Different risk-assessment models for prediction of preeclampsia and fetal growth restriction in the first trimester in a high-risk pregnancy – which models are better?

Abstract

BACKGROUND: An increase in the number of pregnant women with various extragenital and gynecological pathologies and motivation for delayed motherhood form a large cohort of patients with a high risk of adverse obstetric outcomes. In this regard, it is necessary to study new approaches that allow stratification of these risks and personalization of pregnancy management and timing of delivery.

AIM: The aim of this study was to compare the predictive values of using blood placental growth factor and pregnancy-associated plasma protein-A levels in combined first-trimester screening for the prediction of preeclampsia and fetal growth restriction in a high-risk pregnancy.

MATERIALS AND METHODS: This retrospective cohort study enrolled 158 women, who received antenatal care or gave birth on the premises from April 1, 2020 through December 31, 2022. The following comparison groups were defined: pregestational diabetes mellitus (n = 34; group I), chronic arterial hypertension (n = 25; group II); obesity (body mass index more than 30 kg/m²; n = 31; group III), older women (40 years and older) with an assisted reproductive technologies pregnancy (n = 8; group IV), and the control group (n = 60; group V). The endpoints of the study were determined as preeclampsia (early and late forms), fetal growth restriction, and the effect of acetylsalicylic acid administration on the risk of placenta-related complications. Various models were used to evaluate the diagnostic value of pregnancy-associated plasma protein-A and placental growth factor in predicting preeclampsia and fetal growth restriction, including maternal characteristics and history, as well as mean arterial pressure, uterine artery pulsatility index, placental growth factor and pregnancy-associated plasma protein-A levels. Statistical data processing was performed using Prism 9 GraphPad (USA).

RESULTS: In all high-risk groups, there was a significant decrease in placental growth factor levels compared to the control group (p = 0.032). In patients who have developed preeclampsia, placental growth factor levels were statistically lower. Pregnancy-associated plasma protein-A and placental growth factor have demonstrated the greatest validity for predicting preeclampsia [area under curve 0.88 (0.81–0.94), and 0.93 (0.88–0.99)], early [area under curve 0.88 (0.77–0.95), and 0.95 (0.88–0.99)] and late [area under curve 0.86 (0.72–0.9), and 0.91 (0.81–0.97)] forms. Fetal growth restriction prediction was less effective. Administration of acetylsalicylic acid from week 12 to weeks 35–36 of pregnancy contributed to a decrease in the overall risk of developing preeclampsia (relative risk 0.39; 95% confidence interval 0.23–0.65) and fetal growth restriction (in the fetal growth restriction subgroup) (relative risk 0.38; 95% confidence interval 0.12–0.96).

CONCLUSIONS: The most effective approach for predicting preeclampsia and fetal growth restriction should include assessment of maternal factors, mean arterial pressure, uterine artery pulsatility index, and placental growth factor. The combined use of pregnancy-associated plasma protein-A and placental growth factor does not significantly improve prognosis.

Keywords

pregnancy / preeclampsia / fetal growth restriction / pregnancy-associated plasma protein-A / placenta growth factor

References

[1] Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613–622. DOI: 10.1056/NEJMoa1704559

[2] Rolnik D.L., Wright D., Poon L.C., et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia // N. Engl. J. Med. 2017. Vol. 377. No. 7. P. 613–622. DOI: 10.1056/NEJMoa1704559

[3] Wright D, Syngelaki A, Akolekar R, et al. Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obstet Gynecol. 2015;213(1):62.e1–62.e10. DOI: 10.1016/j.ajog.2015.02.018

[4] Wright D., Syngelaki A., Akolekar R., et al. Competing risks model in screening for preeclampsia by maternal characteristics and medical history // Am. J. Obstet. Gynecol. 2015. Vol. 213. No. 1. P. 62.e1–62.e10. DOI: 10.1016/j.ajog.2015.02.018

[5] O’Gorman N, Wright D, Syngelaki A, et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11–13 weeks gestation. Am J Obstet Gynecol. 2016;214(1):103.e1–103.e12. DOI: 10.1016/j.ajog.2015.08.034

[6] O’Gorman N., Wright D., Syngelaki A., et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation // Am. J. Obstet. Gynecol. 2016. Vol. 214. No. 1. P. 103.e1–103.e12. DOI: 10.1016/j.ajog.2015.08.034

[7] Wright D, Wright A, Nicolaides KH. The competing risk approach for prediction of preeclampsia. Am J Obstet Gynecol. 2020;223(1):12–23.e7. DOI: 10.1016/j.ajog.2019.11.1247

[8] Wright D., Wright A., Nicolaides K.H. The competing risk approach for prediction of preeclampsia // Am. J. Obstet. Gynecol. 2020. Vol. 223. No. 1. P. 12–23.e7. DOI: 10.1016/j.ajog.2019.11.1247

[9] Tan MY, Wright D, Syngelaki A, 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(6):743–750. DOI: 10.1002/uog.19039

[10] Tan M.Y., Wright D., Syngelaki A., 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. Vol. 51. No. 6. P. 743–750. DOI: 10.1002/uog.19039

[11] Guy GP, Leslie K, Diaz Gomez D, et al. Implementation of routine first trimester combined screening for pre-eclampsia: a clinical effectiveness study. BJOG. 2021;128(2):149–156. DOI: 10.1111/1471-0528.16361

[12] Guy G.P., Leslie K., Diaz Gomez D., et al. Implementation of routine first trimester combined screening for pre-eclampsia: a clinical effectiveness study // BJOG. 2021. Vol. 128. No. 2. P. 149–156. DOI: 10.1111/1471-0528.16361

[13] Wright D, Tan MY, O’Gorman N, et al. Predictive performance of the competing risk model in screening for preeclampsia. Am J Obstet Gynecol. 2019;220(2):199.e1–199.e13. DOI: 10.1016/j.ajog.2018.11.1087

[14] Wright D., Tan M.Y., O’Gorman N., et al. Predictive performance of the competing risk model in screening for preeclampsia // Am. J. Obstet. Gynecol. 2019. Vol. 220. No. 2. P. 199.e1–199.e13. DOI: 10.1016/j.ajog.2018.11.1087

[15] Poon LC, Zymeri NA, Zamprakou A, et al. Protocol for measurement of mean arterial pressure at 11-13 weeks’ gestation. Fetal Diagn Ther. 2012;31(1):42–48. DOI: 10.1159/000335366

[16] Poon L.C., Zymeri N.A., Zamprakou A., et al. Protocol for measurement of mean arterial pressure at 11–13 weeks’ gestation // Fetal. Diagn. Ther. 2012. Vol. 31. No. 1. P. 42–48. DOI: 10.1159/000335366

[17] Plasencia W, Maiz N, Bonino S, et al. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2007;30(5):742–749. DOI: 10.1002/uog.5157

[18] Plasencia W., Maiz N., Bonino S., et al. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks in the prediction of pre-eclampsia // Ultrasound Obstet. Gynecol. 2007. Vol. 30. No. 5. P. 742–749. DOI: 10.1002/uog.5157

[19] Rossiiskoe obshchestvo akusherov-ginekologov; Assotsiatsiya anesteziologov-reanimatologov; Assotsiatsiya akusherskikh anesteziologov-reanimatologov. Preehklampsiya. Ehklampsiya. Oteki, proteinuriya i gipertenzivnye rasstroistva vo vremya beremennosti, v rodakh i poslerodovom periode. Klinicheskie rekomendatsii. 2021. (In Russ.) [cited 23 Jul 01]. Available from: https://cr.minzdrav.gov.ru/recomend/637_1

[20] Российское общество акушеров-гинекологов; Ассоциация анестезиологов-реаниматологов; Ассоциация акушерских анестезиологов-реаниматологов. Преэклампсия. Эклампсия. Отеки, протеинурия и гипертензивные расстройства во время беременности, в родах и послеродовом периоде. Клинические рекомендации. 2021 [дата обращения 01.07.23]. Доступ по ссылке: https://cr.minzdrav.gov.ru/recomend/637_1

[21] Gestational hypertension and preeclampsia: ACOG Practice Bulletin. Number 222. Obstetrics and gynecology. 2020;135(6):e237–e260. DOI: 10.1097/AOG.0000000000003891

[22] Gestational hypertension and preeclampsia: ACOG Practice Bulletin. Number 222 // Obstet. Gynecol. 2020. Vol. 135. No. 6. P. e237–e260. DOI: 10.1097/AOG.0000000000003891

[23] Villar J, Cheikh Ismail L, Victora CG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the newborn cross-sectional study of the INTERGROWTH-21st Project. Lancet. 2014;384(9946):857–868. DOI: 10.1016/S0140-6736(14)60932-6

[24] Villar J., Cheikh Ismail L., Victora C.G., et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project // Lancet. 2014. Vol. 384. No. 9946. P. 857–868. DOI: 10.1016/S0140-6736(14)60932-6

[25] Roberge S, Bujold E. Nicolaides KH. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis. Am J Obstet Gynecol. 2018;218(3):287–293.e1. DOI: 10.1016/j.ajog.2017.11.561

[26] Roberge S., Bujold E., Nicolaides K.H. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis // Am. J. Obstet. Gynecol. 2018. Vol. 218. No. 3. P. 287–293.e1. DOI: 10.1016/j.ajog.2017.11.561

[27] O’Gorman N, Wright D, Poon LC, 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(6):751–755. DOI: 10.1002/uog.17399

[28] O’Gorman N., Wright D., Poon L.C., 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. Vol. 49. No. 6. P. 751–755. DOI: 10.1002/uog.17399

[29] Tan MY, Syngelaki A, Poon LC, et al. Screening for pre-eclampsia by maternal factors and biomarkers at 11–13 weeks’ gestation. Ultrasound Obstet Gynecol. 2018;52(2):186–195. DOI: 10.1002/uog.19112

[30] Tan M.Y., Syngelaki A., Poon L.C., et al. Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation // Ultrasound Obstet. Gynecol. 2018. Vol.52. No. 2. P. 186–195. DOI: 10.1002/uog.19112

[31] Mazer Zumaeta A, Wright A, Syngelaki A, et al. Screening for trisomy at 11–13 weeks’ gestation: use of pregnancy-associated plasma protein-A, placental growth factor or both. Ultrasound Obstet Gynecol. 2020;56(3):408–415. DOI: 10.1002/uog.22140

[32] Mazer Zumaeta A., Wright A., Syngelaki A., et al. Screening for trisomy at 11-13 weeks’ gestation: use of pregnancy-associated plasma protein-A, placental growth factor or both // Ultrasound Obstet. Gynecol. 2020. Vol. 56. No. 3. P. 408–415. DOI: 10.1002/uog.22140

[33] Poon LC, Wright D, Thornton S, et al. Mini-combined test compared with NICE guidelines for early risk-assessment for pre-eclampsia: the SPREE diagnostic accuracy study. NIHR Journals Library; 2020. DOI: 10.3310/eme07080

[34] Poon L.C., Wright D., Thornton S., et al. Mini-combined test compared with NICE guidelines for early risk-assessment for pre-eclampsia: the SPREE diagnostic accuracy study // NIHR Journals Library. 2020. DOI: 10.3310/eme07080

[35] Noël L, Guy GP, Jones S, et al. Routine first-trimester combined screening for pre-eclampsia: pregnancy-associated plasma protein-A or placental growth factor? Ultrasound Obstet Gynecol. 2021;58(4):540–545. DOI: 10.1002/uog.23669

[36] Noël L., Guy G.P., Jones S., et al. Routine first-trimester combined screening for pre-eclampsia: pregnancy-associated plasma protein-A or placental growth factor? // Ultrasound Obstet. Gynecol. 2021. Vol. 58. No. 4. P. 540–545. DOI: 10.1002/uog.23669

[37] Hu J, Gao J, Liu J, et al. Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China. Ultrasound Obstet Gynecol. 2021;58(4):529–539. DOI: 10.1002/uog.23645

[38] Hu J., Gao J., Liu J., et al. Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China // Ultrasound Obstet. Gynecol. 2021. Vol. 58. No. 4. P. 529–539. DOI: 10.1002/uog.23645

[39] Wright D, Nicolaides KH. Aspirin delays the development of preeclampsia. Am J Obstet Gynecol. 2019;220(6):580.e1–580.e6. DOI: 10.1016/j.ajog.2019.02.034

[40] Wright D., Nicolaides K.H. Aspirin delays the development of preeclampsia // Am. J. Obstet. Gynecol. 2019. Vol. 220. No. 6. P. 580.e1–580.e6. DOI: 10.1016/j.ajog.2019.02.034

[41] Kapustin RV, Tcybuk EM, Korenevsky AV, et al. Efficacy of low doses of acetylsalicylic acid in the prevention of preeclampsia in women with type 1 and 2 diabetes mellitus. Reprod Med. 2021;2(4):144–154. DOI: 10.3390/reprodmed2040015

[42] Kapustin R.V., Tcybuk E.M., Korenevsky A.V., et al. Efficacy of low doses of acetylsalicylic acid in the prevention of preeclampsia in women with type 1 and 2 diabetes mellitus // Reprod. Med. 2021. Vol. 2. No. 4. P. 144–154. DOI: 10.3390/reprodmed2040015

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