Skip to main content
Top
Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Hypertension | Research

Second trimester maternal serum D-dimer combined with alpha-fetoprotein and free β-subunit of human chorionic gonadotropin predict hypertensive disorders of pregnancy: a systematic review and retrospective case–control study

Authors: Yiming Chen, Yijie Chen, Xue Wang, Xuelian Chu, Wenwen Ning, Linyuan Gu, Liyao Li, Zhen Xie, Caihe Wen

Published in: Journal of Translational Medicine | Issue 1/2021

Login to get access

Abstract

Background

This study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotropin (free β-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP).

Materials and methods

In this retrospective case–control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free β-hCG levels for HDP.

Results

DD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free β-hCG > DD > DD + AFP > DD + free β-hCG > AFP + free β-hCG > AFP > free β-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free β-hCG alone and AFP + free β-hCG could reduce false positive rate and improve + LR.

Conclusion

DD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free β-hCG + AFP had the greatest diagnostic value for SPE.
Literature
1.
go back to reference Webster K, Fishburn S, Maresh M, Findlay SC, Chappell LC. Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance. BMJ. 2019;366:l5119.CrossRef Webster K, Fishburn S, Maresh M, Findlay SC, Chappell LC. Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance. BMJ. 2019;366:l5119.CrossRef
2.
go back to reference Boffa RJ, Constanti M, Floyd CN, Wierzbicki AS. Hypertension in adults: summary of updated NICE guidance. BMJ. 2019;367:l5310.CrossRef Boffa RJ, Constanti M, Floyd CN, Wierzbicki AS. Hypertension in adults: summary of updated NICE guidance. BMJ. 2019;367:l5310.CrossRef
3.
go back to reference Chopra HK, Ram C. Recent guidelines for hypertension. Circ Res. 2019;124:984–6.CrossRef Chopra HK, Ram C. Recent guidelines for hypertension. Circ Res. 2019;124:984–6.CrossRef
4.
go back to reference Magee LA, von Dadelszen P. State-of-the-art diagnosis and treatment of hypertension in pregnancy. Mayo Clin Proc. 2018;93:1664–77.CrossRef Magee LA, von Dadelszen P. State-of-the-art diagnosis and treatment of hypertension in pregnancy. Mayo Clin Proc. 2018;93:1664–77.CrossRef
5.
go back to reference Butalia S, Audibert F, Cote AM, Firoz T, Logan AG, Magee LA, et al. Hypertension Canada’s 2018 guidelines for the management of hypertension in pregnancy. Can J Cardiol. 2018;34:526–31.CrossRef Butalia S, Audibert F, Cote AM, Firoz T, Logan AG, Magee LA, et al. Hypertension Canada’s 2018 guidelines for the management of hypertension in pregnancy. Can J Cardiol. 2018;34:526–31.CrossRef
6.
go back to reference Armaly Z, Jadaon JE, Jabbour A, Abassi ZA. Preeclampsia: novel mechanisms and potential therapeutic approaches. Front Physiol. 2018;9:973.CrossRef Armaly Z, Jadaon JE, Jabbour A, Abassi ZA. Preeclampsia: novel mechanisms and potential therapeutic approaches. Front Physiol. 2018;9:973.CrossRef
7.
go back to reference Di Leo V, Capaccio F, Gesualdo L. Preeclampsia and glomerulonephritis: a bidirectional association. Curr Hypertens Rep. 2020;22:36.CrossRef Di Leo V, Capaccio F, Gesualdo L. Preeclampsia and glomerulonephritis: a bidirectional association. Curr Hypertens Rep. 2020;22:36.CrossRef
8.
go back to reference Kibret KT, Chojenta C, D’Arcy E, Loxton D. The effect of dietary patterns on hypertensive disorders of pregnancy in North Shewa, Ethiopia: a propensity score matched case-control study. Pregnancy Hypertension. 2020;22:24–9.CrossRef Kibret KT, Chojenta C, D’Arcy E, Loxton D. The effect of dietary patterns on hypertensive disorders of pregnancy in North Shewa, Ethiopia: a propensity score matched case-control study. Pregnancy Hypertension. 2020;22:24–9.CrossRef
10.
go back to reference Alldred SK, Takwoingi Y, Guo B, Pennant M, Deeks JJ, Neilson JP, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down’s syndrome screening. Cochrane Database Syst Rev. 2017;3:D12600. Alldred SK, Takwoingi Y, Guo B, Pennant M, Deeks JJ, Neilson JP, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down’s syndrome screening. Cochrane Database Syst Rev. 2017;3:D12600.
12.
go back to reference Baboolall U, Zha Y, Gong X, Deng DR, Qiao F, Liu H. Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies: a retrospective observational cohort study. Medicine (Baltimore). 2019;98:e15903.CrossRef Baboolall U, Zha Y, Gong X, Deng DR, Qiao F, Liu H. Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies: a retrospective observational cohort study. Medicine (Baltimore). 2019;98:e15903.CrossRef
13.
go back to reference Kim SJ, Ahn HJ, Park JY, Kim BJ, Hwang KR, Lee TS, et al. The clinical significance of D-dimer concentrations in patients with gestational hypertensive disorders according to the severity. Obstet Gynecol Sci. 2017;60:542–8.CrossRef Kim SJ, Ahn HJ, Park JY, Kim BJ, Hwang KR, Lee TS, et al. The clinical significance of D-dimer concentrations in patients with gestational hypertensive disorders according to the severity. Obstet Gynecol Sci. 2017;60:542–8.CrossRef
14.
go back to reference Tripodi A. D-dimer testing in laboratory practice. Clin Chem. 2011;57:1256–62.CrossRef Tripodi A. D-dimer testing in laboratory practice. Clin Chem. 2011;57:1256–62.CrossRef
15.
go back to reference Ercan S, Ozkan S, Yucel N, Orcun A. Establishing reference intervals for D-dimer to trimesters. J Matern Fetal Neonatal Med. 2015;28:983–7.CrossRef Ercan S, Ozkan S, Yucel N, Orcun A. Establishing reference intervals for D-dimer to trimesters. J Matern Fetal Neonatal Med. 2015;28:983–7.CrossRef
16.
go back to reference Rodriguez-Pena Y, Ibanez-Pinilla M. Elevated levels of D-dimer tested by immunoturbidimetry are associated with the extent of severity of pre-eclampsia. Int J Gynaecol Obstet. 2020;150:241–7.CrossRef Rodriguez-Pena Y, Ibanez-Pinilla M. Elevated levels of D-dimer tested by immunoturbidimetry are associated with the extent of severity of pre-eclampsia. Int J Gynaecol Obstet. 2020;150:241–7.CrossRef
17.
go back to reference Lalic-Cosic S, Dopsaj V, Kovac M, Pruner I, Littmann K, Mandic-Markovic V, et al. Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia. Int J Lab Hematol. 2020;42:322–30.CrossRef Lalic-Cosic S, Dopsaj V, Kovac M, Pruner I, Littmann K, Mandic-Markovic V, et al. Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia. Int J Lab Hematol. 2020;42:322–30.CrossRef
18.
go back to reference Yiming C, Sha LU, Pei HE, et al. Correlation between preeclampsia and second-trimester maternal serum levels of AFP and free β-HCG. J Wenzhou Med Univ. 2018;48:115–8 (Artile in Chinesewith English abstract). Yiming C, Sha LU, Pei HE, et al. Correlation between preeclampsia and second-trimester maternal serum levels of AFP and free β-HCG. J Wenzhou Med Univ. 2018;48:115–8 (Artile in Chinesewith English abstract).
19.
go back to reference Bredaki FE, Matalliotakis M, Wright A, Wright D, Nicolaides KH. Maternal serum alpha-fetoprotein at 12, 22 and 32 weeks’ gestation in screening for pre-eclampsia. Ultrasound Obstet Gynecol. 2016;47:466–71.CrossRef Bredaki FE, Matalliotakis M, Wright A, Wright D, Nicolaides KH. Maternal serum alpha-fetoprotein at 12, 22 and 32 weeks’ gestation in screening for pre-eclampsia. Ultrasound Obstet Gynecol. 2016;47:466–71.CrossRef
20.
go back to reference Hayes-Ryan D, Hemming K, Breathnach F, et al. PARROT Ireland: placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a Stepped Wedge Cluster Randomised Control Trial Research Study Protocol. BMJ Open. 2019;9:e023562.CrossRef Hayes-Ryan D, Hemming K, Breathnach F, et al. PARROT Ireland: placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a Stepped Wedge Cluster Randomised Control Trial Research Study Protocol. BMJ Open. 2019;9:e023562.CrossRef
21.
go back to reference Litwinska M, Wright D, Efeturk T, et al. Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 19–24 weeks’ gestation. Ultrasound Obstet Gynecol. 2017;50:367–72.CrossRef Litwinska M, Wright D, Efeturk T, et al. Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 19–24 weeks’ gestation. Ultrasound Obstet Gynecol. 2017;50:367–72.CrossRef
22.
go back to reference Chinese Medical Association Obstetrics and Gynecology Branch Pregnancy Hypertension Disease Group. Guidelines for diagnosis and treatment of hypertension during pregnancy (2015). Chin J Obstet Gynecol. 2015;50:721–8 (Artile in Chinese). Chinese Medical Association Obstetrics and Gynecology Branch Pregnancy Hypertension Disease Group. Guidelines for diagnosis and treatment of hypertension during pregnancy (2015). Chin J Obstet Gynecol. 2015;50:721–8 (Artile in Chinese).
23.
go back to reference Gosselin Robert C, Dwyre Denis W. Determining the effect of freezing on coagulation testing: comparison of results between fresh and once frozen-thawed plasma. Blood Coagul Fibrinolysis. 2015;26:69–74.CrossRef Gosselin Robert C, Dwyre Denis W. Determining the effect of freezing on coagulation testing: comparison of results between fresh and once frozen-thawed plasma. Blood Coagul Fibrinolysis. 2015;26:69–74.CrossRef
24.
go back to reference Chen Y, Xie Z, Wang X, Xiao Q, Lu X, Lu S, et al. A risk model of prenatal screening markers in first trimester for predicting hypertensive disorders of pregnancy. EPMA J. 2020;11:343–53.CrossRef Chen Y, Xie Z, Wang X, Xiao Q, Lu X, Lu S, et al. A risk model of prenatal screening markers in first trimester for predicting hypertensive disorders of pregnancy. EPMA J. 2020;11:343–53.CrossRef
25.
go back to reference Romero R, Erez O, Maymon E, et al. The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study. Am J Obstet Gynecol. 2017;217:67.e1-67.e21.CrossRef Romero R, Erez O, Maymon E, et al. The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study. Am J Obstet Gynecol. 2017;217:67.e1-67.e21.CrossRef
26.
go back to reference Riise H, Sulo G, Tell GS, et al. Hypertensive pregnancy disorders increase the risk of maternal cardiovascular disease after adjustment for cardiovascular risk factors. Int J Cardiol. 2019;282:81–7.CrossRef Riise H, Sulo G, Tell GS, et al. Hypertensive pregnancy disorders increase the risk of maternal cardiovascular disease after adjustment for cardiovascular risk factors. Int J Cardiol. 2019;282:81–7.CrossRef
27.
go back to reference Sjaus A, McKeen DM, George RB. Hypertensive disorders of pregnancy. Can J Anaesth. 2016;63:1075–97.CrossRef Sjaus A, McKeen DM, George RB. Hypertensive disorders of pregnancy. Can J Anaesth. 2016;63:1075–97.CrossRef
28.
go back to reference Xiong T, Mu Y, Liang J, et al. Hypertensive disorders in pregnancy and stillbirth rates: a facility-based study in China. B World Health Organ. 2018;96:531–9.CrossRef Xiong T, Mu Y, Liang J, et al. Hypertensive disorders in pregnancy and stillbirth rates: a facility-based study in China. B World Health Organ. 2018;96:531–9.CrossRef
29.
go back to reference Dusse LM, Alpoim PN, Lwaleed BA, de Sousa LP, Carvalho M, Gomes KB. Is there a link between endothelial dysfunction, coagulation activation and nitric oxide synthesis in preeclampsia? Clin Chim Acta. 2013;415:226–9.CrossRef Dusse LM, Alpoim PN, Lwaleed BA, de Sousa LP, Carvalho M, Gomes KB. Is there a link between endothelial dysfunction, coagulation activation and nitric oxide synthesis in preeclampsia? Clin Chim Acta. 2013;415:226–9.CrossRef
30.
go back to reference Riley RS, Gilbert AR, Dalton JB, Pai S, McPherson RA. Widely used types and clinical applications of D-dimer assay. Lab Med. 2016;47:90–102.CrossRef Riley RS, Gilbert AR, Dalton JB, Pai S, McPherson RA. Widely used types and clinical applications of D-dimer assay. Lab Med. 2016;47:90–102.CrossRef
31.
go back to reference Favresse J, Lippi G, Roy PM, et al. D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications. Crit Rev Cl Lab Sci. 2018;55:548–77.CrossRef Favresse J, Lippi G, Roy PM, et al. D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications. Crit Rev Cl Lab Sci. 2018;55:548–77.CrossRef
32.
go back to reference Yiming C, Jianxia H, Xiaochun S, Pei He, Yonghai S. Correlation and diagnostic value of maternal plasma D-dimer and preeclampsia in late pregnancy. Lab Med. 2020;35:753–6 (Artile in Chinese with English abstract). Yiming C, Jianxia H, Xiaochun S, Pei He, Yonghai S. Correlation and diagnostic value of maternal plasma D-dimer and preeclampsia in late pregnancy. Lab Med. 2020;35:753–6 (Artile in Chinese with English abstract).
33.
go back to reference Marcq G, Beaugrand Dubart L, Tournoys A, Subtil D, Deruelle P. [Evaluation of D-dimer as a marker for severity in pregnancies with preeclampsia]. Gynecol Obstet Fertil. 2014;42:393–8.CrossRef Marcq G, Beaugrand Dubart L, Tournoys A, Subtil D, Deruelle P. [Evaluation of D-dimer as a marker for severity in pregnancies with preeclampsia]. Gynecol Obstet Fertil. 2014;42:393–8.CrossRef
34.
go back to reference Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem. 2005;51:825–9.CrossRef Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem. 2005;51:825–9.CrossRef
35.
go back to reference Gutierrez GI, Perez CP, Martinez UJ, Garcia IO, Angeles JPM, Garcia DGRL. D-dimer during pregnancy: establishing trimester-specific reference intervals. Scand J Clin Lab Invest. 2018;78:439–42.CrossRef Gutierrez GI, Perez CP, Martinez UJ, Garcia IO, Angeles JPM, Garcia DGRL. D-dimer during pregnancy: establishing trimester-specific reference intervals. Scand J Clin Lab Invest. 2018;78:439–42.CrossRef
36.
go back to reference Arabin B, Baschat AA. Pregnancy: An underutilized window of opportunity to improve long-term maternal and infant health-an appeal for continuous family care and interdisciplinary communication. Front Pediatr. 2017;5:69.CrossRef Arabin B, Baschat AA. Pregnancy: An underutilized window of opportunity to improve long-term maternal and infant health-an appeal for continuous family care and interdisciplinary communication. Front Pediatr. 2017;5:69.CrossRef
37.
go back to reference Ornaghi S, Algeri P, Todyrenchuk L, Vertemati E, Vergani P. Impact of excessive pre-pregnancy body mass index and abnormal gestational weight gain on pregnancy outcomes in women with chronic hypertension. Pregnancy Hypertens. 2018;12:90–5.CrossRef Ornaghi S, Algeri P, Todyrenchuk L, Vertemati E, Vergani P. Impact of excessive pre-pregnancy body mass index and abnormal gestational weight gain on pregnancy outcomes in women with chronic hypertension. Pregnancy Hypertens. 2018;12:90–5.CrossRef
38.
go back to reference Santos S, Voerman E, Amiano P, et al. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European North American and Australian cohorts. BJOG. 2019;126:984–95.PubMedPubMedCentral Santos S, Voerman E, Amiano P, et al. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European North American and Australian cohorts. BJOG. 2019;126:984–95.PubMedPubMedCentral
39.
go back to reference 2020. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstet Gynecol 135:1492–5. 2020. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstet Gynecol 135:1492–5.
40.
go back to reference Cuckle H, Maymon R. Development of prenatal screening—a historical overview. Semin Perinatol. 2016;40:12–22.CrossRef Cuckle H, Maymon R. Development of prenatal screening—a historical overview. Semin Perinatol. 2016;40:12–22.CrossRef
41.
go back to reference Hoffman MK, Goudar SS, Kodkany BS, et al. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2020;395:285–93.CrossRef Hoffman MK, Goudar SS, Kodkany BS, et al. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2020;395:285–93.CrossRef
42.
go back to reference Chaemsaithong P, Cuenca-Gomez D, Plana MN, Gil MM, Poon LC. Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia? Am J Obstet Gynecol. 2020;222:437–50.CrossRef Chaemsaithong P, Cuenca-Gomez D, Plana MN, Gil MM, Poon LC. Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia? Am J Obstet Gynecol. 2020;222:437–50.CrossRef
43.
go back to reference Tritschler T, Kraaijpoel N, Le Gal G, Wells PS. Venous thromboembolism: advances in diagnosis and treatment. JAMA. 2018;320(15):1583–94.CrossRef Tritschler T, Kraaijpoel N, Le Gal G, Wells PS. Venous thromboembolism: advances in diagnosis and treatment. JAMA. 2018;320(15):1583–94.CrossRef
Metadata
Title
Second trimester maternal serum D-dimer combined with alpha-fetoprotein and free β-subunit of human chorionic gonadotropin predict hypertensive disorders of pregnancy: a systematic review and retrospective case–control study
Authors
Yiming Chen
Yijie Chen
Xue Wang
Xuelian Chu
Wenwen Ning
Linyuan Gu
Liyao Li
Zhen Xie
Caihe Wen
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-02718-4

Other articles of this Issue 1/2021

Journal of Translational Medicine 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.