Wednesday, July 20, 2011

Caffeine consumption linked to female infertility


Caffeine reduces muscle activity in the Fallopian tubes that carry eggs from a woman's ovaries to her womb. "Our experiments were conducted in mice, but this finding goes a long way towards explaining why drinking caffeinated drinks can reduce a woman's chance of becoming pregnant," says Sean Ward, professor of physiology and cell biology, at the University of Nevada School of Medicine, who conducted the study.

Ward's study was recently published in the British Journal of Pharmacology.

Human eggs are microscopically small, but need to travel to a woman's womb if she is going to have a successful pregnancy. Although the process is essential for a successful pregnancy, scientists know little about how eggs move through the muscular Fallopian tubes. It was generally assumed that tiny hair-like projections, called cilia, in the lining of the tubes, waft eggs along assisted by muscle contractions in the tube walls.

By studying tubes from mice, Ward and his team discovered that caffeine stops the actions of specialized pacemaker cells in the wall of the tubes. These cells coordinate tube contractions so that when they are inhibited, eggs can't move down the tubes. In fact these muscle contractions play a bigger role than the beating cilia in moving the egg towards the womb.

"This provides an intriguing explanation as to why women with high caffeine consumption often take longer to conceive than women who do not consume caffeine," said Ward.

Discovering the link between caffeine consumption and reduced fertility has benefits.

"As well as potentially helping women who are finding it difficult to get pregnant, a better understanding of the way Fallopian tubes work will help doctors treat pelvic inflammation and sexually-transmitted disease more successfully," said Ward.

It could also increase our understanding of what causes ectopic pregnancy, an extremely painful and potentially life-threatening situation in which embryos get stuck and start developing inside a woman's Fallopian tube.

Tuesday, July 12, 2011

Smoking causes serious birth defects

To dispel any uncertainty about the serious harm caused by smoking to babies and pregnant women, the first-ever comprehensive systematic review of all studies over the past 50 years has established clearly that maternal smoking causes a range of serious birth defects including heart defects, missing/deformed limbs, clubfoot, gastrointestinal disorders, and facial disorders (for example, of the eyes and cleft lip/palate).

Smoking during pregnancy is also a risk factor for premature birth, says Dr. Michael Katz, senior Vice President for Research and Global Programs of the March of Dimes. He says the March of Dimes urges all women planning a pregnancy or who are pregnant to quit smoking now to reduce their chance of having a baby born prematurely or with a serious birth defect. Babies who survive being born prematurely and at low birthweight are at risk of other serious health problems, Dr. Katz notes, including lifelong disabilities such as cerebral palsy, intellectual disabilities and learning problems. Smoking also can make it harder to get pregnant, and increases the risk of stillbirth.

About 20 percent of women in the United States reported smoking in 2009. Around the world, about 250 million women use tobacco every day and this number is increasing rapidly, according to data presented at the 2009 14th World Conference on Tobacco or Health in Mumbai.

The new study, "Maternal smoking in pregnancy and birth defects: a systematic review based on 173,687 malformed cases and 11.7 million controls," by a team led by Allan Hackshaw, Cancer Research UK & UCL Cancer Trials Centre, University College London, will be published online today in Human Reproduction Update from the European Society of Human Reproduction and Embryology.

When women smoke during pregnancy, the unborn baby is exposed to dangerous chemicals like nicotine, carbon monoxide and tar, Dr. Katz says. These chemicals can deprive the baby of oxygen needed for healthy growth and development.

During pregnancy, smoking can cause problems for a woman's own health, including:

ectopic pregnancy;
vaginal bleeding;
placental abruption, in which the placenta peels away, partially or almost completely, from the uterine wall before delivery;
placenta previa, a low-lying placenta that covers part or all of the opening of the uterus.

Smoking is also known to cause cancer, heart disease, stroke, gum disease and eye diseases that can lead to blindness.

Wednesday, July 6, 2011

Undernourishment in Pregnant, Lactating Females = Vulnerability to type 2 diabetes

A new study published by the American Physiological Society offers the strongest evidence yet that vulnerability to type 2 diabetes can begin in the womb, giving new insight into the mechanisms that underlie a potentially devastating disease at the center of a worldwide epidemic. The study, conducted in baboon primates, finds that when mothers are even moderately undernourished while pregnant and breastfeeding, their offspring are consistently found to be prediabetic before adolescence. It is the first time that diabetes has been shown to have prenatal origins in a primate model.

According to Peter W. Nathanielsz, senior author of the study, "We pass more biological milestones before we are born and in the early weeks of life than at any other time." Poor maternal nutrition, which translates to less sustenance for growing fetuses, is a stubborn problem in parts of the U.S. and the developing world, Nathanielsz said. Thus, "Poor nutrition at critical periods of development can hinder growth of essential organs such as the pancreas, which sees a significantly decrease in its ability to secrete insulin. Our study is the first to show in a primate that poor nutrition during fetal and early life can damage the pancreas and predispose one to type 2 diabetes."

The study, "Emergence of insulin resistance in juvenile baboon offspring of mothers exposed to moderate maternal nutrient reduction" was conducted by Nathanielsz and colleagues Jaehyek Choi, Cun Li, and Thomas J. McDonald of the School of Medicine at the University of Texas Health Science Center at San Antonio, and Anthony Comuzzie and Vicki Mattern of the Texas Biomedical Research Institute in San Antonio. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. It is published in the online edition of the American Journal of Physiology -- Regulatory, Integrative and Comparative Physiology.


Type 2 diabetes occurs when the body develops resistance to insulin, a hormone that regulates blood sugar. Although the body may initially compensate by secreting more insulin, eventually the pancreas cannot produce enough of the hormone to keep blood sugar from rising. In poorly controlled diabetes, elevated blood sugar severely damages the heart, blood vessels, eyes, kidneys and nerves. The consequences can be fatal and include heart disease, stroke, amputations, blindness and kidney failure.

Worldwide, diabetes is an escalating public health crisis. According to estimates from the World Health Organization (WHO), 366 million people will be diabetic by the 2030, up from 171 million in 2000. This is a 114 percent projected increase.

Formerly called "adult-onset diabetes," type 2 diabetes is seen increasingly in children at earlier and earlier ages. Excess body weight and physical inactivity are known causes, but Nathanielsz and his collaborators have long been interested in whether some individuals might be predisposed to diabetes from birth, or even earlier. Nathanielsz conducts research on this and similar topics through the Center for Pregnancy and Newborn Research in the UT Health Science Center's Department of Obstetrics and Gynecology.

The Study

For this study, to avoid the complication of influences from genes, researchers selected 18 female baboons similar in age and other observable characteristics and housed them with a fertile male baboon. All females became pregnant. From 30 days of gestation, 12 females were randomly assigned to be fed an appropriate diet for their weight. The other six received 70 percent of the chow given to control females on a weight-adjusted basis. The female baboons continued on their respective diets through delivery and the weaning of their offspring. Once the young baboons were weaned, they were fed normal diets.

Just before they reached puberty, the six young baboons from nutritionally restricted mothers showed increases in fasting glucose, fasting insulin and other hallmarks of prediabetes. The 12 young baboons whose mothers received adequate nutrition displayed none of these traits.

The central importance of this observation is that the mothers' food intake was only moderately restricted -- similar to the decrease faced in the United State by many people living with food insecurity. There are 925 million undernourished people worldwide, including 19 million in developed countries, according to the Food and Agriculture Organization of the United Nations.

The researchers conclude that even moderate nutrient deficiencies during pregnancy result in offspring predisposed to type 2 diabetes, particularly if they are exposed to other risk factors in later life, such as a Western diet and physical inactivity leading to obesity. A fetus may also receive fewer nutrients due to teenage pregnancy, where the growing mother competes with her offspring for resources; in pregnancies complicated by maternal vascular disease, which may occur in women who become pregnant later in their reproductive life; and when placental problems exist. The decrease in fetal growth observed in the newborn baboons was only about 10 percent, very similar to many human babies born growth restricted.

Asthma Linked to Depression during Pregnancy

Anxiety, stress and depression during pregnancy may lead to a greater risk of asthma for your child. Study results are published in the July issue of Annals of Allergy, Asthma & Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI).

“Approximately 70 percent of mothers who said they experienced high levels of anxiety or depression while they were pregnant reported their child had wheezed before age 5,” said Marilyn Reyes, lead author of the study. “Understanding how maternal depression affects a child’s respiratory health is important in developing effective interventions.”

The study of 279 inner-city African-American and Hispanic women was conducted before, during pregnancy and after birth. The study results support growing research that the prenatal period is a time when children are particularly susceptible to asthma-related risks. While somewhat similar findings have been reported in non-minority populations, this study at the Columbia Center for Children’s Environmental Health is the first to report an association between stress and wheeze in minority populations.

Common asthma symptoms include:
• Coughing, especially at night
• Wheezing or whistling sound, especially when breathing out
• Trouble breathing or fast breathing that causes the skin around the ribs or neck to pull in tightly
• Frequent colds that settle in the chest

Mother’s Salt Intake Could be Key to Prenatal Kidney Development

A new animal study from Europe has drawn an association between pregnant mothers’ sodium intake and their newborn’s kidney development. Among the most significant aspects of the study’s findings is that either too much or too little salt during pregnancy had an adverse effect on the prenatal development of the offspring’s kidneys. The consequence of such disruption can lead to high blood pressure in later years.

These are the conclusions reached in the study, “Both High and Low Maternal Salt Intake in Pregnancy Alters Kidney Development in the Offspring,” conducted by Nadezda Koleganova, Grzegorz Piecha, Annett Müller, Monika Weckbach, Peter Schirmacher, and Marie-Luise Gross-Weissmann, Eberhard Ritz and Luis Eduardo Becker, all with the University of Heidelberg in Heidelberg, DE; and Jens Randel Nyengaard of the University of Aarhus, Aarhus, DK. Their study is published in the online edition of the American Journal of Physiology--Renal Physiology.


This research builds upon past studies that recognize that excessive salt intake causes secretion of endogenous cardiotonic steroids such as marinobufagenin (MBG). For the pregnant female, this can be harmful since high concentrations of MBG are correlated to low birth-weight and higher blood pressure in the offspring.
Previous research has also linked high blood pressure with a low nephron number, critical because the nephron is the basic structural and functional unit of the kidney. The nephron eliminates wastes from the body, regulates blood volume and blood pressure, controls levels of electrolytes and metabolites, and regulates blood pH. Its functions are vital to life and are regulated by the endocrine system.


Sprague-Dawley rats were fed low, intermediate or high sodium diets during pregnancy and lactation. The litters were standardized to identical size at birth with 1:1 male to female ratio. The offspring were separated from their mothers at four weeks of age and subsequently received the intermediate sodium diet. The animals had free access to water and food and their body weight, food and water consumption were monitored weekly.
The kidney structure was assessed at postnatal weeks 1 and 12, and the expression of proteins known to be involved in kidney development were examined at birth and 1 week of age. Blood pressure was measured by telemetry in male offspring between the ages of two and nine months.


The researchers found that the number of glomeruli (the main structural unit of the kidney) during weeks 1-12 were significantly lower, and the measured blood pressure for males after the fifth month was higher in offspring of mothers on high- or low- compared with intermediate-sodium diet. High salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both GDNF and its inhibitor, sprouty-1 in the offspring’s kidney. The expression of FGF-10, a genetic signal responsible for kidney development, was lower in offspring of mothers on low-sodium diet and the expression of Pax-2 and FGF-2, tissue-specific genes that determine cell lineages, tissue patterning, and cellular proliferation was lower in offspring of mothers on high-sodium diet.

Importance of the Findings

Taken together the above findings indicate that both too low and too high maternal salt intakes retard development of new glomeruli, resulting in a nephron deficit. If the findings in the animals in this study can be extrapolated to humans, both too low and too high salt intake during pregnancy would be a risk factor for hypertension and renal damage in the offspring.

In women, each mother-to-be has specific health issues and conditions that require guidance from a health provider. This study sheds light on the issue of salt intake during pregnancy and draws attention to the possible consequences of consuming too much or too little salt during pregnancy and the impact it may have on the kidney development of an offspring.

Pre-pregnancy diet affects the health of future offspring

Poor maternal diet before conception can result in offspring with reduced birth weights and increased risk of developing type II diabetes and obesity.

This work, which is being presented at the Society for Experimental Biology Annual Conference in Glasgow on Saturday the 2nd of July, used an animal model to illustrate the importance of maternal diet even before pregnancy begins.

During the study mice that were fed a low protein diet for ten weeks before conception (but had a normal diet during pregnancy) gave birth to offspring that had lower birth weights, showed catch-up growth after weaning and increased insulin sensitivity.

These effects combined can lead to problems later in life. MSc researcher, Ms Anete Dudele, from the University of Aarhus, explains: "Low birth weight and catch-up growth is associated with enhanced insulin-sensitivity in young adults, this then deteriorates into insulin resistance and type II diabetes with increased age. There is also evidence that male offspring are more likely to develop obesity."

Humans and mice respond in the same way to poor diet during pregnancy; their offspring show low birth weights and increased risk of obesity, type II diabetes and cardiovascular disease. "If humans respond in the same way as mice to pre-conception diet as well then women should not only consider what they eat during pregnancy but also before pregnancy if they want to reduce the risk of their future children acquiring lifestyle diseases," says Ms. Dudele.

Cardiovascular disease is often associated with obesity and type II diabetes and future research by the team will determine whether offspring born to mothers who had poor pre-conception diets are predisposed to these types of problems as well.

Exposure to anti-depressants in pregnancy may increase autism risk

Exposure to selective serotonin reuptake inhibitors anti-depressants in early pregnancy may modestly increase risk of autism spectrum disorders, according to a Kaiser Permanente study published online in the current issue of Archives of General Psychiatry. However the researchers cautioned that the number of children exposed prenatally to SSRIs was low and that further studies are needed to validate these results

Funded by the Centers for Disease Control and Prevention, the population-based, case-control study of 1,805 children is the first to systematically address the association between prenatal SSRI exposure and ASD risk.

Researchers reported a two-fold increased risk of ASD associated with maternal treatment with SSRI anti-depressants during the year before delivery. The strongest effect was associated with first trimester treatment, said the study's lead author, Lisa Croen, PhD, director of the Autism Research Program at the Kaiser Permanente Division of Research in Oakland, Calif. She explained that in utero exposure to anti-depressant medications was reported in 6.7 percent of cases and 3.3 percent of controls.

"Our results suggest a possible, albeit small, risk to the unborn child associated with in utero exposure to SSRIs, but this possible risk must be balanced with risk to the mother of untreated mental health disorders," said Croen, who explained that further studies are needed to replicate and extend these findings.

Researchers conducted a population-based, case-control study among 298 children with ASD and 1,507 randomly selected control children drawn from the Kaiser Permanente Northern California membership. Information on maternal use of anti-depressant medications, maternal mental health history, autism and demographic characteristics was collected from medical records.

After adjusting for maternal age, race/ethnicity, education and child's birth weight, gender, birth year, and facility of birth, mothers of children subsequently diagnosed with ASD were twice as likely to have at least one anti-depressant prescription in the year prior to delivery of the study child, and over three times as likely to have a prescription in the first trimester of pregnancy.

To further evaluate whether the observed association between prenatal SSRI exposure and ASD risk could be attributed to SSRI treatment rather than to the women's depression or anxiety for which she was prescribed the medication, researchers conducted an analysis of the subgroup of women with a history of mental health disorders in the year before delivery. Risk of ASD associated with SSRI use anytime during this year remained somewhat elevated in this subgroup, but did not reach statistical significance.

To assess the possibility that women prescribed SSRIs during the year before delivery had a more severe underlying condition that accounts for the finding, researchers examined indicators of severity of psychiatric illness. Among these women, the proportion with previous psychiatric hospitalizations and the mean number of hospitalizations was not significantly different in cases compared to controls.

Prior studies have indicated that abnormalities in serotonin levels and serotonin pathways may play a role in autism. Collectively these studies suggest the possibility that prenatal SSRI exposure may operate directly on the developing brain, perhaps selectively in fetuses with abnormalities in serotonin-related genes, explained Croen. She adds that physiologic changes related to maternal stress or depression during pregnancy, in combination with SSRI exposure, may contribute to changes in fetal brain development leading to later-diagnosed ASD.

Gum disease can increase the time it takes to become pregnant

For the first time, fertility experts have shown that, from the time that a woman starts trying to conceive, poor oral health can have a significant effect on the time to pregnancy.

Professor Roger Hart told the annual meeting of the European Society of Human Reproduction and Embryology that the negative effect of gum disease on conception was of the same order of magnitude as the effect of obesity.

Periodontal (gum) disease is a chronic, infectious and inflammatory disease of the gums and supporting tissues. It is caused by the normal bacteria that exist in everyone's mouths, which, if unchecked, can create inflammation around the tooth; the gum starts to pull away from the tooth, creating spaces (periodontal pockets) that become infected. The inflammation sets off a cascade of tissue-destructive events that can pass into the circulation. As a result, periodontal disease has been associated with heart disease, type 2 diabetes, respiratory and kidney disease, and problems in pregnancy such as miscarriage and premature birth. Around 10% of the population is believed to have severe periodontal disease. Regular brushing and flossing of teeth is the best way of preventing it.

Prof Hart, who is Professor of Reproductive Medicine at the University of Western Australia (Perth, Australia) and Medical Director of Fertility Specialists of Western Australia, said: "Until now, there have been no published studies that investigate whether gum disease can affect a woman's chance of conceiving, so this is the first report to suggest that gum disease might be one of several factors that could be modified to improve the chances of a pregnancy."

The researchers followed a group 3737 pregnant women, who were taking part in a Western Australian study called the SMILE study, and they analysed information on pregnancy planning and pregnancy outcomes for 3416 of them.

They found that women with gum disease took an average of just over seven months to become pregnant – two months longer than the average of five months that it took women without gum disease to conceive.

In addition, non-Caucasian women with gum disease were more likely to take over a year to become pregnant compared to those without gum disease: their increased risk of later conception was 13.9% compared to 6.2% for women without gum disease. Caucasian women with gum disease also tended to take longer to conceive than those who were disease-free but the difference was not statistically significant (8.6% of Caucasian women with gum disease took over one year to conceive and 6.2% of women with gum disease).

Information on time to conception was available for 1,956 women, and of, these, 146 women took longer than 12 months to conceive – an indicator of impaired fertility. They were more likely to be older, non-Caucasian, to smoke and to have a body mass index over 25 kg/m2. Out of the 3416 women, 1014 (26%) had periodontal disease.

Prof Hart said: "Our data suggest that the presence of periodontal disease is a modifiable risk factor, which can increase a woman's time to conception, particularly for non-Caucasians. It exerts a negative influence on fertility that is of the same order of magnitude as obesity. This study also confirms other, known negative influences upon time to conception for a woman; these include being over 35 years of age, being overweight or obese, and being a smoker. There was no correlation between the time it took to become pregnant and the socio-economic status of the woman.

"All women about to plan for a family should be encouraged to see their general practitioner to ensure that they are as healthy as possible before trying to conceive and so that they can be given appropriate lifestyle advice with respect to weight loss, diet and assistance with stopping smoking and drinking, plus the commencement of folic acid supplements. Additionally, it now appears that all women should also be encouraged to see their dentist to have any gum disease treated before trying to conceive. It is easily treated, usually involving no more than four dental visits.

"The SMILE study was one of the three largest randomised controlled trials performed in Western Australia. It showed conclusively that although treatment of periodontal disease does not prevent pre-term birth in any ethnic group, the treatment itself does not have any harmful effect on the mother or foetus during pregnancy*."

Prof Hart said that the reason why pregnancies in non-Caucasian women were more affected by gum disease could be because these women appeared to have a higher level of inflammatory response to the condition.

Giving up smoking averts adverse birth outcomes


Results from a study of over 50 000 pregnancies revealed that women who gave up smoking when their pregnancy was confirmed gave birth to babies with a similar birthweight to those born to mothers who had never smoked, Professor Nick Macklon, from the Department of Obstetrics and Gynaecology, University of Southampton, UK, told the annual conference of the European Society of Human Reproduction and Embryology today (Wednesday).

Low birthweight is the most common negative outcome of smoking during pregnancy, but foetuses exposed to maternal smoking are also at risk of premature birth and the associated problem of brain damage, as well as congenital abnormalities such as cleft lip. Mothers who smoke are encouraged to stop smoking when they become pregnant, but to date there was little evidence that giving up at this late stage could have a positive effect on birthweight.

Professor Macklon and colleagues decided to investigate this question by studying clinical, lifestyle, and socioeconomic data collected from pregnancies registered at the Southampton University Medical Centre between 2002 and 2010. They identified seven groups of women – non-smokers, those who had stopped more than a year prior to conceiving, those who had stopped less than a year prior to conceiving, smokers who stopped once the pregnancy was confirmed, and those who continued to smoke up to 10 a day, between 10 and 20 a day, and more than 20 a day. They proceeded to compare smoking behaviour in the mothers with perinatal outcomes in the children.

After correcting for gestational age, maternal age, BMI and socioeconomic class, all of which are known to affect birth outcomes, the researchers found that those babies whose mothers had stopped smoking in the periconceptional period – around the time of getting pregnant or as soon as the pregnancy was confirmed – had a significantly higher birthweight.

"Not only was birthweight much better in this group than it was in the groups where the mothers had continued to smoke, but we also found that the babies reached the same gestational age and head circumference as those born to women who had never smoked," said Professor Macklon. "While a recent study has shown that the rate of pre-term and small-for-gestational-age births can be reduced by stopping smoking before the 15th week of pregnancy, our research goes much further. We can now give couples hard evidence that making the effort to stop smoking in the periconceptional period will be beneficial for their baby."

Although there is now overwhelming evidence that maternal smoking during pregnancy is damaging to the foetus, some mothers continue to smoke because they like the idea of giving birth to a smaller baby. "It is important that people who believe that a smaller baby means an easier birth take into account the increased risks of complicated deliveries in smokers," said Professor Macklon, "as well as the risk of disease later in life which goes with low birthweight. Smoking during pregnancy is not just bad for the mother and baby, but for the adult it will grow into."

In addition to this, smoking can also make it more difficult for a woman to get pregnant and carry a baby to term. Because of their faster ovarian ageing, women smokers have higher rates of infertility than non-smokers and will undergo an earlier than normal menopause. They are also are more likely to have miscarriages.

"In future we would like to look at the impact of stopping smoking prior to fertility treatments, as we believe that this could bring about improvements to fertility outcomes," said Professor Macklon. "But for now we hope that our research will provide additional encouragement to mothers-to-be to give up cigarettes."