Sequential Plasma Angiogenic Factors Levels in Women with Suspected Preeclampsia

Abstract Background Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Objective Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluatio...

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Veröffentlicht in:American journal of obstetrics and gynecology 2016-07, Vol.215 (1), p.89.e1-89.e10
Hauptverfasser: Baltajian, Kedak, MD, Bajracharya, Surichhya, MD, Salahuddin, Saira, MD, Berg, Anders H., MD, Geahchan, Carl, MD, Wenger, Julia B., MPH, Thadhani, Ravi, MD, MPH, Karumanchi, S. Ananth, MD, Rana, Sarosh, MD, MPH
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container_issue 1
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container_title American journal of obstetrics and gynecology
container_volume 215
creator Baltajian, Kedak, MD
Bajracharya, Surichhya, MD
Salahuddin, Saira, MD
Berg, Anders H., MD
Geahchan, Carl, MD
Wenger, Julia B., MPH
Thadhani, Ravi, MD, MPH
Karumanchi, S. Ananth, MD
Rana, Sarosh, MD, MPH
description Abstract Background Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Objective Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. Study Design We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical center, Boston, MA for evaluation of preeclampsia at less than 37 weeks gestation. Discarded plasma samples were collected upon admission and daily for the first three days and then weekly till delivery. Doppler ultrasound was performed upon admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms like tyrosine kinase – sFlt1 and placental growth factor – PlGF) were measured on automated platform in a single batch after delivery and in a blinded fashion. Data is presented as median (25th -75th centile), mean or proportions as appropriate. Results During the study period, data from 100 women were analyzed for the study and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, lower birth weight and placental weight (all P
doi_str_mv 10.1016/j.ajog.2016.01.168
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Ananth, MD ; Rana, Sarosh, MD, MPH</creator><creatorcontrib>Baltajian, Kedak, MD ; Bajracharya, Surichhya, MD ; Salahuddin, Saira, MD ; Berg, Anders H., MD ; Geahchan, Carl, MD ; Wenger, Julia B., MPH ; Thadhani, Ravi, MD, MPH ; Karumanchi, S. Ananth, MD ; Rana, Sarosh, MD, MPH</creatorcontrib><description>Abstract Background Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Objective Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. Study Design We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical center, Boston, MA for evaluation of preeclampsia at less than 37 weeks gestation. Discarded plasma samples were collected upon admission and daily for the first three days and then weekly till delivery. Doppler ultrasound was performed upon admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms like tyrosine kinase – sFlt1 and placental growth factor – PlGF) were measured on automated platform in a single batch after delivery and in a blinded fashion. Data is presented as median (25th -75th centile), mean or proportions as appropriate. Results During the study period, data from 100 women were analyzed for the study and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, lower birth weight and placental weight (all P&lt;0.01). These patients had higher sFlt1 and sFlt1/PlGF ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th -75th ) sFlt1/PlGF ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P&lt;0.001). The median (25th -75th ) absolute change per day in sFlt1 levels (pg/ml) was 491.0 pg/ml (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/ml (-177.9, 449.0) among women without adverse outcomes (P=0.01). Similarly the absolute change per day for sFlt1/PlGF ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) among the two groups (P=0.004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with sFlt1/PlGF ratio ≥ 85 and 14 (0-39) below a ratio of 85 (P&lt;0.001). The positive predictive value for plasma sFlt1/PlGF ratio ≥ 85 at admission for indicated delivery within 2 weeks was 91% (83%-99%). Admission plasma sFlt1/PlGF ratio positively correlated with pre-delivery uterine artery resistive index (r= 0.35; P=0.004). Conclusions Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher sFlt1/PlGF ratio on admission, which continued to rise until delivery. Women with high sFlt1/PlGF ratios delivered sooner than women with low sFlt1/PlGF levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.</description><identifier>ISSN: 0002-9378</identifier><identifier>EISSN: 1097-6868</identifier><identifier>DOI: 10.1016/j.ajog.2016.01.168</identifier><identifier>PMID: 26827880</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; adverse outcomes ; Angiogenesis Inducing Agents - blood ; angiogenic factors ; Biomarkers - blood ; Female ; Humans ; Obstetrics and Gynecology ; Pre-Eclampsia - blood ; Pre-Eclampsia - diagnosis ; Pre-Eclampsia - diagnostic imaging ; preeclampsia ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Third - blood ; sequential changes</subject><ispartof>American journal of obstetrics and gynecology, 2016-07, Vol.215 (1), p.89.e1-89.e10</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-25b7f949ffd1ac387cd8bd25977f56ccfbbec2992bcb93ab3118210e9aaa878c3</citedby><cites>FETCH-LOGICAL-c455t-25b7f949ffd1ac387cd8bd25977f56ccfbbec2992bcb93ab3118210e9aaa878c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002937816002180$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26827880$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baltajian, Kedak, MD</creatorcontrib><creatorcontrib>Bajracharya, Surichhya, MD</creatorcontrib><creatorcontrib>Salahuddin, Saira, MD</creatorcontrib><creatorcontrib>Berg, Anders H., MD</creatorcontrib><creatorcontrib>Geahchan, Carl, MD</creatorcontrib><creatorcontrib>Wenger, Julia B., MPH</creatorcontrib><creatorcontrib>Thadhani, Ravi, MD, MPH</creatorcontrib><creatorcontrib>Karumanchi, S. Ananth, MD</creatorcontrib><creatorcontrib>Rana, Sarosh, MD, MPH</creatorcontrib><title>Sequential Plasma Angiogenic Factors Levels in Women with Suspected Preeclampsia</title><title>American journal of obstetrics and gynecology</title><addtitle>Am J Obstet Gynecol</addtitle><description>Abstract Background Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Objective Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. Study Design We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical center, Boston, MA for evaluation of preeclampsia at less than 37 weeks gestation. Discarded plasma samples were collected upon admission and daily for the first three days and then weekly till delivery. Doppler ultrasound was performed upon admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms like tyrosine kinase – sFlt1 and placental growth factor – PlGF) were measured on automated platform in a single batch after delivery and in a blinded fashion. Data is presented as median (25th -75th centile), mean or proportions as appropriate. Results During the study period, data from 100 women were analyzed for the study and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, lower birth weight and placental weight (all P&lt;0.01). These patients had higher sFlt1 and sFlt1/PlGF ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th -75th ) sFlt1/PlGF ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P&lt;0.001). The median (25th -75th ) absolute change per day in sFlt1 levels (pg/ml) was 491.0 pg/ml (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/ml (-177.9, 449.0) among women without adverse outcomes (P=0.01). Similarly the absolute change per day for sFlt1/PlGF ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) among the two groups (P=0.004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with sFlt1/PlGF ratio ≥ 85 and 14 (0-39) below a ratio of 85 (P&lt;0.001). The positive predictive value for plasma sFlt1/PlGF ratio ≥ 85 at admission for indicated delivery within 2 weeks was 91% (83%-99%). Admission plasma sFlt1/PlGF ratio positively correlated with pre-delivery uterine artery resistive index (r= 0.35; P=0.004). Conclusions Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher sFlt1/PlGF ratio on admission, which continued to rise until delivery. Women with high sFlt1/PlGF ratios delivered sooner than women with low sFlt1/PlGF levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.</description><subject>Adult</subject><subject>adverse outcomes</subject><subject>Angiogenesis Inducing Agents - blood</subject><subject>angiogenic factors</subject><subject>Biomarkers - blood</subject><subject>Female</subject><subject>Humans</subject><subject>Obstetrics and Gynecology</subject><subject>Pre-Eclampsia - blood</subject><subject>Pre-Eclampsia - diagnosis</subject><subject>Pre-Eclampsia - diagnostic imaging</subject><subject>preeclampsia</subject><subject>Pregnancy</subject><subject>Pregnancy Outcome</subject><subject>Pregnancy Trimester, Third - blood</subject><subject>sequential changes</subject><issn>0002-9378</issn><issn>1097-6868</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFr3DAQhUVJabZJ_0APRcdc7EpyZElQAiE0bWGhC5uQo5Dl8VaObG0kOyX_vjKb9JBDTjMD771hvkHoMyUlJbT-2pemD7uS5b4ktKS1fIdWlChR1LKWR2hFCGGFqoQ8Rh9T6peRKfYBHbNaMiElWaHNFh5mGCdnPN54kwaDL8edCzsYncXXxk4hJryGR_AJuxHfhQFG_NdNf_B2TnuwE7R4EwGsN8M-OXOK3nfGJ_j0XE_Q7fX3m6ufxfr3j19Xl-vCnnM-FYw3olPnqutaamwlhW1l0zKuhOh4bW3XNGCZUqyxjapMU1EqGSWgjDFSSFudoLND7j6GfEGa9OCSBe_NCGFOmgqlOFec8ixlB6mNIaUInd5HN5j4pCnRC0nd64WkXkhqQnUmmU1fnvPnZoD2v-UFXRZ8OwgyGXh0EHWyDkYLrYsZi26Dezv_4pXdepeZG38PT5D6MMcx89NUJ6aJ3i7PW15J69zQvP8fNw6aWw</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Baltajian, Kedak, MD</creator><creator>Bajracharya, Surichhya, MD</creator><creator>Salahuddin, Saira, MD</creator><creator>Berg, Anders H., MD</creator><creator>Geahchan, Carl, MD</creator><creator>Wenger, Julia B., MPH</creator><creator>Thadhani, Ravi, MD, MPH</creator><creator>Karumanchi, S. Ananth, MD</creator><creator>Rana, Sarosh, MD, MPH</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160701</creationdate><title>Sequential Plasma Angiogenic Factors Levels in Women with Suspected Preeclampsia</title><author>Baltajian, Kedak, MD ; Bajracharya, Surichhya, MD ; Salahuddin, Saira, MD ; Berg, Anders H., MD ; Geahchan, Carl, MD ; Wenger, Julia B., MPH ; Thadhani, Ravi, MD, MPH ; Karumanchi, S. Ananth, MD ; Rana, Sarosh, MD, MPH</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-25b7f949ffd1ac387cd8bd25977f56ccfbbec2992bcb93ab3118210e9aaa878c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>adverse outcomes</topic><topic>Angiogenesis Inducing Agents - blood</topic><topic>angiogenic factors</topic><topic>Biomarkers - blood</topic><topic>Female</topic><topic>Humans</topic><topic>Obstetrics and Gynecology</topic><topic>Pre-Eclampsia - blood</topic><topic>Pre-Eclampsia - diagnosis</topic><topic>Pre-Eclampsia - diagnostic imaging</topic><topic>preeclampsia</topic><topic>Pregnancy</topic><topic>Pregnancy Outcome</topic><topic>Pregnancy Trimester, Third - blood</topic><topic>sequential changes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baltajian, Kedak, MD</creatorcontrib><creatorcontrib>Bajracharya, Surichhya, MD</creatorcontrib><creatorcontrib>Salahuddin, Saira, MD</creatorcontrib><creatorcontrib>Berg, Anders H., MD</creatorcontrib><creatorcontrib>Geahchan, Carl, MD</creatorcontrib><creatorcontrib>Wenger, Julia B., MPH</creatorcontrib><creatorcontrib>Thadhani, Ravi, MD, MPH</creatorcontrib><creatorcontrib>Karumanchi, S. Ananth, MD</creatorcontrib><creatorcontrib>Rana, Sarosh, MD, MPH</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of obstetrics and gynecology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baltajian, Kedak, MD</au><au>Bajracharya, Surichhya, MD</au><au>Salahuddin, Saira, MD</au><au>Berg, Anders H., MD</au><au>Geahchan, Carl, MD</au><au>Wenger, Julia B., MPH</au><au>Thadhani, Ravi, MD, MPH</au><au>Karumanchi, S. Ananth, MD</au><au>Rana, Sarosh, MD, MPH</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sequential Plasma Angiogenic Factors Levels in Women with Suspected Preeclampsia</atitle><jtitle>American journal of obstetrics and gynecology</jtitle><addtitle>Am J Obstet Gynecol</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>215</volume><issue>1</issue><spage>89.e1</spage><epage>89.e10</epage><pages>89.e1-89.e10</pages><issn>0002-9378</issn><eissn>1097-6868</eissn><abstract>Abstract Background Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Objective Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. Study Design We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical center, Boston, MA for evaluation of preeclampsia at less than 37 weeks gestation. Discarded plasma samples were collected upon admission and daily for the first three days and then weekly till delivery. Doppler ultrasound was performed upon admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms like tyrosine kinase – sFlt1 and placental growth factor – PlGF) were measured on automated platform in a single batch after delivery and in a blinded fashion. Data is presented as median (25th -75th centile), mean or proportions as appropriate. Results During the study period, data from 100 women were analyzed for the study and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, lower birth weight and placental weight (all P&lt;0.01). These patients had higher sFlt1 and sFlt1/PlGF ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th -75th ) sFlt1/PlGF ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P&lt;0.001). The median (25th -75th ) absolute change per day in sFlt1 levels (pg/ml) was 491.0 pg/ml (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/ml (-177.9, 449.0) among women without adverse outcomes (P=0.01). Similarly the absolute change per day for sFlt1/PlGF ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) among the two groups (P=0.004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with sFlt1/PlGF ratio ≥ 85 and 14 (0-39) below a ratio of 85 (P&lt;0.001). The positive predictive value for plasma sFlt1/PlGF ratio ≥ 85 at admission for indicated delivery within 2 weeks was 91% (83%-99%). Admission plasma sFlt1/PlGF ratio positively correlated with pre-delivery uterine artery resistive index (r= 0.35; P=0.004). Conclusions Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher sFlt1/PlGF ratio on admission, which continued to rise until delivery. Women with high sFlt1/PlGF ratios delivered sooner than women with low sFlt1/PlGF levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26827880</pmid><doi>10.1016/j.ajog.2016.01.168</doi><oa>free_for_read</oa></addata></record>
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subjects Adult
adverse outcomes
Angiogenesis Inducing Agents - blood
angiogenic factors
Biomarkers - blood
Female
Humans
Obstetrics and Gynecology
Pre-Eclampsia - blood
Pre-Eclampsia - diagnosis
Pre-Eclampsia - diagnostic imaging
preeclampsia
Pregnancy
Pregnancy Outcome
Pregnancy Trimester, Third - blood
sequential changes
title Sequential Plasma Angiogenic Factors Levels in Women with Suspected Preeclampsia
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