast milk, but most do not get turned into morphine as the body metabolizes them.

Yesterday’s advisory was the second time this week the FDA discussed the role of genes in the risk for adverse side effects from drugs.

On Thursday, the agency warned physicians that some people taking the blood-thinner warfarin may be unusually sensitive to its effects or build up higher-than-expected concentrations of it in their bloodstreams, because of variations in two genes.

Breastfeeding Benefits Women with Late Age at First Birth

May 11th, 2007

From CancerConsultants.com

According to the results of a study presented at the 2007 annual meeting of the American Association for Cancer Research (AACR), breastfeeding may lessen the increased risk of breast cancer that comes from having a late age at first birth.

Breast cancer is diagnosed in over 200,000 women annually in the United States alone. Due to its prevalence, researchers have focused on evaluating environmental factors with potential links to the risk of breast cancer. Factors such as diet, exercise, age at menarche (first menstrual period), age at first childbirth, and breastfeeding appear to influence the likelihood of breast cancer. The effects of these factors on breast cancer risk, however, may be different for estrogen receptor-positive (ER-positive) and estrogen receptor-negative (ER-negative) breast cancers.

To evaluate the relationships among several reproductive factors and ER-positive and ER-negative breast cancer, researchers conducted a study among 995 women with breast cancer and 1,498 women without breast cancer. All women were age 55 or older.

An early age at first birth (first birth before the age of 25) reduced the risk of ER-positive breast cancer but did not reduce the risk of ER-negative breast cancer.

Breastfeeding reduced the risk of both ER-positive and ER-negative breast cancer. Importantly, breastfeeding appeared to reduce the increased risk of breast cancer experienced by women who had a later age at first birth (first birth after the age of 25).

In a prepared statement, Dr. Giske Ursin, one of the study authors, noted, We suspect that women can reduce the increased risk that comes with later childbearing by choosing to breastfeed.

Reference: Lord SJ, Bernstein L, Johnson K et al. Parity, breastfeeding and breast cancer risk by hormone receptor status in women with late age at first birtha case-control study. Presented at the 2007 meeting of the American Association for Cancer Research, Los Angeles, CA, April 14-18, 2007. Abstract 2610.