Preeclampsia: Universal Screening or Universal Prevention for Low andMiddle-Income Settings? Daniel Lorber Rolnik1 Mario Henrique Burlacchini de Carvalho2 Guilherme Antonio Rago Lobo3 Stefan Verlohren4 Liona Poon5 Ahmet Baschat6 Jon Hyett7 Basky Thilaganathan8 Emmanuel Bujold9 Fabricio da Silva Costa10 1Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia 2Department of Obstetrics and Gynecology, Universidade de São Paulo, São Paulo, SP, Brazil 3Department of Obstetrics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil 4Department of Obstetrics, Charité Universitätsmedizin, Berlin, Germany 5Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong 6The Johns Hopkins Center for Fetal Therapy, Department of Gynecology and Obstetrics, The Johns Hopkins Hospital, Baltimore, United States 7RPA Women’s and Babies, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia 8Fetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, London, United Kingdom 9Department of Obstetrics and Gynaecology, Laval University, Quebec, Canada 10Maternal Fetal Medicine Unit, Gold Coast University Hospital and School of Medicine, Griffith University, Gold Coast, Australia Rev Bras Ginecol Obstet 2021;43(4):334–338. Address for correspondence Daniel Lorber Rolnik, 27-31 Wright St, Clayton VIC 3168, Australia (e-mail: daniel.rolnik2@gmail.com). Dear Editor, We read with interest the Clinical Consensus Recommen- dation about screening and prevention of preeclampsia published by De Oliveira et al.1 The authors recommend that identification of high-risk women should be based on maternal risk factors alone, and that universal treatment (of all pregnant women) with aspirin at a dose of 100mg should be considered in low- and middle-income countries. In this letter, we express our concerns and disagreement with these strategies. The association of certain maternal risk factors with an increased risk of preeclampsia development is well known, and several risk scoring systems have been recommended by Obstetric societies around the world, such as the National Institute for Health and Care Excellence (NICE) criteria in the United Kingdom, and the American College of Obstetrician and Gynecologists (ACOG) in the United States. Such scoring systems are based on experts’ opinions and low levels of evidence, attribute similar weights to very different risk factors, and perform poorly in the clinical practice.2 Recent large studies2 have shown that such methods fail to identify as high-risk 60% to 70% of women who will later develop preeclampsia. Furthermore, physician compliance with these recommendations is low, with only 20% to 30% of high-risk women receiving aspirin prophylaxis.2,3 On the other hand, combined screening with individual risk calcu- lation by incorporating risk factors, mean arterial blood pressure, uterine artery Doppler studies, and placental growth factor (PlGF) far outperforms risk scoring, identifying as high-risk about three quarters of womenwhowill develop preterm preeclampsia, and 90% of those destined to develop early-onset disease.4,5 In addition, combined screening is more cost-effective,6 and is associated with nearly total physician compliance.3 Although resistance to new DOI https://doi.org/ 10.1055/s-0041-1729953. ISSN 0100-7203. © 2021. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda., Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil Letter to the Editor THIEME 334 https://orcid.org/0000-0002-2263-3592 https://orcid.org/0000-0003-0599-0739 https://orcid.org/0000-0003-1587-7385 https://orcid.org/0000-0003-3507-8636 https://orcid.org/0000-0002-3944-4130 https://orcid.org/0000-0003-1927-2084 https://orcid.org/0000-0001-8019-1289 https://orcid.org/0000-0002-5531-4301 https://orcid.org/0000-0002-6936-4369 https://orcid.org/0000-0002-0765-7780 mailto:daniel.rolnik2@gmail.com https://doi.org/10.1055/s-0041-1729953 https://doi.org/10.1055/s-0041-1729953 technologies is common in Medicine, and translation of research into clinical practice usually takes a long time,7 most components of combined screening, such as the mea- surement of arterial blood pressure and ultrasound are readily available and widely in use in most settings (even in low/middle-income countries). Simplified versions of the algorithm (for example, without biochemical markers) out- performed clinical history even in middle-income countries such as Brazil,8,9 and could be rapidly implemented with minimal or no increase in cost, and lead to a significant increase in the detection of high-risk women who would benefit from aspirin prophylaxis and likely be missed by risk scoring screening. As appealing as the suggestion to give aspirin to all pregnant women given its relative safety and low cost may be, a strategy of universal aspirin use has not been properly assessed in adequately-powered prospective studies.10 Pregnant women are naturally resistant to medi- cation use in the absence of convincing medical indication, and such an approach would likely be associated with low adherence to treatment.10 The strong effect of aspirin in the prevention of preeclampsia in high-risk populations11 may not be observed when the treatment is recommended to the entire obstetric population, and side effects will inevitably become more frequent if millions of women are treated. Indeed, data from a previous study on universal aspirin prophylaxis demonstrated no clear treat- ment benefit,12,13 increased risk of postpartum hemor- rhage,14 and other hemorrhagic events,12 as well as low adherence to treatment.12 We argue that early combined prediction with the full or simplified versions of the algo- rithm for individual risk calculation is feasible in low- and middle-income countries, and should be the preferred method of screening whenever possible, in line with recent recommendations from the International Federation of Gynecology and Obstetrics (FIGO),15 the International Soci- ety for the Study of Hypertension in Pregnancy (ISSHP),16 and the International Society of Ultrasound in Obstetrics and Gynecology.17 Conflict of Interests The authors have no conflict of interests to declare. References 1 DeOliveira LG, Diniz ALD, Prado CAC, Da Cunha Filho EV, De Souza FLP, Korkes HA, et al. Pre-eclampsia: universal screening or universal prevention for low and middle-income settings? Rev Bras Ginecol Obstet. 2021;43(01):61–65. Doi: 10.1055/s-0040- 1713803 2 Tan MY,Wright D, Syngelaki A, Akolekar R, Cicero S, Janga D, et al. Comparison of diagnostic accuracy of early screening for pre- eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: results of SPREE. Ultrasound Obstet Gynecol. 2018;51(06):743–750. Doi: 10.1002/uog.19039 3 Guy GP, Leslie K, Diaz Gomez D, Forenc K, Buck E, Khalil A, Thilaganathan B. Implementation of routine first trimester com- bined screening for pre-eclampsia: a clinical effectiveness study. BJOG. 2021;128(02):149–156. Doi: 10.1111/1471-0528.16361 4 Rolnik DL, Wright D, Poon LCY, Syngelaki A, O’Gorman N, Mata- llana CP, et al. ASPRE trial: performance of screening for preterm pre-eclampsia. Ultrasound Obstet Gynecol. 2017;50(04): 492–495. Doi: 10.1002/uog.18816 5 O’Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, Wright A, et al. Accuracy of competing-risks model in screening for pre- eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation. Ultrasound Obstet Gynecol. 2017;49(06):751–755. Doi: 10.1002/uog.17399 6 Park F, Deeming S, Bennett N, Hyett J. Cost effectiveness analysis of a model of first trimester prediction and prevention for preterm preeclampsia against usual care. Ultrasound Obstet Gynecol. 2020;•••;. Doi: 10.1002/uog.22193[ahead of print] 7 Papageorghiou AT. From evidence to implementation. BJOG. 2020;127(10):1173–1174. Doi: 10.1111/1471-0528.16408 8 Rocha RS, Alves JAG, E Holanda Moura SBM, Araujo EJúnior, Peixoto AB, Santana EFM, et al. Simple approach based on mater- nal characteristics and mean arterial pressure for the prediction of preeclampsia in the first trimester of pregnancy. J Perinat Med. 2017;45(07):843–849. Doi: 10.1515/jpm-2016-0418 9 Rocha RS, Gurgel Alves JA, E Holanda Moura SBM, Araujo EJúnior, Martins WP, Vasconcelos CTM, et al. Comparison of three algo- rithms for prediction preeclampsia in the first trimester of pregnancy. Pregnancy Hypertens. 2017;10:113–117. Doi: 10.1016/j.preghy.2017.07.146 10 Cuckle H. Strategies for prescribing aspirin to prevent preeclamp- sia: a cost-effectiveness analysis. Obstet Gynecol. 2020;135(01): 217. Doi: 10.1097/AOG.0000000000003631 11 Rolnik DL,Wright D, Poon LC, O’Gorman N, Syngelaki A, Matallana CP, et al. Aspirin versus placebo in pregnancies at high risk for pretermpreeclampsia. N Engl JMed. 2017;377(07):613–622. Doi: 10.1056/NEJMoa1704559 12 Subtil D, Goeusse P, Puech F, Lequien P, Biausque S, Breart G, et al; Essai Régional Aspirine Mère-Enfant (ERASME) Collaborative Group. Aspirin (100mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 1). BJOG. 2003;110(05):475–484. Doi: 10.1046/ j.1471-0528.2003.02096.x 13 Hoffman MK, Goudar SS, Kodkany BS, Metgud M, Somannavar M, Okitawutshu J, et al; ASPIRIN Study Group. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, pla- cebo-controlled trial. Lancet. 2020;395(10220):285–293. Doi: 10.1016/S0140-6736(19)32973-3 14 Mone F, Mulcahy C, McParland P, Breathnach F, Downey P, McCormack D, et al. Trial of feasibility and acceptability of routine low-dose aspirin versus Early Screening Test indicated aspirin for pre-eclampsia prevention (TEST study): a multicentre random- ised controlled trial. BMJ Open. 2018;8(07):e022056. Doi: 10.1136/bmjopen-2018-022056 15 Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145 (Suppl 1):1–33. Doi: 10.1002/ijgo.12802 16 Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al; International Society for the Study of Hypertension in Pregnancy (ISSHP) Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(01):24–43. Doi: 10.1161/HYPERTENSIONAHA.117.10803 17 Sotiriadis A, Hernandez-Andrade E, da Silva Costa F, Ghi T, Glanc P, Khalil A, et al; ISUOG CSC Pre-eclampsia Task Force. ISUOG Practice Guidelines: role of ultrasound in screening for and follow-up of pre-eclampsia. Ultrasound Obstet Gynecol. 2019; 53(01):7–22. Doi: 10.1002/uog.20105 Rev Bras Ginecol Obstet Vol. 43 No. 4/2021 © 2021. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved. Letter to the Editor 335 Author’s Reply: Leandro De Oliveira1 Angélica Lemos Debs Diniz2 Caio Antônio de Campos Prado3 Edson Vieira Da Cunha Filho4 Francisco Lázaro Pereira De Souza5 Henri Augusto Korkes6 José Geraldo Ramos7 Maria Laura Costa8 Mário Dias Corrêa Junior9 Nelson Sass10 Ricardo De Carvalho Cavalli3 Sérgio Hofmeister De Almeida Martins-Costa7 José Carlos Peraçoli1 1Department of Gynecology and Obstetrics, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Botucatu, São Paulo, SP, Brazil 2Department of Obstetrics and Gynecology, Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, MG, Brazil 3Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, SP, Brazil 4Gynecology and Obstetrics Training Center, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, RS, Brazil 5Department of Tocoginecology, Centro Universitário Lusíada, Santos, São Paulo, SP, Brazil 6Department of Obstetrics and Gynecology, Faculdade de Medicina de Sorocaba, Pontifícia Universidade Católica de São Paulo, Sorocaba, São Paulo, SP, Brazil 7Department of Gynecology and Obstetrics, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, RS, Brazil 8Department of Gynecology and Obstetrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, SP, Brazil 9Department of Gynecology and Obstetrics, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, MG, Brazil 10Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil Rev Bras Ginecol Obstet 2021;43(4):336–338. Address for correspondence Leandro Gustavo De Oliveira, Distrito de Rubião Junior, s/n°, 18618-970, Botucatu, SP, Brazil (e-mail: leandro.gustavo@unesp.br). Dear Editor, We are grateful to the colleague who raised the questions related to our recent publication regarding the use of aspirin and calcium for the prevention of preeclampsia in low- and middle-income countries.1 Discussions like this are funda- mental to raise the importance of the topic, which represents the main cause of maternal death in Brazil. However, we are not sure that the colleague has fully understood our publica- tion, since the costs related to prevention are important, but only part of our text. We initially expressed great uncertainty regarding the impact of using any algorithms currently demonstrated for the screening of preeclampsia. This is remarkable, since a complex screening model, involving biophysical, biochemi- calmarkers, andmaternal data recently identified only 0.26% of women who would be diagnosed with preterm pre- eclampsia in a huge population.2 The colleague then sug- gested that protocol adaptations using less complex algorithms according to the economic possibilities of each location could be implemented. However, Prefumo and Farina3 (2017) raised important considerations about the addition of markers to increase the sensitivity of clinical data in the prediction of preeclampsia. Interestingly, the addition of just one biophysical or biochemical marker does not increase the detection rates, since confidence intervals clear- ly overlap in most large studies. In the study by O’Gorman et al.4 (2017), for example, the simple addition of the mean arterial pressure was as efficient as the addition of the uterine artery Doppler or placental growth factor (PlGF) in the prediction of preeclampsia before 32 weeks, with a false- positive rate of 10%. Recently, Sovio and Smith5 (2019) developed a simple risk score using the same maternal characteristics used for the original algorithm in the Com- binedMultimarker Screening and Randomized Patient Treat- ment with Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) study.2,5 The area under the receiver operating characteristic (ROC) curve of this simplified score was of 0.846 (95% confidence interval [95%CI]: 0.787–0.906), similar to that of the complete algorithm, whichwas of 0.854 (95%CI: 0.795–0.914). In addition to the fact that there actually is no efficient algorithm for the prediction of pre- eclampsia, we speculate that the discussion regarding the Rev Bras Ginecol Obstet Vol. 43 No. 4/2021 © 2021. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved. Letter to the Editor336 https://orcid.org/0000-0002-8422-9907 https://orcid.org/0000-0001-8476-6326 https://orcid.org/0000-0003-1767-4725 https://orcid.org/0000-0001-8100-1926 https://orcid.org/0000-0003-0761-7700 https://orcid.org/0000-0001-5345-3861 https://orcid.org/0000-0002-3789-885X https://orcid.org/0000-0001-8280-3234 https://orcid.org/0000-0003-4198-0546 https://orcid.org/0000-0001-7187-1004 https://orcid.org/0000-0001-5010-4914 https://orcid.org/000-0003-0565-974t https://orcid.org/0000-0002-3273-3001 mailto:leandro.gustavo@unesp.br use of these complex algorithmsmay contribute to divert the attention of many clinicians regarding important epidemio- logical information, leading to low rates of prescription of aspirin and calcium. The colleague who brings the questions refers elusively about the results regarding the use of aspirin. Therefore, we request caution when studying this issue. When referring to the article published by Hoffman et al.6 (2020), the colleague should have noticed the enormous impact of this studywhen the authors demonstrated that nulliparous women from low and middle-income countries who started using aspirin in the period between 6 and 13 weeks and 6 days of pregnancy had a lower incidence of preterm birth and a reduction in perinatal mortality, without adverse effects.6 Simple and safe, as mentioned by Quinlivan7 (2020). Regarding safety, the colleague also raised a question about the increased risk of bleeding among women using aspirin in two studies. The study published by Subtil et al.8 (2003) demonstrated that there was no difference regarding adverse outcomes between the aspirin (19.5%) and placebo (15.8%) groups (relative risk [RR]: 1.23; 95%CI: 1.06–1.43) as the CI reached the null line. Specifically regarding bleeding- related events, such as epistaxis, metrorrhagia and minimal bleeding from the digestive tract, these were considered minimal by the authors. Additionally, when analyzing the results, we realize that the CI also touched the null line (11.6% versus 9.3%; RR: 1.25; 95%CI: 1.03–1.54). ThestudydevelopedbyMoneetal. (2018),9also citedbythe colleague as reporting increased numbers of hemorrhagic events, was a feasibility study with no power for this conclu- sion. Even so, the colleague should be more cautious, since Mone et al. 9 reported in their safety results that the bleeding cases were spottings unrelated tomiscarriages, and that there was only a small number of women who had postpartum bleeding (n¼20 without aspirin; n¼26 with aspirin). In conclusion, the authors also pointed out that there was no difference regarding hemoglobin levels<8g/dL or need for blood transfusion. Finally, this study demonstrated that even low-risk nulliparous women would be happy to take aspirin, which currently contradicts concerns about the lowadherence to thismedication. Inour interpretation, this adherence relates to the impact of the disease on a specific population, which is huge for low- and middle-income countries. Additionally, if clinicians stopped being confused by those who want to introduce complex algorithms for the prediction of pre- eclampsia, they would prescribe more aspirin and calcium. We understand that screenings with innovative technol- ogies such as ultrasound or biological markers are very attractive, but are not feasible in low- and middle-income countries, especially in countries with large territorial areas and huge disparities in terms of resources. The women who actually die in these countries are those with lowest socio- economic status, and our main efforts must converge to really reach this population to provide basic conditions instead of expensive and useless ones. Mallampati et al.10 (2019) developed an elegant study comparing the non-use of aspirin, the use of aspirin by women with positive screening based on biomarkers and Doppler, the use of aspirin based on the presence of clinical markers (USA-Task Force), and the universal use of aspirin in pregnancy. The authors demonstrated that the universal use of aspirin significantly reduced the incidence of preterm preeclampsia when compared with the non-use (805 less cases in 100,000 women), when compared with the use of Doppler and biomarkers (314 less cases in 100,000 women), or when compared with clinical screening (358 less cases in 100,000 women). In addition to improving adherence to prevention, the universal use of aspirin has shown a better cost-benefit ratio, without increasing the incidence of ad- verse events. In addition, when the colleague mentions that combined screening does not increase costs, he does not seem to believe that this screening model during the first trimester mayeven lead to additional concerns, as increased number of antenatal visits, additional tests, and, unfortunately, iatro- genic preterm deliveries due to “altered screening.”All of this using methodologies with little evidence of clinical applica- bility, as published in the systematic review recently pub- lished by De Kat et al. (2019).11 Finally, when the colleague mentions that combined screening is part of the International Federation of Gynecol- ogy and Obstetrics (FIGO) recommendations, he or she refers to the publication by Poon et al.12 (2019). However, the following recommendations have been displayed on the FIGO web site (https://www.figo.org/figo-releases-new- guidelines-combat-pre-eclampsia): “All pregnant women should be screened for preterm PE [preeclampsia] during early pregnancy in the first-trimester with maternal risk factors and blood pressure. Biomarkers offer a potential for early diagnosis and effective treatment, however, the global community recognizes that further evidence for its applicability in all populations and ethnic groups is required at this stage. While several studies have evaluated the role of biomark- ers or a combination of physical and chemical measure- ments, further studies are needed to define their additional role in improving early prediction of preterm PE. FIGO encourages all countries and its member associa- tions to adopt and promote strategies to ensure quality research and eventual consensus.” Regarding the recommendation by the International So- ciety for the Study of Hypertension in Pregnancy ISSHP also mentioned, this society clearly manifested that first trimes- ter screening could be integrated to health systems with capacity for this, and stressed that cost-effectiveness should be evaluated.13 Additionally, the ISSHP did not mention anything specifically to low and middle-income settings, and we know that this society is truly aware about all difficulties that such countries have. Essentially, what often seem to be innovative technologies in the clinical practice may not be cost-effective, may not reach vulnerable populations, and may compromise feasible protocols. At this point, we need to be pragmatic and realistic to support public policies based on the best scientific evi- dence, to reduce maternal mortality related to preeclampsia in low- and middle-income countries. Rev Bras Ginecol Obstet Vol. 43 No. 4/2021 © 2021. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved. Letter to the Editor 337 https://www.figo.org/figo-releases-new-guidelines-combat-pre-eclampsia https://www.figo.org/figo-releases-new-guidelines-combat-pre-eclampsia Conflict of Interests The authors have no conflict of interests to declare. References 1 DeOliveira LG, Diniz ALD, Prado CAC, Da Cunha Filho EV, De Souza FLP, Korkes HA, et al. Pre-eclampsia: universal screening or universal prevention for low and middle-income settings? Rev Bras Ginecol Obstet. 2021;43(01):61–65. Doi: 10.1055/s-0040- 1713803 2 Rolnik DL, Wright D, Poon LCY, Syngelaki A, O’Gorman N, Mata- llana CP, et al. ASPRE trial: performance of screening for preterm pre-eclampsia. Ultrasound Obstet Gynecol. 2017;50(04): 492–495. Doi: 10.1002/uog.18816 3 Prefumo F, Farina A. First-trimester screening for pre-eclampsia: time for reflection. Ultrasound Obstet Gynecol. 2017;50(05): 662–663. Doi: 10.1002/uog.18893 4 O’Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, Alvarado Mde, et al. Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation: comparison with NICE guidelines and ACOG recommenda- tions. Ultrasound Obstet Gynecol. 2017;49(06):756–760. Doi: 10.1002/uog.17455 5 SovioU, SmithG.Evaluationofa simple risk score topredict preterm pre-eclampsia usingmaternal characteristics: a prospective cohort study. BJOG. 2019;126(08):963–970. Doi: 10.1111/1471- 0528.15664 6 Hoffman MK, Goudar SS, Kodkany BS, Metgud M, Somannavar M, Okitawutshu J, et al; ASPIRIN Study Group. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, pla- cebo-controlled trial. Lancet. 2020;395(10220):285–293. Doi: 10.1016/S0140-6736(19)32973-3 7 Quinlivan JA. Simple and safe: preventing preterm birth with aspirin. Lancet. 2020;395(10220):250–252. Doi: 10.1016/S0140- 6736(20)30106-9 8 Subtil D, Goeusse P, Puech F, Lequien P, Biausque S, Breart G, et al; Essai Régional Aspirine Mère-Enfant (ERASME) Collaborative Group. Aspirin (100mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 1). BJOG. 2003;110(05):475–484. Doi: 10.1046/ j.1471-0528.2003. 02096.x 9 Mone F, Mulcahy C, McParland P, Breathnach F, Downey P, McCormack D, et al. Trial of feasibility and acceptability of routine low-dose aspirin versus Early Screening Test indicated aspirin for pre-eclampsia prevention (TEST study): a multicentre random- ised controlled trial. BMJ Open. 2018;8(07):e022056. Doi: 10.1136/bmjopen-2018-022056 10 Mallampati D, Grobman W, Rouse DJ, Werner EF. Strategies for prescribing aspirin to prevent preeclampsia: a cost-effectiveness analysis. Obstet Gynecol. 2019;134(03):537–544. Doi: 10.1097/ AOG.0000000000003413 11 De Kat AC, Hirst J, Woodward M, Kennedy S, Peters SA. Prediction models for preeclampsia: A systematic review. Pregnancy Hyper- tens. 2019;16:48–66. Doi: 10.1016/j.preghy.2019.03.005 12 Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145 (Suppl 1):1–33. Doi: 10.1002/ijgo.12802 13 Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al; International Society for the Study of Hypertension in Pregnancy (ISSHP) Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(01):24–43. Doi: 10.1161/HYPERTENSIONAHA.117.10803 Rev Bras Ginecol Obstet Vol. 43 No. 4/2021 © 2021. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved. Letter to the Editor338 210051 210051-Repply