European Federation of Societies for Ultrasound in Medicine and Biology How good are we at...
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European Federation of Societies for Ultrasound in Medicine and Biology How good are we at first-trimester prevention and prediction of early fetal growth restriction? A series of recent publications have shown that early preeclampsia can be successfully predicted in the first trimester using a com- bination of maternal, biophysical and bio- chemical factors [1 – 4], and administration of low-dose aspirin to women identified as high-risk can reduce the development of preterm preeclampsia by about 60 % [5]. Given that abnormal placentation and pla- cental insufficiency are commons pathway to many cases of preeclampsia and fetal growth restriction (FGR), we intuitively use the same strategies to predict and prevent FGR. However, are we as successful in FGR as we are in preeclampsia? A variety of definitions In contrast to preeclampsia, which is a clearly defined condition, multiple terms describe suboptimal fetal growth, and two of them, i. e. small for gestational age (SGA) and FGR, are often used interchange- ably. This happens despite the two being two different conditions. SGA merely signif- ies a fetus (or a neonate) that is smaller than a given centile (usually the 10 th ), whereas FGR involves the failure of the fetus to reach its developmental potential, and it normally refers to a small fetus with some evidence of hypoxia. Therefore, one might say that FGR is a subset of SGA, and this is the case most of the times, but not always. A growth-restricted fetus can be non-SGA (i. e. > 10 th centile for estimated weight or abdominal circumference) and still be FGR, if its growth potential was meant to be higher. This reality has been acknowledged by the recent consensus definition for FGR, which introduces the option of a fetus crossing centiles, even if its eventual centile is > 10 th [6]. Despite this development, different definitions have traditionally been used in the existing studies, even within the terms SGA and FGR (different cutoffs, Doppler parameters, pre- or postnatal weight etc), adding to the heterogeneity of the literature. Targeting small fetuses Prediction of FGR (or SGA) has been pur- sued along that of preeclampsia, and it was early acknowledged that the yield of screening models is higher when FGR coexists with preeclampsia rather than when it is an isolated condition. Four years ago, the Fetal Medicine Foundation (FMF) developed a dedicated screening algorithm targeting SGA, and they reported that, by combining maternal, biochemical and bio- physical factors, about 50 % of SGA can be predicted for a 10 % false positive rate [7]. However, is this the case? Prediction of small fetuses through preeclampsia- oriented screening What happens in practice is that we screen for preeclampsia, we treat screen-positive cases aiming to prevent preeclampsia, and along the way we predict some of the FGR cases and prevent a subgroup of them. This is beautifully illustrated in a recent publication by the FMF, where data from the SPREE study (which is a screening study) were combined with data of the ASPRE trial (which is an interventional study) to show, among else, what happens with SGA when we screen and treat for preeclampsia. What this study found is that, by screening for preeclampsia, and using a cut-off of 1:100 for preeclampsia, we can predict 31 % of neonates with birth weight < 10 th centile requiring delivery before 37 weeks, and 35 % of such babies requiring delivery before 32 weeks [1]. Of course, the prediction rates significantly increased for small neonates with coexist- ing preeclampsia, but this is a different group whatsoever. Focusing on even smal- ler neonates (birthweight < 3 rd centile) in the absence of preeclampsia, this screening strategy can predict about 40 % of those requiring delivery before 37 or 32 weeks [1]. So, in practice, screening for pree- clampsia with a 10 % screen-positive rate (which is where 1:100 corresponds to) can predict about 35 – 40 % of the small and very small fetuses requiring early delivery. Prevention of small fetuses through preeclampsia- oriented screening Administration of prophylactic aspirin to these screen-positive (for preeclampsia) cases, will significantly reduce the risk for small neonates with preeclampsia, but will only reduce the risk for the subgroup of such neonates without preeclampsia that require delivery before 32 weeks, by about 60 %. Of course this is quite an important group in terms of morbidity, but it only com- prises about 0.25 % of the population [1]. A synopsis… It appears thus that combined first-trime- ster screening for preeclampsia can predict about 40 % of the subgroup of small fetuses who will need a preterm delivery. Prophy- lactic aspirin in screen-positive cases will re- duce the risk for the small but clinically im- portant group of very preterm (< 32 weeks) small fetuses by about 60 %. EFSUMB Newsletter 572 Ultraschall in Med 2018; 39: 572–579 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Transcript of European Federation of Societies for Ultrasound in Medicine and Biology How good are we at...
European Federation of Societies for Ultrasoundin Medicine and Biology
How good are we at first-trimester prevention and prediction of earlyfetal growth restriction?A series of recent publications have shownthat early preeclampsia can be successfullypredicted in the first trimester using a com-bination of maternal, biophysical and bio-chemical factors [1 – 4], and administrationof low-dose aspirin to women identified ashigh-risk can reduce the development ofpreterm preeclampsia by about 60 % [5].Given that abnormal placentation and pla-cental insufficiency are commons pathwayto many cases of preeclampsia and fetalgrowth restriction (FGR), we intuitively usethe same strategies to predict and preventFGR. However, are we as successful in FGRas we are in preeclampsia?
A variety of definitionsIn contrast to preeclampsia, which is aclearly defined condition, multiple termsdescribe suboptimal fetal growth, and twoof them, i. e. small for gestational age(SGA) and FGR, are often used interchange-ably. This happens despite the two beingtwo different conditions. SGA merely signif-ies a fetus (or a neonate) that is smallerthan a given centile (usually the 10th),whereas FGR involves the failure of thefetus to reach its developmental potential,and it normally refers to a small fetus withsome evidence of hypoxia. Therefore, onemight say that FGR is a subset of SGA, andthis is the case most of the times, but notalways. A growth-restricted fetus can benon-SGA (i. e. > 10th centile for estimatedweight or abdominal circumference) andstill be FGR, if its growth potential wasmeant to be higher. This reality has beenacknowledged by the recent consensusdefinition for FGR, which introduces theoption of a fetus crossing centiles, even ifits eventual centile is > 10th [6]. Despitethis development, different definitionshave traditionally been used in the existing
studies, even within the terms SGA and FGR(different cutoffs, Doppler parameters,pre- or postnatal weight etc), adding tothe heterogeneity of the literature.
Targeting small fetusesPrediction of FGR (or SGA) has been pur-sued along that of preeclampsia, and itwas early acknowledged that the yield ofscreening models is higher when FGRcoexists with preeclampsia rather thanwhen it is an isolated condition. Four yearsago, the Fetal Medicine Foundation (FMF)developed a dedicated screening algorithmtargeting SGA, and they reported that, bycombining maternal, biochemical and bio-physical factors, about 50% of SGA can bepredicted for a 10% false positive rate [7].However, is this the case?
Prediction of small fetusesthrough preeclampsia-oriented screeningWhat happens in practice is that we screenfor preeclampsia, we treat screen-positivecases aiming to prevent preeclampsia, andalong the way we predict some of the FGRcases and prevent a subgroup of them.This is beautifully illustrated in a recentpublication by the FMF, where data fromthe SPREE study (which is a screeningstudy) were combined with data of theASPRE trial (which is an interventionalstudy) to show, among else, what happenswith SGA when we screen and treat forpreeclampsia. What this study found isthat, by screening for preeclampsia, andusing a cut-off of 1:100 for preeclampsia,we can predict 31% of neonates with birthweight < 10th centile requiring delivery
before 37 weeks, and 35 % of such babiesrequiring delivery before 32 weeks [1]. Ofcourse, the prediction rates significantlyincreased for small neonates with coexist-ing preeclampsia, but this is a differentgroup whatsoever. Focusing on even smal-ler neonates (birthweight < 3rd centile) inthe absence of preeclampsia, this screeningstrategy can predict about 40 % of thoserequiring delivery before 37 or 32 weeks[1]. So, in practice, screening for pree-clampsia with a 10 % screen-positive rate(which is where 1:100 corresponds to) canpredict about 35 – 40 % of the small andvery small fetuses requiring early delivery.
Prevention of small fetusesthrough preeclampsia-oriented screeningAdministration of prophylactic aspirin tothese screen-positive (for preeclampsia)cases, will significantly reduce the risk forsmall neonates with preeclampsia, but willonly reduce the risk for the subgroup ofsuch neonates without preeclampsia thatrequire delivery before 32 weeks, by about60 %. Of course this is quite an importantgroup in terms of morbidity, but it only com-prises about 0.25% of the population [1].
A synopsis…It appears thus that combined first-trime-ster screening for preeclampsia can predictabout 40% of the subgroup of small fetuseswho will need a preterm delivery. Prophy-lactic aspirin in screen-positive cases will re-duce the risk for the small but clinically im-portant group of very preterm (< 32 weeks)small fetuses by about 60%.
EFSUMB Newsletter
572 Ultraschall in Med 2018; 39: 572–579
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…and some moreunanswered questionsThere are yet more unanswered questions,including the possible role of maternalhemodynamics as part of a combinedscreening, or the ability of the fetal fractionof cell-free DNA in the maternal blood toact as an independent predictor. And, ofcourse, there is the issue with twins. Thereis an ongoing debate whether twin-specificgrowth charts should be used, or charts ofsingleton are applicable as well, so prob-lems like this need to be solved before aim-ing at screening.
Dr Alexandros SotiriadisDr Konstantinos DinasSecond Department of Obstetrics andGynecologyFaculty of Medicine, Aristotle University ofThessaloniki, Greece
References
[1] Tan MY, Poon LC, Rolnik DL et al. Predictionand prevention of small-for-gestational-ageneonates: evidence from SPREE and ASPRE.Ultrasound Obstet Gynecol 2018
[2] Tan MY, Wright D, Syngelaki A et al. Compari-son of diagnostic accuracy of early screeningfor pre-eclampsia by NICE guidelines and amethod combining maternal factors and bio-markers: results of SPREE. Ultrasound ObstetGynecol 2018
[3] O’Gorman N, Wright D, Poon LC et al. Multi-center screening for preeclampsia by mater-nal factors and biomarkers at 11–13 weeks’gestation: comparison to NICE guidelines andACOG recommendations. Ultrasound ObstetGynecol 2017
[4] O’Gorman N, Wright D, Poon LC et al. Accu-racy of competing risks model in screening forpre-eclampsia by maternal factors and bio-markers at 11–13 weeks’ gestation. Ultra-sound Obstet Gynecol 2017
[5] Rolnik DL, Wright D, Poon LC et al. Aspirinversus Placebo in Pregnancies at High Risk forPreterm Preeclampsia. N Engl J Med 2017
[6] Gordijn SJ, Beune IM, Thilaganathan B et al.Consensus definition of fetal growth restric-tion: a Delphi procedure. Ultrasound ObstetGynecol 2016; 48: 333–339
[7] Poon LC, Syngelaki A, Akolekar R et al. Com-bined screening for preeclampsia and smallfor gestational age at 11–13 weeks. FetalDiagn Ther 2013; 33: 16–27
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