To combat the many fetal deaths that occur annually because the placenta is too small, researchers at Yale School of Medicine have developed a method to measure the volume of the placenta, which provides nourishment to the fetus.

Limits in current technology keep doctors from being able to monitor the growth of the placenta, which, like the gas tank of a car, is the source of fuel for the fetus. The placenta can be so small that the fetus literally runs out of food and oxygen and dies, according to lead author Harvey J. Kliman, M.D., a research scientist in the Department of Obstetrics, Gynecology and Reproductive Sciences. He and his colleagues published the results of their findings in the August 3 issue of the American Journal of Perinatology.

Fetal death, or intrauterine fetal demise (IUFD), affects 30,000 women each year in the United States. Until now, there has been no easy way to determine how much gas is left in the placentas tank.

Kliman decided to study this issue after noting that many late-term pregnancy losses were associated with very small placentas. He theorized that in much the same way that an obstetrician uses ultrasounds to follow the growth of the fetus, or a pediatrician weighs and measures children to ensure they are growing normally, the growth of the fetus placenta could be monitored.

When Kliman asked perinatologists (maternal fetal medicine specialists) why they did not look at the placenta when performing routine ultrasounds, the answer was always the same: The placenta is a curved structure and is too difficult to measure. If they had to measure the placental volume they would need a very expensive machine, specialized training and more time.

With the help of his father, Merwin Kliman, a mathematician and electrical engineer, Kliman developed an equation that used the maximal width, height and thickness of the placenta. Kliman and his team at Yale then validated the method by comparing the volume predicted by the Estimated Placenta Volume (EPV) equation taken just before delivery to the actual weight of the placenta at the time of delivery.

In this study, we showed that the equation predicted the actual placental weight with an accuracy of up to 89 percent, said Kliman. The method works best during the second and early third trimesters, just when routine ultrasound screening is done on many women in the U.S.

In addition to validating the equation, the team is also collecting EPV data from centers around the world to create the normative curves that doctors can use to determine if the placenta is normal, too small or even too big. I hope that the EPV test becomes routine for pregnant women, said Kliman.

Other authors on the study include Humberto Azpurua, M.D., Edmund F. Funai, M.D., Luisa M. Coraluzzi, Leo F. Doherty, M.D., Isaac E. Sasson, M.D., and Merwin Kliman.

Citation: American Journal of Perinatology (August 3, 2009)

Yale University

Women who have premature menopause because of medical interventions are at an increased risk of developing lung cancer, according to a new study published in the International Journal of Cancer. The startling link was made by epidemiologists from the Universit de Montral, the Research Centre of the Centre Hospitalier de l’Universit de Montral and the INRSInstitut Armand-Frappier.

“We found that women who experienced non-natural menopause are at almost twice the risk of developing lung cancer compared to women who experienced natural menopause,” says Anita Koushik, a researcher at the Universit de Montral’s Department of Social and Preventive Medicine and a scientist at the Research Centre of the Centre Hospitalier de l’Universit de Montral. “This increased risk of lung cancer was particularly observed among women who had non-natural menopause by having had both their ovaries surgically removed.”

The scientists studied 422 women with lung cancer and 577 control subjects at 18 hospitals across Montreal, Quebec, Canada. They assessed socio-demographic characteristics, residential history, occupational exposures, medical and smoking history, and (among women) menstruation and pregnancy histories.

“A major strength of this study was the detailed smoking information which we obtained from all study participants; this is important because of the role of smoking in lung cancer and because smokers generally have lower estrogen levels than non-smokers,” says Dr. Koushik. “Although smoking is the dominant cause of lung cancer, we know other factors can play an important role in enhancing the impact of tobacco carcinogens; this research suggests that in women hormonal factors may play such a role.”

Women were considered menopausal if their menstrual periods had stopped naturally, surgically (by hysterectomy with bilateral surgical ovary removal) or because of radiation or chemotherapy. Women who had at least one remaining ovary and who still had their menstrual periods at the time of diagnosis/interview were classified as premenopausal. Among participants with natural menopause, the median age for attaining menopause was 50 years old; among those with non-natural menopause, it was at 43 years.

“Non-natural menopause, particularly surgical menopause, may represent an increased risk with younger age at menopause given that surgery is usually done before natural menopause occurs. It’s possible that vulnerability to lung cancer is caused by early and sudden decrease in estrogen levels or potentially long-term use of hormone replacement therapy and further research is needed to explore these hypotheses,” says Jack Siemiatycki a professor at the Universit de Montral’s Department of Social and Preventive Medicine and a scientist at the Research Centre of the Centre Hospitalier de l’Universit de Montral.

About the Study:
The article “Characteristics of menstruation and pregnancy and the risk of lung cancer in women,” published in the International Journal of Cancer, was authored by Anita Koushik and Jack Siemiatycki of the Universit de Montral and Research Centre of the Centre Hospitalier de l’Universit de Montral and Marie-Elise Parent of the INRSInstitut Armand-Frappier.

Partners in Research:
This study was funded by the Canadian Institutes of Health Research, the Fonds de la recherche en sant du Qubec and the Guzzo-SRC Chair in Environment and Cancer.

On the Web:
About cited article from International Journal of Cancer: http://www3.interscience.wiley.com/cgi-bin/fulltext/122380525/PDFSTART
About the Universit de Montral: http://ww.umontreal.ca/english
About the Research Centre of the Centre Hospitalier de l’Universit de Montral: http://www.chumtl.qc.ca/crchum.en.html
About the Environmental Epidemiology and Population Health Research Group: http://www.environepi.ca/
About INRSInstitut Armand-Frappier: http://www.iaf.inrs.ca/anglais/centre_bref.html

UCSF researchers have identified a new “feed-forward” pathway linking estrogen receptors in the membrane of the uterus to a process that increases local estrogen levels and promotes cell growth.

The research is significant in helping determine why tamoxifen and other synthetic estrogens are linked to increased rates of endometriosis and uterine cancer, and identifies a pathway that could be targeted in drug therapies for those diseases, researchers say.

Findings are published in the July 1, 2009 issue of “Cancer Research,” the journal of the American Association for Cancer Research. The paper also can be found online at http://cancerres.aacrjournals.org/current.shtml.

The research found that when activated by estrogens, endometrial cells obtained from patients suffering from endometriosis or human uterine cancer cells initiate a previously unknown cascade of signals that leads to cellular replication and further estrogen production, the paper says.

The ensuing cycle leads to abnormal growth of the cells lining the uterus, or endometrium, which occurs in endometriosis and uterine cancer, according to senior author Holly A. Ingraham, PhD, a professor in the UCSF School of Medicine’s Department of Cellular and Molecular Pharmacology.

“It turns out that displaced endometrial cells, such as those used in this study, are estrogen factories,” said Ingraham, who also is affiliated with the UCSF Helen Diller Family Comprehensive Cancer Center and the UCSF Center for Reproductive Sciences. “They pump out estrogen in a feed-forward pathway, so the more estrogen they produce, the more estrogen they’re capable of producing.”

While this pathway was previously unknown, Ingraham said a June 2009 paper led by researchers at the University of New Mexico and published in the journal “Nature Chemical Biology” showed that blocking the GPR30 receptor in this pathway decreases uterine proliferation in a mouse. The two together, she said, validate what researchers now think may be a key area in addressing both uterine cancer and endometriosis.

Uterine cancer is the fourth most common cancer in women, with more than 37,000 women being diagnosed each year in the United States alone, according to data from the Centers for Disease Control.

Endometriosis, in which endometrial cells grow in areas other than the uterus, is the most common gynecological disease and affects more than 5.5 million women in North America, according to the National Institutes of Health. The disease often causes severe pain and can lead to infertility.

Working in collaboration with clinicians at Northwestern University in Chicago, the UCSF team analyzed cells from women with ectopic endometriosis. By studying those patients’ endometrial cells, the team was able to identify an unusual, circular pathway involving these cells, the transmembrane estrogen receptor GPR30 and the nuclear receptor SF-1.

The researchers propose that this pathway increases local concentrations of estrogen and, together with classic estrogen-receptor signaling, control the proliferative effects of these estrogens in promoting endometriosis and endometrial cancers.

The UCSF team used a unique chemical biology approach, making use of a tamoxifen-like compound developed in the laboratory of co-author Thomas Scanlan, PhD, who is affiliated with both the UCSF Department of Pharmaceutical Chemistry and the Department of Chemical Biology at the Oregon Health Sciences University in Portland.

“Tamoxifen and other synthetic estrogens have been known to increase the risk of uterine cancer, but until now, we didn’t know why that was on a cellular level,” Ingraham said. “We think this pathway is going to be an important one in solving that mystery.”

The lead investigator on the paper was Benjamin C. Lin. Lin and co-author Sandra C. Tobias are affiliated with the Department of Pharmaceutical Chemistry at UCSF. Other co-authors are Miyuki Suzawa, in the UCSF Department of Cellular and Molecular Pharmacology; Raymond D. Blind in the UCSF Department of Pharmaceutical Chemistry and Department of Cellular and Molecular Pharmacology; and Serdar E. Bulun, in the Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University.

The authors report no potential conflicts of interest in this research.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, visit http://www.ucsf.edu.

For the first time, researchers have been able to identify genetic predictors of the potential success or failure of IVF treatment in blood. Dr. Cathy Allen, from the Rotunda Hospital, Dublin, Ireland, told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Wednesday 1 July) that her research would help understand why IVF works for some patients but not for others.

Previous work in this area has looked at gene profiles in such tissues as the uterine lining, but Dr. Allen and her team chose to examine the gene expression patterns in RNA extracted from peripheral (circulating) blood, an easily accessible biological sample. Blood samples were taken at eight different stages during the period around conception and the early stages of the IVF cycle. Five of these samples came from women who achieved clinical pregnancies, three from those who had implantation failure, and three from subfertile women who conceived spontaneously. Analysis showed that 128 genes showed a more than two-fold difference in expression in early clinical pregnancy compared with a non-pregnant state.

The molecular pathways that were most over-represented in this expression were concerned with angiogenesis (the growth of new blood vessels), endothelin signalling (blood vessel constriction), inflammation, oxidative stress (damage to cell structures), vascular endothelial growth factor (signalling processes in blood vessel growth), and pyruvate metabolism (the supply of energy to cells). “All these processes are important in the achievement and maintenance of pregnancy,” said Dr. Allen.

“We found that the gene expression profiles in blood of patients at the time of pituitary down-regulation showed interesting patterns of gene clustering. Over 200 genes were differentially expressed in patients who went on to achieve an IVF pregnancy compared with those who did not,” she said.

The researchers found that the peripheral blood gene expression ’signature’ (also known as the transcriptome) before IVF was predictive of IVF outcome. This finding demonstrates the power of high-dimensional technology in biomarker discovery, and highlights the potential for developing clinically useful tools, they say.

One of the most difficult decisions for patients who have had unsuccessful IVF treatments is whether they should undergo further attempts at IVF, or if there are ways to optimise chances of success. The researchers hope that the results generated by this work will lead to the development of a test to aid in IVF decision-making. They say that their work will help to identity biomarkers that can identify events occurring at implantation, the maintenance of pregnancy and successful or unsuccessful pregnancy outcome.

“IVF technology has advanced tremendously over the past three decades, yet success after IVF remains an unpredictable outcome,” said Dr. Allen. “Our work will help understand whether the implantation of embryos is influenced by the constantly changing expression of human genes.”

Previous studies in the field of gene-expression have focused on single genes as opposed to genome-wide screening of all the human genes with high density DNA microarrays, as used by Dr. Allen and her team. The advent of tools like microarrays that can simultaneously probe for up to 29,000 genes has radically changed scientific approaches to this type of research. “It’s like looking at how a team of players perform together rather than focusing on the individual players,” said Dr. Allen.

“We intend to look further at the most significant genes we have identified as being important in this field in order to be able to understand their exact biological role in reproductive function. We hope that our work will lead to the development of a clinically useful tool to help doctors counsel their patients in the difficult decision-making involved in IVF,” she said.

Abstract no: O-269 Wednesday 14.15 hrs CEST (Elicium 1)

European Society for Human Reproduction and Embryology

Amsterdam, The Netherlands: One-step screening for both genetic and chromosomal abnormalities has come a stage closer as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis.

They told a news briefing at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam today (Tuesday) that, as a result, they would be able to offer clinical trials to couples seeking fertility treatment later this year.

The researchers based in the USA and the UK have been able to prove that the technique, known as genome-wide karyomapping, was capable of not only detecting diseases caused by a specific gene mutation, in this case cystic fibrosis, but that it was also capable of detecting aneuploidy (an abnormal number of any of the 23 pairs of chromosome) at the same time. This is the first time they have been able to demonstrate that the test can work in cells taken from embryos that have already been diagnosed with the cystic fibrosis gene mutation using conventional preimplantation genetic diagnosis (PGD).

Gary Harton, PGD scientific director of the Genetics & IVF Institute in Fairfax, Virginia (USA) told a news briefing: “Karyomapping is a universal method for analysing the inheritance of genetic defects in the preimplantation embryo without any prior patient or disease specific test development, which often delays patient treatment. For the first time, the inheritance of both single gene defects and chromosomal abnormalities can be detected simultaneously at the single cell level. Unlike other methods, this is achieved entirely by analysing the DNA sequence at over 300,000 locations genome-wide in parents and appropriate family members, often children already affected by a disease, and comparing their sequence with that inherited by the embryo. This can be achieved very rapidly using current microchip technology known as microarray.”

With karyomapping it is not necessary to know the exact DNA mutation that is being sought; the scientists just need to take the relevant chunk of DNA from the parent that carries the mutation somewhere along its length, and if it matches a chunk of DNA from the embryo, then they know the embryo has inherited the mutation. As karyomapping involves analysing chromosomes, it also detects the existence of aneuploidy at the same time.

“The range of applications is broad and includes single gene defects, abnormal chromosome number, structural chromosome abnormalities and HLA [human leukocyte antigen] matching in ’saviour sibling’ cases,” said Mr Harton.

Karyomapping was developed by Professor Alan Handyside of the London Bridge Fertility Gynaecology and Genetics Centre in London (UK), and Mr Harton has been providing samples and DNA information in order to test the method and validate it for use in the clinic.

“The hope is that clinicians will be able to test embryos for specific genetic diseases and know that, with one test, they are transferring chromosomally normal embryos. This will be a step forward from current technology that is mostly limited to choosing one test or the other,” explained Prof Handyside.

Karyomapping would also be quicker and cheaper. Currently, developing a PGD test for a single gene defect can take weeks or months, as scientists have to identify the exact patient or disease-specific genetic mutation first before screening for it, which is labour-intensive and costly. By contrast, karyomapping can be carried out without such extended pre-test development; at present, it takes about three days, but Mr Harton and his colleagues believe this could be reduced to 18-24 hours.

In this most recent stage of their research they examined cells from five embryos that had been donated for medical research by a couple who had received successful fertility treatment, including PGD for cystic fibrosis. The embryos had developed to the blastocyst stage, which is about five days after fertilisation. Conventional PGD had already identified which embryos were unaffected, affected or were carriers of the disease. Karyomapping of cells from the donated embryos confirmed these diagnoses, but, in addition, it was able to identify which parent carried the affected chunk of DNA. Karyomapping also revealed two aneuploidies in two embryos, which had not been detected by the earlier PGD.

Mr Harton said: “This demonstrates that karyomapping, following genome-wide analysis of a single cell biopsied from embryos at the blastocyst stage, can provide highly accurate analysis for cystic fibrosis, combined with the detection of chromosomal aneuploidy. Now that vitrification [an improved method of embryo freezing] has improved embryo survival after thawing, it should be possible to vitrify embryos at the blastocyst stage, either before or after biopsy, and analyse the embryos for virtually any genetic disease and screen for aneuploidy of all 23 pairs of chromosomes simultaneously. This approach could make PGD by karyomapping less expensive than conventional single disease PGD because fewer embryos will be biopsied, more embryos will be chromosomally normal following growth to the blastocyst stage, and there is no need to custom develop tests for each disease or couple interested in PGD.”

Prof Handyside concluded: “These tests have helped us to learn everything we can before we start to treat actual patients. I am confident that we will be offering a clinical trial to patients using karyomapping some time this year.”

European Society for Human Reproduction and Embryology

June issue of American Journal of Obstetrics and Gynecology explores topic

New York, New York, June 29, 2009 Cerebral palsy (CP) is the most prevalent chronic childhood motor disability with an estimated lifetime cost of nearly $1 million per individual. There is evidence that magnesium sulfate (MgSO4) can reduce the incidence of CP for very early preterm infants. Many thousands of pregnant women and their fetuses are exposed to MgSO4 every year in the United States for a variety of indications, and most obstetricians are comfortable with its use. Yet, there is still some controversy over whether magnesium sulfate is truly protective against CP. In three articles published in the June 2009 issue of the American Journal of Obstetrics & Gynecology, the authors shed some light on the debate.

Investigators from the Perinatology Research Branch (Division of Intramural Research), Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the NIH, Bethesda, and Detroit, and the Center for Molecular Medicine and Genetics, Wayne State University, Detroit, conducted a systematic review and meta-analysis of six randomized controlled trials involving 4796 women and 5357 infants. Writing in the article, Dr. Roberto Romero and Dr. Agustin Conde-Agudelo concluded that “Antenatal magnesium sulfate should be considered for use in women at high risk of delivery before 34 weeks of gestation, mainly in those with premature rupture of membranes, labor in active phase, and planned delivery within 24 hours.” They found persuasive evidence that administration of magnesium sulfate significantly reduces the risk of cerebral palsy in children at risk.

Continuing the debate, in an article summarizing a roundtable discussion at the 29th Annual Meeting of the Society for MaternalFetal Medicine, San Diego, CA, January 30, 2009, two researchers from the Division of MaternalFetal Medicine, Department of Obstetrics and Gynecology, Washington UniversitySt. Louis,, and the Division of MaternalFetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of CaliforniaSan Francisco, enumerate the pros and cons of magnesium sulfate use for CP prevention. In a spirited conversation, they each talk about the available trials and observational studies and the strengths and weaknesses of each.

Participating in the roundtable, Alison G. Cahill, MD, MSCI, and Aaron B. Caughey, MD, PhD, observe, “Despite well-designed and executed studies, the answer to the question of whether evidence-based medicine supports the use of magnesium for neuroprophylaxis in all preterm pregnancies remains unclear.”

Dwight J. Rouse, MD, of the Center for Women’s Reproductive Health, University of Alabama at Birmingham, offers his clinical opinion on the use of MgSO4 to prevent cerebral palsy. He notes that “three large, randomized placebo-controlled trials of antenatal magnesium sulfate (MgSO4) for fetal neuroprotection have recently been conducted and reported. The results of these trials provide strong support for the utilization of MgSO4 to lower the risk of cerebral palsy among the survivors of early preterm birth. In the United States, the use of MgSO4 for fetal neuroprotection has the potential to prevent 1000 cases of handicapping cerebral palsy annually.”

The articles are:

“Antenatal Magnesium Sulfate for the Prevention of Cerebral Palsy in Preterm Infants < 34 Weeks’ Gestation: A Systematic Review and Meta-Analysis” by Agustn Conde-Agudelo, MD, MPH, and Roberto Romero, MD

“Magnesium for Neuroprophylaxis: Fact or Fiction?” by Alison G. Cahill, MD, MSCI, and Aaron B. Caughey, MD, PhD

“Magnesium Sulfate for the Prevention of Cerebral Palsy” by Dwight J. Rouse, MD

These contributions appear in the American Journal of Obstetrics & Gynecology, Volume 200, Issue 6 (June 2009) published by Elsevier.

Elsevier Health Sciences

Older women suffering from clinical frailty stand to benefit from the first potential medical treatment for the condition, according to a study presented today by Penn Medicine researchers at ENDO, The Endocrine Society’s 91st Annual Meeting. Ghrelin, a hormone that stimulates appetite, was administered to older women diagnosed with frailty, a common geriatric syndrome characterized by unintentional weight loss, weakness, exhaustion and low levels of anabolic hormones which increases risk of falls, hospitalizations, disability, and death. Those who received ghrelin infusions consumed 51 percent more calories than the placebo group, with an increase in carbohydrate and protein intake, not fat. Their growth hormone levels were also higher throughout the ghrelin infusion.

“As Americans are increasingly living into their 80s and 90s, we need to identify ways to prevent or treat common geriatric conditions, such as unexplained weight loss and frailty, which have serious health consequences,” said senior author Anne Cappola, MD, ScM, Assistant Professor of Medicine in Endocrinology, Diabetes, and Metabolism at the University of Pennsylvania School of Medicine. “We’re gaining a better understanding of the hormonal changes that occur as we get older and, with treatments like ghrelin, we can start intervening to prevent some of the common health problems that keep elderly people from living their most productive lives.”

In the pilot study, funded by the National Institutes of Health and Penn’s Institute on Aging, five frail women and five healthy women, all over the age of seventy, were randomized to receive an infusion of the hormone ghrelin or placebo. After a ghrelin transfusion, frail women in the study had a stronger, healthy appetite and increased anabolic hormone activity. The only side effect reported during the treatment was a transient sense of warmth that occurred in four women who received the ghrelin transfusion.

Now that safety and initial efficacy has been proven in this pilot study, larger follow-up studies will look at the potential therapeutic role of ghrelin or ghrelin mimetic agents in the frail population. At this time, these agents are only available for research use.

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System.

Penn’s School of Medicine is currently ranked #3 in the nation in U.S.News & World Report’s survey of top research-oriented medical schools; and, according to the National Institutes of Health, received over $366 million in NIH grants (excluding contracts) in the 2008 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation’s first hospital; and Penn Presbyterian Medical Center, named one of the nation’s “100 Top Hospitals” for cardiovascular care by Thomson Reuters. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

University of Pennsylvania School of Medicine

Because bleeding from the reproductive tract is a naturally occurring event during menstruation and childbirth, women who exhibit menorrhagia, or excessive bleeding after their menstrual cycle, may have underlying diseases that are underdiagnosed. In order to address important issues related to the diagnosis and management of reproductive tract bleeding in women with bleeding disorders, a consensus conference was convened. Results are published in the July 2009 issue of the American Journal of Obstetrics & Gynecology.

The goals of the consensus conference were to highlight the problems these women experience and to provide clinical information and recommend strategies to guide practicing obstetricians and gynecologists. Where the international panel of experts in obstetrics, gynecology and hematology reached consensus, recommendations were made.

Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. VWD results from a deficiency in, or a dysfunction of, von Willebrand factor (VWF), a protein necessary for normal platelet adhesion and protection of factor VIII (FVIII) from proteolysis in the circulation. The prevalence of menorrhagia in women with VWD is 74-92%.

Although the majority of women who present with menorrhagia do not have a bleeding disorder, the conference participants identified more than a dozen symptoms that suggest further evaluation, including menorrhagia since puberty, a family history of a bleeding disorder, and personal history of one, but usually several, of the following symptoms: nosebleeds (generally bilateral for more than 10 minutes), more than once in the past year; notable bruising without injury (and with bruises >2 cm in diameter); minor wound bleeding from trivial cuts lasting for more than 5 minutes; or prolonged or excessive bleeding following dental extraction.

A hematologic evaluation of the patient’s platelet number and function and her coagulation factor profile should be assessed in collaboration with a hematologist. Meeting participants also agreed that hematologic evaluations should be repeated to confirm the diagnosis of a bleeding disorder.

Writing in the article with her co-authors, Andra H. James, MD, Women’s Hemostasis and Thrombosis Clinic, Duke University Medical Center, Durham, NC, states, “Obstetricians and gynecologists should be aware of bleeding disorders such as VWD, rare bleeding disorders and platelet disorders, which remain underdiagnosed in women with menorrhagia and potentially in other cases of abnormal bleeding such as postpartum hemorrhage. Clues, including a family or personal history of bleeding events, should provoke suspicion of an underlying bleeding disorder. Responding to these clues facilitates collaboration among obstetriciangynecologists and hematologists that could lead to a decrease in the diagnosis of “idiopathic” menorrhagia and allow more effective management of bleeding events.”

The article is “Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel” by Andra H. James, MD; Peter A. Kouides, MD; Rezan Abdul-Kadir, MD; Mans Edlund, MD, PhD; Augusto B. Federici, MD; Susan Halimeh, MD; Pieter W. Kamphuisen, MD; Barbara A. Konkle, MD; Oscar Martnez-Perez, MD, PhD; Claire McLintock, MD; Flora Peyvandi, MD, PhD; and Rochelle Winikoff, MD. It appears in the American Journal of Obstetrics & Gynecology, Volume 201, Issue 1 (July 2009) published by Elsevier.

Elsevier Health Sciences

Variations in both milk feeding and in the weaning diet are linked to differences in growth and development, and they have independent influences on body composition in early childhood, according to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

Previous studies suggest that the early environment may be a significant factor in childhood obesity. This study used dual x-ray absorptiometry to make direct measures of body composition in children at four years of age whose diets had been assessed when they were infants. The findings showed that children who had been breastfed longer had a lower fat mass which could not be explained by differences in family background or the child’s height.

“Most studies linking infant feeding to later body composition focus on differences in milk feeding, but our study also considered the influence of the weaning diet,” said Dr. Sin Robinson, PhD, of the MRC Epidemiology Resource Centre, University of Southampton in the United Kingdom and lead author of the study. “We found that, independent of the duration of breastfeeding, children with higher quality weaning diets including fruits, vegetables, and home-prepared foods had a greater lean mass at four years of age.”

In this study, researchers assessed the diets of 536 children at six and 12 months of age. Diet was assessed using a food frequency questionnaire that was administered by trained research nurses to record the average frequency of consumption of specific foods. The age at which solid foods were introduced into the infant’s diet was also recorded. In this study ‘weaning’ is defined as the period of transition in infancy between a diet based on milk feeding to one based on solid foods. The subjects’ body composition was assessed at four years by dual X-ray absorptiometry.

“These findings are enlightening,” said Professor Cyrus Cooper, Director of the MRC Epidemiology Resource Centre. “An influence of qualitative differences in the weaning diet on childhood body composition had not been described before.”

Other researchers working on the study include Lynne Marriott, Sarah Crozier, Nick Harvey, Catharine Gale, Hazel Inskip, Janis Baird, Keith Godfrey, and Cyrus Cooper of the University of Southampton in the United Kingdom and Catherine Law of University College London in the United Kingdom. The study was funded by the UK Medical Research Council, University of Southampton, British Heart Foundation and the Food Standards Agency.

The article “Variations in infant feeding practice are associated with body composition in childhood: a prospective cohort study,” will appear in the August 2009 issue of JCEM.

The Endocrine Society

Findings reinforce March of Dimes message: Start taking a vitamin with folic acid before pregnancy

Women who take folic acid supplements for at least one year before they become pregnant may cut their risk of having a premature baby by half, according to research published this week in the online journal, PLoS Medicine.

The study links pre-conceptional folate supplementation of at least one year to reduced early premature delivery rates of 50 to 70 percent, regardless of age, race or other factors. Of particular note is the drop in very early premature births, those babies who are at the greatest risk of complications such as cerebral palsy, mental retardation, chronic lung disease, and blindness.

The study is an observational analysis based on the self-reporting of folate supplementation by 38,033 participants in an earlier trial sponsored by the National Institutes of Health (NIH.) The current study only examined singleton pregnancies and excluded pregnancies with medical or obstetrical complications such as preeclampsia, chronic hypertension, or other abnormalities.

“Through the NIH trials, we received highly accurate evidence of gestational age enabling us to determine that folate supplementation for at least one year is linked to a 70 percent decrease in very early preterm deliveries (20 to 28 weeks gestation) and up to a 50 percent reduction in early preterm deliveries of 28 to 32 weeks,” said Radek Bukowski, M.D., Ph.D., associate professor, in the Department of Obstetrics and Gynecology, at the University of Texas Medical Branch at Galveston, the lead study author.

“We already know that folic acid supplementation beginning before pregnancy and continuing into the first trimester helps prevent serious birth defects of the brain and spinal cord, such as spina bifida,” said Alan R. Fleischman, M.D., senior vice president and medical director of the March of Dimes. “Dr. Bukowski’s research makes us optimistic that taking folic acid for at least one year before pregnancy also may greatly reduce the risk of premature birth and reinforces our message that every woman of childbearing age should consume 400 micrograms of folic acid daily.”

The March of Dimes honored Dr. Bukowski’s study in January 2008 during the annual meeting of the Society for Maternal Fetal Medicine. “Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study” by Bukowski, et al. is available online at http://medicine.plosjournals.org/perlserv/?request=getdocument&doi=10.1371/journal.pmed.1000061.

March of Dimes Foundation