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    <recommendedItem id="20100101_19_393"
                     title="SMFM: Gene Variants Linked to Preterm Labor (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/SMFM/tb/18295?impressionId=1265773871827"
                     
      Genetic variants involved in regulating inflammation and the extracellular matrix may increase the risk of preterm birth, researchers say.&lt;br&gt;
&lt;br&gt;A single nucleotide polymorphism (SNP) in fetal interleukin-6 (&lt;em&gt;ILR6&lt;/em&gt;) and another in maternal tissue inhibitor of metalloproteinase 2 (&lt;em&gt;TIMP2&lt;/em&gt;) were each associated with a twofold increased risk of spontaneous preterm birth.&lt;br&gt;
&lt;br&gt;Roberto Romero, MD, of the National Institute of Child Health and Human Development, and colleagues reported the findings at the Society for Maternal-Fetal Medicine meeting in Chicago.&lt;/p&gt;
&lt;p&gt;&quot;The genetic makeup of both mother and fetus can contribute to the risk of premature labor,&quot; Romero told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;Our discovery . . . helps explain why some mothers have premature labor and delivery despite having optimal prenatal care.&quot;&lt;/p&gt;
&lt;p&gt;Inflammatory hormones have been shown to play a role in the labor process, and previous studies have found that a third of preterm infants are born to mothers with a silent amniotic infection.&lt;/p&gt;
&lt;p&gt;Now, the findings suggest that individual genetic variation involved in that inflammatory response may account for discrepancies in preterm births.&lt;/p&gt;
&lt;p&gt;&quot;We have a large body of evidence that proves silent infections are a frequent and important cause of premature labor,&quot; Romero said. &quot;These infections can also attack the fetus before it is born.&quot;&lt;/p&gt;
&lt;p&gt;He explained that the mother&apos;s hormones initiate the onset of labor to get rid of the infected tissue, and the fetus seeks to exit a hostile intrauterine environment that threatens its survival.&lt;/p&gt;
&lt;p&gt;To look at the mechanisms by which this process occurs, Romero and colleagues conducted a case-control study of mothers in Chile to assess genetic factors that could predispose women to spontaneous preterm labor and delivery.&lt;/p&gt;
&lt;p&gt;Patients who delivered prior to 37 weeks gestation served as cases, while women who delivered a normal neonate at term served as controls. There were 223 mothers and 179 fetuses in the case group, and 599 mothers and 628 fetuses in the control group.&lt;/p&gt;
&lt;p&gt;The researchers subsequently examined 190 candidate genes and 775 SNPs.&lt;/p&gt;
&lt;p&gt;They found that the strongest fetal single-locus association with risk of spontaneous preterm birth was in &lt;em&gt;ILR6&lt;/em&gt;, (OR 2.07, 95% CI 1.42 to 3.02,&lt;em&gt; P&lt;/em&gt;=0.0001).&lt;/p&gt;
&lt;p&gt;The strongest maternal single-locus association with spontaneous preterm labor and delivery was in tissue inhibitor of metalloproteinase &lt;em&gt;TIMP2&lt;/em&gt; (OR 1.98, 95% CI 1.38 to 2.83, &lt;em&gt;P&lt;/em&gt;=0.0002). This gene is involved in regulating the extracellular matrix, which holds cells within tissues.&lt;/p&gt;
&lt;p&gt;The associations remained significant after controlling for multiple comparisons, Romero said.&lt;/p&gt;
&lt;p&gt;Global haplotype analysis also indicated an association between a fetal DNA variant in insulin-like growth factor 2 (&lt;em&gt;P&lt;/em&gt;=0.004) as well as maternal alpha 3 type IV collagen isoform 1 (&lt;em&gt;COL4A3&lt;/em&gt;) (&lt;em&gt;P&lt;/em&gt;=0.007).&lt;/p&gt;
&lt;p&gt;&quot;Some women and fetuses carry gene variants that predispose them to the early onset of labor,&quot; Romero said.&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 researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_366"
                     title="Placental Infection Could Spur Asthma (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Pediatrics/Asthma/tb/18252?impressionId=1265773871827"
                     
      Preterm birth complicated by chorioamnionitis may modestly increase a child&apos;s risk of later asthma, researchers found.&lt;br&gt;
&lt;br&gt;Children born preterm after a pregnancy complicated by the bacterial infection of placenta and amniotic fluid (chorioamnionitis) were significantly more likely to develop asthma by age eight than preemies without such exposure, according to Darios Getahun, MD, MPH, of Kaiser Permanente Department of Research and Evaluation in Pasadena.&lt;br&gt;
&lt;br&gt;Asthma diagnosis was nearly threefold more common among chorioamnionitis-exposed children who had been born preterm than those carried to term, they wrote in the February &lt;em&gt;Archives of Pediatrics &amp;amp; Adolescent Medicine&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Premature birth may not give an infant&apos;s lungs a chance to fully develop, leading to early infection and inflammation that elevate risk of chronic lung disease, such as asthma.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;However, in utero exposures could be an important contributor as well, Getahun explained in an interview.&lt;/p&gt;
&lt;p&gt;Chorioamnionitis is thought to be associated with more than half of all preterm births.&lt;/p&gt;
&lt;p&gt;Fetal lungs stay in contact with the amniotic fluid which, when infected, may expose the developing lung to microorganisms, toxic substances, and inflammatory mediators, the researchers wrote.&lt;/p&gt;
&lt;p&gt;Animal model evidence suggests the condition may lead to scarring and fibrosis in the lung and damage to other fetal organs &quot;during a very critical time at preterm gestation,&quot; Getahun told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;So, his group retrospectively studied Kaiser&apos;s matched perinatal records on 510,216 singleton children born at the managed care group&apos;s hospitals in Southern California between 1991 and 2007.&lt;/p&gt;
&lt;p&gt;Physician-diagnosed asthma incidence by age 8 years, as expected, was significantly higher overall for preemies born at 23 to 36 weeks&apos; gestation than for those carried full-term (60.2 versus 40.0 per 1,000 person-years).&lt;/p&gt;
&lt;p&gt;But chorioamnionitis diagnosed during pregnancy substantially boosted this risk.&lt;/p&gt;
&lt;p&gt;Incidence of asthma rose to 100.7 per 1,000 person-years in exposed children born preterm, versus 39.6 per 1,000 among exposed, full-term children (IR 2.9, 95% CI 2.6 to 3.3).&lt;/p&gt;
&lt;p&gt;This association between chorioamnionitis and asthma in preemies persisted (HR 1.68, 95% CI 1.52 to 1.87) after adjustment for important confounding variables, including maternal age, race or ethnicity, smoking during pregnancy, prenatal care, and maternal asthma.&lt;/p&gt;
&lt;p&gt;Although the asthma risk appeared to rise with greater prematurity in exposed children, the elevated risk associated with chorioamnionitis exposure in utero was seen in every category of prematurity: &lt;ul&gt; &lt;li&gt; 1.23 times higher risk in children born at 23 to 28 weeks (95% CI 1.02 to 1.49)&lt;/li&gt; &lt;li&gt; 1.51 times higher risk in children born at 28 to 33 weeks (95% CI 1.26 to 1.80)&lt;/li&gt; &lt;li&gt; 1.20 times higher risk in children born at 34 to 36 weeks (95% CI 1.03 to 1.47)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Additional adjustment for bronchopulmonary dysplasia  --  &quot;one of the mechanisms through which preterm birth is presumably associated with respiratory problems in early childhood&quot;  --  had little impact on the findings.&lt;/p&gt;
&lt;p&gt;Thus, the bacterial infection appeared to be an independent risk factor for asthma in prematurely born children, the researchers concluded.&lt;/p&gt;
&lt;p&gt;The risks were particularly high for children born to African-American women who developed chorioamnionitis, suggesting this may be an at-risk group to single out for attention clinically, they suggested.&lt;/p&gt;
&lt;p&gt;Getahun cautioned, though, that his group&apos;s study could not prove causality. The researchers also noted that the study was limited by lack of data on parental atopy and smoking.&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 by Kaiser Permanente Direct Community Benefit funds. The researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_202"
                     title="Survival Rates Vary with Congenital Anomalies (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/tb/18035?impressionId=1265773871827"
                     
      &lt;p&gt;Survival among children with congenital anomalies has increased in recent decades, but still varies notably depending on the condition, a British study found.&lt;/p&gt;
&lt;p&gt;Overall 20-year survival was 85.5% (95% CI 84.8 to 86.3) among children born with at least one congenital anomaly, Peter W.G. Tennant, MsC, of Newcastle University, and colleagues reported online in &lt;em&gt;Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;For specific conditions, the 20-year survival rates were as follows: &lt;ul&gt; &lt;li&gt;Orofacial clefts, 97.6% (95% CI 95.9 to 98.6)&lt;/li&gt; &lt;li&gt;Urinary system, 93.2% (95% CI 91.6 to 94.5)&lt;/li&gt; &lt;li&gt;Cardiovascular system, 89.5% (95% CI 88.4 to 90.6)&lt;/li&gt; &lt;li&gt;Digestive system, 83.2% (95% CI 79.8 to 86)&lt;/li&gt; &lt;li&gt;Chromosomal anomalies, 79.1% (95% CI 76.6 to 81.3)&lt;/li&gt; &lt;li&gt;Nervous system, 66.2% (95% CI 61.5 to 70.5)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Congenital anomalies are recognized as a major cause of perinatal and infant mortality, but little is known about longer-term survival with conditions other than Down syndrome or spina bifida.&lt;/p&gt;
&lt;p&gt;So Tennant and colleagues analyzed data from the Northern Congenital Abnormality Survey, which is a population-based register for the north of England.&lt;/p&gt;
&lt;p&gt;Their study included 13,758 cases of congenital anomaly reported to the registry between January 1985 and December 2003, representing a prevalence of 20.8 per 1,000 births.&lt;/p&gt;
&lt;p&gt;Among these, 0.9% were late miscarriages, 16.3% were terminations after prenatal diagnosis, 3.1% were stillbirths, and 79.7% were live births.&lt;/p&gt;
&lt;p&gt;Of the 10,850 liveborn cases for whom survival status was known, 1,465 (13.5%) died during the course of the study.&lt;/p&gt;
&lt;p&gt;Year of birth was a highly significant predictor of survival, (HR 0.92, 95% CI 0.92 to 0.93, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), which likely relates to important medical and surgical advances such as surfactant therapy and corticosteroid use for respiratory distress syndrome, as well as intrapartum treatment for chorioamnionitis.&lt;/p&gt;
&lt;p&gt;The rate of termination for fetal anomaly increased over time, rising from 12.4% (95% CI 9.8 to 15.5) in 1985 to 18.3% (95% CI 15.6 to 21.2) in 2003.&lt;/p&gt;
&lt;p&gt;The investigators further analyzed survival among specific subtypes of anomalies and found rates of 20-year survival exceeding 95% for the following: &lt;ul&gt; &lt;li&gt;Ventricular septal defects, 98.3% (95% CI 96.6 to 99.1)&lt;/li&gt; &lt;li&gt;Pulmonary valve stenosis, 98.1% (95% CI 96.1 to 99.1)&lt;/li&gt; &lt;li&gt;Cleft lip and palate, 97.7% (95% CI 94.6 to 99.1)&lt;/li&gt; &lt;li&gt;Atrial septal defects, 96.3% (95% CI 93.3 to 98)&lt;/li&gt; &lt;li&gt;Cleft palate, 96.3% (95% CI 92.8 to 98.1)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In contrast, subtypes with less than 50% one-year survival included arhinencephaly/holoprosencephaly, common arterial trunk, and hypoplastic left heart.&lt;/p&gt;
&lt;p&gt;Previous studies have found ten-year survival rates ranging from 76.5% to 88.6% for Down syndrome, 80.9% for all phenotypes of spina bifida, and 64% for spina bifida with hydrocephalus.&lt;/p&gt;
&lt;p&gt;In this study, the ten-year survival for Down syndrome was 83.9%, which probably reflects differences in care over time and by location, as well as surgical management and changing rates of terminations.&lt;/p&gt;
&lt;p&gt;The ten-year survival for spina bifida without hydrocephalus was 86.7% but fell to 53.3% with hydrocephalus, and 20-year survival remained 36.7% lower in those having hydrocephalus (95% CI 24 to 40, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;Previous estimates of survival among children with cardiovascular anomalies ranged from 74.7% to 76.9% at five years, which are substantially lower than the 91.1% reported in the present study.&lt;/p&gt;
&lt;p&gt;As with Down syndrome, this may represent advances in care, but also may reflect the fact that the investigators stratified cases according to the presence of multiple anomalies.&lt;/p&gt;
&lt;p&gt;&quot;This effect is inconsequential for primary anomalies with a high mortality rate, such as hypoplastic left heart syndrome, since the effect of the primary anomaly is likely to overwhelm the effect of any additional anomalies. However, as the severity of the primary anomaly decreases, the confounding effect of any additional anomalies is likely to increase,&quot; they explained.&lt;/p&gt;
&lt;p&gt;For example, the 20-year survival of 98.3% for ventricular septal defect would have fallen to 91.7% if multiple anomalies had not been classified separately.&lt;/p&gt;
&lt;p&gt;The biggest limitation of the study was that only 10% of patients were born twenty years before the matching date of the study (Jan. 28, 2008) so that 20-year survival rates were only estimates for most of the anomaly subtypes.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, David H. Stone, MD, of the University of Glasgow, called for more research and funding for congenital anomalies.&lt;/p&gt;
&lt;p&gt;&quot;Birth-defect registries have had a chequered history since their initial proliferation after the thalidomide disaster,&quot; he wrote.&lt;/p&gt;
&lt;p&gt;They are a crucial source of data, but face an endless struggle for funding, with the result that good quality data on etiology, prevalence, and outcomes are sparse.&lt;/p&gt;
&lt;p&gt;&quot;The publication of today&apos;s findings from the north of England should provide a much-needed boost to the cause of congenital anomaly surveillance,&quot; Stone 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;Funding for the study was provided by BDF Newlife.&lt;/p&gt;&lt;p&gt;All investigators and the editorialist declared no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_5_304"
                     title="Fetal DNA Test Identifies Rh Incompatibility"
                     score="-0.005"
                     href="