Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study

Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.Design A prospective multicentre cohort study.Setting Seven maternity units in England.Participants RhD negative pregnant women who booked for antenatal care before 24...

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Veröffentlicht in:BMJ (Online) 2014-09, Vol.349 (7975), p.g5243-g5243
Hauptverfasser: Chitty, Lyn S, Finning, Kirstin, Wade, Angela, Soothill, Peter, Martin, Bill, Oxenford, Kerry, Daniels, Geoff, Massey, Edwin
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container_end_page g5243
container_issue 7975
container_start_page g5243
container_title BMJ (Online)
container_volume 349
creator Chitty, Lyn S
Finning, Kirstin
Wade, Angela
Soothill, Peter
Martin, Bill
Oxenford, Kerry
Daniels, Geoff
Massey, Edwin
description Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.Design A prospective multicentre cohort study.Setting Seven maternity units in England.Participants RhD negative pregnant women who booked for antenatal care before 24 weeks’ gestation.Interventions Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down’s syndrome screening between 11 and 21 weeks’ gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping. Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at 23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.
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The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping. Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at &lt;11, 11-13, 14-17, 18-23, and &gt;23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.</description><edition>International edition</edition><identifier>ISSN: 0959-8138</identifier><identifier>ISSN: 1756-1833</identifier><identifier>ISSN: 0959-8146</identifier><identifier>EISSN: 1756-1833</identifier><identifier>DOI: 10.1136/bmj.g5243</identifier><identifier>PMID: 25190055</identifier><identifier>CODEN: BMJOAE</identifier><language>eng</language><publisher>England: British Medical Journal Publishing Group</publisher><subject>Accuracy ; Antigens ; Babies ; Blood groups ; Clinical medicine ; Consent ; Diagnostic tests ; Disease prevention ; DNA - analysis ; DNA - blood ; Erythroblastosis, Fetal - diagnosis ; Erythroblastosis, Fetal - genetics ; Erythroblastosis, Fetal - immunology ; False Negative Reactions ; False Positive Reactions ; Female ; Fetal Blood - immunology ; Fetuses ; Genotype ; Genotype &amp; phenotype ; Gestational Age ; Humans ; Immunoglobulins ; Laboratories ; Midwifery ; Plasma ; Pregnancy ; Pregnancy Trimesters ; Prenatal care ; Prenatal Diagnosis ; Prospective Studies ; Rh-Hr Blood-Group System - genetics ; Sensitivity and Specificity ; Serology ; Womens health</subject><ispartof>BMJ (Online), 2014-09, Vol.349 (7975), p.g5243-g5243</ispartof><rights>Chitty et al 2014</rights><rights>Chitty et al 2014.</rights><rights>Copyright BMJ Publishing Group Sep 20, 2014</rights><rights>Copyright BMJ Publishing Group LTD Sep 4, 2014</rights><rights>Chitty et al 2014 2014 Chitty et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b515t-d42be76206c8106a14c1983bf0c5e99c0b067e2105eb3f27b08746aff37db7e33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://bmj.com/content/349/bmj.g5243.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttp://bmj.com/content/349/bmj.g5243.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>114,115,230,314,776,780,799,881,3183,23550,27901,27902,30976,57992,58225,77569,77600</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25190055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chitty, Lyn S</creatorcontrib><creatorcontrib>Finning, Kirstin</creatorcontrib><creatorcontrib>Wade, Angela</creatorcontrib><creatorcontrib>Soothill, Peter</creatorcontrib><creatorcontrib>Martin, Bill</creatorcontrib><creatorcontrib>Oxenford, Kerry</creatorcontrib><creatorcontrib>Daniels, Geoff</creatorcontrib><creatorcontrib>Massey, Edwin</creatorcontrib><title>Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study</title><title>BMJ (Online)</title><addtitle>BMJ</addtitle><description>Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.Design A prospective multicentre cohort study.Setting Seven maternity units in England.Participants RhD negative pregnant women who booked for antenatal care before 24 weeks’ gestation.Interventions Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down’s syndrome screening between 11 and 21 weeks’ gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping. Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at &lt;11, 11-13, 14-17, 18-23, and &gt;23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. 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Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied &amp; Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMJ (Online)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chitty, Lyn S</au><au>Finning, Kirstin</au><au>Wade, Angela</au><au>Soothill, Peter</au><au>Martin, Bill</au><au>Oxenford, Kerry</au><au>Daniels, Geoff</au><au>Massey, Edwin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study</atitle><jtitle>BMJ (Online)</jtitle><addtitle>BMJ</addtitle><date>2014-09-04</date><risdate>2014</risdate><volume>349</volume><issue>7975</issue><spage>g5243</spage><epage>g5243</epage><pages>g5243-g5243</pages><issn>0959-8138</issn><issn>1756-1833</issn><issn>0959-8146</issn><eissn>1756-1833</eissn><coden>BMJOAE</coden><abstract>Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.Design A prospective multicentre cohort study.Setting Seven maternity units in England.Participants RhD negative pregnant women who booked for antenatal care before 24 weeks’ gestation.Interventions Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down’s syndrome screening between 11 and 21 weeks’ gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping. Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at &lt;11, 11-13, 14-17, 18-23, and &gt;23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.</abstract><cop>England</cop><pub>British Medical Journal Publishing Group</pub><pmid>25190055</pmid><doi>10.1136/bmj.g5243</doi><edition>International edition</edition><oa>free_for_read</oa></addata></record>
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source Applied Social Sciences Index & Abstracts (ASSIA); Jstor Complete Legacy; MEDLINE; BMJ Journals - NESLi2
subjects Accuracy
Antigens
Babies
Blood groups
Clinical medicine
Consent
Diagnostic tests
Disease prevention
DNA - analysis
DNA - blood
Erythroblastosis, Fetal - diagnosis
Erythroblastosis, Fetal - genetics
Erythroblastosis, Fetal - immunology
False Negative Reactions
False Positive Reactions
Female
Fetal Blood - immunology
Fetuses
Genotype
Genotype & phenotype
Gestational Age
Humans
Immunoglobulins
Laboratories
Midwifery
Plasma
Pregnancy
Pregnancy Trimesters
Prenatal care
Prenatal Diagnosis
Prospective Studies
Rh-Hr Blood-Group System - genetics
Sensitivity and Specificity
Serology
Womens health
title Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study
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