{"id":2890,"date":"2019-11-14T00:56:51","date_gmt":"2019-11-14T00:56:51","guid":{"rendered":"http:\/\/cms.firststepmart.com\/?p=2890"},"modified":"2019-11-17T04:33:53","modified_gmt":"2019-11-17T04:33:53","slug":"low-dose-aspirin-for-the-prevention-of-preterm-pre-eclampsia-in-pregnant-women","status":"publish","type":"post","link":"https:\/\/fetalradiology.co.in\/?p=2890","title":{"rendered":"Low Dose Aspirin for the prevention of preterm pre-eclampsia in pregnant women"},"content":{"rendered":"\n<p><sup>1<\/sup> &nbsp;Dr. Shweta Nagar\u2019s Ultrasound clinic &amp;\nImaging Centre, Flat no. 101, Princes Center, above Mama Loca cafe , 6\/3 New\nPalasia. Indore.MP-452001<\/p>\n\n\n\n<p><strong>Short Title:<\/strong> Low Dose\nAspirin in Pre-eclampsia <\/p>\n\n\n\n<p>*Corresponding\nAuthor<\/p>\n\n\n\n<p>Dr.\nShweta Nagar, Dr. Shweta Nagar\u2019s Ultrasound clinic &amp; Imaging Centre, Flat\nno. 101, Princes Center, above Mama Loca cafe , 6\/3 New Palasia.\nIndore.MP-452001. E-mail: <a href=\"mailto:shwetarnagar@gmail.com\">shwetarnagar@gmail.com<\/a><\/p>\n\n\n\n<p>Keywords:\nPre-eclampsia, Low dose Aspirin, Doppler Ultrasound, Pregnancy.<br><\/p>\n\n\n\n<p><strong>Established Fact<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Low Dose Aspirin,\nstarted between 11-14+6 weeks of gestation is effective in the prevention of\npreterm pre-eclampsia in pregnant women<\/li><\/ul>\n\n\n\n<p><strong>Insights<\/strong> <\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Maximum benefits\noccur when Low dose Aspirin is started between 11-14+6 gestation weeks,\nhowever, Low dose Aspirin may be beneficial to prevent onset of preterm\npre-eclampsia in high risk pregnant women when started before 16 gestation\nweeks&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <\/li><li>Effectiveness of\nlow dose Aspirin reduces if started after 16 gestation weeks and has minimal or\nno effect if started after 20 gestation weeks <\/li><li>Current evidence\nindicates optimal benefits from a dose of 150mg of aspirin given once daily at\nbedtime<\/li><\/ul>\n\n\n\n<p><strong><br>\nAbstract<\/strong><strong><\/strong><\/p>\n\n\n\n<p>Introduction: There Is\nevidence that Low dose Aspirin, 150mg given once daily at bed time is effective\nto prevent onset of preterm pre-eclampsia in high risk pregnant women.<\/p>\n\n\n\n<p>Case Presentation: A\nmultiparous pregnant woman with a provisional diagnosis of hypertension and a history\nof preterm delivery in the previous pregnancy was referred for a routine\nultrasound exam by the obstetrician. The woman presented at 16 gestation weeks\nand was determined to be at high risk for the development of preterm\npre-eclampsia (PE). She was started on low dose aspirin 150 mg once daily at\nbedtime. She was advised follow up Doppler and ultrasound exams in therefore\nand third trimester but returned only at 37.5 gestation weeks for a routine\ngrowth scan. At 37.5 gestation weeks, she had not developed PE, had normal\nDoppler study and an estimated fetal weight (EFW) of 3020 grams. <\/p>\n\n\n\n<p>Discussion\/Conclusion: &nbsp;Low dose Aspirin at 150mg once daily at bed\ntime, started early in pregnancy, may prevent onset of preterm PE in pregnant\nwomen at high risk for preterm PE. Although the optimal period to start low dose aspirin is 11-13<sup>+6<\/sup>\nweeks, starting low dose aspirin before 20 gestation weeks may still provide\nbenefits.<\/p>\n\n\n\n<p><strong>Introduction<\/strong><\/p>\n\n\n\n<p>The maternal mortality ratio in\nIndia has declined steadily and reported as 130 per 100,000 live births in\n2014-16.[1] Pregnancy induced hypertension remains a major cause for maternal\nmortality, preterm deliveries, fetal growth restriction and low birth weight in\nIndia. [1] A large\nclinical trial, the ASPRE trial, has provided evidence that starting low dose aspirin\nat 150\u2009mg per day from 11\u201314\u2009weeks until 36\u2009weeks&#8217; gestation, in pregnant women\nidentified as at high risk for preterm PE, reduces the incidence of preterm PE\nby &gt;\u200960%.[2]\n\n\n\n<p><strong>Case Report\/Case Presentation<\/strong><strong><\/strong><\/p>\n\n\n\n<p>A multiparous woman presented for\nroutine fetal growth ultrasound scan at 37.5 gestation weeks. On examination,\nshe had mean uterine artery Doppler PI &lt;95<sup>th<\/sup> centile, umbilical\nartery Doppler PI &lt;95<sup>th<\/sup> centile, and Middle cerebral artery and Cerebro-Placental\nratio &gt;5<sup>th<\/sup> centile. The Amniotic Fluid Index was 11. Fetal\nbiometry and growth parameters were within normal ranges&nbsp; and the estimated fetal weight was 3020gms. <\/p>\n\n\n\n<p>The woman had initially presented to\nus at 16 weeks of gestation for a routine ultrasound exam. The referring\nobstetrician had diagnosed hypertension. The woman had a history of preterm\ndelivery (31-32 gestation weeks) in the previous pregnancy. The cause of\npreterm birth in the previous pregnancy could not be verified with medical\nrecords. The woman was screened using a combined screening protocol [3] that\nincorporated demographic details like age, parity, height and weight of the\nwoman, family history of PE, inter-pregnancy interval, use of assisted\nreproductive technology, comorbid conditions in pregnancy especially diabetes\nmellitus, chronic hypertension, systemic lupus erythematosus and\nanti-phospholipid syndrome, two readings of the systolic and diastolic blood\npressure in both arms and determination of the mean arterial pressure using\nvalidated digital instruments and a standardized protocol, Ultrasound scan for dating\nof pregnancy and fetal biometry through a transabdominal approach, and Colour Doppler\nstudy of the right and left uterine arteries and determination of the mean\nuterine artery PI. A sagittal section of the uterus was obtained and the\ncervical canal and internal cervical os were identified. Subsequently, the\ntransducer was gently tilted to the side in the midline and colour flow mapping\nwas used to identify each uterine artery along the side of the cervix and\nuterus at the level of the internal os. Pulsed\u2010wave Doppler was used with the\nsampling gate set at 2&nbsp;mm to cover the whole vessel and care was taken to ensure\nthat the angle of insonation was less than 30\u00b0. When three similar consecutive\nwaveforms were obtained, the Uterine artery PI was measured and the mean Uterine\nArtery PI of the left and right arteries was calculated. Biochemical markers\nwere not assessed. <\/p>\n\n\n\n<p>The woman was determined to be at\nhigh risk for the development preterm PE based on a combined screening protocol\nalgorithm [3] that is used globally to determine risk estimates for preterm PE\nbased on a priori risk factors and based on a 1 in 150 cutoff. The risk\ncalculator is available free of charge at&nbsp;<a href=\"https:\/\/fetalmedicine.org\/research\/assess\/preeclampsia\">https:\/\/fetalmedicine.org\/research\/assess\/preeclampsia<\/a>.&nbsp;<\/p>\n\n\n\n<p>Consistent with current evidence\nbased recommendations for the management of pregnant women at high risk for\npreterm PE, the woman was advised low dose aspirin at 150mg once daily at\nbedtime to be continued till 36 gestation weeks. &nbsp;She was advised further follow up for a\ntargeted fetal anomaly scan and further assessment of the risk for preterm PE\nat 20 gestation weeks and subsequent follow up exams at 4 week intervals.\nHowever, she did not return for follow up ultrasound exams as advised.&nbsp; <\/p>\n\n\n\n<p>The target condition was PE based on the definition of the International Society for the Study of Hypertension in Pregnancy. [4] PE is defined as systolic blood pressure at \u2265140&nbsp;mm&nbsp;Hg and\/or diastolic blood pressure at \u226590&nbsp;mm&nbsp;Hg on at least two occasions measured 4&nbsp;hours apart in previously normotensive women and is accompanied by one or more of the following new\u2010onset conditions at or after 20&nbsp;weeks of gestation: Proteinuria (i.e. \u226530&nbsp;mg\/mol protein: creatinine ratio; \u2265300&nbsp;mg\/24&nbsp;hour; or \u22652&nbsp;+&nbsp;dipstick);Evidence of other maternal organ dysfunction, including: acute kidney injury (creatinine \u226590&nbsp;\u03bcmol\/L; 1&nbsp;mg\/dL); liver involvement (elevated transaminases, e.g. alanine aminotransferase or aspartate aminotransferase &gt;40&nbsp;IU\/L) with or without right upper quadrant or epigastric abdominal pain; neurological complications (e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata); or haematological complications (thrombocytopenia\u2013platelet count &lt;150&nbsp;000\/\u03bcL, disseminated intravascular coagulation, haemolysis); or Uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth).<\/p>\n\n\n\n<p><strong>Discussion<\/strong><\/p>\n\n\n\n<p>This case presentation highlights\nthe potential benefits of starting low dose aspirin early in pregnant women at\nrisk for the development of preterm PE. The case highlights the use of a\ncombined screening protocol to estimate the risk for preterm PE in pregnant\nwomen. On assessment at term (37+ gestation weeks) in the third trimester, the\nwoman had a normally growing fetus and had not developed preterm PE after\nstarting low dose aspirin at 16 weeks and continuing till 36 gestation weeks.<\/p>\n\n\n\n<p>&nbsp;PE occurs in up to 8% of pregnancies, is\nmultifactorial in origin and maybe categorized as Preterm PE (with delivery at\n&lt;37+0&nbsp;weeks of gestation) and term PE (with delivery occurring after 37\ngestation weeks). [5] The aetiology of &nbsp;PE\ndiffers between preterm and term PE although a certain amount of overlap may\noccur. Preterm PE is primarily associated with impaired presentation, placental\nvascular lesions and impaired or incomplete transformation of uterine spiral\narteries while term PE is primarily associated with maternal factors.[5]\n\n\n\n<p>Conventionally, the identification of women at high risk of PE who may benefit from the prophylactic use of aspirin is based on maternal characteristics and medical history. The National Institute for Health and Care Excellence (NICE) recommends the identification of the high\u2010risk group on the basis of 10 factors, including maternal characteristics and features of the medical and obstetric histories. [6] However, screening using the NICE protocol is suboptimal with a detection rate (DR) of preterm PE of 39% at a FPR of 10%. [6] The American College of Obstetricians and Gynecologists (ACOG) recommends the use of aspirin for women with a history of PE in previous pregnancies or a history of PE that resulted in delivery before 34\u2009weeks&#8217; gestation. [7] However, this covers only a small subgroup of women (up to 5%) who may develop preterm PE. [8] The recent ASPRE trial provided evidence that &nbsp;women with singleton pregnancy identified by means of first\u2010trimester combined screening as being at high risk for preterm PE, had a reduction of preterm PE by &gt;60% when administered aspirin at a dose of 150\u2009mg per day from 11\u201314\u2009weeks until 36\u2009weeks&#8217; gestation.<a> <\/a>[2]\n\n\n\n<p>One hypothesis for the development of PE is the deficient production of\nprostacyclin and an increased production of thromboxane A2 (TXA2) by placenta\nand platelets. This selective inhibition of cyclooxygenase and the resulting\nalteration in the prostacyclin to thromboxane A2&nbsp;ratio in the placenta\nforms the basis of using aspirin to prevent or delay the onset of PE. [9,10]\n\n\n\n<p>Several guidelines exist for the administration of low dose &nbsp;aspirin.&nbsp;\n&nbsp;The World Health Organization\nrecommends low dose aspirin (75 mg) before 20 weeks of pregnancy among women at\nhigh risk for PE. [11] The United States Preventive Task Force recommendation\nstatement and ACOG recommend a low dose of aspirin (81 mg) prophylaxis from 12\nweeks onwards. [7] &nbsp;However, the recent ASPRE\ntrial showed a significant reduction in incidence of preterm PE (OR: 0.38, 95%\nCI: 0.20\u20130.74; p = 0.004) with a low dose of aspirin at 150mg once daily. [2]\n\n\n\n<p>The ASPRE trial has led to the evidence based recommendation that women\nidentified at high risk after the first\u2010trimester screening and assessment for\npreterm PE should receive aspirin prophylaxis commencing at 11\u201314+6&nbsp;weeks\nof gestation at a dose of 150&nbsp;mg to be taken every night until either\n36&nbsp;weeks of gestation, when delivery occurs, or when PE is diagnosed. [2]\nThere is also evidence that adverse events are lower when aspirin is taken at\nnight compared to&nbsp; morning or afternoon.[12]\nThere is evidence that only aspirin started&nbsp;\nbefore 16 gestation weeks&nbsp; or at\ndoses &gt;100mg per day is &nbsp;associated\nwith optimal reduction of preterm PE.&nbsp; [13]\n\n\n\n<p>References<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Niti Ayog, India. Maternal Mortality Ratio      (per 100,000 live births). Accessed online from https:\/\/www.niti.gov.in\/content\/maternal-mortality-ratio-mmr-100000-live-births , on Oct 24, 2019<\/li><li>Rolnik DL,&nbsp;Wright D,&nbsp;Poon LC,&nbsp;O&#8217;Gorman N,&nbsp;Syngelaki A,&nbsp;de Paco Matallana C,&nbsp;et al.&nbsp;Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.&nbsp;N Engl J Med 2017;&nbsp; 377:&nbsp;613\u2013&nbsp;622.<\/li><li>Rolnik DL,&nbsp;Wright D,&nbsp;Poon LCY, et&nbsp;al.&nbsp;ASPRE trial: Performance of screening for preterm pre\u2010eclampsia.&nbsp;Ultrasound Obstet Gynecol.&nbsp;2017;&nbsp;50:&nbsp;492\u2013&nbsp;495.<\/li><li>Brown MA,&nbsp;Lindheimer MD,&nbsp;de Swiet M,&nbsp;Van Assche A,&nbsp;Moutquin JM.&nbsp;The classification and diagnosis of the hypertensive disorders of pregnancy: Statement from the international society for the study of hypertension in pregnancy (ISSHP).&nbsp;Hypertens Pregnancy 2001;&nbsp;20:&nbsp;IX\u2013&nbsp;XIV.<\/li><li>FIGO Working Group on Good Clinical Practice in Maternal\u2013Fetal Medicine.&nbsp;Good clinical practice advice: First trimester screening and prevention of pre\u2010eclampsia in singleton pregnancy.&nbsp;Int J Gynecol Obstet.&nbsp;2019;&nbsp;144:&nbsp;325\u2013&nbsp;329.<\/li><li>National Collaborating Centre for Women&#8217;s and Children&#8217;s Health (UK).Hypertension in pregnancy: the management of hypertensive disorders during pregnancy.London: RCOG Press,&nbsp;2010.<\/li><li>Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists&#8217; Task Force on Hypertension in Pregnancy.&nbsp;Obstet Gynecol 2013;&nbsp;122: 1122\u2013&nbsp;31.<\/li><li>O&#8217; Gorman N,&nbsp;Wright D,&nbsp;Poon LC,&nbsp;Rolnik DL,&nbsp;Syngelaki A,&nbsp;de Alvarado M1,&nbsp;et al. Multicenter screening for pre\u2010eclampsia by maternal factors and biomarkers at 11\u201313 weeks&#8217; gestation: comparison with NICE guidelines and ACOG recommendations.&nbsp;Ultrasound Obstet Gynecol 2017; 49:&nbsp;756\u2013&nbsp;760.<\/li><li>Sibai BM.&nbsp;Thrombophilia and severe preeclampsia: Time to screen and treat in future pregnancies?&nbsp;Hypertension.&nbsp;2005;&nbsp;46:&nbsp;1252\u2013&nbsp;1253.<\/li><li>Dekker G,&nbsp;Sibai B.&nbsp;Primary, secondary, and tertiary prevention of pre-eclampsia. Lancet.2001;&nbsp;35 :&nbsp;209\u2013&nbsp;215.<\/li><li>WHO. Recommendations for Prevention and Treatment of Pre-eclampsia and Eclampsia. Geneva. World Health Organization. 2011<\/li><li>Ayala DE,&nbsp;Ucieda R,&nbsp;Hermida RC.&nbsp;Chronotherapy with low\u2010dose aspirin for prevention of complications in pregnancy.&nbsp;Chronobiol Int.&nbsp;2013;&nbsp;30:&nbsp;260\u2013&nbsp;279.<\/li><li>Roberge S,&nbsp;Bujold E,&nbsp;Nicolaides KH.&nbsp;Aspirin for the prevention of preterm and term preeclampsia: Systematic review and meta analysis.&nbsp;Am J Obstet Gynecol. 2018; 218:&nbsp;287\u2013&nbsp;293.e1<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"<p>1 &nbsp;Dr. Shweta Nagar\u2019s Ultrasound clinic &amp; Imaging Centre, Flat no. 101, Princes Center, above Mama Loca cafe , 6\/3 New Palasia. Indore.MP-452001 Short Title: Low Dose Aspirin in Pre-eclampsia *Corresponding Author Dr. Shweta Nagar, Dr. Shweta Nagar\u2019s Ultrasound clinic &amp; Imaging Centre, Flat no. 101, Princes Center, above Mama Loca cafe , 6\/3 New [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":2892,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[16],"tags":[],"class_list":["post-2890","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-case-reports"],"_links":{"self":[{"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/posts\/2890","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2890"}],"version-history":[{"count":4,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/posts\/2890\/revisions"}],"predecessor-version":[{"id":2985,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/posts\/2890\/revisions\/2985"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=\/wp\/v2\/media\/2892"}],"wp:attachment":[{"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2890"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2890"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/fetalradiology.co.in\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2890"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}