<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1688-423X</journal-id>
<journal-title><![CDATA[Archivos de Medicina Interna]]></journal-title>
<abbrev-journal-title><![CDATA[Arch Med Int]]></abbrev-journal-title>
<issn>1688-423X</issn>
<publisher>
<publisher-name><![CDATA[Sociedad de Medicina Interna del Uruguay]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1688-423X2011000400008</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Trombofilia y embarazo: Pautas de diagnóstico y tratamiento Rol de la ecografía y ecodoppler color]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[De Agostini]]></surname>
<given-names><![CDATA[Marcelo]]></given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Alonzo]]></surname>
<given-names><![CDATA[Inés]]></given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Morán]]></surname>
<given-names><![CDATA[Rosario]]></given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cordano]]></surname>
<given-names><![CDATA[Cristina]]></given-names>
</name>
</contrib>
</contrib-group>
<aff id="A">
<institution><![CDATA[,  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>07</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>07</month>
<year>2011</year>
</pub-date>
<volume>33</volume>
<fpage>S11</fpage>
<lpage>S12</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_arttext&amp;pid=S1688-423X2011000400008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_abstract&amp;pid=S1688-423X2011000400008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_pdf&amp;pid=S1688-423X2011000400008&amp;lng=en&amp;nrm=iso"></self-uri><kwd-group>
<kwd lng="es"><![CDATA[Embarazo]]></kwd>
<kwd lng="es"><![CDATA[Trombofilia]]></kwd>
<kwd lng="en"><![CDATA[Pregnancy]]></kwd>
<kwd lng="en"><![CDATA[Thrombophilia]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <p  style="margin-bottom: 0cm; line-height: 0.64cm; widows: 0; orphans: 0; text-align: center;"  lang="es-ES"> <font style="font-size: 13pt" face="Verdana"><i><b>Trombofilia y embarazo</b></i></font></p>     <div style="text-align: center;"><font style="font-size: 13pt" face="Verdana"><i><b>Pautas de diagn&oacute;stico y tratamiento</b></i></font></div>     <div style="text-align: center;"></div>     <p  style="margin-top: 0.2cm; margin-bottom: 0cm; font-style: normal; line-height: 0.49cm; widows: 0; orphans: 0; text-align: center;"  lang="es-ES"><font face="Verdana"><b>Rol de la ecograf&iacute;a y ecodoppler color</b></font></p>     <div style="text-align: left;"></div>     <p  style="margin-top: 0.2cm; margin-bottom: 0cm; font-style: normal; line-height: 0.49cm; widows: 0; orphans: 0; text-align: left;"  lang="es-ES"></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br> </font> </p>     <p  style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="left" lang="es-ES"> <font  style="font-size: 10pt;" size="2" face="Verdana"><b>Dr. Marcelo De Agostini</b></font></p>     <p  style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="left" lang="es-ES"> <font  style="font-size: 10pt;" size="2" face="Verdana"><b>Dra. In&eacute;s Alonzo</b></font></p>     ]]></body>
<body><![CDATA[<p  style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="left" lang="es-ES"> <font  style="font-size: 10pt;" size="2" face="Verdana"><b>Dra. Rosario Mor&aacute;n</b></font></p>     <p  style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="left" lang="es-ES"> <font  style="font-size: 10pt;" size="2" face="Verdana"><b>Dra. Cristina Cordano</b></font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font face="Verdana"><font size="2">     <br> </font><font style="font-size: 10pt;"  size="2"><b>Consideraciones generales</b>    <br> &nbsp;&nbsp;&nbsp; &nbsp; La vigilancia prenatal tiene como objetivo proporcionar informaci&oacute;n acerca de la salud fetal, para lo cual entre otros par&aacute;metros es fundamental el estudio de su crecimiento y hemodinamia.</font></font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">La ecograf&iacute;a obst&eacute;trica hoy d&iacute;a, es una herramienta inocua, no invasiva y de bajo costo que nos permite la determinaci&oacute;n y seguimiento de la biometr&iacute;a fetal en funci&oacute;n de la edad gestacional, con la posibilidad de elaborar &ldquo;curvas&rdquo; de crecimiento <sup>(<a href="#1">1</a>-<a href="#3">3</a>)</sup>. En base a &eacute;stas, es posible la pesquisa precoz de la restricci&oacute;n del crecimiento fetal, que comprende aquellos fetos que no pueden alcanzar su potencial de crecimiento predeterminado (menor al P5) y se asocia a mayor morbi-mortalidad perinatal como ya ha sido ampliamente demostrado<sup> (<a href="#4">4</a>)</sup>.</font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">De los par&aacute;metros biom&eacute;tricos ecogr&aacute;ficos, el &ldquo;per&iacute;metro abdominal&rdquo; ha demostrado ser el de mayor sensibilidad y especificidad para la detecci&oacute;n de la restricci&oacute;n de crecimiento fetal (RCF)<sup> (<a href="#3">3</a>;<a  href="#5.">5</a>;<a href="#6">6</a>)</sup>. El estudio ecogr&aacute;fico se completa con la valoraci&oacute;n del l&iacute;quido amni&oacute;tico y de la placenta (maduraci&oacute;n, decolamientos, hematomas); elementos &eacute;stos que tambi&eacute;n pueden mostrar cambios cuando se altera la salud fetal. </font> </p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">El Eco-Doppler-Color-Feto-Placentario, permite el estudio del flujo sangu&iacute;neo materno-fetal y de la circulaci&oacute;n placentaria de forma no invasiva, inocua y reproducible. Su eficacia ha sido demostrada en el control del embarazo de alto riesgo obst&eacute;trico (EARO), logrando una reducci&oacute;n de la mortalidad perinatal del 49% vinculada a la hipoxia cr&oacute;nica, as&iacute; como otras complicaciones y costos vinculados al embarazo y parto<sup> (<a  href="#7">7</a>-<a href="#10">10</a>)</sup>. </font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">El Eco-Doppler-Feto-Placentario eval&uacute;a los compartimientos maternos (arterias uterinas), placentario (arteria umbilical) y fetal (arteria cerebral media-ACM). Tambi&eacute;n permite el estudio de flujos venosos (Ductus Venoso, Vena Cava Inferior, Vena Umbilical)<sup> (<a href="#10">10</a>,<a href="#11">11</a>)</sup>.</font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font  size="2" face="Verdana">Las arterias uterinas sufren cambios propios del embarazo, que llevan a una disminuci&oacute;n gradual de la impedancia en &eacute;stas hasta las 24 semanas logrando un flujo de baja resistencia que se mantiene normalmente por el resto de la gravidez. Son cambios patol&oacute;gicos los aumentos de la resistencia en estos vasos o la persistencia de Notch (incisi&oacute;n protodiast&oacute;lica) del lado placentario o bilateral (<a href="#12">12</a>)</font><font  size="2" face="Verdana" style="font-size: 10pt">. La persistencia de Notch en el 3&ordm; trimestre es un elemento de alerta y por tanto de vigilancia de la salud fetal (<a href="#13">13</a>).</font></p>     ]]></body>
<body><![CDATA[<p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">La arteria umbilical conceptualmente eval&uacute;a la placenta. La insuficiencia placentaria se refleja en la disminuci&oacute;n de los flujos de fin de di&aacute;stole en &eacute;ste vaso y o por aumentos de su resistencia; lo cual no s&oacute;lo es un marcador de RCF de causa placentaria, sino que adem&aacute;s es un signo de hipoxia fetal y plantea necesidad de vigilancia estricta. La ausencia de flujo de fin de di&aacute;stole o el flujo reverso son indicadores que se asocian con una mortalidad perinatal elevada<sup> (<a href="#11">11</a>,<a  href="#14">14</a>,<a href="#15">15</a>)</sup>. </font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">El feto ante la hipoxia cr&oacute;nica, reacciona poniendo en juego mecanismos compensadores con el fin de preservar &oacute;rganos nobles. En estudios prospectivos, ha sido demostrado que &eacute;ste efecto protector alcanza su m&aacute;xima intensidad 2 a 3 semanas antes de que se presenten alteraciones en el monitoreo fetal<sup> (<a href="#11">11</a>,<a href="#14">14</a>-<a href="#16">16</a>)</sup>. </font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">La aparici&oacute;n de vasodilataci&oacute;n en la ACM se considera un signo de alerta y vigilancia estricta, a diferencia de cuando desaparece (retorna a valores de alta resistencia), momento que se considera de alarma, dado que se corresponde con fetos graves con acidosis y riesgo de muerte fetal inminente. Pueden considerarse adem&aacute;s relaciones en la toma de decisiones obst&eacute;tricas. Se ha visto que la relaci&oacute;n cerebro/umbilical, predice &ldquo;mejor&rdquo; el riesgo y el aumento de la morbi-mortalidad que la arteria umbilical por s&iacute; sola. La alteraci&oacute;n de los flujos venosos es un signo tard&iacute;o y se corresponde con descompensaci&oacute;n de los mecanismos compensadores, por tanto reflejan acidosis e insuficiencia card&iacute;aca y preceden la muerte fetal. De las alteraciones venosas se pueden destacar: vena umbilical puls&aacute;til, flujo reverso en la vena cava inferior y aumento del &iacute;ndice de pulsatilidad en el ductus venoso con flujo ausente o reverso. El hallazgo de un flujo alterado en cualquiera de estos vasos venosos se correlaciona con un PH &lt; a 7,2. Las alteraciones en el ductus preceden en d&iacute;as la muerte fetal<sup> <a href="#8">(8</a>,<a href="#17">17</a>-<a href="#20">20</a>)</sup>. </font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font face="Verdana"><font size="2">     <br> </font><font style="font-size: 10pt;"  size="2"><b>Vigilancia fetal y trombofilia</b>    <br> &nbsp;&nbsp;&nbsp; Las trombofilias son un grupo heterog&eacute;neo de alteraciones, que como se ha discutido a lo largo de la gu&iacute;a, algunas de ellas pueden asociarse a malos resultados obst&eacute;tricos. Sin embargo, no todas las &ldquo;trombofilias&rdquo; se asocian a complicaciones materno-perinatales por lo cual debe identificarse claramente aqu&eacute;llas que requieren de un control m&aacute;s estricto y eventualmente se vean beneficiadas por el tratamiento m&eacute;dico. En nuestro medio se ha generalizado que las pacientes con trombofilia y mala historia obst&eacute;trica deben considerarse de alto riesgo y debe indefectiblemente extremarse el control de salud fetal. Sin embargo, esta recomendaci&oacute;n est&aacute; basada en evidencia indirecta, extrapolada de estudios que demostraron asociaci&oacute;n entre las pruebas de salud fetal y la morbimortalidad perinatal pero en poblaciones especificas (por ejemplo, RCIU, s&iacute;ndrome Pre-E)<sup> (<a href="#4">4</a>)</sup>, pero no precisamente en poblaciones con trombofilias. </font></font> </p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">Se ha determinado que cuando la trombofilia se asocia con estos resultados &ndash;como la presencia de RCIU&ndash; la utilizaci&oacute;n de la ecograf&iacute;a doppler tiene su m&aacute;xima efectividad aumentando el valor predictivo positivo y la posibilidad de detectar poblaciones con alteraci&oacute;n de la salud fetal. Cuando estos estudios se utilizan en forma de tamizaje (por ejemplo, paciente con trombofilia pero ausencia de alteraciones materno fetales cl&iacute;nicas) el valor predictivo positivo desciende dram&aacute;ticamente y se pone en duda la efectividad del estudio.</font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">La b&uacute;squeda bibliogr&aacute;fica actualizada a la fecha en que se finaliz&oacute; esta gu&iacute;a nos demuestra que a&uacute;n no existen publicaciones que nos permitan realizar recomendaciones basadas en buena evidencia y con un claro beneficio. </font> </p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">En cuanto al manejo del tratamiento con anticoagulantes y el control mediante Eco-Doppler-Feto-&Uacute;tero-Placentario, se han publicado estudios observacionales y experimentales muy limitados (en calidad y en tama&ntilde;o muestral) que han sugerido que el tratamiento con anticoagulantes logra una mejora de los diferentes par&aacute;metros hemodin&aacute;micos a nivel de la arterial umbilical<sup> (<a  href="#21">21</a>-<a href="#23">23</a>)</sup> sin identificar beneficios cl&iacute;nicos relevantes. </font> </p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font style="font-size: 10pt;"  size="2" face="Verdana">En base a lo previamente descrito surge que a nivel internacional no existen gu&iacute;as cl&iacute;nicas espec&iacute;ficas para el seguimiento ecogr&aacute;fico ni con Doppler-Feto-Placentario de los embarazos complicados con trombofilia. Sin embargo, existe la necesidad de pautar el seguimiento de estos embarazos realizando recomendaciones gen&eacute;ricas para ayudar a los cl&iacute;nicos en el seguimiento ecogr&aacute;fico y con Doppler-Feto-Placentario. Las evidencias relacionadas al control de la salud fetal y extrapoladas de poblaciones de alto riesgo obst&eacute;trico nos permiten clasificarla como evidencia de buena calidad asociadas con beneficio (1A y 1B). Sin embargo, el uso de la ecograf&iacute;a doppler en pacientes para guiar el tratamiento anticoagulante se basa en recomendaciones donde no existe evidencia para aconsejar ni desaconsejar su uso, por lo cual deber&aacute; ser evaluado por el cl&iacute;nico tratante. </font> </p>     ]]></body>
<body><![CDATA[<p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br> </font> </p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font  style="font-size: 10pt;" size="2" face="Verdana"><b>*Recomendaciones consensuadas en PARO (ver anexo).</b></font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> </p>     <p style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES">&nbsp;</p>     <p style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font size="2" face="Verdana"><b>Palabras clave:</b> Embarazo; Trombofilia.</font></p>     <p style="margin-bottom: 0.35cm;" lang="es-ES"> <font size="2" face="Verdana"><b>Keywords:</b></font><font  size="2"><font face="Verdana"> </font> <span style="font-family: Verdana;">Pregnancy; Thrombophilia.</span></font></p>     <p  style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br> </font> </p>     <p  style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="left" lang="es-ES"> &nbsp;</p>     ]]></body>
<body><![CDATA[<p  style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="left" lang="es-ES"> <font  style="font-size: 10pt;" size="2" face="Verdana"><b>Bibliograf&iacute;a</b></font><font face="Verdana" size="2">    <br> </font> </p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="1"></a>1. Campbell S, Dewhurst CJ. Diaqgnosis of the small for datae foetus by serial ultrasonic cephalometry. Lancet 1971 Nov;2(7732):1002-6.     </font> </p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="2"></a>2. Fescina RH, Ucieda FC, Cordano MC, Nieto F, Tenzer SM, L&oacute;pez R. Ultrasonic patterns of intrauterine foetal growth in a Latin American Country. Early Hum Dev 1982 Jul;6(3):239-48.     </font> </p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="3"></a>3. Royal College of Obstetricians and Gynecologists. The investigation and management of the small-for-gestational-age fetus. Guideline No. 31. London UK: Royal College of Obstetricians and Gynecologists; 2002.     </font> </p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="4"></a>4. Resnik R. Intrauterine growth restriction. Obstet Gynecol 2002 Mar;99(3):490-6.    </font></p>     ]]></body>
<body><![CDATA[<!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="5."></a>5. Cordano MC, Compte E, Bessis R, Papiernik E. Longitudinal follow-up of 100 patients at risk of intrauterine growth retardation: comparison of diagnosis in two periods. J Perinat Med 1988;16(1):61-6.     </font> </p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="6"></a>6. American College of Obstetricians and Gynecologists. Intrauterine Growth Restriction. ACOG Practice Bulletin. 12. Washington DC: ACOG; 2000.    </font></p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="7"></a>7. Campbell S, D Wilkin D. Ultrasonic measurements of foetal head to abdomen circumference in the estimation of foetal weight. Br J Obstet Gynaecol 1975 Sep;82(9):689-97.     </font> </p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="8"></a>8. Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev 2010;(1):CD007529.    </font></p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="9"></a>9. Cnossen JS, Morris RK, ter RG, Mol BW, van der Post JA, Coomarasamy A, Zwinderman AH, Robson SC, Bindels PJ, Kleijnen J, Khan KS. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ 2008 Mar 11;178(6):701-11.    </font></p>     ]]></body>
<body><![CDATA[<!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="10"></a>10. Gagnon R, Van den Hof M. The use of fetal Doppler in obstetrics. J Obstet Gynaecol Can 2003 Jul;25(7):601-14.    </font></p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana">11. Baschat AA, Gembruch U, Harman CR. The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsens. Ultrasound Obstet Gynecol 2001 Dec;18(6):571-7.    </font></p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="12"></a>12. Becker R, Vonk R. Doppler sonography of uterine arteries at 20-23 weeks: depth of notch gives information on probability of adverse pregnancy outcome and degree of fetal growth restriction in a low-risk population. Fetal Diagn Ther 2010;27(2):78-86.    </font></p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="13"></a>13. Harrington K, Cooper D, Less C, Hecher K, Campbell S. Doppler ultrasound of the uterine arteries: the importance of bilateral notching in the prediction of the pre-eclampsia placental abruption, or delivery of a small for gestational age baby. Ultrasound Obstet Gynecol 1996 Mar;7(3):182-8.    </font></p>     <!-- ref --><p  style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;"  align="justify" lang="en-US"> <font style="font-size: 10pt;"  size="1" face="Verdana"><a name="14"></a>14. Bilardo CM, Wolf H, Stigter RH, Ville Y, Baez E, Visser GH, Hecher K. Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction. Ultrasound Obstet Gynecol 2004 Feb;23(2):119-25.    </font></p>     ]]></body>
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