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sequences" /></a></div><div class="bkr_bib"><h1 id="_NBK578083_"><span itemprop="name">Evidence review for ultrasound screening for twin anaemia polycythaemia sequences</span></h1><div class="subtitle">Twin and Triplet Pregnancy</div><p><b>Evidence review C</b></p><p><i>NICE Guideline, No. 137</i></p><p class="contrib-group"><h4>Authors</h4><span itemprop="author">National Guideline Alliance (UK)</span>.</p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2019 Sep</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-3513-0</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2019.</div></div><div class="bkr_clear"></div></div><div id="ch3.s1"><h2 id="_ch3_s1_">Ultrasound screening for Twin Anaemia Polycythaemia Sequences</h2><div id="ch3.s1.1"><h3>Review question</h3><p>What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><div id="ch3.s1.1.1"><h4>Introduction</h4><p>The aim of this review is to determine what is the most accurate screening strategy for complicated, uncomplicated and post laser TAPS in monochorionic twin and triplet pregnancies considering the optimum frequency and gestational age of ultrasound scans.</p></div><div id="ch3.s1.1.2"><h4>Summary of the protocol</h4><p><a class="figpopup" href="/books/NBK578083/table/ch3.tab1/?report=objectonly" target="object" rid-figpopup="figch3tab1" rid-ob="figobch3tab1">Table 1</a> summarises the Population, Index test, Reference standard and Outcome (PIRO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch3tab1"><a href="/books/NBK578083/table/ch3.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figch3tab1" rid-ob="figobch3tab1"><img class="small-thumb" src="/books/NBK578083/table/ch3.tab1/?report=thumb" src-large="/books/NBK578083/table/ch3.tab1/?report=previmg" alt="Table 1. Summary of protocol (PIRO table)." /></a><div class="icnblk_cntnt"><h4 id="ch3.tab1"><a href="/books/NBK578083/table/ch3.tab1/?report=objectonly" target="object" rid-ob="figobch3tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">Summary of protocol (PIRO table). </p></div></div><p>For full details see the review protocol in <a href="#ch3.appa">appendix A</a>.</p></div><div id="ch3.s1.1.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>
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<u>2014</u>. Methods specific to this review question are described in the review protocol in <a href="#ch3.appa">appendix A</a> and for a full description of the methods see supplementary document C.</p><p>Declaration of interests were recorded according to NICE’s 2014 conflicts of interest policy from March 2017 until March 2018. From April 2018 onwards they were recorded according to NICE’s 2018 <a href="https://www.nice.org.uk/About/Who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">conflicts of interest policy</a>. Those interests declared until April 2018 were reclassified according to NICE’s 2018 conflicts of interest policy (see Interests Register).</p></div><div id="ch3.s1.1.4"><h4>Clinical evidence</h4><div id="ch3.s1.1.4.1"><h5>Included studies</h5><p>Two prospective cohort studies (<a class="bibr" href="#ch3.s1.1.ref1" rid="ch3.s1.1.ref1">Fishel-Bartal 2016</a>; <a class="bibr" href="#ch3.s1.1.ref3" rid="ch3.s1.1.ref3">Veujoz 2015</a>) and 1 retrospective cohort study (<a class="bibr" href="#ch3.s1.1.ref2" rid="ch3.s1.1.ref2">Tollenaar 2018</a>) were included. All studies used ultrasound (US) fetal middle cerebral arterial peak systolic velocity (MCA-PSV) to detect postnatally diagnosed TAPS in monochorionic diamniotic (MCDA) twins, using the reference test of inter-twin haemoglobin (Hb) discordance at birth.</p><p>One study (<a class="bibr" href="#ch3.s1.1.ref3" rid="ch3.s1.1.ref3">Veujoz 2015</a>) reported sensitivity and specificity based on 9 cases of MCDA twin pregnancies, from an initial 20 cases of TAPS (only 9 cases had MCA-PSV scans within the assigned 48 hour period before birth), assessed prenatally within 48 hours of birth. One study (<a class="bibr" href="#ch3.s1.1.ref2" rid="ch3.s1.1.ref2">Tollenaar 2018</a>) reported sensitivity and specificity based on 35 MCDA twins with TAPS, assessed prenatally within one-week of birth. In this study the authors used 2 different cut-offs for ultrasound MCA-PSV discordancy, that is >1.5 and >0.5 multiples of the median.</p><p>Another study (<a class="bibr" href="#ch3.s1.1.ref1" rid="ch3.s1.1.ref1">Fishel-Bartel 2016</a>) reported area under the curve (AUC) for TAPS based on 69 MCDA twin pregnancies, assessed prenatally within 1 week of birth.</p><p>The clinical studies included in this evidence review are summarised in <a class="figpopup" href="/books/NBK578083/table/ch3.tab2/?report=objectonly" target="object" rid-figpopup="figch3tab2" rid-ob="figobch3tab2">Table 2</a>.</p><p>See also the literature search strategy in <a href="#ch3.appb">appendix B</a>, study selection flow chart in <a href="#ch3.appc">appendix C</a>, study evidence tables in <a href="#ch3.appd">appendix D</a> and GRADE profiles in <a href="#ch3.appf">appendix F</a>.</p></div><div id="ch3.s1.1.4.2"><h5>Excluded studies</h5><p>Studies not included in this review with reasons for their exclusions are provided in <a href="#ch3.appk">appendix K</a>.</p></div></div><div id="ch3.s1.1.5"><h4>Summary of clinical studies included in the evidence review</h4><p><a class="figpopup" href="/books/NBK578083/table/ch3.tab2/?report=objectonly" target="object" rid-figpopup="figch3tab2" rid-ob="figobch3tab2">Table 2</a> provides a brief summary of the included studies.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch3tab2"><a href="/books/NBK578083/table/ch3.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figch3tab2" rid-ob="figobch3tab2"><img class="small-thumb" src="/books/NBK578083/table/ch3.tab2/?report=thumb" src-large="/books/NBK578083/table/ch3.tab2/?report=previmg" alt="Table 2. Summary of included studies for twin pregnancy." /></a><div class="icnblk_cntnt"><h4 id="ch3.tab2"><a href="/books/NBK578083/table/ch3.tab2/?report=objectonly" target="object" rid-ob="figobch3tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of included studies for twin pregnancy. </p></div></div><p>See <a href="#ch3.appd">appendix D</a> for the full evidence tables.</p></div><div id="ch3.s1.1.6"><h4>Quality assessment of clinical studies included in the evidence review</h4><p>See <a href="#ch3.appf">appendix F</a> for the full GRADE tables.</p></div><div id="ch3.s1.1.7"><h4>Economic evidence</h4><div id="ch3.s1.1.7.1"><h5>Included studies</h5><p>A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.</p><p>See the <a href="#ch3.appb">appendix B</a> for the economic search strategy and <a href="#ch3.appg">appendix G</a> for the economic evidence selection flow chart for further information.</p></div><div id="ch3.s1.1.7.2"><h5>Excluded studies</h5><p>No economic studies were identified which were applicable to this review question.</p></div></div><div id="ch3.s1.1.8"><h4>Summary of studies included in the economic evidence review</h4><p>No full-text copies of articles were requested for this review and so there is no excluded studies list.</p></div><div id="ch3.s1.1.9"><h4>Economic model</h4><p>No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.</p></div><div id="ch3.s1.1.10"><h4>Evidence statements</h4><p>Only sensitivity and specificity values are provided in the evidence statements below. When assessing the diagnostic accuracy of sensitivity and specificity the following thresholds were used: high accuracy: more than 90%; moderate accuracy: 75% to 90%; and, low accuracy: less than 75%. AUC up to 70% are described as having poor ability to discriminate and AUC of 71% and above would be described as having moderate (71 to 80%), good (81 to 90%), or excellent (91 to 100%) ability to discriminate. Estimates are reported for information in <a href="#ch3.appd">appendix D</a> and <a href="#ch3.appf">appendix F</a>. For further details see the methods described in supplement document C.</p><div id="ch3.s1.1.10.1"><h5>Sensitivity and Specificity</h5><p>Very low quality evidence from 1 study (N=9) showed the sensitivity and specificity for prenatal middle cerebral artery peak systolic velocity (MCA-PSV) inter-twin discordancy (MCA-PSV >1.5 multiple of the median [MoM] in 1 fetus; and MCA-PSV <1 MoM in the other) for monochorionic diamniotic (MCDA) twins was 71% (29 to 96) and 50% (1 to 99) to detect TAPS (defined as post-natal Hb inter-twin discordance of >8g/dL and one of: reticulocyte count ratio>1.7, or placenta with only small vascular anastomoses [diameter<1mm]).</p><p>Moderate quality evidence from 1 study (N=35 twins with TAPS and N=45 without TAPS) showed that the sensitivity and specificity for prenatal MCA-PSV (MCA-PSV >1.5 MoM in 1 fetus and <1 MoM in another fetus) inter-twin discordancy for MCDA twins was 46% (30 to 62) and 100% (92 to 100) to detect TAPS (defined as an inter-twin haemoglobin difference > 8 g/dL and at least one of the following: reticulocyte count ratio > 1.7 or the presence of minuscule anastomoses (diameter < 1.0 mm) on the placental surface, detected through placental colour dye injection). Very low quality evidence from the same study showed that the sensitivity and specificity for prenatal MCA-PSV (MCA-PSV >0.5 MoM) inter-twin discordancy for MCDA twins was 83% (67 to 93) and 100% (92 to 100).</p></div><div id="ch3.s1.1.10.2"><h5>Area under the curve</h5><p>Low quality evidence from 1 study (N=69) showed the AUC for prenatal MCA-PSV inter-twin discordancy (MCA-PSV >1.5 MoM in 1 fetus; and MCA-PSV <1 MoM in the other) for MCDA twins was 87.1% (75.7 to 98.5) to detect TAPS (defined as post-natal Hb inter-twin discordance of >8g/dL and one of: reticulocyte count ratio>1.7 or placenta with only small vascular anastomoses (diameter<1mm)).</p></div></div><div id="ch3.s1.1.11"><h4>The committee’s discussion of the evidence</h4><div id="ch3.s1.1.11.1"><h5>Interpreting the evidence</h5><div id="ch3.s1.1.11.1.1"><h5>The outcomes that matter most</h5><p>Sensitivity and specificity were regarded as critical outcomes, and AUC was an important outcome.</p><p>Sensitivity was regarded as the more critical measure (compared to specificity) for decision making, as these tests are primarily screening diagnostic tests. The committee prioritised the diagnostic accuracy measure of sensitivity because it is important to identify women with twin or triplet pregnancy who have TAPS, to potentially treat or manage where possible.</p><p>Area under the curve was rated as an important rather than critical outcome because it does not provide precise information on the false positive or false negative rates that would have the biggest impact on patient level outcomes.</p></div><div id="ch3.s1.1.11.1.2"><h5>The quality of the evidence</h5><p>The evidence was assessed using modified GRADE criteria. Of the 3 identified studies, 2 studies had very serious risks of bias due to lack of clarity whether the reference standard was interpreted without knowledge of the index tests. There was also uncertainty around the estimate because the populations were small which meant that the evidence was downgraded for imprecision. One study contained a study pre-selected sample (all of the twins had TAPS) and the reference standard was poorly described.</p><p>Due to these limitations accuracy outcomes were assessed as very low to moderate quality according to modified GRADE criteria.</p></div><div id="ch3.s1.1.11.1.3"><h5>Benefits and harms</h5><div id="ch3.s1.1.11.1.3.1"><h5>Simultaneous monitoring</h5><p>There are several complications that are restricted to monochorionicity (feto-fetal transfusion syndrome and TAPS) and others, such as intrauterine growth restriction, are more common in monochorionic babies. All of these are monitored by ultrasound. The committee highlighted that measurements from one ultrasound would be used to monitor for all complications simultaneously (such as feto-fetal transfusion syndrome (FFTS), intrauterine growth restriction and TAPS) rather than having separate ultrasound scans for each because they are not mutually exclusive conditions. An explanation about the relative likelihood of each complication and when they can occur during her pregnancy should be given to the woman so that she knows the reasons for the different ultrasound measurements that are taken.</p></div><div id="ch3.s1.1.11.1.3.2"><h5>Diagnostic monitoring for TAPS</h5><p>The committee noted that the evidence base for TAPS was limited by study design (retrospective cohorts, timing of assessment), sample size, and heterogeneity in results. Variation in study design and the small number of studies included, meant meta-analysis was not possible. The evidence was also restricted to only one diagnostic test (MCA-PSV). They therefore had little confidence in the evidence and based their recommendations on their experience and expertise.</p><p>The committee discussed whether to make a recommendation against screening for TAPS in uncomplicated monochorionic pregnancies. However, they decided against this because the natural history of antenatally diagnosed TAPS based purely on MCA-PSV measurements is unknown. Additionally the evidence showed that the antenatal diagnosis of TAPS based on MCA-PSV measurements has a false positive rate of approximately 17% and therefore may be associated with neonatal morbidity from iatrogenic preterm birth. It was therefore not deemed to be beneficial to screen all monochorionic pregnancies as the risk of unnecessary intervention was high, but to focus on the particular subgroup of twin or triplet pregnancies (those involving monochorionic babies who had additional complications) where risks of all complications (including TAPS) are higher. Despite the large variability in the results, and the low quality of the available evidence, ultrasound using MCA-PSV was deemed potentially useful when compared to no screening at all, in these specific populations. The committee therefore made a recommendation to screen for TAPS in pregnancies complicated by FFTS that has been treated by fetoscopic laser therapy or those complicated by selective growth restriction (defined by a difference in estimated fetal weight of 25% or above and estimated fetal weight of one baby is below the 10<sup>th</sup> centile for gestational age); they also recommended to screen for TAPS in monochorionic twin sets who had additional complications (that had potential to increase the chance of developing TAPS such as cardiovascular compromise or unexplained isolated polyhydramnios, or abnormal umbilical artery). The committee decided that in cases where there were complicated monochorionic pregnancies it was beneficial to screen for TAPS because the risk of complications including fetal death and neonatal morbidity and mortality would outweigh the harms of intervention including preterm birth and in utero transfusion. Given the seriousness of the outcomes the committee decided that strong recommendations were warranted for this group despite the limited evidence base.</p><p>The committee decided not to specify diagnostic criteria because they wanted to emphasise the importance of referral to a tertiary level referral centre when TAPS is suspected, so that decisions about further assessment and management can be made with each individual woman. The committee agreed that cases of suspected TAPS should be managed in a tertiary fetal medicine centre. The benefit of managing complicated monochorionic pregnancies in this setting outweighed potential risks of inconvenience of travel and transfer to units away from home.</p></div><div id="ch3.s1.1.11.1.3.3"><h5>Further research</h5><p>The prenatal diagnosis of TAPS is currently based on discordant measurements of the MCA-PSV (>1.5 multiples of the median [MoM] in donors and 8 g/dL), and at least 1 of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. However, it is unclear whether these are the most accurate measurements (inter-twin discordancy: MCA-PSV >1.5 MoM in 1 fetus and MCA-PSV <1 MoM in the other; or MCA-PSV inter-twin discordancy >0.5 MoM) because evidence is very limited and the committee’s confidence in the evidence was low. The committee therefore drafted a research recommendation which would investigate whether this is the most accurate combination of test measures or whether other additional measures could also be useful (on their own or in combination). The committee agreed that finding an accurate diagnostic test would lead to better detection and potentially earlier treatment. Since there is uncertainty about the accuracy for screening measures for TAPS for all monochorionic twins types (including uncomplicated pregnancies) the committee recommended this research, despite making a strong recommendation for screening using MCA-PSV measurement for those twins who are at greatest risk. For further details related to the research recommendation see <a href="#ch3.appl">appendix L</a>.</p></div></div></div><div id="ch3.s1.1.11.2"><h5>Cost effectiveness and resource use</h5><p>In the absence of any economic evidence or de novo analysis, the committee made a qualitative assessment about the cost effectiveness of screening and diagnostic monitoring for TAPS.</p><p>The committee acknowledged that there could be a small resource impact to the NHS arising from their recommendations with a potential increase in the number of assessments and referrals in women with complicated monochorionic pregnancies. However, they thought any resource impact would be relatively small given the small population of women with twin or triplet pregnancy to which the recommendations apply. Furthermore, they considered that the recommendations would be cost-effective as reductions in the risk of fetal death, neonatal morbidity and mortality from diagnosis and intervention would be worth any costs of detection.</p></div></div><div id="ch3.rl.r1"><h4>References</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="ch3.s1.1.ref1"><p id="p-74">
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<strong>Fishel-Bartal 2016</strong>
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</p>Fishel-Bartal, M, Weisz, B, Mazaki-Tovi, S, et al. Can middle cerebral artery peak systolic velocity predict polycythemia in monochorionic-diamniotic twins? Evidence from a prospective cohort study. Ultrasound in Obstetrics & Gynaecology
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48 (4): 470–475, 2016 [<a href="https://pubmed.ncbi.nlm.nih.gov/26663574" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26663574</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ch3.s1.1.ref2"><p id="p-75">
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<strong>Tollenaar 2018</strong>
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</p>Tollenaar
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LSA, Lopriore
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E, Middeldorp
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JM, Haak
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MC, Klumper
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FJ, Oepkes
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D, Slaghekke
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F. Improved antenatal prediction of twin anemia-polycythemia sequence by delta middle cerebral artery peak systolic velocity: a new antenatal classification system. Ultrasound Obstet Gynecol. 2018
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Aug
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20 [Epub ahead of print] [<a href="/pmc/articles/PMC6593803/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6593803</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30125414" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30125414</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ch3.s1.1.ref3"><p id="p-76">
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<strong>Veujoz 2015</strong>
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</p>Veujoz, M, Sananes, N, Severac, F, et al. Evaluation of prenatal and postnatal diagnostic criteria for twin anemia-polycythemia sequence. Prenatal Diagnosis
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35 (3): 281–8, 2015 [<a href="https://pubmed.ncbi.nlm.nih.gov/25484182" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25484182</span></a>]</div></p></li></ul></div></div></div><div id="appendixesappgroup3"><h2 id="_appendixesappgroup3_">Appendices</h2><div id="ch3.appa"><h3>Appendix A. Review protocols</h3><p>1.3: Review protocol – diagnostic component for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p id="ch3.appa.tab1"><a href="/books/NBK578083/table/ch3.appa.tab1/?report=objectonly" target="object" rid-ob="figobch3appatab1" class="figpopup">Table 3. Review protocol for ultrasound screening / diagnostic monitoring for twin anaemia polycythaemia sequences (TAPS)</a></p></div><div id="ch3.appb"><h3>Appendix B. Literature search strategies</h3><p>Literature search for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><div id="ch3.appb.s1"><h4>Clinical searches</h4><p>Date of initial search: 03/04/18</p><p>Database(s): Embase Classic+Embase 1947 to 2018 April 02, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present</p><p>Date of updated search: 06/09/2018</p><p>Database(s): Embase Classic+Embase 1947 to 2018 September 06, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch3appbtab1"><a href="/books/NBK578083/table/ch3.appb.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figch3appbtab1" rid-ob="figobch3appbtab1"><img class="small-thumb" src="/books/NBK578083/table/ch3.appb.tab1/?report=thumb" src-large="/books/NBK578083/table/ch3.appb.tab1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ch3.appb.tab1"><a href="/books/NBK578083/table/ch3.appb.tab1/?report=objectonly" target="object" rid-ob="figobch3appbtab1">Table</a></h4></div></div><p>Date of initial search: 03/04/2018</p><p>Database(s): The Cochrane Library, issue 4 of 12, April 2018</p><p>Date of updated search: 06/09/2018</p><p>Database(s): The Cochrane Library, issue 9 of 12, September 2018</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch3appbtab2"><a href="/books/NBK578083/table/ch3.appb.tab2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figch3appbtab2" rid-ob="figobch3appbtab2"><img class="small-thumb" src="/books/NBK578083/table/ch3.appb.tab2/?report=thumb" src-large="/books/NBK578083/table/ch3.appb.tab2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ch3.appb.tab2"><a href="/books/NBK578083/table/ch3.appb.tab2/?report=objectonly" target="object" rid-ob="figobch3appbtab2">Table</a></h4></div></div></div><div id="ch3.appb.s2"><h4>Health Economics Searches</h4><p>(For the Cochrane Library, see above)</p><p>Date of initial search: 04/04/18</p><p>Database(s): Embase Classic+Embase 1947 to 2018 April 03, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present</p><p>Date of updated search: 06/09/2018</p><p>Database(s): Embase Classic+Embase 1947 to 2018 September 06, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch3appbtab3"><a href="/books/NBK578083/table/ch3.appb.tab3/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figch3appbtab3" rid-ob="figobch3appbtab3"><img class="small-thumb" src="/books/NBK578083/table/ch3.appb.tab3/?report=thumb" src-large="/books/NBK578083/table/ch3.appb.tab3/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ch3.appb.tab3"><a href="/books/NBK578083/table/ch3.appb.tab3/?report=objectonly" target="object" rid-ob="figobch3appbtab3">Table</a></h4></div></div></div></div><div id="ch3.appc"><h3>Appendix C. Clinical evidence study selection</h3><p>Clinical evidence study selection for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p id="ch3.appc.fig1"><a href="/books/NBK578083/figure/ch3.appc.fig1/?report=objectonly" target="object" rid-ob="figobch3appcfig1" class="figpopup">Figure 1. Flow diagram of clinical article selection for the optimal screening programme to detect TAPS in twin and triplet pregnancy</a></p></div><div id="ch3.appd"><h3>Appendix D. Clinical evidence tables</h3><p>Clinical evidence tables for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p id="ch3.appd.et1"><a href="/books/NBK578083/bin/ch3-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (262K)</span></p></div><div id="ch3.appe"><h3>Appendix E. Forest plots</h3><p>Forest plots for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p>No forest plots were included in this review.</p></div><div id="ch3.appf"><h3>Appendix F. GRADE tables</h3><p>GRADE profile for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p id="ch3.appf.tab1"><a href="/books/NBK578083/table/ch3.appf.tab1/?report=objectonly" target="object" rid-ob="figobch3appftab1" class="figpopup">Table 4. Clinical evidence profile for screening to identify TAPS in twin pregnancy in the second trimester</a></p></div><div id="ch3.appg"><h3>Appendix G. Economic evidence study selection</h3><p>Economic evidence study selection for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p>No economic evidence was identified for this review.</p><p id="ch3.appg.fig1"><a href="/books/NBK578083/figure/ch3.appg.fig1/?report=objectonly" target="object" rid-ob="figobch3appgfig1" class="figpopup">Figure 2. Flow diagram of economic article selection for the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy</a></p></div><div id="ch3.apph"><h3>Appendix H. Economic evidence tables</h3><p>Economic evidence tables for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p>No economic evidence was identified for this review.</p></div><div id="ch3.appi"><h3>Appendix I. Economic evidence profiles</h3><p>Economic evidence profiles for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p>No economic evidence was identified for this review.</p></div><div id="ch3.appj"><h3>Appendix J. Economic analysis</h3><p>Economic analysis for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p>No economic evidence was identified for this review.</p></div><div id="ch3.appk"><h3>Appendix K. Excluded studies</h3><p>Excluded studies for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><div id="ch3.appk.s1"><h4>Clinical studies</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch3appktab1"><a href="/books/NBK578083/table/ch3.appk.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figch3appktab1" rid-ob="figobch3appktab1"><img class="small-thumb" src="/books/NBK578083/table/ch3.appk.tab1/?report=thumb" src-large="/books/NBK578083/table/ch3.appk.tab1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ch3.appk.tab1"><a href="/books/NBK578083/table/ch3.appk.tab1/?report=objectonly" target="object" rid-ob="figobch3appktab1">Table</a></h4><p class="float-caption no_bottom_margin">AUC: area under the curve; IUGR: intrauterine growth rate; MCA-PSV: middle cerebral artery peak systolic velocity; MCDA: monochorionic diamniotic; TAPS: twin anemia polycythemia sequence; TTTS: twin-to-twin transfusion syndrome; US: ultrasound </p></div></div></div><div id="ch3.appk.s2"><h4>Economic studies</h4><p>No economic evidence was identified for this review.</p></div></div><div id="ch3.appl"><h3>Appendix L. Research recommendations</h3><p>Research recommendations for review question: What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</p><p>Research recommendation:</p><p>
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<b>What is the most accurate prenatal screening marker for TAPS, including MCA-PSV?</b>
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</p><p>
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<b>Why this is important</b>
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</p><p>Monochorionic twins share a single placenta and are connected to each other through vascular anastomoses, allowing inter-twin blood transfusion. Unbalanced net inter-twin blood transfusion can lead to various disorders, including chronic feto-fetal transfusion syndrome (FFTSS), acute peripartum TTTS and TAPS.</p><p>TAPS is characterised by a chronic and slow blood transfusion from donor to recipient through miniscule vascular anastomoses during the course of pregnancy, causing the donor to become anaemic and the recipient to become polycythaemia, without discordances in amniotic fluid. TAPS may occur spontaneously (spontaneous TAPS) in 2% of the monochorionic twin pregnancies or in any monochorionic twin complications, especially after laser surgery for chronic TTTS (post-laser TAPS) in 3–16% of the chronic TTTS cases (Slaghekke F et al, Fetal Diagn Ther. 2010; 27(4):181–90).</p><p>Short-term neonatal outcome ranges from isolated inter-twin haemoglobin (Hb) differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS.</p><p>The prenatal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and 8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. However, it is unclear whether these are the most accurate measurements because evidence is very limited. Finding an accurate diagnostic test would lead to better detection and potentially earlier treatment.</p><p id="ch3.appl.tab1"><a href="/books/NBK578083/table/ch3.appl.tab1/?report=objectonly" target="object" rid-ob="figobch3appltab1" class="figpopup">Table 5. Research recommendation rationale</a></p><p id="ch3.appl.tab2"><a href="/books/NBK578083/table/ch3.appl.tab2/?report=objectonly" target="object" rid-ob="figobch3appltab2" class="figpopup">Table 6. Research recommendation modified PIRO table</a></p></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>Evidence review</p><p>This evidence review was developed by the National Guideline Alliance which is a part of the Royal College of Obstetricians and Gynaecologists</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2019.</div><div class="small"><span class="label">Bookshelf ID: NBK578083</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/35192251" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">35192251</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobch3tab1"><div id="ch3.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Summary of protocol (PIRO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.tab1_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_ch3.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_ch3.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>For twin pregnancies:</b>
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<ul id="ch3.l1"><li id="ch3.lt1" class="half_rhythm"><div>Monochorionic diamniotic</div></li><li id="ch3.lt2" class="half_rhythm"><div>Monochorionic monoamniotic</div></li></ul>
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<b>For triplet pregnancies:</b>
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<ul id="ch3.l2"><li id="ch3.lt3" class="half_rhythm"><div>Monochorionic triamniotic</div></li><li id="ch3.lt4" class="half_rhythm"><div>Dichorionic, diamniotic (in relation to the monochorionic pair)</div></li><li id="ch3.lt5" class="half_rhythm"><div>Monochorionic monoamniotic</div></li></ul>
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Setting: Secondary or tertiary care centres</td></tr><tr><th id="hd_b_ch3.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Index Test</th><td headers="hd_b_ch3.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Ultrasound scan at 16 weeks onwards:
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<ul id="ch3.l3"><li id="ch3.lt6" class="half_rhythm"><div>Doppler studies (fetal middle cerebral arterial peak systolic velocity [MCA-PSV])</div></li><li id="ch3.lt7" class="half_rhythm"><div>Umbilical artery doppler velocity (UA-AREDV)</div></li><li id="ch3.lt8" class="half_rhythm"><div>Ductus venosus atrial systolic velocity (DV-RAV)</div></li><li id="ch3.lt9" class="half_rhythm"><div>Hydrops or fetal effusion or ascites skin oedema</div></li></ul>
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The above tests will be considered in isolation or in combination.</p>
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<p>Details regarding frequency and duration of testing throughout pregnancy presented in included studies will be recorded</p></td></tr><tr><th id="hd_b_ch3.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference Standard</th><td headers="hd_b_ch3.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recognised postnatal diagnostic criteria reference standard for TAPS</td></tr><tr><th id="hd_b_ch3.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</th><td headers="hd_b_ch3.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><b>Diagnostic value of tests</b></p>
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<p><b>Critical outcomes</b>
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<ul id="ch3.l4"><li id="ch3.lt10" class="half_rhythm"><div>Sensitivity (detection rate)</div></li><li id="ch3.lt11" class="half_rhythm"><div>Specificity</div></li></ul>
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Sensitivity was regarded as the more important measure for decision making as these are primarily screening diagnostic tests</p>
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<p><b>Important outcomes</b>
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<ul id="ch3.l5"><li id="ch3.lt12" class="half_rhythm"><div>area under curve (AUC)</div></li></ul></p></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">TAPS: twin anaemia-polycythaemia sequences</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch3tab2"><div id="ch3.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of included studies for twin pregnancy</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch3.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_ch3.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_ch3.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Index test</th><th id="hd_h_ch3.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Reference standard</th><th id="hd_h_ch3.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_ch3.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Frequency and duration of screening for each study</th></tr></thead><tbody><tr><td headers="hd_h_ch3.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><a class="bibr" href="#ch3.s1.1.ref1" rid="ch3.s1.1.ref1">Fishel-Bartal 2016</a><sup>1</sup></p>
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<p>Prospective cohort</p><p>France</p></td><td headers="hd_h_ch3.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N=69/162<sup>2</sup> MCDA twin pregnancies (138 twins: n=131 neonates analysed [7 excluded due to fetal death or selective reduction])</td><td headers="hd_h_ch3.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrasound MCA-PSV discordancy: MCA-PSV >1.5 MoM in one twin (anaemic/donor), and concordant decrease MCA-PSV (<1.0) MoM in the co-twin (polycythaemic/recipient)</td><td headers="hd_h_ch3.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inter-twin Hb difference >8g/dL, combined with reticulocyte count ratio >1.7 or finding of infra-millimetric anastomoses</td><td headers="hd_h_ch3.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diagnostic accuracy of ultrasound MCA-PSV discordancy (AUC)</td><td headers="hd_h_ch3.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fortnightly (every 2 weeks) until complications were noted (for example, IUGR, discordant fetal growth, fluid volumes, Doppler flow in MCA-PSV), then “surveillance was intensified accordingly” no other detail</td></tr><tr><td headers="hd_h_ch3.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><a class="bibr" href="#ch3.s1.1.ref2" rid="ch3.s1.1.ref2">Tollenaar 2018</a></p>
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<p>Retrospective cohort</p>
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<p>The Netherlands</p></td><td headers="hd_h_ch3.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N=35 twins with TAPS, N=45 uncomplicated monochorionic twins</td><td headers="hd_h_ch3.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrasound MCA-PSV discordancy: MCA-PSV >1.5 or >0.5 MoM in one fetus (anaemic/donor), and MCA-PSV <1 or >0.5 MoM in the other (polycythaemic/recipient)</td><td headers="hd_h_ch3.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inter-twin Hb difference >8 g/dL combined with reticulocyte count ratio > 1.7 or finding of minuscule anastomoses (diameter <1.0 mm) on the placental surface, detected through placental colour dye injection</td><td headers="hd_h_ch3.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diagnostic accuracy of ultrasound MCA-PSV discordancy (sensitivity and specificity)</td><td headers="hd_h_ch3.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrasound doppler measurement was performed in both twins within 1 week before birth</td></tr><tr><td headers="hd_h_ch3.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><a class="bibr" href="#ch3.s1.1.ref3" rid="ch3.s1.1.ref3">Veujoz 2015</a><sup>1</sup></p>
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<p>Prospective cohort</p>
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<p>France</p></td><td headers="hd_h_ch3.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N=9/20<sup>3</sup> MCDA twin pregnancies with TAPS</td><td headers="hd_h_ch3.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrasound MCA-PSV discordancy: MCA-PSV > 1.5 MoM in one foetus, and MCA-PSV < 1 MoM in the other</td><td headers="hd_h_ch3.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inter-twin Hb difference > 8g/dL, combined with reticulocyte ratio > 1.7 or finding of infra-millimetric anastomoses</td><td headers="hd_h_ch3.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diagnostic accuracy of ultrasound MCA-PSV discordancy (sensitivity and specificity)</td><td headers="hd_h_ch3.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fortnightly (every 2 weeks)</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AUC: area under the curve; Hb: haemoglobin; IUGR: intrauterine growth restriction; MCA-PSV: middle cerebral artery peak systolic velocity; MCDA: monochorionic diamniotic; MoM: multiples of the median; N: number of women; TAPS: twin anaemia-polycythaemia sequences</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch3.tab2_1"><p class="no_margin">In both studies, a proportion were treated ‘in utero’ using transfusion or laser – it is not clear whether these were reported as no longer having TAPS or as false positives or other method of analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch3.tab2_2"><p class="no_margin">N=69/162: only 69 MCDA twin pregnancies were analysed out of a total of 162 as the MCA-PSV screening had to be within 1-week before birth for accurate comparison</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="ch3.tab2_3"><p class="no_margin">N=9/20: only 9 included in analysis as MCA-PSV screening had to be within 48 hours before birth for accurate comparison</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch3appatab1"><div id="ch3.appa.tab1" class="table"><h3><span class="label">Table 3</span><span class="title">Review protocol for ultrasound screening / diagnostic monitoring for twin anaemia polycythaemia sequences (TAPS)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appa.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appa.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">ID</th><th id="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Field (based on <a href="http://www.prisma-statement.org/Extensions/Protocols.aspx" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PRISMA-P</a>)</th><th id="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Content</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">I</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">What is the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy?</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">II</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type of review question</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diagnostic accuracy</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">III</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective of the review</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To determine what is the most accurate screening strategy for complicated, uncomplicated and post laser TAPS in monochorionic twin and triplet pregnancies considering the optimum frequency and gestational age of ultrasound scans</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IV</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – population/disease/condition/issue/domain</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>For twin pregnancies:</b>
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<ul id="ch3.l6"><li id="ch3.lt13" class="half_rhythm"><div>Monochorionic diamniotic</div></li><li id="ch3.lt14" class="half_rhythm"><div>Monochorionic monoamniotic</div></li></ul>
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<b>For triplet pregnancies:</b>
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<ul id="ch3.l7"><li id="ch3.lt15" class="half_rhythm"><div>Monochorionic triamniotic</div></li><li id="ch3.lt16" class="half_rhythm"><div>Dichorionic, diamniotic (in relation to the monochorionic pair)</div></li><li id="ch3.lt17" class="half_rhythm"><div>Monochorionic monoamniotic</div></li></ul>
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Setting: Secondary or tertiary care centres</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">V</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – intervention(s)/exposure (s)/prognostic factor(s)</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><b>Index tests</b></p>
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<p>Ultrasound scan at 16 weeks onwards:
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<ul id="ch3.l8"><li id="ch3.lt18" class="half_rhythm"><div>Doppler studies (fetal middle cerebral arterial peak systolic velocity [MCA-PSV])</div></li><li id="ch3.lt19" class="half_rhythm"><div>Umbilical artery Doppler velocity (UA-AREDV)</div></li><li id="ch3.lt20" class="half_rhythm"><div>Ductus venosus atrial systolic velocity (DV-RAV)</div></li><li id="ch3.lt21" class="half_rhythm"><div>Hydrops or fetal effusion or ascites skin oedema</div></li></ul>
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The above tests will be considered in isolation or in combination.</p>
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<p>Details regarding frequency and duration of testing throughout pregnancy presented in included studies will be recorded</p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VI</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – comparator(s)/control or reference (gold) standard</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p><b>Reference standard</b></p>
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<p>Recognised postnatal diagnostic criteria reference standard for TAPS</p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes and prioritisation</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Diagnostic value of tests</p>
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<p><b>Critical</b>
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<ul id="ch3.l9"><li id="ch3.lt22" class="half_rhythm"><div>Sensitivity (detection rate)</div></li><li id="ch3.lt23" class="half_rhythm"><div>Specificity</div></li></ul>
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Sensitivity was regarded as the more important measure for decision making as these are primarily screening diagnostic tests</p>
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<p><b>Important</b>
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<ul id="ch3.l10"><li id="ch3.lt24" class="half_rhythm"><div>area under curve (AUC)</div></li></ul></p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VIII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – study design</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Systematic reviews of diagnostic accuracy studies</p>
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<p>Individual diagnostic accuracy studies including
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<ul id="ch3.l11"><li id="ch3.lt25" class="half_rhythm"><div>Cross-sectional studies</div></li><li id="ch3.lt26" class="half_rhythm"><div>Cohort studies</div></li></ul>
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Prospective cohort studies will be prioritised.</p>
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<p>If insufficient data are available from prospective cohort studies, then retrospective cohort studies will be considered</p>
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<p>Conference abstracts will not be considered</p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IX</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other inclusion exclusion criteria</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Exclude:
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<ul id="ch3.l12"><li id="ch3.lt27" class="half_rhythm"><div>studies that report on quadruplet or higher-order multiple pregnancies</div></li><li id="ch3.lt28" class="half_rhythm"><div>studies that do not report results specifically for twin and/or triplet pregnancies</div></li><li id="ch3.lt29" class="half_rhythm"><div>studies that include <5 pregnant women</div></li><li id="ch3.lt30" class="half_rhythm"><div>structural or chromosomal anomalies</div></li><li id="ch3.lt31" class="half_rhythm"><div>intra-uterine death at study entry</div></li></ul>
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Studies where 95% CIs for point estimates are not presented or where 95% CI for point estimates cannot be calculated</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">X</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Proposed sensitivity/sub-group analysis, or meta-regression</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Special consideration will be given to the following groups for which data will be reviewed and analysed separately if available:
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<ul id="ch3.l13"><li id="ch3.lt32" class="half_rhythm"><div>twin pregnancies</div></li><li id="ch3.lt33" class="half_rhythm"><div>triplet pregnancies</div></li></ul>
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<b>For twin pregnancies:</b>
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<ul id="ch3.l14"><li id="ch3.lt34" class="half_rhythm"><div>Women with uncomplicated TAPS</div></li><li id="ch3.lt35" class="half_rhythm"><div>Women with complicated TAPS</div></li><li id="ch3.lt36" class="half_rhythm"><div>Women who have had feto-fetal transfusion syndrome (FFTS) laser treatment</div></li></ul>
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<b>For triplet pregnancies:</b>
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<ul id="ch3.l15"><li id="ch3.lt37" class="half_rhythm"><div>Women with uncomplicated TAPS</div></li><li id="ch3.lt38" class="half_rhythm"><div>Women with complicated TAPS</div></li><li id="ch3.lt39" class="half_rhythm"><div>Women who have had FFTS laser treatment</div></li></ul></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XI</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Selection process – duplicate screening/selection/analysis</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Formal duplicate screening will not be undertaken for this question (as it has not been prioritised for economic analysis), although there will be senior supervision of the selection process. Hard copies of retrieved papers will be read by two reviewers and any disputes will be resolved in discussion with the Topic Advisor. Data extraction will be supervised by a senior reviewer. Draft excluded studies and evidence tables will be discussed with the Topic Advisor, prior to circulation to the Topic Group for their comments. Resolution of disputes will be by discussion between the senior reviewer, Topic Advisor and Chair</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data management (software)</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>NGA STAR software will be used for generating bibliographies/citations, study sifting, data extraction and recording quality assessment using checklists</p>
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<p>Meta-analyses will be performed using Cochrane Review Manager (RevMan5) and WinBUGS if available data permit</p>
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<p>A modified ‘GRADE’ method will be used to assess the quality of evidence for each index test. A full description of this is provided in the methods in supplementary material C</p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XIII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Information sources – databases and dates</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Sources to be searched: Medline, Medline In-Process, CCTR, CDSR, DARE, HTA, Embase</p>
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<p>Limits (e.g. date, study design):</p>
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<p>Apply standard animal/non-English language exclusion</p>
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<p>Consider cut-off dates if an update</p>
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<p>Date limit searches: 2005</p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XIV</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Identify if an update</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This is not an update of a review</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XV</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Author contacts</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Developer: National Guideline Alliance</p>
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<p><a href="https://www.nice.org.uk/guidance/indevelopment/gid-ng10063" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.nice.org<wbr style="display:inline-block"></wbr>​.uk/guidance/indevelopment/gid-ng10063</a></p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XVI</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Highlight if amendment to previous protocol</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 4.5 of <a href="https://www.nice.org.uk/article/pmg20/chapter/4-Developing-review-questions-and-planning-the-evidence-review#planning-the-evidence-review" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014</a></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XVII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Search strategy – for one database</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see <a href="#ch3.appb">appendix B</a></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XVIII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data collection process – forms/duplicate</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A standardised evidence table format will be used, and published as <a href="#ch3.appg">appendix G</a> (clinical evidence tables) or <a href="#ch3.apph">H</a> (economic evidence tables)</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XIX</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data items – define all variables to be collected</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see evidence tables in <a href="#ch3.appg">appendix G</a> (clinical evidence tables) or <a href="#ch3.apph">H</a> (economic evidence tables)</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XX</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for assessing bias at outcome/study level</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Quality assessment of individual studies will be performed using the following checklists:
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<ul id="ch3.l16"><li id="ch3.lt40" class="half_rhythm"><div>AMSTAR for systematic reviews</div></li><li id="ch3.lt41" class="half_rhythm"><div>QUADAS II for cross sectional or cohort studies reporting diagnostic outcomes</div></li></ul>
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For details please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014</a></p>
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<p>The risk of bias across all available evidence will be evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group <a href="http://www.gradeworkinggroup.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.gradeworkinggroup.org/</a></p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXI</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Criteria for quantitative synthesis (where suitable)</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see the methods chapter of the guideline and section 6.4 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014</a></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for analysis – combining studies and exploring (in)consistency</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A full description of this is provided in the methods in supplementary material C</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXIII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-bias assessment – publication bias, selective reporting bias</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014</a></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXIV</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assessment of confidence in cumulative evidence</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see sections 6.4 and 9.1 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1-Introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014</a></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXV</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rationale/context – Current management</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see the introduction to the evidence review in the full guideline</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXVI</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Describe contributions of authors and guarantor</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>A multidisciplinary committee developed the guideline. The committee was convened by the National Guideline Alliance and chaired by Anthony Pearson in line with section 3 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1%20Introduction%20and%20overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014</a></p>
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<p>Staff from the National Guideline Alliance undertook systematic literature searches, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the guideline in collaboration with the committee. A full description of this is provided in the methods in supplementary material C</p></td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXVII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sources of funding/support</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The National Guideline Alliance is funded by NICE and hosted by the Royal College of Obstetricians and Gynaecologists</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXVIII</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Name of sponsor</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The National Guideline Alliance is funded by NICE and hosted by the Royal College of Obstetricians and Gynaecologists</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXIX</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Roles of sponsor</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE funds the National Guideline Alliance to develop guidelines for those working in the NHS, public health, and social care in England</td></tr><tr><td headers="hd_h_ch3.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XXX</td><td headers="hd_h_ch3.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_ch3.appa.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered with PROSPERO</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AMSTAR: Assessing the Methodological Quality of Systematic Reviews; CDSR: Cochrane Database of Systematic Reviews; CCTR: Cochrane Controlled Trials Register; CI: confidence interval; DARE: Database of Abstracts of Reviews of Effects; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HTA: Health Technology Assessment; NICE: National Institute for Health and Care Excellence; NGA: National Guideline Alliance; QUADAS: Quality Assessment of Diagnostic Accuracy Studies</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch3appbtab1"><div id="ch3.appb.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appb.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appb.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Pregnancy, Multiple/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp multiple pregnancy/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple* or twin* or triplet* or monozygotic or dizygotic or trizygotic) adj3 (birth* or pregnan* or gestation* or f?etus* or f?etal)).tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(chorionicity or monochorionic* or dichorionic* or trichorionic*).tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diseases in Twins/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp twins/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1–6</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Polycythemia/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Anemia/ and Placenta/) use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">polycythemia/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(anemia/ and placenta/) use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">twin anemia polycythemia sequence/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TAPS.tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/8–13</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 and 14</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">twin* an?emi* polycyth?emi* sequence*.tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">twin* an?emia*.tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 or 16 or 17</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Letter/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter.pt. or letter/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">note.pt.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial.pt.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Editorial/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">News/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Historical Article/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anecdotes as Topic/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comment/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Case Report/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/ or case study/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/19–30</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">random*.ti,ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/32–34</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31 not 35</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animals/ not humans/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal/ not human/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">nonhuman/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animals, Laboratory/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experimentation/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experiment/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Experimental Animal/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Models, Animal/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal model/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodentia/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodent/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/36–48</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18 not 49</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 50 to english language</td></tr><tr><td headers="hd_h_ch3.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52</td><td headers="hd_h_ch3.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">remove duplicates from 51</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch3appbtab2"><div id="ch3.appb.tab2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appb.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appb.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID</th><th id="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Search</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Pregnancy, Multiple] explode all trees</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple* or twin* or triplet* or monozygotic or dizygotic or trizygotic) near/3 (birth* or pregnan* or gestation* or foetus* or fetus or foetal or fetal))</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(chorionicity or monochorionic or dichorionic or trichorionic)</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Diseases in Twins] this term only</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Twins] explode all trees</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">{or #1–#5}</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Polycythemia] this term only</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Anemia] this term only</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Placenta] this term only</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8 and #9</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7 or #10</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6 and #11</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(twin* anemia* polycythemia* sequence*)</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(twin* anaemia* polycythaemia* sequence*)</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(twin* anemia* or twin* anaemia*)</td></tr><tr><td headers="hd_h_ch3.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#16</td><td headers="hd_h_ch3.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">{or #12–#15}</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch3appbtab3"><div id="ch3.appb.tab3" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appb.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appb.tab3_lrgtbl__"><table><thead><tr><th id="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Pregnancy, Multiple/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp multiple pregnancy/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple* or twin* or triplet* or monozygotic or dizygotic or trizygotic) adj3 (birth* or pregnan* or gestation* or f?etus* or f?etal)).tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(chorionicity or monochorionic* or dichorionic* or trichorionic*).tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diseases in Twins/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp twins/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1–6</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Polycythemia/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Anemia/ and Placenta/) use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">polycythemia/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(anemia/ and placenta/) use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">twin anemia polycythemia sequence/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TAPS.tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/8–13</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 and 14</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">twin* an?emi* polycyth?emi* sequence*.tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">twin* an?emia*.tw.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 or 16 or 17</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Letter/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter.pt. or letter/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">note.pt.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial.pt.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Editorial/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">News/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Historical Article/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anecdotes as Topic/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comment/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Case Report/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/ or case study/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/19–30</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">random*.ti,ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/32–34</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31 not 35</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animals/ not humans/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal/ not human/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">nonhuman/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animals, Laboratory/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experimentation/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experiment/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Experimental Animal/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Models, Animal/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal model/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodentia/ use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodent/ use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/36–48</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18 not 49</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 50 to english language</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">remove duplicates from 51</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Economics/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Value of life/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Costs and Cost Analysis”/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Economics, Hospital/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Economics, Medical/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Economics, Nursing/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">59</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Economics, Pharmaceutical/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Fees and Charges”/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">61</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Budgets/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or/53–61) use ppez</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">health economics/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">64</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp economic evaluation/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">65</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp health care cost/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">66</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp fee/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">67</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">budget/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">68</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">funding/</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">69</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or/63–68) use emczd</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">budget*.ti,ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">71</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cost*.ti.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">72</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(economic* or pharmaco?economic*).ti.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(price* or pricing*).ti,ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">74</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">75</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(financ* or fee or fees).ti,ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">76</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(value adj2 (money or monetary)).ti,ab.</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/70–75</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">78</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62 or 69 or 77</td></tr><tr><td headers="hd_h_ch3.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">79</td><td headers="hd_h_ch3.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52 and 78</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobch3appcfig1"><div id="ch3.appc.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20Flow%20diagram%20of%20clinical%20article%20selection%20for%20the%20optimal%20screening%20programme%20to%20detect%20TAPS%20in%20twin%20and%20triplet%20pregnancy.&p=BOOKS&id=578083_ch3appcf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578083/bin/ch3appcf1.jpg" alt="Figure 1. Flow diagram of clinical article selection for the optimal screening programme to detect TAPS in twin and triplet pregnancy." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">Flow diagram of clinical article selection for the optimal screening programme to detect TAPS in twin and triplet pregnancy</span></h3></div></article><article data-type="table-wrap" id="figobch3appftab1"><div id="ch3.appf.tab1" class="table"><h3><span class="label">Table 4</span><span class="title">Clinical evidence profile for screening to identify TAPS in twin pregnancy in the second trimester</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appf.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appf.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Index test</th><th id="hd_h_ch3.appf.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Number of studies</th><th id="hd_h_ch3.appf.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Number of participants</th><th id="hd_h_ch3.appf.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Risk of bias</th><th id="hd_h_ch3.appf.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inconsistency</th><th id="hd_h_ch3.appf.tab1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Indirectness</th><th id="hd_h_ch3.appf.tab1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Imprecision</th><th id="hd_h_ch3.appf.tab1_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sensitivity (95%CI)</th><th id="hd_h_ch3.appf.tab1_1_1_1_9" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Specificity (95%CI)</th><th id="hd_h_ch3.appf.tab1_1_1_1_10" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">AUC (95% CI)</th><th id="hd_h_ch3.appf.tab1_1_1_1_11" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Quality of the evidence (GRADE)</th><th id="hd_h_ch3.appf.tab1_1_1_1_12" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Importance</th></tr></thead><tbody><tr><th headers="hd_h_ch3.appf.tab1_1_1_1_1 hd_h_ch3.appf.tab1_1_1_1_2 hd_h_ch3.appf.tab1_1_1_1_3 hd_h_ch3.appf.tab1_1_1_1_4 hd_h_ch3.appf.tab1_1_1_1_5 hd_h_ch3.appf.tab1_1_1_1_6 hd_h_ch3.appf.tab1_1_1_1_7 hd_h_ch3.appf.tab1_1_1_1_8 hd_h_ch3.appf.tab1_1_1_1_9 hd_h_ch3.appf.tab1_1_1_1_10 hd_h_ch3.appf.tab1_1_1_1_11 hd_h_ch3.appf.tab1_1_1_1_12" id="hd_b_ch3.appf.tab1_1_1_1_1" colspan="12" rowspan="1" style="text-align:left;vertical-align:middle;">TAPS defined as post-natal inter-twin Hb discordance</th></tr><tr><td headers="hd_h_ch3.appf.tab1_1_1_1_1 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pre-natal US MCA-PSV discordancy (MCA-PSV >1.5 MoM in 1 fetus; and MCA-PSV <1 MoM in the other)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_2 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch3.appf.tab1_1_1_1_3 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 twin sets</td><td headers="hd_h_ch3.appf.tab1_1_1_1_4 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>1</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_5 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious inconsistency</td><td headers="hd_h_ch3.appf.tab1_1_1_1_6 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>2</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_7 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>3</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_8 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">71% (29 to 96)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_9 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50% (1 to 99)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_10 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch3.appf.tab1_1_1_1_11 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>⊕⊝⊝⊝</p>
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<p>VERY LOW</p></td><td headers="hd_h_ch3.appf.tab1_1_1_1_12 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><td headers="hd_h_ch3.appf.tab1_1_1_1_1 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pre-natal US MCA-PSV discordancy (MCA-PSV >1.5 MoM in 1 fetus; and MCA-PSV <1 MoM in the other)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_2 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch3.appf.tab1_1_1_1_3 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35 twins with TAPS and 45 without TAPS</td><td headers="hd_h_ch3.appf.tab1_1_1_1_4 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>4</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_5 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious inconsistency</td><td headers="hd_h_ch3.appf.tab1_1_1_1_6 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious indirectness</td><td headers="hd_h_ch3.appf.tab1_1_1_1_7 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious imprecision</td><td headers="hd_h_ch3.appf.tab1_1_1_1_8 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46% (30 to 62)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_9 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">100% (92 to 100)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_10 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch3.appf.tab1_1_1_1_11 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>⊕⊕⊕⊝</p>
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<p>MODERATE</p></td><td headers="hd_h_ch3.appf.tab1_1_1_1_12 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><td headers="hd_h_ch3.appf.tab1_1_1_1_1 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pre-natal US MCA-PSV discordancy (>0.5 MoM)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_2 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch3.appf.tab1_1_1_1_3 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35 twins with TAPS and 45 without TAPS</td><td headers="hd_h_ch3.appf.tab1_1_1_1_4 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>4</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_5 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious inconsistency</td><td headers="hd_h_ch3.appf.tab1_1_1_1_6 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious indirectness</td><td headers="hd_h_ch3.appf.tab1_1_1_1_7 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>3</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_8 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">83% (67 to 93)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_9 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">100% (92 to 100)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_10 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch3.appf.tab1_1_1_1_11 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>⊕⊝⊝⊝</p>
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<p>VERY LOW</p></td><td headers="hd_h_ch3.appf.tab1_1_1_1_12 hd_b_ch3.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch3.appf.tab1_1_1_1_1 hd_h_ch3.appf.tab1_1_1_1_2 hd_h_ch3.appf.tab1_1_1_1_3 hd_h_ch3.appf.tab1_1_1_1_4 hd_h_ch3.appf.tab1_1_1_1_5 hd_h_ch3.appf.tab1_1_1_1_6 hd_h_ch3.appf.tab1_1_1_1_7 hd_h_ch3.appf.tab1_1_1_1_8 hd_h_ch3.appf.tab1_1_1_1_9 hd_h_ch3.appf.tab1_1_1_1_10 hd_h_ch3.appf.tab1_1_1_1_11 hd_h_ch3.appf.tab1_1_1_1_12" id="hd_b_ch3.appf.tab1_1_1_5_1" colspan="12" rowspan="1" style="text-align:left;vertical-align:middle;">TAPS defined as post-natal inter-twin Hb discordance</th></tr><tr><td headers="hd_h_ch3.appf.tab1_1_1_1_1 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pre-natal US MCA-PSV discordancy (MCA-PSV >1.5 MoM in 1 fetus; and MCA-PSV <1 MoM in the other)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_2 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch3.appf.tab1_1_1_1_3 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">69 twin sets</td><td headers="hd_h_ch3.appf.tab1_1_1_1_4 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious risk of bias</td><td headers="hd_h_ch3.appf.tab1_1_1_1_5 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious inconsistency</td><td headers="hd_h_ch3.appf.tab1_1_1_1_6 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious indirectness</td><td headers="hd_h_ch3.appf.tab1_1_1_1_7 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>5</sup></td><td headers="hd_h_ch3.appf.tab1_1_1_1_8 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch3.appf.tab1_1_1_1_9 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch3.appf.tab1_1_1_1_10 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.871 (0.757 to 0.985)</td><td headers="hd_h_ch3.appf.tab1_1_1_1_11 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>⊕⊕⊝⊝</p>
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<p>LOW</p></td><td headers="hd_h_ch3.appf.tab1_1_1_1_12 hd_b_ch3.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AUC: area under the curve; CI: confidence interval; Hb: haemoglobin; MCA-PSV: middle cerebral artery peak systolic velocity; MID: minimally important difference; MoM: multiples of the median; N: number of women; QUADAS-2: Quality Assessment Tool for Diagnostic Accuracy Studies 2; TAPS: twin anaemia-polycythaemia sequence; US: ultrasound</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch3.appf.tab1_1"><p class="no_margin">The quality of the evidence was downgraded by 2 levels because: 3 areas with high risk of bias (patient selection (part B); reference standard (part B); flow and timing – based on QUADAS2</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch3.appf.tab1_2"><p class="no_margin">The quality of the evidence was downgraded by 1 level because: Indirectness in Populations - the use of n=20 TAPS cases as complete population, when this is really the subset, and the target population should be all monochorionic diamniotic twin pregnancies to determine diagnostic accuracy of the US MCA-PSV test</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="ch3.appf.tab1_3"><p class="no_margin">The judgement of precision was based on the CI of test sensitivity as this was considered to be the primary measure of interest. If the 95% CI crosses either 75% or 90%, the result was judged to be seriously imprecise (90% was considered to be the cut-off for the test to be highly sensitive and if the sensitivity was less than 75% the test was considered to be of low sensitivity). If the 95% CI crosses both 75% and 90%, the results are judged to be very seriously imprecise</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="ch3.appf.tab1_4"><p class="no_margin">Unclear if the index test results were interpreted without knowledge of the results of the reference standard and if the reference standard results were interpreted without knowledge of the results of the index test</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="ch3.appf.tab1_5"><p class="no_margin">The quality of the evidence was downgraded by 2 levels for imprecision as the 95%CI crossed 2 thresholds above and below the estimate (AUC 80% and AUC 90%)</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobch3appgfig1"><div id="ch3.appg.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Flow%20diagram%20of%20economic%20article%20selection%20for%20the%20optimal%20screening%20programme%20to%20detect%20twin%20anaemia%20polycythaemia%20sequences%20(TAPS)%20in%20twin%20and%20triplet%20pregnancy.&p=BOOKS&id=578083_ch3appgf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578083/bin/ch3appgf1.jpg" alt="Figure 2. Flow diagram of economic article selection for the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Flow diagram of economic article selection for the optimal screening programme to detect twin anaemia polycythaemia sequences (TAPS) in twin and triplet pregnancy</span></h3></div></article><article data-type="table-wrap" id="figobch3appktab1"><div id="ch3.appk.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appk.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appk.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Study</th><th id="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reason for Exclusion</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ashwal, E., Yinon, Y., Fishel-Bartal, M., Tsur, A., Chayen, B., Weisz, B., Lipitz, S., Twin Anemia-Polycythemia Sequence: Perinatal Management and Outcome, Fetal Diagnosis and Therapy, 40, 28–34, 2016</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant diagnostic accuracy data reported. The article describes the management and short-term neonatal outcomes in monochorionic twins with twin anaemia polycythaemia sequence (TAPS)</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bamberg, C, Diemert, A, Glosemeyer, P, Hecher, K., Quantified discordant placental echogenicity in twin anemia-polycythemia sequence (TAPS) and middle cerebral artery peak systolic velocities, Ultrasound in Obstetrics & Gynecology, 27, 27, 2017</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant diagnostic accuracy data reported. The article examines sonographic placental echogenicity in TAPS and its correlation with doppler middle cerebral artery peak systolic velocity (MCA-PSV) findings in twins</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Baschat, A. A, Oepkes, D., Twin anemia-polycythemia sequence in monochorionic twins: implications for diagnosis and treatment, American Journal of Perinatology, 31 Suppl 1, S25–30, 2014</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A narrative article about the pathophysiology, diagnosis, and management of TAPS</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Gucciardo, L., Lewi, L., Vaast, P., Debska, M., De Catte, L., Van Mieghem, T., Done, E., Devlieger, R., Deprest, J., Twin anemia polycythemia sequence from a prenatal perspective, Prenatal Diagnosis, 30, 438–442, 2010</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant diagnostic accuracy data reported. The article describes the prevalence, management and outcome of TAPS in monochorionic twin pregnancies. Also includes a description of 3 cases.</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ishii, K., Murakoshi, T., Hayashi, S., Matsuoka, K., Sago, H., Matsushita, M., Shinno, T., Naruse, H., Torii, Y., Anemia in a recipient twin unrelated to twin anemia-polycythemia sequence subsequent to sequential selective laser photocoagulation of communicating vessels for twin-twin transfusion syndrome, Prenatal Diagnosis, 28, 262–263, 2008</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Case report</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lopriore, E, Slaghekke, F, Oepkes, D, Middeldorp, J. M, Vandenbussche, F. P, Walther, F. J., Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS), Prenatal Diagnosis, 30, 251–5, 2010</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No ultrasound / doppler (index) tests</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lucewicz, A, Fisher, K, Henry, A, Welsh, A. W., Review of the correlation between blood flow velocity and polycythemia in the fetus, neonate and adult: appropriate diagnostic levels need to be determined for twin anemia-polycythemia sequence, Ultrasound in Obstetrics & GynecologyUltrasound Obstet Gynecol, 47, 152–7, 2016</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review - references checked for relevance to protocol</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">McDonald, R, Hodges, R, Knight, M, Teoh, M, Edwards, A, Neil, P, Wallace, E. M, DeKoninck, P., Optimal Interval between Ultrasound Scans for the Detection of Complications in Monochorionic Twins, Fetal Diagnosis & Therapy, 41, 197–201, 2017</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">n=2 TAPS, cannot separate TAPS data from other “complications” aimed to compare monochorionic diamniotic (MCDA) twins at the research institution with and without twin-twin transfusion syndrome (TTTS), selective intrauterine growth restriction (IUGR), TAPS and fetal demise, and then examine whether their antenatal ultrasound surveillance differed</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nakayama, S, Ishii, K, Kawaguchi, H, Yamamoto, R, Murata, M, Hayashi, S, Mitsuda, N., Perinatal complications of monochorionic diamniotic twin gestations with discordant crown-rump length determined at mid-first trimester, Journal of Obstetrics & Gynaecology Research, 40, 418–23, 2014</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The article examines the value of discordance of crown rump length at mid-first trimester to predict adverse outcomes in twin gestations</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pappas, A., Delaney-Black, V., Differential diagnosis and management of polycythemia, Pediatric Clinics of North America, 51, 1063–1086, 2004</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A narrative review on the differential diagnosis, clinical presentation and management of neonatal polycythaemia</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Robyr,R., Lewi,L., Salomon,L.J., Yamamoto,M., Bernard,J.P., Deprest,J., Ville,Y., Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome, American Journal of Obstetrics and Gynecology, 194, 796–803, 2006</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not diagnostic, cases reported for sensitivity use in utero or at birth diagnosis (instead of reference test of US postnatally)</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rossi, A. C, Prefumo, F., Perinatal outcomes of twin anemia-polycythemia sequence: a systematic review, Journal of Obstetrics & Gynaecology Canada: JOGCJ Obstet Gynaecol Can, 36, 701–7, 2014</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review of case series - references checked for relevant studies</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sen, D, Newcastle twin antenatal programme (TAP) an RCT study, National research register, 2003</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not relevant question as the study is examining whether a complex intervention involving attendance at a twin clinic and provision of additional antenatal education, information, and support by a specialist midwife improve psychosocial outcomes after twin birth.</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Slaghekke, F, Kist, W. J, Oepkes, D, Pasman, S. A, Middeldorp, J. M, Klumper, F. J, Walther, F. J, Vandenbussche, F. P, Lopriore, E., Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome, Fetal Diagnosis & Therapy, 27, 181–90, 2010</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A narrative review on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Slaghekke, F, Pasman, S, Veujoz, M, Middeldorp, J. M, Lewi, L, Devlieger, R, Favre, R, Lopriore, E, Oepkes, D., Middle cerebral artery peak systolic velocity to predict fetal hemoglobin levels in twin anemia-polycythemia sequence, Ultrasound in Obstetrics & Gynecology, 46, 432–6, 2015</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference standard is not relevant to the protocol (based on fetal anaemia definition rather than postnatal definition in protocol)</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Slaghekke, F., Lopriore, E., Lewi, L., Middeldorp, J. M., Van Zwet, E. W., Weingertner, A. S., Klumper, F. J., DeKoninck, P., Devlieger, R., Kilby, M. D., Rustico, M. A., Deprest, J., Favre, R., Oepkes, D., Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: An open-label randomized controlled trial, Obstetrical and Gynecological Survey, 69, 569–571, 2014</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract only</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Suzuki, S., Perinatal Outcomes of Monochorionic-Diamniotic Twin Pregnancies Uncomplicated at 28 Weeks of Gestation, Japanese Clinical Medicine, 7, 15–7, 2016</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The article examines the prevalence of TTTS and TAPS in uncomplicated MCDA twin pregnancies</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tollenaar, L. S, Slaghekke, F, Middeldorp, J. M, Klumper, F. J, Haak, M. C, Oepkes, D, Lopriore, E., Twin Anemia Polycythemia Sequence: Current Views on Pathogenesis, Diagnostic Criteria, Perinatal Management, and Outcome, Twin Research & Human Genetics: the Official Journal of the International Society for Twin Studies, 19, 222–33, 2016</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A narrative review on the epidemiology, pathogenesis, diagnostic criteria, management options, and short- and long-term outcome in TAPS</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Turan, S., Turan, O. M., Arterial and Venous Doppler in Evaluation of the “at-Risk” Fetus, Clinical Obstetrics and Gynecology, 60, 668–678, 2017</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The article describes the application of arterial and venous Doppler techniques in assessing and managing various diseases and conditions for high-risk fetuses</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wang, Q., Zhou, Y., Xu, H., Qin, G., Diagnosis of abnormal pregnancy and outcomes by color doppler ultrasound, Biomedical Research (India), 28, 3063–3065, 2017</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">n=3 TAPS cases no specificity/sensitivity/AUC</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Yokouchi, T, Murakoshi, T, Mishima, T, Yano, H, Ohashi, M, Suzuki, T, Shinno, T, Matsushita, M, Nakayama, S, Torii, Y., Incidence of spontaneous twin anemia-polycythemia sequence in monochorionic-diamniotic twin pregnancies: Single-center prospective study, Journal of Obstetrics & Gynaecology Research, 41, 857–60, 2015</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not diagnostic - assesses incidence rate from postnatal diagnosis only N=3 cases to prospectively estimate the incidence of spontaneous TAPS at Seirei Hamamatsu General Hospital, Shizuoka, Japan</td></tr><tr><td headers="hd_h_ch3.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zhao, D, Slaghekke, F, Middeldorp, J. M, Duan, T, Oepkes, D, Lopriore, E., Placental share and hemoglobin level in relation to birth weight in twin anemia-polycythemia sequence, Placenta, 35, 1070–4, 2014</td><td headers="hd_h_ch3.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not diagnostic (no sensitivity/specificity) does not use US (index test) - looks at placental share only</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AUC: area under the curve; IUGR: intrauterine growth rate; MCA-PSV: middle cerebral artery peak systolic velocity; MCDA: monochorionic diamniotic; TAPS: twin anemia polycythemia sequence; TTTS: twin-to-twin transfusion syndrome; US: ultrasound</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch3appltab1"><div id="ch3.appl.tab1" class="table"><h3><span class="label">Table 5</span><span class="title">Research recommendation rationale</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appl.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appl.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Research question</th><th id="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">What is the most accurate prenatal screening marker for TAPS, including MCA-PSV?</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Importance to ‘patients’ or the population</td><td headers="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch3.l17"><li id="ch3.lt42" class="half_rhythm"><div>Improve the antenatal detection of TAPS</div></li><li id="ch3.lt43" class="half_rhythm"><div>Avoid false positive prenatal diagnosis of TAPS and possible unnecessary intervention or iatrogenic premature birth</div></li><li id="ch3.lt44" class="half_rhythm"><div>Enable a more accurate ascertainment of the natural history of TAPS</div></li><li id="ch3.lt45" class="half_rhythm"><div>Reduce unnecessary parental anxiety</div></li></ul></td></tr><tr><td headers="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relevance to NICE guidance</td><td headers="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The ability to more accurately diagnose TAPS prenatally is relevant to this guidance because it would allow earlier detection.</td></tr><tr><td headers="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relevance to the NHS</td><td headers="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch3.l18"><li id="ch3.lt46" class="half_rhythm"><div>Reduce perinatal mortality and morbidity associated with TAPS</div></li><li id="ch3.lt47" class="half_rhythm"><div>Reduce unnecessary intervention or iatrogenic premature birth</div></li><li id="ch3.lt48" class="half_rhythm"><div>Reduce costs from unnecessary intervention arising from false positive diagnosis</div></li><li id="ch3.lt49" class="half_rhythm"><div>Reduce costs from adverse perinatal outcomes associated with TAPS, such as neurodevelopmental impairment</div></li></ul></td></tr><tr><td headers="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">National priorities</td><td headers="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch3.l19"><li id="ch3.lt50" class="half_rhythm"><div>Reduce stillbirth in twin pregnancies</div></li><li id="ch3.lt51" class="half_rhythm"><div>Reduce prematurity in twin pregnancies</div></li><li id="ch3.lt52" class="half_rhythm"><div>Reduce unnecessary intervention in twin pregnancies</div></li></ul></td></tr><tr><td headers="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Current evidence base</td><td headers="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Current evidence was not clear and was graded as very low quality with high rates of imprecision.</td></tr><tr><td headers="hd_h_ch3.appl.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Equality</td><td headers="hd_h_ch3.appl.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This applies to all women with monochorionic twin pregnancies</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MCA-PSV: middle cerebral artery peak systolic velocity; TAPS: twin anaemia polycythaemia sequence</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch3appltab2"><div id="ch3.appl.tab2" class="table"><h3><span class="label">Table 6</span><span class="title">Research recommendation modified PIRO table</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578083/table/ch3.appl.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch3.appl.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Criterion</th><th id="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Explanation</th></tr></thead><tbody><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Monochorionic twin pregnancies:
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<ul id="ch3.l20"><li id="ch3.lt53" class="half_rhythm"><div>Monochorionic diamniotic pregnancies</div></li><li id="ch3.lt54" class="half_rhythm"><div>Monochorionic monoamniotic pregnancies</div></li></ul></td></tr><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Index test</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch3.l21"><li id="ch3.lt55" class="half_rhythm"><div>MCA-PSV</div></li><li id="ch3.lt56" class="half_rhythm"><div>The detection of fetal effusions in the anaemic co-twin</div></li><li id="ch3.lt57" class="half_rhythm"><div>Prenatal ultrasound surveillance for placental dichotomy and /or ‘starry sky’ liver</div></li></ul>
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The above tests could be used in isolation or in combination.</td></tr><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference standard</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><p>Recognised postnatal diagnostic criteria reference standard for TAPS</p>
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<p>Postnatal diagnostic criteria of TAPS:
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<ul id="ch3.l22"><li id="ch3.lt58" class="half_rhythm"><div>Inter-twin Hb difference ≥8.0 g/dL</div></li><li id="ch3.lt59" class="half_rhythm"><div>and at least one of the following criteria:
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<ul id="ch3.l23" class="circle"><li id="ch3.lt60" class="half_rhythm"><div>reticulocyte count ratio ≥1.7</div></li><li id="ch3.lt61" class="half_rhythm"><div>small anastomoses (<1 mm) at the placental surface</div></li></ul></div></li></ul></p></td></tr><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch3.l24"><li id="ch3.lt62" class="half_rhythm"><div>True positive</div></li><li id="ch3.lt63" class="half_rhythm"><div>False positive</div></li><li id="ch3.lt64" class="half_rhythm"><div>True negative</div></li><li id="ch3.lt65" class="half_rhythm"><div>False negative</div></li></ul></td></tr><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Multicentre large observational cohort study</td></tr><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Timeframe</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3–5 years</td></tr><tr><td headers="hd_h_ch3.appl.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Additional information</td><td headers="hd_h_ch3.appl.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The diagnosis of TAPS is for the most part is a ‘prenatal diagnosis’. The diagnostic criteria are based upon each ultrasound test (MCA-PSV) that one is evaluating.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Hb: haemoglobin; MCA-PSV: middle cerebral artery peak systolic velocity; TAPS: twin anaemia polycythaemia sequence</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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