A sensibilidade e a especificidade de teste de triagem urinário usado em um cenário de emergência para detectar gravidezes anormais no primeiro
trimestre
João L. G. Teixeira, Licenciatura; Paola Rabaioli, Licenciatura; Ricardo F. Savaris, MD, PhD
OBJETIVO: Avaliar o desempenho de um teste urinário para triagem de Gravidezes anormais no primeiro trimestre em mulheres em sala de emergência.
FORMA DE ESTUDO: Nesta coorte observacional, prospectiva, as mulheres com primeiro trimestre da gravidez confirmada (idade gestacional <12 semanas) forneciam uma amostra de urina para diagnosticar a viabilidade da gestação. Viabilidade de gravidez e testes de localização foram confirmadas por ultrassome / ou laparoscopia.
RESULTADOS: De 815 pacientes elegíveis para o estudo, 12 foram excluídas por não ter uma gravidez confirmada (n ¼ 6) ou foram perdidos para follow-up(n ¼ 6). Um total de 803 pacientes foram submetidas a testes e completaram o seguimento. A
52 probabilidade pré-teste de uma gravidez anormal foi de 44%(9% para a gravidez ectópica e 35% para aborto).
O ensaio teve os seguintes parâmetros para identificar uma gravidez anormal no primeiro trimestre:
(sensibilidade, 13%; 95% intervalo de confiança [IC], 10 e 17; especificidade, 82%; 95% CI, 78 e 86; valor preditivo positivo, 36; 95% CI, 28 e 46;valor preditivo negativo, 54; 95% CI, 50 e 58; exatidão, 47%; razão de verossimilhança positiva, 0,74; 95% CI, 0.53 e 1.03; verossimilhança negativa proporção, 1,06; 95% CI, 1 e 1.12). A reprodutibilidade do teste no nosso estudo foi alta (índice de kappa entre os leitores, 0,89; 95% CI,0.77 e 1).
CONCLUSÃO: Em nosso cenário de emergência, o teste comercial não foi adequado para confirmar ou excluir uma gravidez anormal no primeiro trimestre.
PALAVRAS-CHAVE: gravidez anormal, primeiro trimestre, Inexscreen, gravidez, teste de triagem, sensibilidade, especificidade
53 ANEXOS
Nosso artigo teve uma citação em formato Editorial, publicado pelo Dr. Kurt Barnhart na revista internacional “American Journal of Obstetrics & Gynecology”.
Parte do texto destaca nosso estudo. “Mais uma vez, gostaria de elogiar os autores pela condução e publicação de um estudo de validação de fase IV de alta qualidade.
54 REFERÊNCIAS BIBLIOGRÁFICAS
1. Creanga AA, Syverson C, Seed K, Callaghan WM. Pregnancy-Related Mortality in the United States, 2011-2013. Obstetrics and gynecology. 2017. Epub 2017/07/12.
2. Crochet JR, Bastian LA, Chireau MV. Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review. Jama. 2013;309(16):1722-9. Epub 2013/04/25. 3. Seow KM, Wang PH, Huang LW, Hwang JL. Transvaginal sono-guided aspiration of gestational sac concurrent with a local methotrexate injection for the treatment of unruptured cesarean scar pregnancy. Archives of gynecology and obstetrics. 2013;288(2):361-6. Epub 2013/02/28.
4. Eaton JL, Zhang X, Kazer RR. First-trimester bleeding and twin pregnancy outcomes after in vitro fertilization. Fertility and sterility. 2016;106(1):140-3. Epub 2016/04/10.
5. Rana P, Kazmi I, Singh R, Afzal M, Al-Abbasi FA, Aseeri A, et al. Ectopic pregnancy: a review. Archives of gynecology and obstetrics. 2013;288(4):747-57. Epub 2013/06/25.
6. Aaboud M, Aad G, Abbott B, Abdallah J, Abdinov O, Abeloos B, et al. A measurement of the calorimeter response to single hadrons and determination of the jet energy scale uncertainty using LHC Run-1 pp-collision data with the ATLAS detector. The European physical journal C, Particles and fields. 2017;77(1):26. Epub 2017/03/07.
7. Kharazmi E, Dossus L, Rohrmann S, Kaaks R. Pregnancy loss and risk of cardiovascular disease: a prospective population-based cohort study (EPIC-Heidelberg). Heart. 2011;97(1):49- 54. Epub 2010/12/03.
8. Barnhart KT. Novel diagnostic tests of ectopic pregnancy, if at first you don't succeed. American journal of obstetrics and gynecology. 2015;212(1):4-6. Epub 2014/12/23.
9. Mazouz S, Lee JK, Fernandez H. Evaluation of a urinary test as a diagnostic tool of a nonprogressive pregnancy. Fertility and sterility. 2011;95(2):783-6. Epub 2010/09/21.
10. Li C, Zhao WH, Zhu Q, Cao SJ, Ping H, Xi X, et al. Risk factors for ectopic pregnancy: a multi-center case-control study. BMC pregnancy and childbirth. 2015;15:187. Epub 2015/08/25. 11. Belics Z, Gerecz B, Csakany MG. [Early diagnosis of ectopic pregnancy]. Orvosi hetilap. 2014;155(29):1158-66. Epub 2014/07/14. A mehen kivuli fogamzas korai diagnosztikaja. 12. Bouyer J. [Epidemiology of ectopic pregnancy: incidence, risk factors and outcomes]. Journal de gynecologie, obstetrique et biologie de la reproduction. 2003;32(7 Suppl):S8-17. Epub 2003/12/31. Epidemiologie de la grossesse extra-uterine: incidence, facteurs de risque et consequences.
55 13. Zee J, Sammel MD, Chung K, Takacs P, Bourne T, Barnhart KT. Ectopic pregnancy prediction in women with a pregnancy of unknown location: data beyond 48 h are necessary. Hum Reprod. 2014;29(3):441-7. Epub 2013/12/20.
14. Alkemade HA, de Jongh GJ, Arnold WP, van de Kerkhof PC, Schalkwijk J. Levels of skin- derived antileukoproteinase (SKALP)/elafin in serum correlate with disease activity during treatment of severe psoriasis with cyclosporin A. The Journal of investigative dermatology. 1995;104(2):189-93. Epub 1995/02/01.
15. Li C, Meng CX, Zhao WH, Lu HQ, Shi W, Zhang J. Risk factors for ectopic pregnancy in women with planned pregnancy: a case-control study. European journal of obstetrics, gynecology, and reproductive biology. 2014;181:176-82. Epub 2014/08/26.
16. Shaw JL, Diamandis EP, Horne AW, Barnhart K, Bourne T, Messinis IE. Ectopic pregnancy. Clinical chemistry. 2012;58(9):1278-85. Epub 2012/03/06.
17. de Castro MB, Freitas Vilela AA, Oliveira AS, Cabral M, Souza RA, Kac G, et al. Sociodemographic characteristics determine dietary pattern adherence during pregnancy. Public health nutrition. 2015:1-7. Epub 2015/09/25.
18. Al-Turki HA. Ectopic pregnancy. Prevalence and risk factors in women attending a tertiary care hospital in Saudi Arabia. Saudi medical journal. 2012;33(8):875-8. Epub 2012/08/14.
19. Kumar V, Gupta J. Tubal ectopic pregnancy. BMJ clinical evidence. 2015;2015. Epub 2015/11/17.
20. Vichnin M. Ectopic pregnancy in adolescents. Current opinion in obstetrics & gynecology. 2008;20(5):475-8. Epub 2008/09/18.
21. Wirth N, Abou-Hamdan K, Spinosa A, Bohadana A, Martinet Y. [Passive smoking]. Revue de pneumologie clinique. 2005;61(1 Pt 1):7-15. Epub 2005/03/18. Le tabagisme passif.
22. Risk factor for ectopic pregnancy. Canadian family physician Medecin de famille canadien. 1999;45:300, 9-10. Epub 1999/03/05.
23. Li Z, Sullivan EA, Chapman M, Farquhar C, Wang YA. Risk of ectopic pregnancy lowest with transfer of single frozen blastocyst. Hum Reprod. 2015;30(9):2048-54. Epub 2015/07/24. 24. Menon S, Timms P, Allan JA, Alexander K, Rombauts L, Horner P, et al. Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women. Clinical microbiology reviews. 2015;28(4):969-85. Epub 2015/08/28.
25. Brito LR, Guedes Neto Ede P, Furich DG, Savaris RF. MUC1 (VPM654 and EPR1023) Expression in Mucosa of Fallopian Tubes With Ectopic Pregnancy is Altered. Applied immunohistochemistry & molecular morphology : AIMM. 2016;24(8):569-74. Epub 2015/10/09.
56 26. Soundravally R, Krishna Latha T, Soundara Raghavan S, Ananthanarayanan PH, Srilatha K. Diagnostic significance of total creatine kinase and its isoform in tubal ectopic pregnancy. The journal of obstetrics and gynaecology research. 2013;39(12):1587-91. Epub 2013/07/24. 27. Cartwright J, Duncan WC, Critchley HO, Horne AW. Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities. Reproduction. 2009;138(1):9-22. Epub 2009/03/27.
28. Daponte A, Pournaras S, Zintzaras E, Kallitsaris A, Lialios G, Maniatis AN, et al. The value of a single combined measurement of VEGF, glycodelin, progesterone, PAPP-A, HPL and LIF for differentiating between ectopic and abnormal intrauterine pregnancy. Hum Reprod. 2005;20(11):3163-6. Epub 2005/08/02.
29. Kuscu E, Vicdan K, Turhan NO, Oguz S, Zorlu G, Gokmen O. The hormonal profile in ectopic pregnancies. Materia medica Polona Polish journal of medicine and pharmacy. 1993;25(3-4):149-52. Epub 1993/07/01.
30. Mueller MD, Raio L, Spoerri S, Ghezzi F, Dreher E, Bersinger NA. Novel placental and nonplacental serum markers in ectopic versus normal intrauterine pregnancy. Fertility and sterility. 2004;81(4):1106-11. Epub 2004/04/07.
31. Shahinian JH, Fuellgraf H, Tholen S, Mastroianni J, Knopf JD, Kuehs M, et al. Pregnancy Specific beta-1 Glycoprotein 1 is Expressed in Pancreatic Ductal Adenocarcinoma and its Subcellular Localization Correlates with Overall Survival. Journal of Cancer. 2016;7(14):2018-27. Epub 2016/11/24.
32. Rajtar-Ciosek A, Wyroba J, Kacalska-Jansen O, Zmaczynski A, Figula J, Babczyk D, et al. Markers of implantation in ectopic and high-risk early eutopic pregnancies. Folia medica Cracoviensia. 2016;56(3):41-50. Epub 2016/01/01.
33. Petraglia F, Sawchenko P, Lim AT, Rivier J, Vale W. Localization, secretion, and action of inhibin in human placenta. Science. 1987;237(4811):187-9. Epub 1987/07/10.
34. Florio P, Severi FM, Bocchi C, Luisi S, Mazzini M, Danero S, et al. Single serum activin a testing to predict ectopic pregnancy. The Journal of clinical endocrinology and metabolism. 2007;92(5):1748-53. Epub 2007/03/08.
35. Mantzavinos T, Phocas I, Chrelias H, Sarandakou A, Zourlas PA. Serum levels of steroid and placental protein hormones in ectopic pregnancy. European journal of obstetrics, gynecology, and reproductive biology. 1991;39(2):117-22. Epub 1991/04/16.
36. Witt BR, Wolf GC, Wainwright CJ, Johnston PD, Thorneycroft IH. Relaxin, CA-125, progesterone, estradiol, Schwangerschaft protein, and human chorionic gonadotropin as predictors of outcome in threatened and nonthreatened pregnancies. Fertility and sterility. 1990;53(6):1029-36. Epub 1990/06/01.
57 37. Dhiman P, Senthilkumar GP, Rajendiran S, Sivaraman K, Soundararaghavan S, Kulandhasamy M. Serum activin B concentration as predictive biomarker for ectopic pregnancy. Clinical biochemistry. 2016. Epub 2016/03/13.
38. Matthews CP, Coulson PB, Wild RA. Serum progesterone levels as an aid in the diagnosis of ectopic pregnancy. Obstetrics and gynecology. 1986;68(3):390-4. Epub 1986/09/01.
39. Buck RH, Joubert SM, Norman RJ. Serum progesterone in the diagnosis of ectopic pregnancy: a valuable diagnostic test? Fertility and sterility. 1988;50(5):752-5. Epub 1988/11/01. 40. Illingworth PJ, Groome NP, Duncan WC, Grant V, Tovanabutra S, Baird DT, et al. Measurement of circulating inhibin forms during the establishment of pregnancy. The Journal of clinical endocrinology and metabolism. 1996;81(4):1471-5. Epub 1996/04/01.
41. Treetampinich C, O'Connor AE, MacLachlan V, Groome NP, de Kretser DM. Maternal serum inhibin A concentrations in early pregnancy after IVF and embryo transfer reflect the corpus luteum contribution and pregnancy outcome. Hum Reprod. 2000;15(9):2028-32. Epub 2000/09/01.
42. D'Antona D, Mamers PM, Lowe PJ, Balazs N, Groome NP, Wallace EM. Evaluation of serum inhibin A as a surveillance marker after conservative management of tubal pregnancy. Hum Reprod. 1998;13(8):2305-7. Epub 1998/10/02.
43. Segal S, Gor H, Correa N, Mercado R, Veenstra K, Rivnay B. Inhibin A: marker for diagnosis of ectopic and early abnormal pregnancies. Reproductive biomedicine online. 2008;17(6):789-94. Epub 2008/12/17.
44. Guillaume J, Benjamin F, Sicuranza BJ, Deutsch S, Seltzer VL, Tores W. Serum estradiol as an aid in the diagnosis of ectopic pregnancy. Obstetrics and gynecology. 1990;76(6):1126-9. Epub 1990/12/01.
45. Jones EA, Clement-Jones M, James OF, Wilson DI. Differences between human and mouse alpha-fetoprotein expression during early development. Journal of anatomy. 2001;198(Pt 5):555-9. Epub 2001/06/30.
46. Grosskinsky CM, Hage ML, Tyrey L, Christakos AC, Hughes CL. hCG, progesterone, alpha- fetoprotein, and estradiol in the identification of ectopic pregnancy. Obstetrics and gynecology. 1993;81(5 ( Pt 1)):705-9. Epub 1993/05/01.
47. Canney PA, Moore M, Wilkinson PM, James RD. Ovarian cancer antigen CA125: a prospective clinical assessment of its role as a tumour marker. British journal of cancer. 1984;50(6):765-9. Epub 1984/12/01.
48. Halila H, Stenman UH, Seppala M. Ovarian cancer antigen CA 125 levels in pelvic inflammatory disease and pregnancy. Cancer. 1986;57(7):1327-9. Epub 1986/04/01.
58 49. Brumsted JR, Nakajima ST, Badger G, Riddick DH, Gibson M. Serum concentration of CA- 125 during the first trimester of normal and abnormal pregnancies. The Journal of reproductive medicine. 1990;35(5):499-502. Epub 1990/05/01.
50. Weiss G, O'Byrne EM, Steinetz BG. Relaxin: a product of the human corpus luteum of pregnancy. Science. 1976;194(4268):948-9. Epub 1976/11/26.
51. Szlachter BN, Quagliarello J, Jewelewicz R, Osathanondh R, Spellacy WN, Weiss G. Relaxin in normal and pathogenic pregnancies. Obstetrics and gynecology. 1982;59(2):167-70. Epub 1982/02/01.
52. Garcia A, Skurnick JH, Goldsmith LT, Emmi A, Weiss G. Human chorionic gonadotropin and relaxin concentrations in early ectopic and normal pregnancies. Obstetrics and gynecology. 1990;75(5):779-83. Epub 1990/05/01.
53. Meunier K, Mignot TM, Maria B, Guichard A, Zorn JR, Cedard L. Predictive value of the active renin assay for the diagnosis of ectopic pregnancy. Fertility and sterility. 1991;55(2):432- 5. Epub 1991/02/01.
54. Rausch ME, Beer L, Sammel MD, Takacs P, Chung K, Shaunik A, et al. A disintegrin and metalloprotease protein-12 as a novel marker for the diagnosis of ectopic pregnancy. Fertility and sterility. 2011;95(4):1373-8. Epub 2011/02/01.
55. Birkhahn RH, Gaeta TJ, Suzuki T, Katoh H, Nagai R, Bove J. Serum levels of smooth muscle heavy-chain myosin in patients with ectopic pregnancy. Annals of emergency medicine. 2000;36(2):101-7. Epub 2000/08/05.
56. Fernandes da Silva MO, Elito J, Jr., Daher S, Camano L, Fernandes Moron A. Association of serum levels of vascular endothelial growth factor and early ectopic pregnancy. Clinical and experimental obstetrics & gynecology. 2013;40(4):489-91. Epub 2013/01/01.
57. Soriano D, Hugol D, Quang NT, Darai E. Serum concentrations of interleukin-2R (IL-2R), IL-6, IL-8, and tumor necrosis factor alpha in patients with ectopic pregnancy. Fertility and sterility. 2003;79(4):975-80. Epub 2003/05/17.
58. Rausch ME, Barnhart KT. Serum biomarkers for detecting ectopic pregnancy. Clinical obstetrics and gynecology. 2012;55(2):418-23. Epub 2012/04/19.
59. Mulayim N, Palter SF, Selam B, Arici A. Expression and regulation of interleukin-8 in human fallopian tubal cells. American journal of obstetrics and gynecology. 2003;188(3):651-6. Epub 2003/03/14.
60. Senturk LM, Arici A. Leukemia inhibitory factor in human reproduction. Am J Reprod Immunol. 1998;39(2):144-51. Epub 1998/03/20.
61. Bischof P. [Pregnancy proteins]. Annales d'endocrinologie. 1987;48(4):289-99. Epub 1987/01/01. Proteines de la grossesse.
59 62. Haenggi W, Bersinger NA, Altermatt HJ, Birkhaeuser MH. Placental protein 14 (PP14) does not predict endometrial status under hormone replacement therapy. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 1997;11(1):51-7. Epub 1997/02/01.
63. Nylund L, Gustafson O, Lindblom B, Pousette A, Seppala M, Riittinen L, et al. Placental protein 14 in human in-vitro fertilization early pregnancies. Hum Reprod. 1992;7(1):128-30. Epub 1992/01/01.
64. Zhao Z, Moley KH, Gronowski AM. Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases. Clinical biochemistry. 2013;46(10-11):953-60. Epub 2013/02/12. 65. Miura K, Higashijima A, Mishima H, Miura S, Kitajima M, Kaneuchi M, et al. Pregnancy- associated microRNAs in plasma as potential molecular markers of ectopic pregnancy. Fertility and sterility. 2015;103(5):1202-8 e1. Epub 2015/03/17.
66. Patrelli TS, Gizzo S, Plebani M, Basso D, Capobianco G, Bartolucci C, et al. The trend of VEGF-A and PlGF in pregnant patients: a perspective case-control study on 214 women. Clinical and experimental obstetrics & gynecology. 2012;39(1):57-64. Epub 2012/06/09.
67. Cederqvist LL, Killackey MA, Abdel-Latif N, Gupta R, Saxena BB. Alpha-fetoprotein and ectopic pregnancy. Br Med J (Clin Res Ed). 1983;286(6373):1247-8. Epub 1983/04/16.
68. Lazar L, Nagy B, Ban Z, Nagy GR, Papp Z. Presence of cell-free fetal DNA in plasma of women with ectopic pregnancies. Clinical chemistry. 2006;52(8):1599-601. Epub 2006/06/03.