<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_430"
                     title="HRT Linked to Asthma Risk (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Endocrinology/Menopause/tb/18342?impressionId=1265804679512"
                     
      &lt;p&gt;Estrogen-only hormone replacement therapy is associated with an increased risk of asthma in postmenopausal women, a large prospective observational cohort study showed.&lt;/p&gt;
&lt;p&gt;Recent and current users of estrogen had a 54% increase in the risk of being diagnosed with asthma, according to Isabelle Romieu, MD, ScD, of the National Institute of Public Health in Cuernavaca, Mexico, and colleagues.&lt;/p&gt;
&lt;p&gt;The risk was even higher in nonsmokers or those who reported an allergic disease before they developed asthma, the researchers reported online in &lt;em&gt;Thorax&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Epidemiological studies suggest that an endocrine mechanism  --  perhaps endogenous estrogen synthesis  --  is involved in asthma in women and girls, the researchers wrote.&lt;/p&gt;
&lt;p&gt;It&apos;s plausible that hormone replacement therapy &quot;might therefore play a role in asthma onset,&quot; they theorized in the journal.&lt;/p&gt;
&lt;p&gt;To delve into the question, Romieu and colleagues turned to the E3N cohort study, which is the French component of the continuing European Prospective Investigation into Cancer and Nutrition (EPIC) study.&lt;/p&gt;
&lt;p&gt;The study started in 1990 and includes 98,995 French women born between 1925 and 1950. The participants complete self-administered questionnaires every two years, giving details of their medical history, menopausal status, and a variety of lifestyle characteristics.&lt;/p&gt;
&lt;p&gt;Women were deemed to have a new case of asthma if  --  after being free of the disease at baseline  --  they later reported both that they had suffered asthma attacks and that the diagnosis had been confirmed by a physician.&lt;/p&gt;
&lt;p&gt;Among the participants, Romieu and colleagues found 57,664 women who were free of asthma at menopause. In that group, the researchers found, there were 569 incident cases of asthma during a total of 495,448 years of follow-up.&lt;/p&gt;
&lt;p&gt;Analysis showed that hormone replacement therapy in general was related to an increased risk of asthma onset among recent users, with a hazard ratio of 1.20. But the 95% confidence interval ranged from 0.98 to 1.46, so the finding was not statistically significant.&lt;/p&gt;
&lt;p&gt;Instead, the researchers found, the association only reached significance among women reporting the use of estrogen alone, where the hazard ratio was 1.54, with a 95% confidence interval from 1.13 to 2.09.&lt;/p&gt;
&lt;p&gt;The risk was particularly great in estrogen-using women who had never smoked or who had reported allergic disease before the asthma onset. Those hazard ratios were 1.80 and 1.84, respectively, and both reached significance.&lt;/p&gt;
&lt;p&gt;The increased risk among never smokers might reflect an anti-estrogen effect of tobacco smoke, the researchers speculated, or difficulty isolating the additional effect of the therapy in smokers.&lt;/p&gt;
&lt;p&gt;The strengths of the study include its large size, prospective design, and relatively low loss to follow-up of 3.8%, Romieu and colleagues said.&lt;/p&gt;
&lt;p&gt;They added that the results might be biased if users of hormone replacement therapy reported more asthma attacks or were diagnosed more often because of more frequent visits to the doctor.&lt;/p&gt;
&lt;p&gt;Indeed, hormone therapy users had more mammograms than nonusers, they noted, but added that the participants all had free medical care and &quot;there is no reason to believe&quot; that hormone users had more medical visits for non-gynecological reasons than nonusers.&lt;/p&gt;
&lt;p&gt;Hormone therapy has been controversial  --  and on the decline  --  since the landmark Women&apos;s Health Initiative study was stopped in 2002 when the researchers found that participants taking estrogen plus progestin had a greater incidence of coronary heart disease, breast cancer, stroke, and pulmonary embolism than those receiving placebo.&lt;/p&gt;
&lt;p&gt;In the current study, the combination hormone therapy was not associated with an increase in asthma incidence.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study and researchers had support from Mutuelle G&amp;#233;n&amp;#233;rale de l&apos;Education Nationale, the Institut de Canc&amp;#233;rologie Gustave Roussy, the Institut National de la Sant&amp;#233; et de la Recherche M&amp;#233;dicale, the CDC, the Canc&amp;#233;rop&amp;#244;le R&amp;#233;gion Ile de France, and the GA&lt;sup&gt;2&lt;/sup&gt;LEN project.&lt;/p&gt;&lt;p&gt;The authors did not report any potential conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_331"
                     title="Physicians Must Treat Transplant Tourists"
                     score="0.007"
                     href="http://www.medpagetoday.com/Gastroenterology/LiverTransplantation/tb/18203?impressionId=1265804679512"
                     
      &lt;p&gt;Patients who travel to foreign countries for organ transplants may return with more problems than they left with  --  and physicians here have a moral responsibility to treat them, researchers asserted in a transplant journal.&lt;/p&gt;
&lt;p&gt;&quot;Medical tourism&quot; has been on the rise as demand for organs outpaces supply and U.S. healthcare costs skyrocket, Thomas D. Schiano, MD, and Rosamond Rhodes, PhD, of Mount Sinai School of Medicine, reported in &lt;em&gt;Liver Transplantation&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Researchers have estimated that 300 medical tourism transplants occurred between 2004 and 2006, with more than 40% of transplant tourists residing in New York or California, which have only 18% of the total U.S. population. (See &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/12564&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/12564&quot; target=&quot;_blank&quot;&gt;International Medical Trade Turns Big Business&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Yet physicians have had little guidance on delivering care to these patients, and some transplant centers may turn them away, based on their actions, Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;Their questions about treatment arose with a 46-year-old Chinese patient who had been put on a waiting list for a liver transplant here because of end-stage liver disease.&lt;/p&gt;
&lt;p&gt;The patient waited on the list for a year as his disease progressed from 18 points to 21 points on a 40-point severity scale.&lt;/p&gt;
&lt;p&gt;Rather than wait any longer, the patient flew to China and had a liver transplant there.&lt;/p&gt;
&lt;p&gt;Many transplanted organs in China come from executed prisoners, raising concerns about disease. Also, foreign transplants may be compromised by poor organ matching, unhealthy donors, and post-transplant infections, while some transplant centers abroad may use substandard surgical techniques, the researchers said.&lt;/p&gt;
&lt;p&gt;Foreign centers are also less likely to send patients home with adequate records and education than centers here, they asserted.&lt;/p&gt;
&lt;p&gt;Three months after his transplant in China, the patient came back to the clinic at Mount Sinai for follow-up care because he was about to run out of imunosuppressive medication.&lt;/p&gt;
&lt;p&gt;Two months after that, the patient developed sepsis due to diffuse intrahepatic biliary stricturing related to hepatic artery thrombosis.&lt;/p&gt;
&lt;p&gt;He required three additional hospitalizations for biliary sepsis, and at that point, retransplantation was the only viable option, Schiano said.&lt;/p&gt;
&lt;p&gt;However, members of the medical team had conflicting views about giving the patient another new liver.&lt;/p&gt;
&lt;p&gt;&quot;He was a medically suitable candidate,&quot; Schiano and Rhodes wrote, &quot;but there was disagreement about whether it was morally right to provide him with a transplant.&quot;&lt;/p&gt;
&lt;p&gt;The clinicians had few ethical guidelines to refer to in making their decision because many deal solely with moral issues related to donors and foreign medical standards.&lt;/p&gt;
&lt;p&gt;For example, the International Society for Heart and Lung Transplantation issued a statement against accepting organs from prisoners in April 2007, and the American Association for the Study of Liver Diseases and the International Liver Transplant Society endorsed similar policies.&lt;/p&gt;
&lt;p&gt;The American Medical Association&apos;s guidelines on medical tourism focus on best practices  --  for example, the procedure must be voluntary, it can&apos;t limit the alternatives offered to patients, and patients should only be referred to accredited institutions.&lt;/p&gt;
&lt;p&gt;While the United Network for Organ Sharing (UNOS)&apos;s statement on medical tourism does maintain that the medical community has an obligation to provide care for these patients, it stops short of offering further direction to transplant programs.&lt;/p&gt;
&lt;p&gt;&quot;Little guidance is provided for dealing with the specific problems of patients who choose to become transplant tourists,&quot; Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;Instead, they created some ethical guidance for the &quot;moral quandary.&quot;&lt;/p&gt;
&lt;p&gt;Physicians have a &quot;professional obligation to promote the good of patients&quot; as well as a &quot;professional responsibility to adhere to medicine&apos;s commitment to nonjudgmental regard,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;Taken together, the moral principles of beneficence and nonjudgmental regard direct us to treat potential or returning transplant tourists as we would treat other patients under our care by focusing on providing the medical treatment and support they need,&quot; they continued.&lt;/p&gt;
&lt;p&gt;Physicians shouldn&apos;t deny patients post-transplantation care, and they ought to provide emergent care at the very least. They may refer the patient to another transplant center for long-term follow-up if they regard it as unethical to continue treatment.&lt;/p&gt;
&lt;p&gt;Patients should also be informed about the possibility of transplant tourism when they are not eligible for a transplant in the U.S. or when they are likely to die before reaching the top of the transplant list, Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;&quot;Patients should not be threatened with abandonment by a center&apos;s refusal to provide care upon their return,&quot; they added.&lt;/p&gt;
&lt;p&gt;As for the 46-year-old patient who was transplanted in China, the Mount Sinai team decided a transplant program must treat all patients on the basis of their need &quot;regardless of what they might have done or how they secured their transplant organ.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Although [the patient] had a long, complicated transplantation course,&quot; they wrote, &quot;he is currently doing well.&quot;&lt;/p&gt;
&lt;p&gt;Mount Sinai has seen a total of nine patients who pursued transplants in China. Three of those had post-transplant problems but had been turned away elsewhere &quot;because several transplant centers in our region do not render care to transplant tourists,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Seven of those nine patients have hepatitis B. Another three had had a renal transplant in India, and subsequently developed liver failure, the authors reported.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265804679512"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_288"
                     title="SSRIs Affect Breast Milk Production (CME/CE)"
                     score="0.001"
                     href="http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/tb/18149?impressionId=1265804679512"
                     
      &lt;p&gt;Women taking selective serotonin reuptake inhibitor (SSRI) antidepressants may experience delays in postpartum breast milk production, researchers said.&lt;/p&gt;
&lt;p&gt;Delayed secretory activation occurred in 87.5% of a small group of women taking SSRIs, compared with 43.5% of those not taking the drugs (RR 2, 95% CI 1.51 to 2.67, &lt;em&gt;P&lt;/em&gt;=0.02), according to Aaron M. Marshall, PhD, of the University of Cincinnati.&lt;/p&gt;
&lt;p&gt;The relative risk of delayed activation remained significantly higher (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) among SSRI users after adjustment for maternal age, obesity, cesarean delivery, infant gestational age, and infant breastfeeding behavior, the researchers reported online in the &lt;em&gt;Journal of Clinical Endocrinology and Metabolism&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;An early breastfeeding difficulty faced by many women, particularly those who are primiparous, is milk secretion delayed beyond 72 hours postpartum.&lt;/p&gt;
&lt;p&gt;These women also are at risk of early cessation of breastfeeding. In fact, only 11% of mothers in the U.S. breastfeed exclusively for the recommended six months.&lt;/p&gt;
&lt;p&gt;Studies in animal models and cell cultures suggested that serotonin (5-HT) is an important local regulator of lactation homeostasis, and the 5-HT transporter is expressed in mammary tissue at the apical membrane of epithelial cells.&lt;/p&gt;
&lt;p&gt;Serotonin is controlled intracellularly by a balance between synthesis and degradation, while extracellularly its availability is controlled through recycling by the 5-HT transporter.&lt;/p&gt;
&lt;p&gt;The 5-HT transporter also is the target for the most commonly prescribed class of antidepressants in the U.S. and other developed countries. These SSRI antidepressants are typically used to treat postpartum depression.&lt;/p&gt;
&lt;p&gt;The investigators conducted in vitro and animal studies to establish that the 5-HT transporter is expressed in breast tissue, particularly in the apical membranes of mammary epithelial cells, and that pharmacologic inhibition of the transporter disrupts tight junctures leading to a local involution-like effect.&lt;/p&gt;
&lt;p&gt;To examine the potential effect of SSRI inhibition on milk production in women, Marshall and colleagues enrolled 431 mothers as part of a longitudinal cohort study examining barriers to early lactation success.&lt;/p&gt;
&lt;p&gt;All were expecting their first live-born infants, had no known absolute contraindication to breastfeeding, and were at least 19 years old.&lt;/p&gt;
&lt;p&gt;Women taking SSRIs were more likely to have scored higher on a depressive symptom scale (as expected), and were somewhat more likely to be obese or to have had a cesarean delivery.&lt;/p&gt;
&lt;p&gt;Participating mothers were visited between 72 and 96 hours after giving birth to assess their breastfeeding experience and to determine the timing of secretory activation, and then seen again one week later.&lt;/p&gt;
&lt;p&gt;Delayed secretory activation was defined as initiation more than 72 hours postpartum.&lt;/p&gt;
&lt;p&gt;Median onset of secretory activation among the SSRI-treated mothers was 85.8 hours compared with 69.1 hours in mothers not using the drugs (&lt;em&gt;P&lt;/em&gt;=0.004).&lt;/p&gt;
&lt;p&gt;Eight women reported regular use of an SSRI medication. Seven experienced definite delayed secretory activation, and the eighth reported activation at 72 hours and therefore did not meet the defined cutoff for delayed activation.&lt;/p&gt;
&lt;p&gt;All women taking SSRIs had experienced secretory activation by their second visit a week after the first interview.&lt;/p&gt;
&lt;p&gt;The researchers noted that most studies on the effects of SSRI use during pregnancy and lactation have focused on the risks for developmental defects or whether the drugs passed into milk during lactation.&lt;/p&gt;
&lt;p&gt;This study, they said, is the first to report data on another important aspect of SSRI use during the peripartum, the effect on milk production.&lt;/p&gt;
&lt;p&gt;They concluded that the risk of delayed secretory activation was twice as great among primiparous women using an SSRI medication, and although the fraction of women taking the drugs was small, the risk was significant and remained so after adjustment for potential confounding factors.&lt;/p&gt;
&lt;p&gt;Further examination of this relationship is needed in larger groups of mothers, the researchers said, and in studies to determine if there are differences among the antidepressant medications.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;This work was supported by the National Institutes of Health, the USDA Cooperative State Research, Education, and Extension Service, and the Department of Health and Human Services.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_235"
                     title="Congenital Anomalies Linked to Mom&apos;s Diabetes (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/OBGYN/Pregnancy/tb/18065?impressionId=1265804679512"
                     
      &lt;p&gt;Pregestational maternal diabetes was associated with an increased risk of a major congenital anomaly, but obesity itself was not, a cross-sectional study found.&lt;/p&gt;
&lt;p&gt;In a multivariable logistic model, the major contributor to a rising rate of congenital anomalies was maternal pregestational diabetes (OR 3.8, 95% CI 2.1 to 6.6), according to Joseph R. Biggio, Jr., MD, and colleagues from the University of Alabama at Birmingham.&lt;/p&gt;
&lt;p&gt;&quot;Because hyperglycemia is a major contributor to developmental malformations, interventions to address obesity and identify women at risk for diabetes and hyperglycemia should be considered in efforts to reduce the occurrence of congenital anomalies,&quot; they wrote in the February issue of &lt;em&gt;Obstetrics &amp;amp; Gynecology.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Maternal obesity has been linked with numerous problems, including preeclampsia, gestational diabetes, fetal and neonatal death, and birth trauma, but scientists have disagreed over whether it also contributes to the risk of fetal malformations, the researchers noted.&lt;/p&gt;
&lt;p&gt;To help settle the issue, Biggio and colleagues used a perinatal database in their university health system that included all women with singletons delivered between 1991 and 2004.&lt;/p&gt;
&lt;p&gt;They divided the cohort into three time periods  --  1991 to 1994, 1995 to 1999, and 2000 to 2004, with a total of 41,902 pregnancies.&lt;/p&gt;
&lt;p&gt;For their primary analysis, they defined maternal obesity as a first prenatal visit weight greater than 200 lb, because during the earlier epochs many women did not have body mass index (BMI) calculated. For their secondary analyses they used BMI greater than 29 kg/m&lt;sup&gt;2&lt;/sup&gt; as the criterion for obesity.&lt;/p&gt;
&lt;p&gt;In each epoch, there were increases in mean maternal weight, mean BMI, the proportion of women weighing more than 200 lb, the proportion with a BMI greater than 29 kg/m&lt;sup&gt;2&lt;/sup&gt;, and the prevalence of pregestational diabetes (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for all).&lt;/p&gt;
&lt;p&gt;Univariable analysis determined that the rate of major anomalies, particularly involving the cardiac and pulmonary systems, also increased during each time period.&lt;/p&gt;
&lt;p&gt;But there was no independent association between congenital anomalies and maternal obesity using either definition, during any of the three time periods or during the study overall.&lt;/p&gt;
&lt;p&gt;Although no direct association was seen between congenital malformations and maternal obesity, the investigators reported that the proportion of anomalies that could be attributed to obesity increased from 0% to 23% during the overall study period.&lt;/p&gt;
&lt;p&gt;The proportion of anomalies that could be attributed to diabetes ranged from 58% to 76%.&lt;/p&gt;
&lt;p&gt;Moreover, for obese women with diabetes the proportion of anomalies attributed to diabetes increased sharply, from 48% in the first epoch to 74% in the third epoch.&lt;/p&gt;
&lt;p&gt;In contrast, for the obstetric population as a whole, the population-attributable risk of congenital malformation related to obesity rose from near zero in the first epoch to 6.1% in the third epoch, while that related to diabetes increased from 3.3% to 9.2%, the investigators reported.&lt;/p&gt;
&lt;p&gt;During the course of the study there was a nearly 15-lb increase in maternal weight and a 30% increase in the proportion of women whose BMI exceeded 29 kg/m&lt;sup&gt;2&lt;/sup&gt;.&lt;/p&gt;
&lt;p&gt;There also was a nearly twofold increase in the rate of major anomalies  --  and a 250% increase in the prevalence of diabetes.&lt;/p&gt;
&lt;p&gt;The authors observed that there has been much interest in the effects of maternal obesity on birth defects.&lt;/p&gt;
&lt;p&gt;Although the pathophysiologic basis for this possible association have not been identified, hypotheses have included increased serum insulin, lower levels of folic acid, chronic hypoxia, and increased inflammatory mediators.&lt;/p&gt;
&lt;p&gt;&quot;Our study provides evidence that the defects may not be due solely to the maternal obesity per se but may be due to undiagnosed diabetes,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;From a public health standpoint, the study findings suggest that efforts to reduce the prevalence of congenital anomalies should be focused less on obesity and aimed more closely at correcting hyperglycemia.&lt;/p&gt;
&lt;p&gt;&quot;If euglycemia could be achieved before pregnancy, or at least embryogenesis and organogenesis, the majority of these anomalies could potentially be avoided,&quot; they observed.&lt;/p&gt;
&lt;p&gt;They also suggested that even women of normal weight, but with other diabetes risk factors, could benefit from closer attention to glycemic control.&lt;/p&gt;
&lt;p&gt;A weakness of the study was the fact that detailed data on glycemic control was not available in the perinatal database, &quot;and therefore we cannot comment on the association between glycemic control and anomaly rates,&quot; the investigators wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported in part by the National Institute of Child Health and Human Development.&lt;/p&gt;&lt;p&gt;The authors did not report any potential conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>