Loading…

Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?

Abstract Objective To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Study design Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and place...

Full description

Saved in:
Bibliographic Details
Published in:Placenta (Eastbourne) 2008-12, Vol.29 (12), p.1034-1040
Main Authors: Costa, S.L, Proctor, L, Dodd, J.M, Toal, M, Okun, N, Johnson, J.-A, Windrim, R, Kingdom, J.C.P
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3
cites cdi_FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3
container_end_page 1040
container_issue 12
container_start_page 1034
container_title Placenta (Eastbourne)
container_volume 29
creator Costa, S.L
Proctor, L
Dodd, J.M
Toal, M
Okun, N
Johnson, J.-A
Windrim, R
Kingdom, J.C.P
description Abstract Objective To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Study design Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11–13+6 weeks and at 18–23+6 weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery < 32 weeks, or stillbirth). Results Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses < 20 weeks, 2 (3.3%) stillbirths > 20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries < 32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3–8.5; −LR: 0.63, 95% CI: 0.36–0.93; p = 0.025], as was ≥1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6–24; −LR: 0.68, 95% CI: 0.59–0.89; p = 0.005] or ≥2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3–7.7; −LR: 0.58, 95% CI: 0.27–0.94; p = 0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency ( p = 0.05, power 80%, z -test). Conclusions In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.
doi_str_mv 10.1016/j.placenta.2008.09.004
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69834931</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0143400408003068</els_id><sourcerecordid>69834931</sourcerecordid><originalsourceid>FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhi0EokvhL1S-wC1hHNvZmANfVaErVaKicLYcZ7x4m3UWO0Haf4_DBpC4cLI0fuad0TOEXDAoGbD65a489MZiGE1ZATQlqBJAPCArJnlVcAbVQ7ICJnghcv2MPElpBwBKsOoxOWON4iBFtSKf72xEDD5sqRsivV1Ce7oJaXLOW4_BHqkP9NpvvxXRp3t6G3EbTMhf6RXdJHplYu8x0vc4jhjfPCWPnOkTPlvec_L1w9WXy-vi5tPHzeW7m8IKycbCyC5vYGVjRdcih5bVgM2aoekMb2XbWVUx10rJlXNr1yq35kxInksNirXh5-TFKfcQh-8TplHvfbLY9ybgMCVdq4YLxVkG6xNo45BSRKcP0e9NPGoGerapd_q3TT3b1KB0tpYbL5YJU7vH7m_boi8DzxfAJGt6F2cr6Q9XgZJS1TJzb08cZh8_siudfonFzke0o-4G__9dXv8TYXsffJ56j0dMu2GKIdvWTKdKg76bbz-fHhoADnXDfwJBhasv</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69834931</pqid></control><display><type>article</type><title>Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?</title><source>ScienceDirect Journals</source><creator>Costa, S.L ; Proctor, L ; Dodd, J.M ; Toal, M ; Okun, N ; Johnson, J.-A ; Windrim, R ; Kingdom, J.C.P</creator><creatorcontrib>Costa, S.L ; Proctor, L ; Dodd, J.M ; Toal, M ; Okun, N ; Johnson, J.-A ; Windrim, R ; Kingdom, J.C.P</creatorcontrib><description>Abstract Objective To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Study design Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11–13+6 weeks and at 18–23+6 weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery &lt; 32 weeks, or stillbirth). Results Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses &lt; 20 weeks, 2 (3.3%) stillbirths &gt; 20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries &lt; 32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3–8.5; −LR: 0.63, 95% CI: 0.36–0.93; p = 0.025], as was ≥1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6–24; −LR: 0.68, 95% CI: 0.59–0.89; p = 0.005] or ≥2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3–7.7; −LR: 0.58, 95% CI: 0.27–0.94; p = 0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency ( p = 0.05, power 80%, z -test). Conclusions In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.</description><identifier>ISSN: 0143-4004</identifier><identifier>EISSN: 1532-3102</identifier><identifier>DOI: 10.1016/j.placenta.2008.09.004</identifier><identifier>PMID: 18930542</identifier><identifier>CODEN: PLACDF</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adult ; Adverse perinatal outcome ; Arteries - diagnostic imaging ; Biological and medical sciences ; Early Diagnosis ; Embryology: invertebrates and vertebrates. Teratology ; Female ; First and second trimesters ; Fundamental and applied biological sciences. Psychology ; Humans ; Internal Medicine ; Mass Screening ; Maternal serum screening ; Middle Aged ; Obstetrics and Gynecology ; Pilot Projects ; Placenta - blood supply ; Placenta - diagnostic imaging ; Placental Insufficiency - diagnostic imaging ; Placental Insufficiency - epidemiology ; Placental morphology ; Placental pathology ; Predictive Value of Tests ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; Risk Factors ; Ultrasonography, Doppler ; Uterine artery Doppler ; Young Adult</subject><ispartof>Placenta (Eastbourne), 2008-12, Vol.29 (12), p.1034-1040</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3</citedby><cites>FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20955965$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18930542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costa, S.L</creatorcontrib><creatorcontrib>Proctor, L</creatorcontrib><creatorcontrib>Dodd, J.M</creatorcontrib><creatorcontrib>Toal, M</creatorcontrib><creatorcontrib>Okun, N</creatorcontrib><creatorcontrib>Johnson, J.-A</creatorcontrib><creatorcontrib>Windrim, R</creatorcontrib><creatorcontrib>Kingdom, J.C.P</creatorcontrib><title>Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?</title><title>Placenta (Eastbourne)</title><addtitle>Placenta</addtitle><description>Abstract Objective To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Study design Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11–13+6 weeks and at 18–23+6 weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery &lt; 32 weeks, or stillbirth). Results Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses &lt; 20 weeks, 2 (3.3%) stillbirths &gt; 20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries &lt; 32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3–8.5; −LR: 0.63, 95% CI: 0.36–0.93; p = 0.025], as was ≥1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6–24; −LR: 0.68, 95% CI: 0.59–0.89; p = 0.005] or ≥2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3–7.7; −LR: 0.58, 95% CI: 0.27–0.94; p = 0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency ( p = 0.05, power 80%, z -test). Conclusions In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.</description><subject>Adult</subject><subject>Adverse perinatal outcome</subject><subject>Arteries - diagnostic imaging</subject><subject>Biological and medical sciences</subject><subject>Early Diagnosis</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Female</subject><subject>First and second trimesters</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Mass Screening</subject><subject>Maternal serum screening</subject><subject>Middle Aged</subject><subject>Obstetrics and Gynecology</subject><subject>Pilot Projects</subject><subject>Placenta - blood supply</subject><subject>Placenta - diagnostic imaging</subject><subject>Placental Insufficiency - diagnostic imaging</subject><subject>Placental Insufficiency - epidemiology</subject><subject>Placental morphology</subject><subject>Placental pathology</subject><subject>Predictive Value of Tests</subject><subject>Pregnancy</subject><subject>Pregnancy Trimester, First</subject><subject>Pregnancy Trimester, Second</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Ultrasonography, Doppler</subject><subject>Uterine artery Doppler</subject><subject>Young Adult</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhi0EokvhL1S-wC1hHNvZmANfVaErVaKicLYcZ7x4m3UWO0Haf4_DBpC4cLI0fuad0TOEXDAoGbD65a489MZiGE1ZATQlqBJAPCArJnlVcAbVQ7ICJnghcv2MPElpBwBKsOoxOWON4iBFtSKf72xEDD5sqRsivV1Ce7oJaXLOW4_BHqkP9NpvvxXRp3t6G3EbTMhf6RXdJHplYu8x0vc4jhjfPCWPnOkTPlvec_L1w9WXy-vi5tPHzeW7m8IKycbCyC5vYGVjRdcih5bVgM2aoekMb2XbWVUx10rJlXNr1yq35kxInksNirXh5-TFKfcQh-8TplHvfbLY9ybgMCVdq4YLxVkG6xNo45BSRKcP0e9NPGoGerapd_q3TT3b1KB0tpYbL5YJU7vH7m_boi8DzxfAJGt6F2cr6Q9XgZJS1TJzb08cZh8_siudfonFzke0o-4G__9dXv8TYXsffJ56j0dMu2GKIdvWTKdKg76bbz-fHhoADnXDfwJBhasv</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Costa, S.L</creator><creator>Proctor, L</creator><creator>Dodd, J.M</creator><creator>Toal, M</creator><creator>Okun, N</creator><creator>Johnson, J.-A</creator><creator>Windrim, R</creator><creator>Kingdom, J.C.P</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>20081201</creationdate><title>Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?</title><author>Costa, S.L ; Proctor, L ; Dodd, J.M ; Toal, M ; Okun, N ; Johnson, J.-A ; Windrim, R ; Kingdom, J.C.P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Adverse perinatal outcome</topic><topic>Arteries - diagnostic imaging</topic><topic>Biological and medical sciences</topic><topic>Early Diagnosis</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Female</topic><topic>First and second trimesters</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Mass Screening</topic><topic>Maternal serum screening</topic><topic>Middle Aged</topic><topic>Obstetrics and Gynecology</topic><topic>Pilot Projects</topic><topic>Placenta - blood supply</topic><topic>Placenta - diagnostic imaging</topic><topic>Placental Insufficiency - diagnostic imaging</topic><topic>Placental Insufficiency - epidemiology</topic><topic>Placental morphology</topic><topic>Placental pathology</topic><topic>Predictive Value of Tests</topic><topic>Pregnancy</topic><topic>Pregnancy Trimester, First</topic><topic>Pregnancy Trimester, Second</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Ultrasonography, Doppler</topic><topic>Uterine artery Doppler</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Costa, S.L</creatorcontrib><creatorcontrib>Proctor, L</creatorcontrib><creatorcontrib>Dodd, J.M</creatorcontrib><creatorcontrib>Toal, M</creatorcontrib><creatorcontrib>Okun, N</creatorcontrib><creatorcontrib>Johnson, J.-A</creatorcontrib><creatorcontrib>Windrim, R</creatorcontrib><creatorcontrib>Kingdom, J.C.P</creatorcontrib><collection>Pascal-Francis</collection><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>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Costa, S.L</au><au>Proctor, L</au><au>Dodd, J.M</au><au>Toal, M</au><au>Okun, N</au><au>Johnson, J.-A</au><au>Windrim, R</au><au>Kingdom, J.C.P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>29</volume><issue>12</issue><spage>1034</spage><epage>1040</epage><pages>1034-1040</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><coden>PLACDF</coden><abstract>Abstract Objective To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Study design Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11–13+6 weeks and at 18–23+6 weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery &lt; 32 weeks, or stillbirth). Results Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses &lt; 20 weeks, 2 (3.3%) stillbirths &gt; 20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries &lt; 32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3–8.5; −LR: 0.63, 95% CI: 0.36–0.93; p = 0.025], as was ≥1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6–24; −LR: 0.68, 95% CI: 0.59–0.89; p = 0.005] or ≥2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3–7.7; −LR: 0.58, 95% CI: 0.27–0.94; p = 0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency ( p = 0.05, power 80%, z -test). Conclusions In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>18930542</pmid><doi>10.1016/j.placenta.2008.09.004</doi><tpages>7</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0143-4004
ispartof Placenta (Eastbourne), 2008-12, Vol.29 (12), p.1034-1040
issn 0143-4004
1532-3102
language eng
recordid cdi_proquest_miscellaneous_69834931
source ScienceDirect Journals
subjects Adult
Adverse perinatal outcome
Arteries - diagnostic imaging
Biological and medical sciences
Early Diagnosis
Embryology: invertebrates and vertebrates. Teratology
Female
First and second trimesters
Fundamental and applied biological sciences. Psychology
Humans
Internal Medicine
Mass Screening
Maternal serum screening
Middle Aged
Obstetrics and Gynecology
Pilot Projects
Placenta - blood supply
Placenta - diagnostic imaging
Placental Insufficiency - diagnostic imaging
Placental Insufficiency - epidemiology
Placental morphology
Placental pathology
Predictive Value of Tests
Pregnancy
Pregnancy Trimester, First
Pregnancy Trimester, Second
Prospective Studies
Risk Factors
Ultrasonography, Doppler
Uterine artery Doppler
Young Adult
title Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T13%3A28%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Screening%20for%20Placental%20Insufficiency%20in%20High-risk%20Pregnancies:%20Is%20Earlier%20Better?&rft.jtitle=Placenta%20(Eastbourne)&rft.au=Costa,%20S.L&rft.date=2008-12-01&rft.volume=29&rft.issue=12&rft.spage=1034&rft.epage=1040&rft.pages=1034-1040&rft.issn=0143-4004&rft.eissn=1532-3102&rft.coden=PLACDF&rft_id=info:doi/10.1016/j.placenta.2008.09.004&rft_dat=%3Cproquest_cross%3E69834931%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c451t-a5d542c58c4dbe30b160e871eada3b5bdc921fb5539ff7fb9f731453fb58e47a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=69834931&rft_id=info:pmid/18930542&rfr_iscdi=true